Journal articles on the topic 'Robinson Research Institute'

In June 1985 a group of researchers involved in the study of alcohol problems in general practice in the UK met informally in York for discussion and exchange of ideas. The meeting was arranged under the auspices of Professor David Robinson of the Addiction Research Centre, Institute for Health Studies of the University of Hull. The group included GPs, psychiatrists, psychologists, sociologists, and other related research workers.

Dr. Amos Paran teaches MA and PhD students at the University College London’s Institute of Education. Fluent and literate in English, Hebrew, and German himself (with a bit of Spanish and French), he is probably best known for his research and writing on literature in foreign language learning. Among the recent books he has written, edited and co-edited are Literature —Into the Classroom with Pauline Robinson (2016), Testing the Untestable in Language Education (Multilingual Matters, 2010) with Lies Sercu, and Literature in Language Teaching and Learning (2006, TESOL).

The 2017 Annual General Meeting of the Canadian Society of Clinician Investigators (CSCI) and Clinician Investigator Trainee Association of Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was a national Annual General Meeting (AGM) held in Toronto, Ontario November 20–22, 2017, in conjunction with the University of Toronto Clinician Investigator Program Research Day. The theme for this year’s meeting was “Roll up your sleeves—How to manage your physician scientist career”, emphasizing lectures and workshops that were designed to provide tools for being proactive and successful in career planning. The keynote speakers were Dr. Rod McInnes (McGill University and Canadian Institutes of Health Research Acting President), who was the Distinguished Scientist Award recipient, Dr. David Goltzman (McGill University), who was the 2017 Henry Friesen Award recipient, Dr. Gillian Hawker (University of Toronto), Dr. Mike Sapieha (Université de Montréal), who was the 2017 Joe Doupe Award recipient, and Dr. Alex MacKenzie (Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa). The workshops, focusing on career development for clinician scientists, were hosted by Dr. Lisa Robinson, Dr. Nicola Jones, Kevin Vuong, Fran Brunelle, Dr. Jason Berman and Dr. Alan Underhill. Further to this, the Young Investigators’ Forum encompasses presentations from scientist-clinician trainees from across the country. All scientific abstracts are summarized in this review. There were over 100 abstracts showcased at this year’s meeting during the highlighted poster sessions, with six outstanding abstracts selected for oral presentations during the President’s Forum.

Although pareiasaurs are one of the most abundant and conspicuous elements of Late Permian terrestrial ecosystems, small individuals of these reptiles (either small species or juveniles of large species) are extremely rare. Until now, the smallest known pareiasaur is the type of the late, heavily armored form Anthodon (=Nanoparia) pricei (Bernard Price Institute of Palaeontological Research, Johannesburg 1/6), with a skull length of 10 cm and an inferred snout-vent length of approximately 50 cm. This is presumably an adult of a dwarf form, since all elements of the skull and postcranial skeleton are fully ossified, sutures are closed, and the dermal armor is more highly developed than in any other pareiasaur (Broom and Robinson, 1948; Brink, 1955; Findlay, 1970; Lee, 1997). A second and as yet undescribed specimen (Geological Survey, Pretoria CM86/544) is approximately the same size, being only very slightly larger (Lee, 1997). No other specimens of this taxon are known. An unnumbered humerus in the Amalitsky collection of the Palaeontological Institute, Moscow, is from a pareiasaur of similar size to the second specimen of A. pricei. However, this specimen is presumably a juvenile of a large form: the ends of the humerus are unossified, and the specimen comes from the North Dvina bone beds, which have yielded numerous specimens of the large pareiasaur Scutosaurus but no other pareiasaur taxon. Here, we re-evaluate a specimen originally described as a dicynodont tail, and later as a procolophonoid, and demonstrate that it is actually a juvenile of the pareiasaur Elginia mirabilis. It is also by far the smallest pareiasaur so far known, being approximately half the dimensions of the next smallest individual, the type specimen of Anthodon pricei. The newly recognized specimen provides new information on the ontogeny of pareiasaurs and the homology of some problematic skull elements.

The survey of these two sites was resumed on 1 July 1987. The Cremna season, directed by Stephen Mitchell, ran until 25 July; from 27 July to 20 August the team worked at Sagalassus under Marc Waelkens. The other participants were Mustafa Büyükkolancı, Sarah Cormack, Christopher Lightfoot and Edwin Owens (archaeologists), William Hargrove and Claire Robinson (student assistants), Anthea Cudworth, Robin Fursdon, Duncan Mallace, and Mark Willy (surveyors), Greg Horsley (epigraphist), and Kirsty Norman (conservator). Our representative was Sabri Aydal of Antalya Museum, who also provided valuable and expert assistance to the surveyors. We are grateful, as in previous seasons, to many local people for help and support: to Selçuk Başer, Ali Harmankaya and the staff of the Burdur Museum; to the officers of the Emniyet Müdürlüǧü at Burdur and of the Jandarma at Bucak and Aǧlasun; to the villagers at Çamlık, and to Sabit Kaya, Kaymakam of Aǧlasun, who provided us with accommodation. The work was funded by the British Academy, the British Institute of Archaeology at Ankara, the Craven Committee of Oxford University, the Roman Society, and the National Fund for Scientific Research (Belgium). Above all we are grateful to the Director General of Antiquities and Museums in Turkey, Nurettin Yardımcı, and to his staff, especially to Nimet Berkok and Mustafa Karahan, for granting permission for the survey and for much other assistance.

As the journal nears the end of its second official year, we are pleased to start accepting submissions to our first two Special Issues. The first Special Issue is on Resilience of complex coupled Socio-Technical-Environmental systems through the modeling lens with guest editors Tatiana Filatova, Tina Comes (4TU Resilience Engineering Centre), Christoph Hoelscher (ETH Zurich) and Juliet Mian (Resilence Shift). This Special Issue aims to bring together cutting-edge research and international practice to offer insights into the latest scientific modelling methods, gaps, challenges and opportunities and best practice examples relating to operationalising resilience across a range of socio-technical-environmental applications. The second Special Issue is on Large-scale behavioural models of land use change with guest editors Calum Brown (Karlsruhe Institute of Technology), Tatiana Filatova (University of Twente), Birgit Müller (Helmholtz Centre for Environmental Research – UFZ), and Derek Robinson (University of Waterloo). This Special Issue is focussed on better understanding and modelling of temporal or spatial scales in land use dynamics. We invite new proposals for Special Issues that fit within SESMO’s aims and scope. Our Special Issues are cohesive collections of articles focussed on a specific contemporary theme related to socio-environmental systems modelling. The Special Issue can build on previous work and research gaps, but can also explore new and emerging terrain relevant to our aims. Although the conceptualisation of a Special Issue may be initiated in a conference or workshop, it is critical that such a proposal also builds on the original dialogue. Articles should also be canvassed from across the globe. SESMO is an open access journal with no article processing or publication charges for authors. If you have a topic to propose, please contact us to discuss further.

Abstract Introduction Reviews of medication are vital to support medicine effectiveness and optimise person-centred care outcomes. However, inequalities negatively impact ethnic minority populations when accessing medicine review services.1 It is important to identify opportunities to improve access for these communities. Previous studies have demonstrated the significance of overcoming accessibility barriers, but specific detail about how best to achieve this is lacking.2,3 Through co-design workshops, this study seeks to integrate the voices of those people from ethnic minority populations to gain better insight into improving access to medicines review services for ethnic minority communities. Aim This qualitative, person-centred co-design study sought to build greater knowledge and understanding by involving representatives from communities whose needs may remain unmet. When considering the value that medication reviews can offer in optimising a person’s medication, this study aimed to: (i) better understand existing barriers that may impact those from ethnic minority communities when accessing services and to (ii) identify measures that may facilitate improved service accessibility for these groups. Methods A series of co-design workshops, with four groups of patient-stakeholders, were conducted between September-November 2021; they took place in-person or via video call whilst adhering to COVID-19 restrictions. Existing evidence-based perceptions affecting access to medicines services were critiqued and recommendations were generated to improve access for ethnic minority patients. The workshops were audio-recorded and transcribed verbatim to enable thematic analysis. QSR NVivo (Version 12) facilitated data analysis. The Health Research Authority granted ethical approval (ref: 21/HRA/1426). Results Twelve participants were recruited: including 8 UK citizens, 2 asylum seekers and 2 participants in receipt of residency visas. In total, 4 different ethnic minority groups were represented. Each participant took part in a first and second workshop to share and co-create recommendations. Three recommendations were developed and centred on: (i) delivering culturally competent medicines review services; (ii) building awareness of medicines review services and how to access them; and (iii) enabling better discussions with patients from ethnic minority communities. Discussion/Conclusion The results have important implications for overcoming ethnic inequalities in access to medicines reviews. The data highlighted the significance of raising awareness of the medicine review services and understanding each person’s lived experiences in order to address barriers that currently affect access. Delivering medication review services with cultural competency is vital; steps should be taken to address potential language barriers and build patient-provider relationships through in-person medication reviews. Collaborative co-production approaches could enable better design, implementation and delivery of medication services that are accessible and culturally competent, in order to best meet the needs of ethnic minority communities. Steps should be taken to address knowledge gaps around cultural competence training to enable the creation of pharmacies as inclusive, person-centred healthcare settings. Methods for improving person-centred communication within pharmacies should be further explored. Close, collaborative working with individual populations could enable specific tailoring of medicines review services that best meet the needs of the community. The National Institute for Health Research Applied Research Collaboration (NIHR ARC) and Newcastle University Patient and Public Involvement and Engagement group had extensive input in the study design and conceptualisation. Seven patient champions were appointed to the steering group to ensure that the research was conducted, and the findings were reported, with cultural competence and sensitivity. References 1. Robinson A, et al. A qualitative exploration of the barriers and facilitators affecting ethnic minority patient groups when accessing medicine review services: perspectives of healthcare professionals. Health Expectations, 2021. DOI: 10.1111/hex.13410. 2. Robinson A, et al. “He or she maybe doesn’t know there is such a thing as a review”: a qualitative investigation exploring barriers and facilitators to accessing medication reviews from the perspective of people from ethnic minority communities. Health Expectations, 2022. DOI: 10.1111/hex.13482. 3. Latif A, et al. A qualitative exploration to understand access to pharmacy medication reviews: views from marginalized patient groups. Pharmacy, 2020. DOI: 10.3390/pharmacy8020073.

The object of research was the pedigrees of strawberry varieties. An analysis of the genetic relationship of 129 varieties of domestic strawberry breeding, 6 parent forms, 2 of which are foreign varieties was carried out. Until the 1930s, strawberry culture in the USSR was based exclusively on Western European varieties: König Albert von Sachsen, Roschinskaya, Victoria, White Pine, Apricose, Konigin Luise, Noble Laxton, Siger, Spate von Leopoldshall, Kent’s Miracle, Sharpliss, Muto, etc. During the transition to the commercial production, these varieties were not insufficiently tolerant, which required the creation of a new assortment for various conditions of cultivation, and served as the beginning of the implementation of domestic strawberry breeding programs. At present, the State register of breeding achievements approved for use in 2020 includes 106 strawberry varieties, of which 82 are of domestic breeding. Existing domestic varieties have different geographical origins. The main Centers for strawberry breeding are: All-Russian Horticultural Institute for Breeding, Agrotechnology and Nursery, I.V. Michurin Federal Research Center, N. I. Vavilov All-Russian Institute of Plant Genetic Resources, North Caucasus Federal Research Center For Horticulture, Viticulture, and Winemaking, etc. Initially, the parent forms for creating a domestic assortment were European and American varieties: Culver, Deutsch Evern, Georg Soltwedel, Konigin Luise, Markee, König Albert von Sachsen Marshall, Macherauchs Marieva, Macherauchs Fruhernte, Muto, Premier, Red Coat, Red Gauntlet, Robinson, Senga Sengana, Sieger, Sparkle, Spate von Leopoldshall, Wander von Kothen. Analysis of pedigrees of 135 varieties from the 23 literature sources allowed to identify the most effective in the formation of domestic assortment genotypes of strawberry: Komsomolska (10 varieties in the first generation; 12 in the second; 14 in the third, 2 in the fourth), Mysovka (12 varieties in the first generation; 20 in the second; 21 – in the third; 2 in the fourth), Obilnaya (7 varieties in the first generation; 22 – the second; 20 for the third; 6 for the fourth), Festivalnaya (21 varieties in the first generation; 19 – in the second; 6 in the third), Culver (20 varieties in the first generation; 16 – in the second, 3 – in the third), Senga Sengana (13 varieties in the first generation; 7 – in the second; 4-in the third). The originator of 37.8% of domestic varieties included in the State register is the Obilnaya variety (Wander von Kothen × Deutsch Evern). On the basis of the Festivalnaya variety obtained with his participation (Obilnaya × Premier), an assortment was created that has not lost its relevance at the present time (26 varieties are included in the State register). The varieties Mysovka (Wander von Kothen × Deutsch Evern) and Zenga Zengana (Markee × Sieger) are included in the pedigree of 13 and 14 modern varieties, respectively. Based on the Komsomolka and Culver varieties, 7 and 9 varieties were created, respectively, which are currently included in the State register. Intraspecific hybridization has not exhausted the possibility of creating a genetically diverse breeding material. Taking into account the fact that domestic varieties often have closely related origin, it is desirable to involve introduced forms and varieties obtained with their participation in the breeding process more widely. The results of using various methods of breeding (inbreeding, saturating crosses) indicate that it is possible to further improve strawberry varieties creating donors of a high level of economically valuable traits. The current level of scientific knowledge and development of biotechnological research allows us to “model” varieties, including in the genotype of strawberry genes and gene blocks of valuable traits from closely related species, reducing the duration of the breeding process.

_ This article, written by JPT Technology Editor Chris Carpenter, contains highlights of paper OTC 31940, “Repurposing Gulf of Mexico Oil and Gas Facilities for the Blue Economy,” by Roy Robinson, SPE, Excipio Energy; Georg Englemann, Diamond Infrastructure Development; and Kent Saterlee, Gulf Offshore Research Institute. The paper has not been peer reviewed. _ This synopsis presents portions of the results of a Department of Energy (DOE) study of the potential for repurposing legacy oil and gas facilities in the Gulf of Mexico (GOM) for uses in a blue economy. The study was limited and was designed to summarize practical options for repurposing. The conclusions list those areas in which further modeling or studies are warranted, with the objective of building an integrated modeling tool to assist companies, government agencies, and nongovernmental organizations in assessing benefits and risks of repurposing facilities. Scope Limits of the Repurposing Study The term “blue economy” is defined by the World Bank as a sustainable use of ocean resources for economic growth, improved livelihoods and jobs, and ocean ecosystem health. The study upon which the paper is based was confined to the repurposing of oil and gas facilities in the GOM, specifically platforms, wells, pipelines, and rights of way. Producing, idle, and abandoned assets were considered. The objective was to explore how leveraging these existing facilities can reduce the carbon load of offshore oil and gas production, speed the energy transition by tapping the tremendous energy potential of the ocean, reduce US dependence on imported seafood and minerals, and create secure long-term employment along the Gulf Coast. Energy Resource Potential and Definition In 2020, the US National Renewable Energy Laboratory (NREL), at the request of the Bureau of Ocean Energy Management (BOEM), produced a report on the renewable energy potential of the GOM. NREL divides resource assessments into gross and technical potential. “Gross” is intended to be the total available resource. “Technical” is based on NREL’s assessment of how much of the resource could be captured economically using proven technology. Details are included in the complete paper because the NREL/BOEM report has caused some questions to be raised by those reviewing the DOE study. The authors’ commentary on this report is detailed in the complete paper.

BackgroundGliomas represent the most common brain tumors within the central nervous system, with glioblastoma being the most aggressive type.1 Conventional treatment combines several approaches including surgery, chemotherapy, and radiation.2 However, the prognosis for glioblastoma remains unfavorable, with only 5% of patients surviving more than 5 years post-diagnosis.3 Thus, new treatment approaches are urgently needed. Natural killer (NK) cells directly lyse malignantly transformed or virally infected cells and secrete inflammatory cytokines that polarize cytotoxic immunity. Allogeneic NK cell adoptive transfer has shown clinical benefit in patients with advanced cancer.4–7 However, limitations of this approach include relatively low numbers of donor NK cells that can be isolated during an apheresis and variability in the quality of NK cells between donors. To overcome these limitations, we have developed a GMP manufacturing strategy to mass produce NK cells from induced pluripotent stem cells (iPSCs) as an approach to off-the-shelf cancer immunotherapy. We refer to these cells as ‘iNK’ (iPSC-derived NK) cells. Here, we provide preclinical data demonstrating the efficacy of iNK cells for immunotherapy against glioblastoma.Abstract 155 Figure 1Engineered iNK cells exhibit highly effective antitumor function in a xenogeneic model of glioblastoma. (A) Schematic of the experimental design to test iNK cell function against glioblastoma in vivo. (B) Kaplan Meier plots showing survival for groups of mice that received either vehicle alone or iNK cells after tumor engraftment (n=5 mice/group)MethodsWe generated iNK cells using previously published methods.8–10 iNK cells were used as effectors against an array of patient-derived glioblastoma lines in 2-dimensional live imaging IncuCyte assays where iNK cell-mediated killing was observed over the course of 48 hours. To investigate iNK cell infiltration and cytotoxicity in a more physiological context that accounts for the 3-dimensional architecture of the tumor, we also performed live imaging IncuCyte assays using iNK cells as effectors against glioblastoma spheroids. To test the anti-tumor function of iNK cells in vivo, we implanted patient-derived glioblastoma cells into mice via intracranial injection. Seven days later, 5 mice received intratumoral injections of iNK cells, and 5 mice received vehicle alone (as a control; figure 1A). All mice were monitored for weight and survival over 100 days.Results iNK cells exhibited strong and sustained cytotoxicity against 6 primary patient-derived mesenchymal glioblastoma lines in 2-dimensional IncuCyte assays and complete infiltration and destruction of glioblastoma spheroids in 3-dimensional IncuCyte assays. In xenogeneic adoptive transfer experiments, all mice receiving intratumoral injections of iNK cells survived out to day 100, while all mice in the vehicle group became moribund and had to be sacrificed by day 60 (figure 1B).ConclusionsiNK cells are highly cytotoxic against glioblastoma cells, and our preclinical in vivo data provides proof-of-concept for future clinical trials.Ethics ApprovalThis project has been approved by the University of Minnesota IACUC. Approval ID: 1812-36595AReferencesLouis D N, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee W K, Ohgaki H, Wiestler O D, Kleihues P, Ellison D W. The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 2016;131:803–820.Stupp R, Mason W P, van den Bent M J, Weller M, Fisher B, Taphoorn M J B, Belanger K, Brandes A A, Marosi C, Bogdahn U, Curschmann J, Janzer R C, Ludwin S K, Gorlia T, Allgeier A, Lacombe D, Cairncross J G, Eisenhauer E, Mirimanoff R O, European Organization for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987–996.Thakkar JP, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD, Barnholz-Sloan JS, Villano JL. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev 2017;23:1985–1996.Miller J S, Soignier Y, Panoskaltsis-Mortari A, McNearney S A, Yun G H, Fautsch S K, McKenna D, Le C, Defor T E, Burns L J, Orchard P J, Blazar B R, Wagner J E, Slungaard A, Weisdorf D J, Okazaki J, McGlave P B. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 2005;105:3051–3057.Bachanova V, Cooley S, Defor T E, Verneris M R, Zhang B, McKenna D H, Curtsinger J, Panoskaltsis-Mortari A, Lewis D, Hippen K, McGlave P, Weisdorf D J, Blazar B R, Miller J S. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood 2014;123:3855.Ciurea S O, Schafer J R, Bassett R, Denman C J, Cao K, Willis D, Rondon G, Chen J, Soebbing D, Kaur I, Gulbis A, Ahmed S, Rezvani K, Scpall E J, Lee D A, Champlin R E. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplant. Blood 2017;130:1857–1868.Romee R, Rosario M, Berrien-Elliott M M, Wagner J A, Jewell B A, Schappe T, Leong J W, Abdel-Latif S, Schneider S E, Willey S, Neal C C, Yu L, Oh T, Lee S, Mulder A, Cooper M A, Fehniger T A. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukiemia. Sci Transl Med 2016:8;375ra123.Valamehr B, Abujarour R, Robinson M, Le T, Robbins D, Shoemaker D, Flynn P. A novel platform to enable the high-throughput derivation and characterization of feeder-free human iPSCs. Sci Rep 2012:2;213.Valamehr B, Robinson M, Abujarour R, Rezner B, Vranceanu F, Le T, Medcalf A, Lee T T, Fitch M, Robbins D, Flynn P. Platform for induction and maintenance of transgene-free hiPSCs resembling ground state pluripotent stem cells. Stem Cell Reports 2014;2:366–381.Zhu H, Blum R H, Bjordahl R, Gaidarova S, Rogers P, Lee T T, Abujarour R, Bonello G B, Wu J, Tsai P-F, Miller J S, Walcheck B, Valamehr B, Kaufman D S. Pluripotent stem cell-derived NK cells with high-affinity noncleavable CD16a mediate improved antitumor immunity. Blood 2020;135:399–410.

- G.W.J. Drewes, Taufik Abdullah, Islam and society in Southeast Asia, Institute of Southeast Asian studies, Singapore, 1986, XII and 348 pp., Sharon Siddique (eds.) - Th. van den End, T.Valentino Sitoy, A history of Christianity in the Philippines. The initial encounter , Vol. I, Quezon City (Philippines): New day publishers, 1985. - R. Hagesteijn, David G. Marr, Southeast Asia in the 9th to 14th centuries, Singapore: Institute of Southeast Asian studies and the research school of Pacific studies of the Australian National University, 1986, 416 pp., A.C. Milner (eds.) - R. Hagesteijn, Constance M. Wilson, The Burma-Thai frontier over sixteen decades - Three descriptive documents, Ohio University monographs in international studies, Southeast Asia series No. 70, 1985,120 pp., Lucien M. Hanks (eds.) - Barbara Harrisson, John S. Guy, Oriental trade ceramics in South-east Asia, ninth to sixteenth century, Oxford University Press, Singapore, 1986. [Revised, updated version of an exhibition catalogue issued in Australia in 1980, in the enlarged format of the Oxford in Asia studies of ceramic series.] 161 pp. with figs. and maps, 197 catalogue ills., numerous thereof in colour, extensive bibliography, chronol. tables, glossary, index. - V.J.H. Houben, G.D. Larson, Prelude to revolution. Palaces and politics in Surakarta, 1912-1942. VKI 124, Dordrecht/Providence: Foris publications 1987. - Marijke J. Klokke, Stephanie Morgan, Aesthetic tradition and cultural transition in Java and Bali. University of Wisconsin, Center for Southeast Asian studies, Monograph 2, 1984., Laurie Jo Sears (eds.) - Liaw Yock Fang, Mohamad Jajuli, The undang-undang; A mid-eighteenth century law text, Center for South-East Asian studies, University of Kent at Canterbury, Occasional paper No. 6, 1986, VIII + 104 + 16 pp. - S.D.G. de Lima, A.B. Adam, The vernacular press and the emergence of modern Indonesian consciousness (1855-1913), unpublished Ph. D. thesis, School of Oriental and African studies, University of London, 1984, 366 pp. - J. Thomas Lindblad, K.M. Robinson, Stepchildren of progress; The political economy of development in an Indonesian mining town, Albany: State University of New York Press, 1986, xv + 315 pp. - Pauline Lunsingh Scheurleer, J.E. van Lohuizen-de Leeuw, Indo-Javanese Metalwork, Linden-Museum, Stuttgart, Staatliches Museum für Völkerkunde, 1984, 218 pp. - H.M.J. Maier, V. Matheson, Perceptions of the Haj; Five Malay texts, Singapore: Institute of Southeast Asian studies (Research notes and discussions paper no. 46), 1984; 63 pp., A.C. Milner (eds.) - Wolfgang Marschall, Sandra A. Niessen, Motifs of life in Toba Batak texts and textiles, Verhandelingen KITLV 110. Dordrecht/Cinnaminson: Foris publications, 1985. VIII + 249 pp., 60 ills. - Peter Meel, Ben Scholtens, Opkomende arbeidersbeweging in Suriname. Doedel, Liesdek, De Sanders, De kom en de werklozenonrust 1931-1933, Nijmegen: Transculturele Uitgeverij Masusa, 1986, 224 pp. - Anke Niehof, Patrick Guinness, Harmony and hierarchy in a Javanese kampung, Asian Studies Association of Australia, Singapore: Oxford University Press, 1986, 191 pp. - C.H.M. Nooy-Palm, Toby Alice Volkman, Feasts of honor; Ritual and change in the Toraja Highlands, Urbana and Chicago: University of Illinois Press, Illinois Studies in Anthropology no. 16, 1985, IX + 217 pp., 2 maps, black and white photographs. - Gert J. Oostindie, Jean Louis Poulalion, Le Surinam; Des origines à l’indépendance. La Chapelle Monligeon, s.n., 1986, 93 pp. - Harry A. Poeze, Bob Hering, The PKI’s aborted revolt: Some selected documents, Townsville: James Cook University of North Queensland. (Occasional Paper 17.) IV + 100 pp. - Harry A. Poeze, Biografisch woordenboek van het socialisme en de arbeidersbeweging in Nederland; Deel I, Amsterdam: Stichting tot Beheer van Materialen op het Gebied van de Sociale Geschiedenis IISG, 1986. XXIV + 184 pp. - S. Pompe, Philipus M. Hadjon, Perlindungan hukum bagi rakyat di Indonesia, Ph.D thesis Airlangga University, Surabaya: Airlangga University Press, 1985, xviii + 308 pp. - J.M.C. Pragt, Volker Moeller, Javanische bronzen, Staatliche Museen Preussischer Kulturbesitz, Museum für Indische Kunst, Berlin, 1985. Bilderheft 51. 62 pp., ill. - J.J. Ras, Friedrich Seltmann, Die Kalang. Eine Volksgruppe auf Java und ihre Stamm-Myth. Ein beitrag zur kulturgeschichte Javas, Stuttgart: Franz Steiner Verlag Wiesbaden GmbH, 1987, 430 pp. - R. Roolvink, Russell Jones, Hikayat Sultan Ibrahim ibn Adham, Berkeley: Center for South and Southeast Asia Studies, University of California, Monograph Series no. 57, 1985. ix, 332 pp. - R. Roolvink, Russell Jones, Hikayat Sultan Ibrahim, Dordrecht/Cinnaminson: Foris, KITLV, Bibliotheca Indonesica vol. 24, 1983. 75 pp. - Wim Rutgers, Harry Theirlynck, Van Maria tot Rosy: Over Antilliaanse literatuur, Antillen Working Papers 11, Caraïbische Afdeling, Koninklijk Instituut voor Taal-, Land- en Volkenkunde, Leiden, 1986, 107 pp. - C. Salmon, John R. Clammer, ‘Studies in Chinese folk religion in Singapore and Malaysia’, Contributions to Southeast Asian Ethnography no. 2, Singapore, August 1983, 178 pp. - C. Salmon, Ingo Wandelt, Wihara Kencana - Zur chinesischen Heilkunde in Jakarta, unter Mitarbeit bei der Feldforschung und Texttranskription von Hwie-Ing Harsono [The Wihara Kencana and Chinese Therapeutics in Jakarta, with the cooperation of Hwie-Ing Harsono for the fieldwork and text transcriptions], Kölner ethopgraphische Studien Bd. 10, Berlin: Dietrich Reimer Verlag, 1985, 155 pp., 1 plate. - Mathieu Schoffeleers, 100 jaar fraters op de Nederlandse Antillen, Zutphen: De Walburg Pers, 1986, 191 pp. - Mathieu Schoffeleers, Jules de Palm, Kinderen van de fraters, Amsterdam: De Bezige Bij, 1986, 199 pp. - Henk Schulte Nordholt, H. von Saher, Emanuel Rodenburg, of wat er op het eiland Bali geschiedde toen de eerste Nederlanders daar in 1597 voet aan wal zetten. De Walburg Pers, Zutphen, 1986, 104 pp., 13 ills. and map. - G.J. Schutte, W.Ph. Coolhaas, Generale missiven van Gouverneurs-Generaal en Raden aan Heren XVII der Verenigde Oostindische Compagnie, VIII: 1725-1729, Rijks Geschiedkundige Publicatiën, Grote Serie 193, ‘s-Gravenhage, 1985, 275 pp. - H. Steinhauer, Jeff Siegel, Language contact in a plantation environment. A sociolinguistic history of Fiji, Cambridge: Cambridge University Press, 1987, xiv + 305 pp. [Studies in the social and cultural foundations of language 5.] - H. Steinhauer, L.E. Visser, Sahu-Indonesian-English Dictionary and Sahu grammar sketch, Verhandelingen van het KITLV 126, Dordrecht: Foris Publications, 1987, xiv + 258 pp., C.L. Voorhoeve (eds.) - Taufik Abdullah, H.A.J. Klooster, Indonesiërs schrijven hun geschiedenis: De ontwikkeling van de Indonesische geschiedbeoefening in theorie en praktijk, 1900-1980, Verhandelingen KITLV 113, Dordrecht/Cinnaminson: Foris Publications, 1985, Bibl., Index, 264 pp. - Maarten van der Wee, Jan Breman, Control of land and labour in colonial Java: A case study of agrarian crisis and reform in the region of Ceribon during the first decades of the 20th century, Verhandelingen of the Royal Institute of Linguistics and Anthropology, Leiden, No. 101, Dordrecht: Foris Publications, 1983. xi + 159 pp.

BackgroundRituximab is widely used to treat rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) but clinical response varies. Efficacy is determined by the efficiency of depletion, which may depend on a variety of Fc gamma receptor (FcγR)-dependent mechanisms. Previous research was limited by complexity of the FCGR locus, not integrating copy number variation with functional SNP, and small sample size.ObjectivesThe study objectives were to assess the effect of the full range of FcγRs variants on depletion, clinical response and functional effect on NK-cell-mediated killing in two rheumatic diseases with a view to personalised B-cell depleting therapies.MethodsA prospective longitudinal cohort study was conducted in 873 patients [RA=611; SLE=262] from four cohorts (BSRBR-RA and BILAG-BR registries, Leeds RA and Leeds SLE Biologics). For RA, the outcome measures were 3C-DAS28CRP and 2C-DAS28CRP at 6 (+/-3) months post-rituximab (adjusted for baseline DAS28). For SLE, major clinical response (MCR) was defined as improvement of active BILAG-2004 domains to grade C/better at 6 months. B-cell depletion was evaluated by highly-sensitive flow cytometry. Qualitative and quantitative polymorphisms for five major FcγRs were measured using a commercial multiplex ligation-dependent probe amplification. Median NK cell FcγRIIIa expression (CD3-CD56+CD16+) and NK-cell degranulation (CD107a) in the presence of rituximab-coated Daudi/Raji B-cell lines were assessed using flow cytometry.ResultsIn RA, for FCGR3A, carriage of V allele (coefficient -0.25 (SE 0.11); p=0.02) and increased copies of V allele (-0.20 (0.09); p=0.02) were associated with greater 2C-DAS28 response. Irrespective of FCGR3A genotype, increased gene copies were associated with a better response. In SLE, 177/262 (67.6%) achieved BILAG response [MCR=34.4%; Partial=33.2%]. MCR was associated with increased copies of FCGR3A-158V allele, OR 1.64 (95% CI 1.12-2.41) and FCGR2C-ORF allele 1.93 (1.09-3.40). Of patients with B-cells data in the combined cohort, 236/413 (57%) achieved complete depletion post-rituximab. Only homozygosity for FCGR3A-158V and increased FCGR3A-158V copy number were associated with increased odds of complete depletion. Patients with complete depletion had higher NK cell FcγRIIIa expression at rituximab initiation than those with incomplete depletion (p=0.04) and this higher expression was associated with improved EULAR response in RA. Moreover, for FCGR3A, degranulation activity was increased in V allele carriers vs FF genotype in the combined cohort; p=0.02.ConclusionFcγRIIIa is the major low affinity FcγR and increased copies of the FCGR3A-158V allele, encoding the allotype with a higher affinity for IgG1, was associated with clinical and biological responses to rituximab in two autoimmune diseases. This was supported by functional data on NK cell-mediated cytotoxicity. In SLE, increased copies of the FCGR2C-ORF allele was also associated with improved response. Our findings indicate that enhancing FcγR-effector functions could improve the next generation of CD20-depleting therapies and genotyping could stratify patients for optimal treatment protocols.ReferencesNoneAcknowledgementsThis research was funded/supported by the joint funding from the Medical Research Council (MRC) and Versus Arthritis of MATURA (grant codes 36661 and MR/K015346/1). MASTERPLANS was funded by the MRC (grant code MR/M01665X/1). The Leeds Biologics Cohort was part funded by programme grants from Versus Arthritis (grant codes 18475 and 18387), the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (BRC) and Diagnostic Evaluation Co-operative and the Ann Wilks Charitable Foundation. The BILAG-BR has received funding support from Lupus UK, and unrestricted grants from Roche and GSK.The functional studies were in part supported through a NIHR/HEFCE Clinical Senior Lectureship and a Versus Arthritis Foundation Fellowship (grant code 19764) to AWM, the Wellcome Trust Institutional Strategic Support Fund to JIR and MYMY (204825/Z/16/Z), NIHR Doctoral Research Fellowship to MYMY (DRF-2014-07-155) and NIHR Clinician Scientist to EMV (CS-2013-13-032). . AWM, INB, JDI and PE were supported by NIHR Senior Investigator awards. Work in JDI’s laboratory is supported by the NIHR Newcastle BRC, the Research Into Inflammatory Arthritis Centre Versus Arthritis, and Rheuma Tolerance for Cure (European Union Innovative Medicines Initiative 2, grant number 777357). INB is funded by the NIHR Manchester BRC.This article/paper/report presents independent research funded/supported by the NIHR Leeds BRC and the NIHR Guy’s and St Thomas’ BRC. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.Disclosure of InterestsMd Yuzaiful Md Yusof: None declared, James Robinson: None declared, Vinny Davies: None declared, Dawn Wild: None declared, Michael Morgan: None declared, John Taylor: None declared, Yasser El-Sherbiny: None declared, David Morris: None declared, Lu Liu: None declared, Andrew Rawstron: None declared, Maya H Buch: None declared, Darren Plant: None declared, Heather Cordell: None declared, John Isaacs: None declared, Ian N. Bruce: None declared, Paul Emery Speakers bureau: Roche, Consultant of: Roche, Grant/research support from: Roche, Anne Barton: None declared, Timothy Vyse: None declared, Jennifer Barrett: None declared, Edward Vital Consultant of: Roche, Grant/research support from: Roche, Ann Morgan Speakers bureau: Roche/Chugai, Consultant of: GSK, Roche, Chugai, AstraZeneka, Regeneron, Sanofi, Vifor, Grant/research support from: Roche, Kiniksa Pharmaceuticals

- R. Anderson Sutton, Wim van Zanten, Ethnomusicology in the Netherlands: present situation and traces of the past. Leiden: Centre of Non-Western Studies, Leiden University, 1995, ix + 330 pp. [Oideion; The performing arts worldwide 2. Special Issue]., Marjolijn van Roon (eds.) - T.E. Behrend, Willem Remmelink, The Chinese War and the collapse of the Javanese state, 1725-1743. Leiden: KITLV Press, 1994, 297 pp. [Verhandelingen 162]. - Erik Brandt, Eric Venbrux, A death in the Tiwi Islands; Conflict, ritual and social life in an Australian Aboriginal Community. Cambridge: Cambridge University Press, 1995, xvii + 269 pp. - Madelon Djajadiningrat-Nieuwenhuis, Tineke Hellwig, In the shadow of change; Images of women in Indonesian literature. Berkeley: University of California, Centers for South and Southeast Asia Studies, 1994, xiii + 259 pp. [Monograph 35]. - M. Estellie Smith, Peter J.M. Nas, Issues in urban development; Case studies from Indonesia. Leiden: Research School CNWS, 1995, 293 pp. [CNWS Publications 33]. - Uta Gärtner, Jan Becka, Historical dictionary of Myanmar. Metuchen, N.J.: Scarecrow Press, xxii + 328 pp. [Asian Historical Dictionaries 15]. - Beatriz van der Goes, H. Slaats, Wilhelm Middendorp over de Karo Batak, 1914-1919. Deel 1. Nijmegen: Katholieke Universiteit, Faculteit der Rechtsgeleerdheid, 1994, xvii + 313 pp. [Reeks Recht en Samenleving 11]., K. Portier (eds.) - Stephen C. Headley, Janet Carsten, About the house, Lévi-Strauss and beyond. Cambridge: Cambridge University Press, 1995, xiv + 300 pp., Stephen Hugh-Jones (eds.) - Stephen C. Headley, James J. Fox, Inside Austronesian houses; Perspectives on domestic designs for living. Canberra: Department of Anthropology, Research School of Pacific Studies, The Australian National University, 1993, x + 237 pp. - M. Hekker, Helmut Buchholt, Continuity, change and aspirations; Social and cultural life in Minahasa, Indonesia. Singapore: Institute of Southeast Asian Studies, 1994, vii + 231 pp., Ulricht Mai (eds.) - Tineke Hellwig, Brigitte Müller, Op de wipstoel; De niet-gewettigde inheemse vrouw van de blanke Europeaan in Nederlands-Indië (1890-1940); Een literatuuronderzoek naar beeldvorming en werkelijkheid. Amsterdam: Vakgroep Culturele Antropologie/Sociologie der Niets-Westerse Samenlevingen, 1995, xii + 131 pp. - Jan van der Putten, Liaw Yock Fang, Standard Malay made simple. Singapore: Times Books International, 1988. - Jan van der Putten, Liaw Yock Fang, Standard Indonesian made simple, written with the assistance of Nini Tiley-Notodisuryo, Singapore: Times Books International, 1990. - Jan van der Putten, Liaw Yock Fang, Speak standard Malay; A beginner’s guide. Singapore: Times Books International, 1993, xxii + 280 pp. - Jan van der Putten, Liaw Yock Fang, Speak Indonesian; A beginner’s guide, written in collaboration with Munadi Padmadiwiria and Abdullah Hassan. Singapore: Times Books International, 1990. - Alle G. Hoekema, Chr.G.F. de Jong, Geschiedenis van de Nederlandse Zending op Zuid-Sulawesi 1852-1966; Een bronnenpublicatie. Oegstgeest: Raad voor de Zending der Nederlands Hervormde Kerk, 1995, xi + 524 pp. - George Hotze, Ronald G. Gill, De Indische stad op Java en Madura; Een morfologische studie van haar ontwikkeling. Delft: Publikatieburo Bouwkunde, Technische Universiteit Delft, 1995, 350 pp. - H.A.J. Klooster, Holk H. Dengel, Neuere Darstellung der Geschichte Indonesiens in Bahasa Inonesia; Entwicklung und Tendenzen der indonesischen Historiographie. Stuttgart: Steiner, 1994, vii + 269 pp. - Harry A. Poeze, Hans Antlöv, Imperial policy and Southeast Asian nationalism 1930-1957. Richmond: Curzon Press, 1995, xiii + 323 pp., Stein Tonnesson (eds.) - P.W. Preston, Michael Hill, The politics of nation building and citizenship in Singapore. London: Routledge, 1995, x + 285 pp., Lian Kwen Fee (eds.) - J.W. (Pim) Schoorl, Michael Southon, The navel of the perahu; Meaning and values in the maritime trading economy of a Butonese village. Canberra: Department of Anthropology, Research School of Pacific and Asian Studies, The Australian National University, 1995, xiv + 150 pp. - Henk Schulte Nordholt, Geoffrey Robinson, The dark side of paradise; Political violence in Bali. Ithaca/London: Cornell University Press, 1995, xxii + 341 pp. - Herman A.O. de Tollenaere, Th. Stevens, Vrijmetselarij en samenleving in Nederlands-Indië en Indonesië 1764-1962. Hilversum: Verloren, 1994, 400 pp. - Donald E. Weatherbee, Mpu Prapañca, Desawarnana (Nagarakrtagama) by Mpu Prapañca, translated and edited by Stuart Robson. Leiden: KITLV Press, 1995, viii + 158 pp. [Verhandelingen 169]. - E.P. Wieringa, Jennifer Lindsay, Kraton Yogyakarta. Diterjemahkan oleh R.M. Soetanto dan T.E. Behrend. Jakarta: Yayasan Obor Indonesia, 1994, xvi + 330 pp. [Seri katalog Induk Naskah-Naskah Nusantara 2]., R.M. Soetanto, Alan Feinstein (eds.) - E.P. Wieringa, Wouter Smit, De islam binnen de horizon; Een missiologische studie over de benadering van de islam door vier Nederlandse zendingscorporaties (1797-1951). Zoetermeer: Boekencentrum, 1995, xix + 312 pp. [MISSION 11].

Lithium-ion batteries (LIBs) find use in a wide range of applications, each of which has its own design specifications and practical requirements. With regards to the role of LIBs in mitigating carbon emissions, and therefore climate change, it is desirable to support the rapidly growing adoption of electric vehicles and renewable grid-storage systems via development of higher energy density, lower cost, and improved rate capability. However, the design of energy-dense, low-cobalt, and/or high-rate cell chemistries is impeded by inherent trade-offs with cycling and calendar lifetimes. A key goal for the automotive and utilities industries is therefore to predict battery lifetime for new cell designs and chemistries at a very high level of confidence, for example through improved understanding of the physical and chemical processes that determine the state of health of battery systems. As part of the Faraday Institution, the UK’s independent institute for electrochemical energy storage technology, the Battery Degradation Project has built new understanding of the underlying physical and chemical processes that can lead to degradation in energy-dense NMC811/graphite lithium-ion cells as a model system. Led by the University of Cambridge (Clare Grey PI) in collaboration with eight UK universities, the research consortium is working closely with industry partners to create a new hub for lithium-ion battery research and to address key challenges and opportunities in the field. This presentation will give an overview of the research consortium’s diverse membership, key milestones, and technical progress. To date, the consortium has been applying a variety of analytical techniques to study degradation processes in NMC811/graphite cells. For example, electrochemical testing and operando solid-state 7Li nuclear magnetic resonance spectroscopy (NMR) were combined to monitor processes in both electrodes individually, including Li-ion mobility and its changes with temperature.1 The method is now being applied to understand how the dynamics are affected by long-term structural damage to the NMC811 material. A series of differential voltage analysis experiments have been paired with operando X-ray diffraction measurements to propose the mechanism behind a critical ‘turning point’ in NMC811/graphite cells, following which degradation accelerates significantly.2 New operando cell designs have been developed to measure changes in cell pressure,3 which are being paired with solution NMR spectroscopy,4 and differential electrochemical mass spectrometry to quantify electrolyte oxidation. The role and rate of transition-metal dissolution in cells under stressed cycling conditions, namely cycling at high temperature (60 °C) and high upper cut-off voltages (4.4, 4.6 V), has been investigated.5 Scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDX) measurements were coupled with time-of-flight secondary-ion mass spectrometry (Tof-SIMS) to observe the Al-containing phases at NMC811 surfaces and grain boundaries.7 New spectroscopic methods are also being developed, including Kerr-gated Raman, which allows sensitive measurements of electrode materials and electrolytes with lower background signal than conventional Raman spectroscopy.6 Finally, X-ray computed tomography methods have been developed that enable operando imaging and spectroscopic mapping of heterogeneities at a sub-particle length scale and across large areas of electrodes, which are being applied to study the origins of microstructural defects, cracking, and redox activity during charging, cycling, or storage.8,9 Reference s: K. Märker, C. Xu, and C. P. Grey, J. Am. Chem. Soc., 142, 17447–17456 (2020). W. M. Dose, C. Xu, C. P. Grey, and M. F. L. De Volder, Cell Rep. Phys. Sci., 1, 100253 (2020). N. Ryall and N. Garcia-Araez, J. Electrochem. Soc., 167, 110511 (2020). B. L. D. Rinkel, D. S. Hall, I. Temprano, and C. P. Grey, J. Am. Chem. Soc., 142, 15058–15074 (2020). Z. Ruff, C. Xu, and C. P. Grey, J. Electrochem. Soc., 168, 060518 (2021). L. Cabo-Fernandez, A. R. Neale, F. Braga, I. V. Sazanovich, R. Kostecki, and L. J. Hardwick, Phys. Chem. Chem. Phys., 21, 23833–23842 (2019). J. Lee, H. Amari, M. Bahri, Z. Shen, C. Xu, Z. Ruff, C. P. Grey, O. Ersen, A. Aguadero, N. D. Browning, and B. L. Mehdi, Batter. Supercaps, 4, 1813–1820 (2021). T. M. M. Heenan, A. Wade, C. Tan, J. E. Parker, D. Matras, A. S. Leach, J. B. Robinson, A. Llewellyn, A. Dimitrijevic, R. Jervis, P. D. Quinn, D. J. L. Brett, and P. R. Shearing, Adv. Energy Mater., 10, 2002655 (2020). C. Tan, A. S. Leach, T. M. M. Heenan, H. Parks, R. Jervis, J. N. Weker, D. J. L. Brett, and P. R. Shearing, Cell Rep. Phys. Sci., 100647 (2021).

Background:Acute Respiratory Distress Syndrome (ARDS) is a life-threatening complication of COVID-19 and has been reported in approximately one-third of hospitalized patients with COVID-191. Risk factors associated with the development of ARDS include older age and diabetes2. However, little is known about factors associated with ARDS in the setting of COVID-19, in patients with rheumatic disease or those receiving immunosuppressive medications. Prediction algorithms using traditional regression methods perform poorly with rare outcomes, often yielding high specificity but very low sensitivity. Machine learning algorithms optimized for rare events are an alternative approach with potentially improved sensitivity for rare events, such as ARDS in COVID-19 among patients with rheumatic disease.Objectives:We aimed to develop a prediction model for ARDS in people with COVID-19 and pre-existing rheumatic disease using a series of machine learning algorithms and to identify risk factors associated with ARDS in this population.Methods:We used data from the COVID-19 Global Rheumatology Alliance (GRA) Registry from March 24 to Nov 1, 2020. ARDS diagnosis was indicated by the reporting clinician. Five machine learning algorithms optimized for rare events predicted ARDS using 42 variables covering patient demographics, rheumatic disease diagnoses, medications used at the time of COVID-19 diagnosis, and comorbidities. Model performance was assessed using accuracy, area under curve, sensitivity, specificity, positive predictive value, and negative predictive value. Adjusted odds ratios corresponding to the 10 most influential predictors from the best performing model were derived using hierarchical multivariate mixed-effects logistic regression that accounted for within-country correlations.Results:A total of 5,931 COVID-19 cases from 67 countries were included in the analysis. Mean (SD) age was 54.9 (16.0) years, 4,152 (70.0%) were female, and 2,399 (40.5%) were hospitalized. ARDS was reported in 388 (6.5% of total and 15.6% of hospitalized) cases. Statistically significant differences in the risk of ARDS were observed by demographics, diagnoses, medications, and comorbidities using unadjusted univariate comparisons (data not shown). Gradient boosting machine (GBM) had the highest sensitivity (0.81) and was considered the best performing model (Table 1). Hypertension, interstitial lung disease, kidney disease, diabetes, older age, glucocorticoids, and anti-CD20 monoclonal antibodies were associated with the development of ARDS while tumor necrosis factor inhibitors were associated with a protective effect (Figure 1).Table 1.Performance of machine learning algorithms.GBMSVMGLMNETNNETRFAccuracy0.790.680.660.660.67AUC0.750.700.740.580.74Sensitivity0.810.680.650.680.67Specificity0.490.600.730.480.68PPV0.960.960.970.950.97NPV0.160.120.130.090.13GBM: Gradient Boosting Machine, SVM: Support vector machines, GLMNET: Lasso and Elastic-Net Regularized Generalized Linear Models, NNET: Neural Networks, RF: Random Forest. AUC: Area Under Curve; PPV: Positive Predictive Value; NPV: Negative Predictive Value.Conclusion:In this global cohort of patients with rheumatic disease, a machine learning model, GBM, predicted the onset of ARDS with 81% sensitivity using baseline information obtained at the time of COVID-19 diagnosis. These results identify patients who may be at higher risk of severe COVID-19 outcomes. Further studies are necessary to validate the proposed prediction model in external cohorts and to evaluate its clinical utility. Disclaimer: The views expressed here are those of the authors and participating members of the COVID-19 Global Rheumatology Alliance, and do not necessarily represent the views of the ACR, NIH, (UK) NHS, NIHR, or the department of Health.References:[1]Tzotzos SJ, Fischer B, Fischer H, Zeitlinger M. 2020;24(1):516.[2]Wu C, Chen X, Cai Y, et al. JAMA Intern Med. 2020;180(7):934-943.Acknowledgements:The COVID-19 Global Rheumatology Alliance.Disclosure of Interests:Zara Izadi: None declared, Milena Gianfrancesco: None declared, Kimme Hyrich Speakers bureau: Abbvie and grant income from BMS, UCB, and Pfizer, all unrelated to this study., Anja Strangfeld Speakers bureau: AbbVie, MSD, Roche, BMS, Pfizer, outside the submitted work., Grant/research support from: A consortium of 13 companies (among them AbbVie, BMS, Celltrion, Fresenius Kabi, Lilly, Mylan, Hexal, MSD, Pfizer, Roche, Samsung, Sanofi-Aventis, and UCB) supporting the German RABBIT register., Laure Gossec Consultant of: Abbvie, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis, UCB., Grant/research support from: Lilly, Mylan, Pfizer, all unrelated to this study., Loreto Carmona Consultant of: Loreto Carmona’s institute works by contract for laboratories among other institutions, such as Abbvie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, S.A., Novartis, Farmaceutica, Pfizer, Roche Farma, Sanofi Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal GmbH, and UCB Pharma., Elsa Mateus Grant/research support from: LPCDR received grants from Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal S.A., MSD, Celgene, Medac, Pharmakern, GAfPA and Pfizer., Saskia Lawson-Tovey: None declared, Laura Trupin: None declared, Stephanie Rush: None declared, Gabriela Schmajuk: None declared, Lindsay Jacobsohn: None declared, Patti Katz: None declared, Samar Al Emadi: None declared, Leanna Wise: None declared, Emily Gilbert: None declared, Maria Valenzuela-Almada: None declared, Ali Duarte-Garcia: None declared, Jeffrey Sparks Consultant of: Bristol-Myers Squibb, Gilead, Inova, Janssen, and Optum unrelated to this work., Grant/research support from: Amgen and Bristol-Myers Squibb., Tiffany Hsu: None declared, Kristin D’Silva: None declared, Naomi Serling-Boyd: None declared, Suleman Bhana Employee of: Suleman Bhana reports non-branded marketing campaigns for Novartis (<$10,000)., Wendy Costello: None declared, Rebecca Grainger Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, Cornerstones and travel assistance from Pfizer (all < $10,000)., Jonathan Hausmann Consultant of: Novartis, unrelated to this work (<$10,000)., Jean Liew Grant/research support from: Pfizer, outside the submitted work., Emily Sirotich Grant/research support from: Emily Sirotich is a Board Member of the Canadian Arthritis Patient Alliance, a patient run, volunteer-based organization whose activities are largely supported by independent grants from pharmaceutical companies., Paul Sufka: None declared, Zachary Wallace Consultant of: Viela Bio and MedPace, outside the submitted work., Grant/research support from: Bristol-Myers Squibb and Principia/Sanofi., Pedro Machado Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this study (all < $10,000)., Philip Robinson Consultant of: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB and travel assistance from Roche (all < $10,000)., Jinoos Yazdany Consultant of: Eli Lilly and Astra Zeneca, unrelated to this project.

Background:An increased risk of severe COVID-19 outcomes may be seen in patients with autoimmune diseases on moderate to high daily doses of glucocorticoids, as well as in those with comorbidities. However, specific information about COVID-19 outcomes in SLE is scarce.Objectives:To determine the characteristics associated with severe COVID-19 outcomes in a multi-national cross-sectional registry of COVID-19 patients with SLE.Methods:SLE adult patients from a physician-reported registry of the COVID-19 GRA were studied. Variables collected at COVID-19 diagnosis included age, sex, race/ethnicity, region, comorbidities, disease activity, time period of COVID-19 diagnosis, glucocorticoid (GC) dose, and immunomodulatory therapy. Immunomodulatory therapy was categorized as: antimalarials only, no SLE therapy, traditional immunosuppressive (IS) drug monotherapy, biologics/targeted synthetic IS drug monotherapy, and biologic and traditional IS drug combination therapy. We used an ordinal COVID-19 severity outcome defined as: not hospitalized/hospitalized without supplementary oxygen; hospitalized with non-invasive ventilation; hospitalized with mechanical ventilation/extracorporeal membrane oxygenation; and death. An ordinal logistic regression model was constructed to assess the association between demographic characteristics, comorbidities, medications, disease activity and COVID-19 severity. This assumed that the relationship between each pair of outcome groups is of the same direction and magnitude.Results:Of 1069 SLE patients included, 1047 (89.6%) were female, with a mean age of 44.5 (SD: 14.1) years. Patient outcomes included 815 (78.8%) not hospitalized/hospitalized without supplementary oxygen; 116 (11.2) hospitalized with non-invasive ventilation, 25 (2.4%) hospitalized with mechanical ventilation/extracorporeal membrane oxygenation and 78 (7.5%) died. In a multivariate model (n=804), increased age [OR=1.03 (1.01, 1.04)], male sex [OR =1.93 (1.21, 3.08)], COVID-19 diagnosis between June 2020 and January 2021 (OR =1.87 (1.17, 3.00)), no IS drug use [OR =2.29 (1.34, 3.91)], chronic renal disease [OR =2.34 (1.48, 3.70)], cardiovascular disease [OR =1.93 (1.34, 3.91)] and moderate/high disease activity [OR =2.24 (1.46, 3.43)] were associated with more severe COVID-19 outcomes. Compared with no use of GC, patients using GC had a higher odds of poor outcome: 0-5 mg/d, OR =1.98 (1.33, 2.96); 5-10 mg/d, OR =2.88 (1.27, 6.56); >10 mg/d, OR =2.01 (1.26, 3.21) (Table 1).Table 1.Characteristics associated with more severe COVID-19 outcomes in SLE. (N=804)OR (95% CI)Age, years1.03 (1.01, 1.04)Sex, Male1.93 (1.21, 3.08)Race/Ethnicity, Non-White vs White1.47 (0.87, 2.50)RegionEuropeRef.North America0.67 (0.29, 1.54)South America0.67 (0.29, 1.54)Other1.93 (0.85, 4.39)Season, June 16th 2020-January 8th 2021 vs January-June 15th 20201.87 (1.17, 3.00)Glucocorticoids0 mg/dayRef.0-5 mg/day1.98 (1.33, 2.96)5-10 mg/day2.88 (1.27, 6.56)=>10 mg/day2.01 (1.26, 3.21)Medication CategoryAntimalarial onlyRef.No IS drugs2.29 (1.34, 3.91)Traditional IS drugs as monotherapy1.17 (0.77, 1.77)b/ts IS drugs as monotherapy1.00 (0.37, 2.71)Combination of traditional and b/ts IS1.00 (0.55, 1.82)Comorbidity BurdenNumber of Comorbidities (excluding renal and cardiovascular disease)1.39 (0.97, 1.99)Chronic renal disease2.34 (1.48, 3.70)Cardiovascular disease1.93 (1.34, 3.91)Disease Activity, Moderate/ high vs Remission/ low 2.24 (1.46, 3.43)IS: immunosuppressive. b/ts: biologics/targeted syntheticsConclusion:Increased age, male sex, glucocorticoid use, chronic renal disease, cardiovascular disease and moderate/high disease activity at time of COVID-19 diagnosis were associated with more severe COVID-19 outcomes in SLE. Potential limitations include possible selection bias (physician reporting), the cross-sectional nature of the data, and the assumptions underlying the outcomes modelling.Acknowledgements:The views expressed here are those of the authors and participating members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the ACR, EULAR) the UK National Health Service, the National Institute for Health Research (NIHR), or the UK Department of Health, or any other organization.Disclosure of Interests:Manuel F. Ugarte-Gil Grant/research support from: Pfizer, Janssen, Graciela S Alarcon: None declared, Andrea Seet: None declared, Zara Izadi: None declared, Cristina Reategui Sokolova: None declared, Ann E Clarke Consultant of: AstraZeneca, BristolMyersSquibb, GlaxoSmithKline, Exagen Diagnostics, Leanna Wise: None declared, Guillermo Pons-Estel: None declared, Maria Jose Santos: None declared, Sasha Bernatsky: None declared, Lauren Mathias: None declared, Nathan Lim: None declared, Jeffrey Sparks Consultant of: Bristol-Myers Squibb, Gilead, Inova, Janssen, and Optum unrelated to this work., Grant/research support from: Amgen and Bristol-Myers Squibb, Zachary Wallace Consultant of: Viela Bio and MedPace, Grant/research support from: Bristol-Myers Squibb and Principia/Sanofi, Kimme Hyrich Speakers bureau: Abbvie, Grant/research support from: MS, UCB, and Pfizer, Anja Strangfeld Speakers bureau: AbbVie, MSD, Roche, BMS, Pfizer, Grant/research support from: AbbVie, BMS, Celltrion, Fresenius Kabi, Lilly, Mylan, Hexal, MSD, Pfizer, Roche, Samsung, Sanofi-Aventis, and UCB, Laure Gossec Consultant of: Abbvie, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis, UCB, Grant/research support from: Lilly, Mylan, Pfizer, Loreto Carmona: None declared, Elsa Mateus Grant/research support from: Pfizer, Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal S.A., MSD, Celgene, Medac, Pharmakern, GAfPA, Saskia Lawson-Tovey: None declared, Laura Trupin: None declared, Stephanie Rush: None declared, Gabriela Schmajuk: None declared, Patti Katz: None declared, Lindsay Jacobsohn: None declared, Samar Al Emadi: None declared, Emily Gilbert: None declared, Ali Duarte-Garcia: None declared, Maria Valenzuela-Almada: None declared, Tiffany Hsu: None declared, Kristin D’Silva: None declared, Naomi Serling-Boyd: None declared, Philippe Dieudé Consultant of: Boerhinger Ingelheim, Bristol-Myers Squibb, Lilly, Sanofi, Pfizer, Chugai, Roche, Janssen unrelated to this work, Grant/research support from: Bristol-Myers Squibb, Chugaii, Pfizer, unrelated to this work, Elena Nikiphorou: None declared, Vanessa Kronzer: None declared, Namrata Singh: None declared, Beth Wallace: None declared, Akpabio Akpabio: None declared, Ranjeny Thomas: None declared, Suleman Bhana Consultant of: AbbVie, Horizon, Novartis, and Pfizer (all <$10,000) unrelated to this work, Wendy Costello: None declared, Rebecca Grainger Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, Cornerstones, Jonathan Hausmann Consultant of: Novartis, Sobi, Biogen, all unrelated to this work (<$10,000), Jean Liew Grant/research support from: Pfizer outside the submitted work, Emily Sirotich Grant/research support from: Board Member of the Canadian Arthritis Patient Alliance, a patient run, volunteer based organization whose activities are largely supported by independent grants from pharmaceutical companies, Paul Sufka: None declared, Philip Robinson Speakers bureau: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB (all < $10,000), Consultant of: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB (all < $10,000), Pedro Machado Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this study (all < $10,000)., Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this study (all < $10,000), Milena Gianfrancesco: None declared, Jinoos Yazdany Consultant of: Eli Lilly and AstraZeneca unrelated to this project

Background:Targeted DMARDs may dampen the inflammatory response in COVID-19, perhaps leading to a less severe clinical course. However, some DMARD targets may impair viral immune defenses. Due to sample size limitations, previous studies of DMARD use and COVID-19 outcomes have combined several heterogeneous rheumatic diseases and medications, investigating a single outcome (e.g., hospitalization).Objectives:To investigate the associations of baseline use of biologic or targeted synthetic (b/ts) DMARDs with a range of poor COVID-19 outcomes in rheumatoid arthritis (RA).Methods:We analyzed voluntarily reported cases of COVID-19 in patients with rheumatic diseases in the COVID-19 Global Rheumatology Alliance physician registry (March 12, 2020 - January 6, 2021). We investigated RA treated with b/tsDMARD at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAK), interleukin-6 inhibitors (IL6i), or tumor necrosis factor inhibitors (TNFi). The outcome was an ordinal scale (1-4) for COVID-19 severity: 1) no hospitalization, 2) hospitalization without oxygen need, 3) hospitalization with any oxygen need or ventilation, or 4) death. Baseline covariates including age, sex, smoking, obesity, comorbidities (e.g., cardiovascular disease, cancer, interstitial lung disease [ILD]), concomitant non-biologic DMARD use, glucocorticoid use/dose, RA disease activity, country, and calendar time were used to estimate propensity scores (PS) for b/tsDMARD. The primary analysis used PS matching to compare each drug class to TNFi. Ordinal logistic regression estimated ORs for the COVID-19 severity outcome. In a sensitivity analysis, we used traditional multivariable ordinal logistic regression adjusting for covariates without matching.Results:Of the 1,673 patients with RA on b/tsDMARDs at the onset of COVID-19, (mean age 56.7 years, 79.6% female) there were n=154 on ABA, n=224 on RTX, n=306 on JAK, n=180 on IL6i, and n=809 on TNFi. Overall, 498 (34.3%) were hospitalized and 112 (6.7%) died. Among all patients, 353 (25.3%) were ever smokers, 197 (11.8%) were obese, 462 (27.6%) were on glucocorticoids, 1,002 (59.8%) were on concomitant DMARDs, and 299 (21.7%) had moderate/high RA disease activity. RTX users were more likely than TNFi users to have ILD (11.6% vs. 1.7%) and history of cancer (7.1% vs. 2.0%); JAK users were more likely than TNFi users to be obese (17.3% vs. 9.0%). After propensity score matching, RTX was strongly associated with greater odds of having a worse outcome compared to TNFi (OR 3.80, 95% CI 2.47, 5.85; Figure). Among RTX users, 42 (18.8%) died compared to 27 (3.3%) of TNFi users (Table). JAK use was also associated with greater odds of having a worse COVID-19 severity (OR 1.52, 95%CI 1.02, 2.28). ABA or IL6i use were not associated with COVID-19 severity compared to TNFi. Results were similar in the sensitivity analysis and after excluding cancer or ILD.Table 1.Frequencies for the ordinal COVID-19 severity outcome for patients with RA on biologic or targeted synthetic DMARDs (n=1673).COVID-19 outcomes by severity scale (n,%)ABAn=154RTXn=224JAKn=306IL6in=180TNFi n=8091)Not hospitalized113 (73.3%)121 (54.0%)220 (71.9%)150 (83.3%)666 (82.3%)2)Hospitalization without oxygenation10 (6.5%)14 (6.2%)11 (3.6%)9 (5.0%)53 (6.5%)3)Hospitalization with any oxygenation or ventilation16 (10.4%)47 (21.0%)52 (17.0%)16 (8.9%)63 (7.8%)4)Death15 (9.7%)42 (18.8%)23 (7.5%)5 (2.8%)27 (3.3%)Conclusion:In this large global registry of patients with RA and COVID-19, baseline use of RTX or JAK was associated with worse severity of COVID-19 compared to TNFi use. The very elevated odds for poor COVID-19 outcomes in RTX users highlights the urgent need for risk-mitigation strategies, such as the optimal timing of vaccination. The novel association of JAK with poor COVID-19 outcomes requires replication.Acknowledgements:The views expressed here are those of the authors and participating members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the ACR, EULAR, the UK National Health Service, the National Institute for Health Research, the UK Department of Health, or any other organization.Disclosure of Interests:Jeffrey Sparks Consultant of: Bristol-Myers Squibb, Gilead, Inova, Janssen, and Optum, unrelated to this work, Grant/research support from: Amgen and Bristol-Myers Squibb, unrelated to this work, Zachary Wallace Consultant of: Viela Bio and MedPace, outside the submitted work., Grant/research support from: Bristol-Myers Squibb and Principia/Sanofi, Andrea Seet: None declared, Milena Gianfrancesco: None declared, Zara Izadi: None declared, Kimme Hyrich Speakers bureau: Abbvie unrelated to this study, Grant/research support from: BMS, UCB, and Pfizer, all unrelated to this study, Anja Strangfeld Paid instructor for: AbbVie, MSD, Roche, BMS, Pfizer, outside the submitted work, Grant/research support from: grants from a consortium of 13 companies (among them AbbVie, BMS, Celltrion, Fresenius Kabi, Lilly, Mylan, Hexal, MSD, Pfizer, Roche, Samsung, Sanofi-Aventis, and UCB) supporting the German RABBIT register, outside the submitted work, Laure Gossec Consultant of: Abbvie, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis, UCB, unrelated to this study, Grant/research support from: Lilly, Mylan, Pfizer, all unrelated to this study, Loreto Carmona: None declared, Elsa Mateus Grant/research support from: grants from Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal S.A., MSD, Celgene, Medac, Pharmakern, GAfPA; grants and non-financial support from Pfizer, outside the submitted work, Saskia Lawson-Tovey: None declared, Laura Trupin: None declared, Stephanie Rush: None declared, Gabriela Schmajuk: None declared, Patti Katz: None declared, Lindsay Jacobsohn: None declared, Samar Al Emadi: None declared, Leanna Wise: None declared, Emily Gilbert: None declared, Ali Duarte-Garcia: None declared, Maria Valenzuela-Almada: None declared, Tiffany Hsu: None declared, Kristin D’Silva: None declared, Naomi Serling-Boyd: None declared, Philippe Dieudé Consultant of: Boerhinger Ingelheim, Bristol-Myers Squibb, Lilly, Sanofi, Pfizer, Chugai, Roche, Janssen unrelated to this work, Grant/research support from: Bristol-Myers Squibb, Chugaii, Pfizer, unrelated to this work, Elena Nikiphorou: None declared, Vanessa Kronzer: None declared, Namrata Singh: None declared, Manuel F. Ugarte-Gil Grant/research support from: Janssen and Pfizer, Beth Wallace: None declared, Akpabio Akpabio: None declared, Ranjeny Thomas: None declared, Suleman Bhana Consultant of: AbbVie, Horizon, Novartis, and Pfizer (all <$10,000) unrelated to this work, Wendy Costello: None declared, Rebecca Grainger Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, Cornerstones, Jonathan Hausmann Consultant of: Novartis, Sobi, Biogen, all unrelated to this work (<$10,000), Jean Liew Grant/research support from: Yes, I have received research funding from Pfizer outside the submitted work., Emily Sirotich Grant/research support from: Board Member of the Canadian Arthritis Patient Alliance, a patient run, volunteer based organization whose activities are largely supported by independent grants from pharmaceutical companies, Paul Sufka: None declared, Philip Robinson Speakers bureau: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB (all < $10,000), Consultant of: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB (all < $10,000), Pedro Machado Speakers bureau: Yes, I have received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this study (all < $10,000)., Consultant of: Yes, I have received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this study (all < $10,000)., Jinoos Yazdany Consultant of: Eli Lilly and AstraZeneca unrelated to this project

Abstract Introduction. Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) is an adeno-associated virus gene therapy that transfers a B-domain deleted factor VIII (FVIII) cDNA to hepatocytes. The open-label, single-arm, multicenter phase 3 GENEr8-1 trial (NCT03370913) evaluated valoctocogene roxaparvovec in 134 men with severe hemophilia A (HA) and demonstrated an 83.8% reduction in annualized treated bleeding rate (ABR) and superiority to FVIII prophylaxis (P &lt;0.001). The relationship between baseline FVIII activity and ABR was estimated in congenital HA (den Uijl, et al. Haemophilia 2011;17[1]:41-4); it is unknown if a similar relationship exists after gene transfer. We present here post-hoc analyses of transgene-derived FVIII activity and bleeds in GENEr8-1. Methods. Men ≥18 years of age with severe HA previously on FVIII prophylaxis who were negative for FVIII inhibitors and anti-AAV5 antibodies received one 6x10 13 vg/kg infusion of valoctocogene roxaparvovec. FVIII activity was measured by chromogenic substrate (CSA; lower limit of quantitation [LLOQ], 3.0 IU/dL) and one stage assays (OSA; LLOQ, 1.0 IU/dL); median FVIII activity in every 4- or 6-week window was assessed. Self-reported treated bleeds were counted after week 4, when routine prophylaxis was scheduled to end. The relationship between number of treated joint bleeds and matched median FVIII activity levels in each 4- or 6-week window was modeled using negative binomial regression. Results. As of the data cut date, mean follow-up was 71.6 weeks; 1 participant was lost to follow-up at week 66. At weeks 49-52 (latest time with data for all participants; intent-to-treat population), 9% (12/134) had CSA FVIII activity &lt;3 IU/dL, 3% (4/134) had median FVIII activity ≥3-&lt;5 IU/dL, 17% (23/134) had median FVIII activity ≥5-&lt;15 IU/dL, and 71% (95/134) had median FVIII activity ≥15 IU/dL. While on FVIII prophylaxis prior to gene transfer, 32% of participants (43/134) had an ABR of 0. Following gene transfer, 75% of participants (101/134) were bleed-free through their last follow-up prior to the data cut. The remaining 33 participants reported 149 treated bleeds total, 62% (93/149) as traumatic and 38% (56/149) as spontaneous. By location, 53% (79/149) occurred in joints, 19% (28/149) in muscle, 14% (21/149) in soft tissue, and 14% (21/149) in other or unspecified locations. Relative to FVIII level, 54% of treated bleeds (80/149) occurred when CSA FVIII was &lt;3 IU/dL (LLOQ), 12% (18/149) when FVIII was ≥3-&lt;5 IU/dL, 23% (35/149) when FVIII was ≥5-&lt;15 IU/dL, and 11% (16/149) when FVIII was ≥15 IU/dL. Of 16 treated bleeds that occurred when FVIII was ≥15 IU/dL, 13 were traumatic. Treated joint bleeds followed a similar pattern: 51% (40/79) occurred when FVIII was &lt;3 IU/dL, 15% (12/79) when FVIII was ≥3-&lt;5 IU/dL, 27% (21/79) when FVIII was ≥5-&lt;15 IU/dL, and 8% (6/79) when FVIII was ≥15 IU/dL. A negative binomial regression model based on these data and matched FVIII activity levels predicts &lt;1 treated joint bleed in 2 years for individuals treated with valoctocogene roxaparvovec with FVIII activity ≥15 IU/dL (CSA; Figure). Clinical value of the CSA at low FVIII levels is limited by its LLOQ of 3 IU/dL. Of 12 participants with median FVIII levels below the CSA LLOQ at weeks 49-52, 9 had improved or the same ABR post-gene therapy relative to prophylaxis. The OSA, with its LLOQ of 1 IU/dL, provided important information here. By OSA, 1 had FVIII &lt;1 IU/dL, 5 had FVIII ≥1-&lt;5 IU/dL, and 3 had FVIII ≥5 IU/dL. The remaining 3 participants who had increased ABR after gene transfer had FVIII levels by OSA of 0, 2.1, and 4.8 IU/dL. For participants with OS FVIII &lt;5 IU/dL at week 52 (n = 11), median (IQR) ABR was 1.2 (0-7.9), similar to the median (IQR) ABR of 1.6 (0.6-3.5) reported for people with moderate HA (Abdi, et al. J Throm Haemost 2020;18[12]:3203-10). Conclusions. Gene transfer with valoctocogene roxaparvovec led to sustained endogenous FVIII production and reduced ABR in this phase 3 trial. After gene transfer, the majority of bleeds were traumatic. When FVIII was ≥15 IU/dL, reports of treated bleeds, including joint bleeds, were rare. CSA FVIII activity was predictive of bleeding risk post-gene transfer, as for epidemiologic congenital HA results. At FVIII levels below the CSA LLOQ, the OSA provided clinically relevant information; bleeding with OSA FVIII &lt;5 IU/dL was similar to observations in people with moderate HA, though further exploration with more data is needed. Figure 1 Figure 1. Disclosures Pipe: Biomarin: Consultancy, Other: Clinical trial investigator; Regeneron/ Intellia: Consultancy; uniQure: Consultancy, Other; Spark Therapeutics: Consultancy; Takeda: Consultancy; Sanofi: Consultancy, Other; Sangamo Therapeutics: Consultancy; Roche/Genentech: Consultancy, Other; Pfizer: Consultancy; Novo Nordisk: Consultancy; Freeline: Consultancy, Other: Clinical trial investigator; HEMA Biologics: Consultancy; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy; Genventiv: Consultancy; Grifols: Consultancy; Bayer: Consultancy; ASC Therapeutics: Consultancy; Apcintex: Consultancy; Octapharma: Consultancy; Shire: Consultancy. Ozelo: BioMarin Pharmaceutical Inc.: Consultancy, Other: Clinical trial investigator, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Other: Clinical trial investigator, Travel support, Speakers Bureau; Pfizer: Consultancy, Other: Clinical trial investigator, Research Funding; Roche: Consultancy, Other: Clinical trial investigator, Travel support, Research Funding, Speakers Bureau; Sanofi: Consultancy, Other: Clinical trial investigator; Takeda: Consultancy, Other: Clinical trial investigator, Travel support, Research Funding, Speakers Bureau; Grifols: Other: Grants review. Kenet: Takeda: Consultancy; Roche: Consultancy; Novo Nordisk: Consultancy; Shire: Research Funding; Pfizer: Consultancy, Research Funding; Opko Biologics: Research Funding; Bayer: Consultancy, Research Funding; Alnylam: Consultancy, Research Funding. Reding: Bayer, CSL Behring, Sanofi Genzyme, Takeda: Speakers Bureau; Bayer, Biomarin (institutional research funding): Research Funding; Bayer, CSL Behring, NovoNordisk, Sanofi Genzyme, Takeda: Honoraria; Bayer, CSL Behring, NovoNordisk, Sanofi Genzyme, Takeda (advisory committees): Membership on an entity's Board of Directors or advisory committees. Mason: BioMarin Pharmaceutical Inc.: Other: Participation as a clinical trial investigator; Roche: Other: Participation as a clinical trial investigator, Travel support, Speakers Bureau. Leavitt: Syntimmune: Research Funding; Sangamo Therapeutics: Research Funding; Pfizer: Research Funding; Merck: Consultancy; CSL DOVA: Consultancy; Catalys: Consultancy; BioMarin: Consultancy, Research Funding; BPL: Consultancy; Behring: Consultancy; HEMA Biologics: Consultancy; Rigel: Consultancy. Laffan: Shire: Membership on an entity's Board of Directors or advisory committees; Leo-Pharma: Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Speakers Bureau; AstraZeneca: Consultancy; Sobi: Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Bayer: Other: Travel support, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BioMarin Pharmaceutical Inc.: Research Funding. Quon: Orthopaedic Institute for Children: Current Employment. von Drygalski: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hematherix, Inc: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Super FVa; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Research Funding; CSL Behring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biomarin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; uniQure: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Chou: Bayer: Other: Clinical trial investigator, Speakers Bureau; Novo Nordisk: Consultancy, Other: Clinical trial investigator, Speakers Bureau; BioMarin: Other: Clinical trial investigator; Sanofi: Consultancy, Other: Clinical trial investigator, Speakers Bureau; Chugai: Consultancy, Other: Clinical trial investigator, Speakers Bureau; Pfizer: Other: Clinical trial investigator, Speakers Bureau; CSL: Consultancy, Other: Clinical trial investigator, Speakers Bureau. Shapiro: Sobi: Consultancy; Shire: Consultancy; Pfizer: Consultancy, Speakers Bureau; Bayer: Other: Travel support, Speakers Bureau; Takeda: Speakers Bureau; Roche: Speakers Bureau; CSL Behring: Other: travel support. Dunn: Genentech/Roche: Consultancy, Speakers Bureau; ATHN: Research Funding; Biomarin: Consultancy, Research Funding; Freeline: Research Funding; Takeda: Research Funding; World Federation of Hemophilia USA: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy; Uniqure: Consultancy; Sanofi: Research Funding; Kedrion: Consultancy. Wang: Bioverativ: Consultancy, Other: Clinical trial investigator; CSL Behring: Consultancy, Other: Clinical trial investigator; Novo Nordisk: Consultancy, Other: Clinical trial investigator; Genentech: Consultancy, Other: Clinical trial investigator; Takeda: Consultancy, Other: Clinical trial investigator; Hema Biologics: Consultancy, Other: Clinical trial investigator; uniQure: Consultancy, Other: Clinical trial investigator; Pfizer/Spark: Other: clinical trial investigator; Octapharma: Other; Bayer: Consultancy, Other: Clinical trial investigator; BioMarin: Consultancy, Other: Clinical trial investigator. Key: Grifols: Research Funding; Takeda: Research Funding; BioMarin: Honoraria, Other: Participation as a clinical trial investigator; Sanofi: Consultancy; Uniqure: Consultancy, Other: Participation as a clinical trial investigator. Kaczmarek: Bayer: Research Funding. Symington: Biomarin: Research Funding; CSL Behring: Other: Travel support; Novonordisk: Other: Travel support. Lawal: BioMarin Pharmaceutical Inc.: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Mahajan: BioMarin Pharmaceutical: Current Employment, Current equity holder in publicly-traded company. Chavele: BioMarin Pharmaceutical: Current Employment, Current equity holder in publicly-traded company. Reddy: BioMarin Pharmaceutical: Current Employment, Current equity holder in publicly-traded company. Yu: BioMarin Pharmaceutical: Current Employment, Current equity holder in publicly-traded company. Wong: BioMarin Pharmaceutical Inc.: Current Employment, Current equity holder in publicly-traded company. Robinson: BioMarin Pharmaceutical Inc.: Current Employment, Current equity holder in publicly-traded company. Kim: BioMarin Pharmaceutical Inc.: Current Employment, Current equity holder in publicly-traded company.

Objetivo: sintetizar as evidências disponíveis na literatura sobre o efeito do uso tópico de óleos essenciais na cicatrização de feridas em humanos. Método: o protocolo dessa revisão sistemática foi desenvolvido conforme o PRISMA for systematic review protocols e está registrado na base de dados PROSPERO (CRD42021269456). A busca dos estudos será realizada nas bases de dados MEDLINE via PubMed, LILACS, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Web of Science e Scopus. A busca manual ocorrerá por meio das referências dos estudos selecionados. A literatura cinzenta também será pesquisada. Dois revisores participarão da seleção dos estudos de forma cega e independente. A avaliação do risco de viés será realizada com as ferramentas ROB-2.0 para estudos randomizados e ROBINS-I para os estudos sem randomização. A análise da qualidade da evidência será feita com os instrumentos propostos pelo Joanna Briggs Institute. A análise quantitativa dos estudos incluídos será representada por a metanálise, no entanto, caso não seja viável, os dados serão apresentados mediante análise descritiva. Considerações finais: os resultados dessa revisão sistemática poderão contribuir para a prática baseada em evidência quanto ao uso de óleos essenciais na cicatrização de feridas.

Abstract STUDY QUESTION Are intrauterine insemination (IUI) performance characteristics and post-processing total motile sperm count (TMC) related to live birth rate in couples with unexplained infertility? SUMMARY ANSWER Patient discomfort with IUI and lower inseminate TMC were associated with a reduced live birth rate, while time from hCG injection to IUI, sperm preparation method and ultrasound guidance for IUI were not associated with live birth success. WHAT IS ALREADY KNOWN We previously determined that some baseline characteristics of couples with unexplained infertility, including female age, duration of infertility, history of prior loss and income, were related to live birth rate across a course of ovarian stimulation and IUI treatment. However, the relationship between treatment outcomes and per-cycle characteristics, including ultrasound guidance for IUI, timing of IUI relative to hCG injection, difficult or painful IUI and inseminate TMC, are controversial, and most prior investigations have not evaluated live birth outcome. STUDY DESIGN, SIZE, DURATION This was a secondary analyses of 2462 cycles from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. This prospective, randomised, multicentre clinical trial determined live birth rates following IUI after ovarian stimulation with clomiphene citrate, letrozole or gonadotropins in 854 couples with unexplained infertility. It was conducted between 2011 and 2014, and couples could undergo up to four consecutive treatment cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS AMIGOS was an NIH-sponsored Reproductive Medicine Network trial conducted at 12 clinical sites. Participants were women with unexplained infertility who were between 18 and 40 years of age. Cluster-weighted generalised estimating equations (GEE), which account for informative clustering of multiple IUI treatment cycles within the same patient, were used to determine associations between IUI performance characteristics, including inseminate TMC, and live birth rate. Efficiency curves were also generated to examine the relationship between inseminate TMC and live birth rate. MAIN RESULTS AND THE ROLE OF CHANCE After adjustment for treatment group and baseline factors previously associated with live birth across a course of OS-IUI treatment, patient discomfort during the IUI procedure was associated with a reduction in live birth rate (aRR 0.40 (0.16–0.96)). Time from hCG trigger injection to IUI was not significantly associated with outcome. Higher TMC was associated with greater live birth rate (TMC 15.1–20.0 million (14.8%) compared to ≤5 million (5.5%)) (aRR 2.09 (1.31–3.33)). However, live births did occur with TMC ≤ 1 million (5.1%). LIMITATIONS, REASONS FOR CAUTION This investigation is a secondary analysis, and AMIGOS was not designed to address the present question. Since timed intercourse was allowed as part of the AMIGOS trial, we cannot rule out the possibility that any given pregnancy resulted from intercourse rather than IUI. WIDER IMPLICATIONS OF THE FINDINGS Most factors associated with the performance of IUI were not significantly related to obtaining live birth. Our findings suggest that higher TMC inseminated leads to an increase in live birth rate up to TMC ~20 million. However, there may be no reasonable threshold below which live birth is not possible with IUI. STUDY FUNDING/COMPETING INTEREST(S) Funding was received through grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936 and U10 HD055925. This research was made possible by funding by the American Recovery and Reinvestment Act. Dr Hansen reports grants from NIH/NICHD and Yale University during the conduct of the study, grants from Roche Diagnostics and grants from Ferring International Pharmascience Center US outside the submitted work. Dr Peck reports support from Ferring Pharmaceuticals outside the submitted work. Dr Coward has nothing to disclose. Dr Wild reports grants from NICHD during the conduct of the study. Dr Trussell has nothing to disclose. Dr Krawetz reports grants from NICHD during the conduct of the study, grants from Merck and support from Taylor and Frances and from Springer, outside the submitted work. Dr Diamond reports grants from NIH/NICHD, Yale University, during the conduct of the study and support from Advanced Reproductive Care AbbVie, Bayer and ObsEva, outside the submitted work. Dr Legro reports support from Bayer, Kindex, Odega, Millendo and AbbVie and grants and support from Ferring, outside the submitted work. Dr Coutifaris reports grants from NICHD/NIH and personal fees from American Society for Reproductive Medicine, outside the submitted work. Dr Alvero has nothing to disclose. Dr Robinson reports grants from NIH during the conduct of the study. Dr Casson has nothing to disclose. Dr Christman reports grants from NICHD during the conduct of the study. Dr Santoro reports grants from NIH during the conduct of the study. Dr Zhang reports grants from NIH during the conduct of the study and support from Shangdong University outside the submitted work. TRIAL REGISTRATION NUMBER n/a

Background: Based on a literature review of various studies, comparisons between BH and RL are inconclusive regarding some outcomes. However, in the last 5 years, some studies have been published that may contribute to clarifying which cannulation technique (CT) allows better fistula survival. Aim: To review which cannulation technique allows better primary patency of the arteriovenous fistula in haemodialysis patients. Methods: We will include all randomised controlled trials and observational studies that include comparisons among CTs and thus define the benefits and risks of each CT. A PRISMA-compliant systematic review and meta-analysis will be performed in accordance with the quality and homogeneity of studies. A comprehensive search strategy will be applied to the CINAHL, MEDLINE and Embase electronic databases from January 2000 to September 2021. The primary outcome is the arteriovenous fistula primary patency. To assess the risk of bias in randomised controlled trials or quasi-experimental studies, we will use the tool Revised Cochrane Risk-of-Bias Tool for Randomized Trials (RoB 2). For nonrandomised studies, the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) will be used. Discussion: The evidence generated from this systematic review of current evidence could inform the design and implementation of continuous quality improvement programs in cannulation techniques in haemodialysis patients, as well as contributing to improving the curricula within haemodialysis courses. This protocol was registered with the National Institute for Health Research PROSPERO database prior to commencement (registration number CRD42021237050).

To improve online learning pedagogy within the field of paralegal education, this study investigated how paralegal students and paralegal instructors perceived the effectiveness of synchronous and asynchronous online paralegal courses. This study intended to inform paralegal instructors and course developers how to better design, deliver, and evaluate effective online course instruction in the field of paralegal studies.Survey results were analyzed using independent samples t-test and correlational analysis, and indicated that overall, paralegal students and paralegal instructors positively perceived synchronous and asynchronous online paralegal courses. Paralegal instructors reported statistically significant higher perceptions than paralegal students: (1) of instructional design and course content in synchronous online paralegal courses; and (2) of technical assistance, communication, and course content in asynchronous online paralegal courses. Instructors also reported higher perceptions of the effectiveness of universal design, online instructional design, and course content in synchronous online paralegal courses than in asynchronous online paralegal courses. Paralegal students reported higher perceptions of asynchronous online paralegal course effectiveness regarding universal design than paralegal instructors. No statistically significant differences existed between paralegal students’ perceptions of the effectiveness of synchronous and asynchronous online paralegal courses. A strong, negative relationship existed between paralegal students’ age and their perceptions of effective synchronous paralegal courses, which were statistically and practically significant. Lastly, this study provided practical applicability and opportunities for future research. Akyol, Z., & Garrison, D. R. (2008). The development of a community of inquiry over time in an online course: Understanding the progression and integration of social, cognitive and teaching presence. Journal of Asynchronous Learning Networks, 12, 3-22. Retrieved from https://files.eric.ed.gov/fulltext/EJ837483.pdf Akyol, Z., Garrison, D. R., & Ozden, M. Y. (2009). Online and blended communities of inquiry: Exploring the developmental and perceptional differences. The International Review of Research in Open and Distributed Learning, 10(6), 65-83. Retrieved from http://www.irrodl.org/index.php/irrodl/article/view/765/1436 Allen, I. E., & Seaman, J. (2014). Grade change: Tracking online education in the United States. Babson Park, MA: Babson Survey Research Group and Quahog Research Group, LLC. Retrieved from https://www.utc.edu/learn/pdfs/online/sloanc-report-2014.pdf Alreck, P. L., & Settle, R. B. (2004). The Survey Research Handbook (3rd ed.) New York, NY: McGraw-Hill Irwin. American Association for Paralegal Education (2013, Oct.). AAfPE core competencies for paralegal programs. Retrieved from https://cdn.ymaws.com/www.aafpe.org/resource/resmgr/Docs/AAfPECoreCompetencies.pdf American Bar Association, Standing Committee on Paralegals. (2017). https://www.americanbar.org/groups/paralegals.html American Bar Association, Standing Committee on Paralegals (2013, September). Guidelines for the approval of paralegal education programs. Retrieved from https://www.americanbar.org/content/dam/aba/administrative/paralegals/ls_prlgs_2013_paralegal_guidelines.authcheckdam.pdf Astani, M., Ready, K. J., & Duplaga, E. A. (2010). Online course experience matters: Investigating students’ perceptions of online learning. Issues in Information Systems, 11(2), 14-21. Retrieved from http://iacis.org/iis/2010/14-21_LV2010_1526.pdf Bailey, C. J., & Card, K. A. (2009). Effective pedagogical practices for online teaching: Perception of experienced instructors. The Internet and Higher Education, 12, 152-155. doi: 10.1016/j.iheduc.2009.08.002 Bernard, R., Abrami, P., Borokhovski, E., Wade, C., Tamim , R., Surkes, M., & Bethel, E. (2009). A meta-analysis of three types of interaction treatments in distance education. Review of Educational Research, 79, 1243-1289. doi: 10.3102/0034654309333844 Cherry, S. J., & Flora, B. H. (2017). Radiography faculty engaged in online education: Perceptions of effectiveness, satisfaction, and technological self-efficacy. Radiologic Technology, 88(3), 249-262. http://www.radiologictechnology.org/ Cohen, J. (1988). Statistical power analysis for the behavioral sciences (2nd ed.). New York: Taylor & Francis Group. Colorado, J. T., & Eberle, J. (2010). Student demographics and success in online learning environments. Emporia State Research Studies, 46(1), 4-10. Retrieved from https://esirc.emporia.edu/bitstream/handle/123456789/380/205.2.pdf?sequence=1 Dutcher, C. W., Epps, K. K., & Cleaveland, M. C. (2015). Comparing business law in online and face to face formats: A difference in student learning perception. Academy of Educational Leadership Journal, 19, 123-134. http://www.abacademies.org/journals/academy-of-educational-leadership-journal-home.html Faul, F., Erdfelder, E., Lang, A.-G., & Buchner, A. (2007). G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior Research Methods, 39, 175-191. Retrieved from http://www.gpower.hhu.de/fileadmin/redaktion/Fakultaeten/Mathematisch-Naturwissenschaftliche_Fakultaet/Psychologie/AAP/gpower/GPower3-BRM-Paper.pdf Field, A. (2009). Discovery statistics using SPSS. (3rd ed.). Thousand Oaks, CA: Sage Publications, Inc. Gall M., Borg, W., & Gall, J. (1996). Educational research: An introduction (6th ed.). White Plains, NY: Longman Press. Garrison, D. R., Anderson, T., & Archer, W. (2001). Critical thinking, cognitive presence, and computer conferencing in distance education. American Journal of distance education, 15(1), 7-23. Retrieved from http://cde.athabascau.ca/coi_site/documents/Garrison_Anderson_Archer_CogPres_Final.pdf Green, S. B., & Salkind, N. J. (2005). Using SPSS for Windows and Macintosh: Internal consistency estimates of reliability. Upper Saddle River, NJ: Pearson Prentice Hall. Harrell, I. L. (2008). Increasing the Success of Online Students. Inquiry, 13(1), 36-44. Retrieved from http://files.eric.ed.gov/fulltext/EJ833911.pdf Horspool, A., & Lange, C. (2012). Applying the scholarship of teaching and learning: student perceptions, behaviours and success online and face-to-face. Assessment & Evaluation in Higher Education, 37, 73-88. doi: 10.1080/02602938.2010.496532 Inman, E., Kerwin, M., & Mayes, L. (1999). Instructor and student attitudes toward distance learning. Community College Journal of Research & Practice, 23, 581-591. doi:10.1080/106689299264594 Institute of Legal Executives (ILEX). https://www.cilexcareers.org.uk/ Johnson, J. & Taggart, G. (1996). Computer assisted instruction in paralegal education: Does it help? Journal of Paralegal Education and Practice, 12, 1-21. Johnstone, Q. & Flood, J. (1982). Paralegals in English and American law offices. Windsor YB Access to Justice 2, 152. Jones, S. J. (2012). Reading between the lines of online course evaluations: Identifiable actions that improve student perceptions of teaching effectiveness and course value. Journal of Asynchronous Learning Networks, 16(1), 49-58. doi:http://dx.doi.org/10.24059/olj.v16i1.227 Krejcie, R. V., & Morgan, D. W. (1970). Determining sample size for research activities. Educational and psychological measurement, 30, 607-610. http://journals.sagepub.com/home/epm Liu, S., Gomez, J., Khan, B., & Yen, C. J. (2007). Toward a learner-oriented community college online course dropout framework. International Journal on ELearning, 6(4), 519-542. https://www.learntechlib.org/j/IJEL/ Lloyd, S. A., Byrne, M. M., & McCoy, T. S. (2012). Faculty-perceived barriers of online education. Journal of online learning and teaching, 8(1), 1-12. Retrieved from http://jolt.merlot.org/vol8no1/lloyd_0312.pdf Lockee, B., Burton, J., & Potter, K. (2010, March). Organizational perspectives on quality in distance learning. In D. Gibson & B. Dodge (Eds.), Proceedings of SITE 2010—Society for Information Technology & Teacher Education International Conference (pp. 659-664). San Diego, CA: Association for the Advancement of Computing in Education (AACE). https://www.learntechlib.org/p/33419/ Lowerison, G., Sclater, J., Schmid, R. F., & Abrami, P. C. (2006). Student perceived effectiveness of computer technology use in post-secondary classrooms. Computers & Education, 47(4), 465-489. doi:10.1016/j.compedu.2004.10.014 Retrieved from https://pdfs.semanticscholar.org/fc9c/13f0187d3967217aa82cc96c188427e29ec9.pdf Martins, L. L., & Kellermanns, F. W. (2004). A model of business school students' acceptance of a web-based course management system. Academy of Management Learning & Education, 3(1), 7-26. doi: 10.5465/AMLE.2004.12436815 Mayes, J. T. (2001). Quality in an e-University. Assessment & Evaluation in Higher Education, 26, 465-473. doi:10.1080/02602930120082032 McCabe, S. (2007). A brief history of the paralegal profession. Michigan Bar Journal, 86(7), 18-21. Retrieved from https://www.michbar.org/file/barjournal/article/documents/pdf4article1177.pdf McMillan, J. H. (2008). Educational Research: Fundamentals for the customer. Boston, MA: Pearson Education, Inc. Myers, C. B., Bennett, D., Brown, G., & Henderson, T. (2004). Emerging online learning environments and student learning: An analysis of faculty perceptions. Educational Technology & Society, 7(1), 78-86. Retrieved from http://www.ifets.info/journals/7_1/9.pdf Myers, K. (2002). Distance education: A primer. Journal of Paralegal Education & Practice, 18, 57-64. Nunnaly, J. (1978). Psychometric theory. New York: McGraw-Hill. Otter, R. R., Seipel, S., Graeff, T., Alexander, B., Boraiko, C., Gray, J., Petersen, K., & Sadler, K. (2013). Comparing student and faculty perceptions of online and traditional courses. The Internet and Higher Education, 19, 27-35. doi:10.1016/j.iheduc.2013.08.001 Popham, W. J. (2000). Modern educational measurement: Practical guidelines for educational leaders. Boston, MA: Allyn & Bacon. Rich, A. J., & Dereshiwsky, M. I. (2011). Assessing the comparative effectiveness of teaching undergraduate intermediate accounting in the online classroom format. Journal of College Teaching and Learning, 8(9), 19. https://www.cluteinstitute.com/ojs/index.php/TLC/ Robinson, C., & Hullinger, H. (2008). New benchmarks in higher education: Student engagement in online learning. The Journal of Education for Business, 84(2), 101-109. Retrieved from http://anitacrawley.net/Resources/Articles/New%20Benchmarks%20in%20Higher%20Education.pdf Salkind, N. J. (2008). Statistics for people who think they hate statistics. Los Angeles, CA: Sage Publications. Santos, J. (1999, April). Cronbach's Alpha: A tool for assessing the reliability of scales. Journal of Extension, 37, 2. Retrieved from https://www.joe.org/joe/1999april/tt3.php Seok, S., DaCosta, B., Kinsell, C., & Tung, C. K. (2010). Comparison of instructors' and students' perceptions of the effectiveness of online courses. Quarterly Review of Distance Education, 11(1), 25. Retrieved from http://online.nuc.edu/ctl_en/wp-content/uploads/2015/08/Online-education-effectiviness.pdf Sheridan, K., & Kelly, M. A. (2010). The indicators of instructor presence that are important to students in online courses. Journal of Online Learning and Teaching, 6(4), 767-779. Retrieved from http://jolt.merlot.org/vol6no4/sheridan_1210.pdf Shook, B. L., Greer, M. J., & Campbell, S. (2013). Student perceptions of online instruction. International Journal of Arts & Sciences, 6(4), 337. Retrieved from https://s3.amazonaws.com/academia.edu.documents/34496977/Ophoff.pdf?AWSAccessKeyId=AKIAIWOWYYGZ2Y53UL3A&Expires=1508119686&Signature=J1lJ8VO0xardd%2FwH35pGj14UeBg%3D&response-content-disposition=inline%3B%20filename%3DStudent_Perceptions_of_Online_Learning.pdf Song, L., Singleton, E. S., Hill, J. R., & Koh, M. H. (2004). Improving online learning: Student perceptions of useful and challenging characteristics. The Internet and Higher Education, 7, 59-70. doi:10.1016/j.iheduc.2003.11.003 Steiner, S. D., & Hyman, M. R. (2010). Improving the student experience: Allowing students enrolled in a required course to select online or face-to-face instruction. Marketing Education Review, 20, 29-34. doi:10.2753/MER1052-8008200105 Stoel, L., & Hye Lee, K. (2003). Modeling the effect of experience on student acceptance of web-based courseware. Internet Research, 13(5), 364-374. http://www.emeraldinsight.com/loi/intr Taggart, G., & Bodle, J. H. (2003). Example of assessment of student outcomes data from on-line paralegal courses: Lessons learned. Journal of Paralegal Education & Practice, 19, 29-36. Tanner, J. R., Noser, T. C., & Totaro, M. W. (2009). Business faculty and undergraduate students' perceptions of online learning: A comparative study. Journal of Information Systems Education, 20, 29-40. http://jise.org/ Tung, C.K. (2007). Perceptions of students and instructors of online and web-enhanced course effectiveness in community colleges (Doctoral dissertation). Retrieved from ProQuest Dissertations and Theses database (Publication No. AAT 3284232). Vodanovich, S. J. & Piotrowski, C., & (2000). Are the reported barriers to Internet-based instruction warranted? A synthesis of recent research. Education, 121(1), 48-53. http://www.projectinnovation.com/education.html Ward, M. E., Peters, G., & Shelley, K. (2010). Student and faculty perceptions of the quality of online learning experiences. The International Review of Research in Open and Distributed Learning, 11, 57-77. Retrieved from http://www.irrodl.org/index.php/irrodl/article/view/867/1610? Wilkes, R. B., Simon, J. C., & Brooks, L. D. (2006). A comparison of faculty and undergraduate students' perceptions of online courses and degree programs. Journal of Information Systems Education, 17, 131-140. http://jise.org/

Abstract Objective To summarize and produce aggregated evidence on the effect of simulation-based teaching on skill performance in the nursing profession. Simulation is an active learning strategy involving the use of various resources to assimilate the real situation. It enables learners to improve their skills and knowledge in a coordinated environment. Methods Systematic literature search of original research articles was carried out through Google Scholar, Medline, and Cochrane Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Studies conducted on simulation-based teaching and skill performance among nursing students or clinical nursing staff from 2010 to 2019, and published in the English language, were included in this study. Methodological quality was assessed by Joanna Briggs Institute, and the risk of bias was also assessed by Cochrane risk of bias and the risk of bias assessment tool for non-randomized studies (ROBINS-I) checklists. Results Initially, 638 titles were obtained from 3 sources, and 24 original studies with 2209 study participants were taken for the final analysis. Of the total studies, 14 (58.3%) used single group prep post design, 7 (29.1%) used high fidelity simulator (HFS), and 7 (29.1%) used a virtual simulator (VS). Twenty (83.3%) studies reported improved skill performance following simulation-based teaching. Simulation-based teaching improves skill performance among types of groups (single or double), study regions, high fidelity (HF), low fidelity (LF), and standard patient (SP) users. But the effect over virtual and medium fidelity simulators was not statistically significant. Overall, simulation-based teaching improves the skill performance score among the experimental group (d = 1.01, 95% confidence interval [CI] [0.69–1.33], Z = 6.18, P < 0.01, 93.9%). Significant heterogeneity and publication bias were observed during the pooled analysis. Conclusions Simulation did improve skill performance among the intervention groups, but the conclusion is uncertain due to the significant heterogeneity. The large extent of difference among original research has necessitated the development of well-defined assessment methods for skills and standardized simulation set-up for proper assessment of their effects.

The much shorter Archaiologikon Deltion for the single year of 2005 invariably offers far fewer reports on the work of the Archaeological Service than the four-year volume with which we were presented last year. This, in itself, is no bad thing, although the geographical and chronological balance generated by such a large dataset is notable by its absence. This unevenness is, as ever, partially offset by the publication of fieldwork, although certain areas maintain a far more visible archaeological presence than others. This is particularly true for the northeastern Peloponnese, which has, in recent years, been the recipient of an almost unparalleled focus of both research and rescue excavation; a fact reflected in the significant contribution made to this year's report by the edited proceedings of the conference The Corinthia and the Northeast Peloponnese: Topography and History from Prehistoric Times until the End of Antiquity (Kissas and Niemeier 2013). A total of 56 individual papers provide details on sites that range in date from the Neolithic to the Byzantine period. A great strength of this collection lies in the contribution of so many current and former staff of the Archaeological Service, and, of the numerous papers that engage directly or indirectly with the archaeology of the Archaic to Roman period, several are discussed in greater depth in the course of this report. A complementary Hesperia supplement detailing the current state of prehistoric and historic research on the Corinthian Isthmus is due to appear before the end of the year (Gebhard and Gregory forthcoming), as is a study of material from Henry Robinson's 1961–1962 excavation in the North Cemetery (Slane forthcoming). The study of religious practice during the Classical period benefits from the publication of the first volume of material from excavations conducted by the Canadian Institute in Greece between 1994 and 2001 in the Sanctuary of Athena at Stymphalos (Schaus 2014a), while the consolidation of synthetic regional studies and individual site reports within Villae Rusticae: Family and Market-oriented Farms in Greece under Roman Rule (Rizakis and Touratsoglou 2013) will no doubt ensure that it becomes a standard text for the study of the rural economy of Roman Greece (see Stewart, this volume).

IntroductionProviding patients with access to electronic health records (EHRs) has emerged as a promising solution to improve quality of care and safety. As the efforts to develop and implement EHR-based data sharing platforms mature and scale up worldwide, there is a need to evaluate the impact of these interventions and to weigh their relative risks and benefits, in order to inform evidence-based health policies. The aim of this work is to systematically characterise and appraise the demonstrated benefits and risks of sharing EHR with patients, by mapping them across the six domains of quality of care of the Institute of Medicine (IOM) analytical framework (ie, patient-centredness, effectiveness, efficiency, timeliness, equity and safety).Methods and analysisCINAHL, Cochrane, Embase, HMIC, Medline/PubMed and PsycINFO databases will be searched from January 1997 to August 2017. Primary outcomes will include measures related with the six domains of quality of care of the IOM analytical framework. The quality of the studies will be assessed using the Cochrane Risk of Bias Tool, the ROBINS-I Tool and the Drummond’s checklist. A narrative synthesis will be conducted for all included studies. Subgroup analysis will be performed by domain of quality of care domain and by time scale (ie, short-term, medium-term or long-term impact). The body of evidence will be summarised in a Summary of Findings table and its strength assessed according to the GRADE criteria.Ethics and disseminationThis review does not require ethical approval as it will summarise published studies with non-identifiable data. This protocol complies with the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols guidelines. Findings will be disseminated widely through peer-reviewed publication and conference presentations, and patient partners will be included in summarising the research findings into lay summaries and reports.PROSPERO registration numberCRD42017070092.

IntroductionMultiple Sclerosis is a progressive, degenerating disease of the central nervous system (CNS), which affects more than 2.5 million people worldwide. The monoclonal antibody natalizumab (TysabriTM) has been approved by the European Medicines Agency in 2006. Yet, the treatment is associated with an increased risk of developing progressive multifocal encephalopathy (PML). The aim of the systematic review was to investigate whether natalizumab is more effective and safer than alternative pharmacological therapies or placebo over a prolonged period (≥ 36 months) with respect to annualised relapse rate (ARR), disability progression, quality of life and number of serious adverse events (SAEs).MethodsA systematic literature search was conducted considering randomized controlled trials (no restriction in length) and prospective, non-randomized controlled trials. In terms of safety, prospective single arm studies were additionally included. The risk of bias (RoB) was assessed using the Cochrane RoB tool (RCT), the ROBINS-I tool (NRCT) and the Institute of Health Economics quality appraisal checklist (IHE-20) for case series (single-arm studies). The quality of evidence was determined using the GRADE-method (Grading of Recommendations, Assessment, Development and Evaluation).ResultsFor the assessment of clinical effectiveness, three studies (one RCT and two NRCTs) met the inclusion criteria. No significant differences regarding the ARR and disability progression were detected, if natalizumab was compared to an alternative treatment with fingolimod. Yet, if compared to placebo or a group of natalizumab interrupters, a 70 percent reduction in the ARR was observed. For the assessment of safety, seven studies met the inclusion criteria. The proportion of patients suffering from SAEs ranged from 2.4 percent to 16.0 percent. In total, 35 cases of PML occurred. The results were supported by a very low quality of evidence.ConclusionsFuture research should provide more head-to-head RCTs comparing natalizumab with other disease modulating drugs along with a comprehensive documentation of adverse events.

ObjectivesTo summarise evidence on intrawork breaks and their associated effect on doctors’ well-being and/or performance at work.DesignSystematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement guidelinesData sourcesEmbase, PubMed, Web of Science (Core Collection) and PsychINFO were systematically searched on 6 June 2021.Eligibility criteriaNo restrictions were placed on language, study design or date of publication.Data extraction and analysisMethodological quality was appraised using Cochrane’s Risk of Bias (ROB-2), Cochrane’s Risk of Bias in Non-randomised Studies (ROBINS-I), and the Johanna Briggs Institute (JBI) checklists for cross-sectional, cohort and qualitative studies. Quantitative synthesis was not undertaken due to substantial heterogeneity of design and outcomes. Results are presented narratively.ResultsDatabase searches returned 10 557 results and searches of other sources returned two additional records. Thirty-two papers were included in the systematic review, comprised of 29 unique studies, participants and topics and 3 follow-up studies. A variety of well-being and performance outcome measures were used. Overall, findings indicate that intrawork breaks improved some measures of well-being and/or work performance. However, methodological quality was judged to be low with a high risk of bias in most included studies.DiscussionUsing existing evidence, it is not possible to conclude with confidence whether intrawork breaks improve well-being and/or work performance in doctors. There is much inconsistency regarding how breaks are defined, measured and the outcomes used to assess effectiveness. Future research should seek to: (a) define and standardise the measurement of breaks, (b) use valid, reliable outcome measures to evaluate their impact on well-being and performance and (c) minimise the risk of bias in studies where possible.PROSPERO registration numberCRD42020156924;https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=156924.

One of the main democratic institutions in Russia is local selfgovernment (LSG). This institution is characterized by instability of legal regulation, which is reflected in regular changes and amendments to existing laws. The most significant transformation of the Institute of LSG was in 2003–2009, when the «big» municipal reform was carried out. In 2014, a «small» reform of the LSG was launched, which made it possible to introduce a two-level system of city administration. The new model of local government organization operates only in three cities – Chelyabinsk, Makhachkala and Samara. The purpose of the article is to understand the reasons for the transition of some cities to a new system of organization of local government. The conceptual foundations of the article are the structure-oriented approach of D. North, the «distributional» theory of institutional changes of G. Libecap, and the political and economic approach of D. Acemoglu and G. Robinson's. The research is based on the theory of reforms by J. Roland. The author concluded that limited political autonomy at the bodies and local self-government officials, the lack of mayors during the period of reforms Governor-cartridge a result of the change of the head of the region, the timing of the reform with the end of the term of powers of authorities and local selfgovernment officials, as well as the inclusion of regional authorities compensatory strategies for the urban ruling elite, are factors, which contributed to the implementation of institutional reform. It is shown that the obstacles that prevented the «small» reform of the local government act of political autonomy from consolidated municipal ruling elite, interested in preserving the status quo; the existence of an urban political machine; the lack of compensation of the urban ruling elite for losses which are due to the implementation of the reform; the discrepancy between the time of the reform by the end of the term of authorities and local self-government officials.

Background Rheumatoid arthritis is a chronic autoimmune disease that primarily causes inflammation, pain and stiffness in the joints. People with severe disease may be treated with biological disease-modifying anti-rheumatic drugs, including tumour necrosis factor-α inhibitors, but the efficacy of these drugs is hampered by the presence of anti-drug antibodies. Monitoring the response to these treatments typically involves clinical assessment using response criteria, such as Disease Activity Score in 28 joints or European League Against Rheumatism. Enzyme-linked immunosorbent assays can also be used to measure drug and antibody levels in the blood. These tests may inform whether or not adjustments to treatment are required or help clinicians to understand the reasons for treatment non-response or a loss of response. Methods Systematic reviews were conducted to identify studies reporting on the clinical effectiveness and cost-effectiveness of using enzyme-linked immunosorbent assays to measure drug and anti-drug antibody levels to monitor the response to tumour necrosis factor-α inhibitors [adalimumab (Humira®; AbbVie, Inc., North Chicago, IL, USA), etanercept (Enbrel®; Pfizer, Inc., New York, NY, USA), infliximab (Remicade®, Merck Sharp & Dohme Limited, Hoddesdon, UK), certolizumab pegol (Cimzia®; UCB Pharma Limited, Slough, UK) and golimumab (Simponi®; Merck Sharp & Dohme Limited)] in people with rheumatoid arthritis who had either achieved treatment target (remission or low disease activity) or shown primary or secondary non-response to treatment. A range of bibliographic databases, including MEDLINE, EMBASE and CENTRAL (Cochrane Central Register of Controlled Trials), were searched from inception to November 2018. The risk of bias was assessed using the Cochrane ROBINS-1 (Risk Of Bias In Non-randomised Studies – of Interventions) tool for non-randomised studies, with adaptations as appropriate. Threshold and cost–utility analyses that were based on a decision tree model were conducted to estimate the economic outcomes of adding therapeutic drug monitoring to standard care. The costs and resource use were considered from the perspective of the NHS and Personal Social Services. No discounting was applied to the costs and effects owing to the short-term time horizon of 18 months that was adopted in the economic analysis. The impact on the results of variations in testing and treatment strategies was explored in numerous clinically plausible sensitivity analyses. Results Two studies were identified: (1) a non-randomised controlled trial, INGEBIO, that compared standard care with therapeutic drug monitoring using Promonitor® assays [Progenika Biopharma SA (a Grifols–Progenika company), Derio, Spain] in Spanish patients receiving adalimumab who had achieved remission or low disease activity; and (2) a historical control study. The economic analyses were informed by INGEBIO. Different outcomes from INGEBIO produced inconsistent results in both threshold and cost–utility analyses. The cost-effectiveness of therapeutic drug monitoring varied, from the intervention being dominant to the incremental cost-effectiveness ratio of £164,009 per quality-adjusted life-year gained. However, when the frequency of testing was assumed to be once per year and the cost of phlebotomy appointments was excluded, therapeutic drug monitoring dominated standard care. Limitations There is limited relevant research evidence and much uncertainty about the clinical effectiveness and cost-effectiveness of using enzyme-linked immunosorbent assay-based testing for therapeutic drug monitoring in rheumatoid arthritis patients. INGEBIO had serious limitations in relation to the National Institute for Health and Care Excellence scope: only one-third of participants had rheumatoid arthritis, the analyses were mostly not by intention to treat and the follow-up was 18 months only. Moreover, the outcomes might not be generalisable to the NHS. Conclusions Based on the available evidence, no firm conclusions could be made about the cost-effectiveness of therapeutic drug monitoring in England and Wales. Future work Further controlled trials are required to assess the impact of using enzyme-linked immunosorbent assays for monitoring the anti-tumour necrosis factors in people with rheumatoid arthritis. Study registration This study is registered as PROSPERO CRD42018105195. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 8. See the NIHR Journals Library website for further project information.

Sharenting is a habit of using social media to share content that disseminates pictures, videos, information, and parenting styles for their children. The purpose of this article is to describe the sharenting phenomenon that occurs among young parents, and the importance of parenting programs, rather than protecting children's privacy. Writing articles use a qualitative approach as a literature review method that utilizes various scientific articles describing the sharenting phenomenon in various countries. The findings show that sharenting behaviour can create the spread of children's identity openly on social media and tends not to protect children's privacy and even seems to exploit children. Apart from that, sharenting can also create pressure on the children themselves and can even have an impact on online crime. This article is expected to provide benefits to parents regarding the importance of maintaining attitudes and behaviour when sharing and maintaining children's privacy and rights on social media. Keywords: Sharenting on social media, Children's Privacy, Parenting Program References: Åberg, E., & Huvila, J. (2019). Hip children, good mothers – children’s clothing as capital investment? Young Consumers, 20(3), 153–166. https://doi.org/10.1108/YC-06-2018-00816 Altafim, E. R. P., & Linhares, M. B. M. (2016). Universal violence and child maltreatment prevention programs for parents: A systematic review. Psychosocial Intervention, 25(1), 27–38. https://doi.org/10.1016/j.psi.2015.10.003 Archer, C., & Kao, K.-T. (2018). Mother, baby, and Facebook makes three: Does social media provide social support for new mothers? Media International Australia, 168(1), 122–139. https://doi.org/10.1177/1329878X18783016 Bartholomew, M. K., Schoppe-Sullivan, S. J., Glassman, M., Kamp Dush, C. M., & Sullivan, J. M. (2012). New Parents’ Facebook Use at the Transition to Parenthood. Family Relations, 61(3), 455–469. https://doi.org/10.1111/j.1741-3729.2012.00708.x Belk, R. W. (1988). Possessions and the Extended Self. Journal of Consumer Research, 15(2), 139. https://doi.org/10.1086/209154 Belk, R. W. (2013). Extended Self in a Digital World: Table 1. Journal of Consumer Research, 40(3), 477–500. https://doi.org/10.1086/671052 Benedetto, L., & Ingrassia, M. (2021). Digital Parenting: Raising and Protecting Children in Media World. In L. Benedetto & M. Ingrassia (Eds.), Parenting. IntechOpen. https://doi.org/10.5772/intechopen.92579 Berns, R. (2016). Child, family, school, community. Socialization and support. Stanford. United States of America, 5(64), 93–98. Bessant, C. (2017). Parental sharenting and the privacy of children. Northumbria University Faculty of Business and Law, Faculty and Doctoral Conference, 28th - 29th June 2017, Newcastle, UK. Bessant, C. (2018). Sharenting: Balancing the Conflicting Rights of Parents and Children. Communications Law, 23(1), 7–24. Bessant, C., & Nottingham, E. (2020). Sharenting in a socially distanced world. Parenting for a Digital Future., 1–2. Biglan, A., Flay, B. R., Embry, D. D., & Sandier, I. N. (2012). The Critical Role of Nurturing Environments for Promoting Human Weil-Being. American Psychologist, 16. Blum-Ross, A., & Livingstone, S. (2017). “Sharenting,” parent blogging, and the boundaries of the digital self. Popular Communication, 15(2), 110–125. https://doi.org/10.1080/15405702.2016.1223300 Brooks, J. (2008). The Process of Parenting. In The Process of Parenting (pp. 116–117). Pustaka Belajar. Brosch, A. (2016). When the child is born into the internet: Sharenting as a growing trend among parents on Facebook. New Educational Review, 43(1), 224–235. https://doi.org/10.15804/tner.2016.43.1.19 Brosch, A. (2018). Sharenting – Why do parents violate their children’s privacy? New Educational Review, 54(4), 75–85. https://doi.org/10.15804/tner.2018.54.4.06 Byrne, S., Rodrigo, M. J., & Máiquez, M. L. (2014). Patterns of individual change in a parenting program for child maltreatment and their relation to family and professional environments. Child Abuse & Neglect, 38(3), 457–467. https://doi.org/10.1016/j.chiabu.2013.12.008 Centers for Disease Control and Prevention. (2014). Understanding Child Maltreatment 2014 (p. 2). http://www.cdc.gov/violenceprevention/pdf/cm-factsheet-a.pdf Children’s Online Privacy Protection Act (COPPA). (2002). Protecting Children’s Privacy Under COPPA: A Survey on Compliance. Federal Trade Commission. http://www.ftc.gov/ogc/coppa1.htm Choi, G. Y., & Lewallen, J. (2018). “Say Instagram, Kids!”: Examining Sharenting and Children’s Digital Representations on Instagram. Howard Journal of Communications, 29(2), 144–164. https://doi.org/10.1080/10646175.2017.1327380 Collins English Dictionary. (2014). Opinion—Definition of opinion by The Free Dictionary. 12th Edition. http://dictionary.reference.com/browse/database Comer, J. S., & Barlow, D. H. (2014). The occasional case against broad dissemination and implementation: Retaining a role for specialty care in the delivery of psychological treatments. American Psychologist, 69(1), 1–18. https://doi.org/10.1037/a0033582 Durkin, K. F., & Bryant, C. D. (1999). Propagandizing pederasty: A thematic analysis of the on-line exculpatory accounts of unrepentant pedophiles. Deviant Behavior, 20(2), 103–127. https://doi.org/10.1080/016396299266524 Fitri, S. (2017). Dampak Foditif dan Negatif Sosial Media terhadap Sosial Anak. NATURALISTIC: Jurnal Kajian Penelitian Pendidikan Dan Pembelajaran, 1(2), 118–123. https://doi.org/10.35568/naturalistic.v1i2.5 Fox, A. K., & Hoy, M. G. (2019). Smart Devices, Smart Decisions? Implications of Parents’ Sharenting for Children’s Online Privacy: An Investigation of Mothers. Journal of Public Policy & Marketing, 38(4), 414–432. https://doi.org/10.1177/0743915619858290 Fridha, M., & Irawan, R. E. (2020). Eksploitasi Anak Melalui Akun Instagram (Analisis Wacana Kritis Praktek Sharenting oleh Selebgram Ashanty & Rachel Venya). Komuniti: Jurnal Komunikasi dan Teknologi Informasi, 12(1), 68–80. https://doi.org/10.23917/komuniti.v12i1.10703 Friedman, S. J. (2000). Children and the World Wide Web. University Press of America. Hammond, S. I., Müller, U., Carpendale, J. I. M., Bibok, M. B., & Liebermann-Finestone, D. P. (2012). The effects of parental scaffolding on preschoolers’ executive function. Developmental Psychology, 48(1), 271–281. https://doi.org/10.1037/a0025519 Holzer, P. J., Higgins, J., Bromfield, L., Richardson, N., & Higgins, D. (2006). The effectiveness of parent education and home visiting child maltreatment prevention programs. Australian Institute of Family Studies. Koetse, M. (2019). ‘Sharenting’ on Chinese Social Media: When Parents Are Posting Too Many Baby Pics on WeChat. What’s on Weibo Reporting Social Trends in China. Krisnawati, E. (2016). Mempertanyakan Privasi di Era Selebgram: Masih Adakah? Jurnal IIlmu Komunikasi, 13(2), 179. https://doi.org/10.24002/jik.v13i2.682 Latipah, E., Adi Kistoro, H. C., Hasanah, F. F., & Putranta, H. (2020). Elaborating motive and psychological impact of sharenting in millennial parents. Universal Journal of Educational Research, 8(10), 4807–4817. https://doi.org/10.13189/ujer.2020.081052 Leaver, T. (2020). Balancing privacy: Sharenting, intimate surveillance, and the right to be forgotten. In The Routledge Companion to Digital Media and Children. https://doi.org/10.33767/osf.io/fwmr2 Lee, S. J., Ward, K. P., Chang, O. D., & Downing, K. M. (2021). Parenting activities and the transition to home-based education during the COVID-19 pandemic. Children and Youth Services Review, 122, 105585. https://doi.org/10.1016/j.childyouth.2020.105585 Lundahl, B., Risser, H., & Lovejoy, M. (2006). A meta-analysis of parent training: Moderators and follow-up effects. Clinical Psychology Review, 26(1), 86–104. https://doi.org/10.1016/j.cpr.2005.07.004 Lwin, M., Stanaland, A., & Miyazaki, A. (2008). Protecting children’s privacy online: How parental mediation strategies affect website safeguard effectiveness. Journal of Retailing, 84(2), 205–217. https://doi.org/10.1016/j.jretai.2008.04.004 Manganello, J. A., Falisi, A. L., Roberts, K. J., Smith, K. C., & McKenzie, L. B. (2016). Pediatric injury information seeking for mothers with young children: The role of health literacy and ehealth literacy. Journal of Communication in Healthcare, 9(3), 223–231. https://doi.org/10.1080/17538068.2016.1192757 Manotipya, P., & Ghazinour, K. (2020). Children’s Online Privacy from Parents’ Perspective. Procedia Computer Science, 177, 178–185. https://doi.org/10.1016/j.procs.2020.10.026 Marasli, M., Sühendan, E., Yilmazturk, N. H., & Cok, F. (2016). Parents’ shares on social networking sites about their children: Sharenting. Anthropologist, 24(2), 399–406. https://doi.org/10.1080/09720073.2016.11892031 Mikton, C., & Butchart, A. (2009). Child maltreatment prevention: A systematic review of reviews. Bulletin of the World Health Organization, 87(5), 353–361. https://doi.org/10.2471/BLT.08.057075 Miyazaki, A. D. (2008). Online Privacy and the Disclosure of Cookie Use: Effects on Consumer Trust and Anticipated Patronage. Journal of Public Policy & Marketing, 27(1), 19–33. https://doi.org/10.1509/jppm.27.1.19 Morris, A. S., Robinson, L. R., Hays-Grudo, J., Claussen, A. H., Hartwig, S. A., & Treat, A. E. (2017). Targeting Parenting in Early Childhood: A Public Health Approach to Improve Outcomes for Children Living in Poverty. Child Development, 88(2), 388–397. https://doi.org/10.1111/cdev.12743 Moser, C., Chen, T., & Schoenebeck, S. Y. (2017). Parents? And Children?s Preferences about Parents Sharing about Children on Social Media. Proceedings of the 2017 CHI Conference on Human Factors in Computing Systems, 5221–5225. https://doi.org/10.1145/3025453.3025587 Nooraeni, R. (2017). Implementasi Program Parenting Dalam Menumbuhkan Perilaku Pengasuhan Positif Orang Tua Di PAUD Tulip Tarogong Kaler Garut. Jurnal Pendidikan Luar Sekolah, 13(2). Nottingham, E. (2013). ‘Dad! Cut that Part Out!’ Children’s Rights to Privacy in the Age of ‘Generation Tagged’: Sharenting, digital kidnapping and the child micro-celebrity. In Journal of Chemical Information and Modeling. O’Keeffe, G. S., Clarke-Pearson, K., & Council on Communications and Media. (2011). The Impact of Social Media on Children, Adolescents, and Families. PEDIATRICS, 127(4), 800–804. https://doi.org/10.1542/peds.2011-0054 Pan, X., & Yu, H. (2018). Different Effects of Cognitive Shifting and Intelligence on Creativity. The Journal of Creative Behavior, 52(3), 212–225. https://doi.org/10.1002/jocb.144 Prasetyo, Dimas., Syahnas, A. N. R., Fajriani, A., Nugraha, H. G., & Suryani, S. (2019). “Saya hanya mengunggah foto dan video anak saya ”. Intenational Conference on ECEP. Putra, A. M., & Febrina, A. (2019). Fenomena Selebgram Anak: Memahami Motif Orang tua. Jurnal ASPIKOM, 3(6), 1093–1108. https://doi.org/10.24329/aspikom.v3i6.396 Sakashita, M., & Kimura, J. (2011). Daughter as Mother’s Extended Self. In European advances in consumer research (In A. Bradshaw, C. Hackley, P. Maclaran (Eds.), Vol. 9, pp. 283–289). Association for Consumer Research. Salleh, A. S., & Noor, N. A. Mohd. (2019). Sharenting: Implikasinya dari Persepektif Perundangan Malaysia. Jurnal Undangundang Malaysia, 31(1), 121–156. Sanders, M. (2012). Development, evaluation, and multinational dissemination of the triple P-Positive Parenting Program. Annual Review of Clinical Psychology, 8, 345–379. Santini, P. M., & Williams, L. C. (2016). Parenting Programs to Prevent Corporal Punishment: A Systematic Review. Paidéia (Ribeirão Preto), 26(63), 121–129. https://doi.org/10.1590/1982-43272663201614 Sarkadi, A., Dahlberg, A., Fängström, K., & Warner, G. (2020). Children want parents to ask for permission before ‘sharenting’. Journal of Paediatrics and Child Health, 56(6), 981–983. https://doi.org/10.1111/jpc.14945 Shumaker, C., Loranger, D., & Dorie, A. (2017). Dressing for the Internet: A study of female self-presentation via dress on Instagram. Fashion, Style & Popular Culture, 4(3), 365–382. https://doi.org/10.1386/fspc.4.3.365_1 Siibak, A., & Traks, K. (2019). Viewpoints The dark sides of sharenting. Catalan Journal of Communication & Cultural Studies, 11(1), 115–121. https://doi.org/10.1386/cjcs.11.1.115 Sobur, A. (2001). Pers, Hak Privasi, dan Hak Publik. Mediator, 2(1), 81–91. http://dx.doi.org/10.24329/aspikom.v3i6.396 Steinberg, S. B. (2017). Sharenting: Children’s Privacy in the Age of social media. EMORY LAW JOURNAL, 66, 47. Traube, D. E., Hsiao, H.-Y., Rau, A., Hunt-O’Brien, D., Lu, L., & Islam, N. (2020). Advancing Home Based Parenting Programs through the Use of Telehealth Technology. Journal of Child and Family Studies, 29(1), 44–53. https://doi.org/10.1007/s10826-019-01458-w Trivette, C. M., & Dunst, C. J. (2009). Community-Based Parent Support Programs. 7. van der Velden, M., & El Emam, K. (2013). “Not all my friends need to know”: A qualitative study of teenage patients, privacy, and social media. Journal of the American Medical Informatics Association, 20(1), 16–24. https://doi.org/10.1136/amiajnl-2012-000949 Verswijvel, K., Walrave, M., Hardies, K., & Heirman, W. (2019). Sharenting, is it a good or a bad thing? Understanding how adolescents think and feel about sharenting on social network sites. Children and Youth Services Review, 104, 104401. https://doi.org/10.1016/j.childyouth.2019.104401 Wagner, A., & Gasche, L. A. (2018). Sharenting: Making decisions about other’s privacy on social networking sites. MKWI 2018 - Multikonferenz Wirtschaftsinformatik. World Health Organization (WHO). (2016). INSPIRE seven strategies for ending violence against children. World Health Organization. Wyatt Kaminski, J., Valle, L. A., Filene, J. H., & Boyle, C. L. (2008). A Meta-analytic Review of Components Associated with Parent Training Program Effectiveness. Journal of Abnormal Child Psychology, 36(4), 567–589. https://doi.org/10.1007/s10802-007-9201-9 Zeeuw, A. De, Media, M. A. N., & Culture, D. (2018). Exposing Childhoods Online (Issue June).

The research deals with recent invasions of bird-dispersed shrubs in specially protected natural reservations of St.Petersburg and Leningrad Region. The results of bird-dispersed woody species inventory in 5 partial nature reserves and nature sanctuaries of the area (See Fig. 1), based upon the extensive phytocoenological research data of 2014-2018, are given (See Table 1). Out of the adventive shrub species listed, the two most aggressive invaders were chosen according to their constancy and abundance in natural forest communities. These are Lonicera nigra in Komarovskiy Bereg [Komarovo Coast] Nature Sanctuary and Amelanchier spicata in Lisinskiy [Lisino] Partial Nature Reserve. For this purpose, distributions of these species are traced along with different forest types they invade, paying attention to species constancy and projective cover in different layers of forest communities (See Tables 2 and 4). Values of intralandscape species activeness, based upon the proper relevé sets, were also calculated for both aboriginal and adventitious plant species from different community types in each study area (See Tables 3 and 5). Lonicera nigra has never been detected as an invader before. It is presumably dispersed by robins, thrushes, and warblers, also by means of barochory and secondary hydrochory. The latter is proved by the occurrence of the oldest shrubs in riverine Norway spruce and Scots pine forests on the Littorine terrace of the Gulf of Finland within Komarovo Coast Nature Sanctuary. The results of secondary bird dispersal of this species are observed in sorrel spruce forests where the untypical low shrub layer is being formed (See Fig. 2). These plants are remote form brooks or drainage channels (See Table 2). L. nigra acts as one of the most active species in the sanctuary forest coenofloras studied (See Table 3). Nevertheless, floristic composition of these forest communities remains yet unchanged in its main features. The invasion of L. nigra in the sanctuary area was first mentioned in literature by NN Tzvelev in 2000 but it took place much earlier, as the ancestral plant specimens were likely to grow in a transplant nursery near the present-day sanctuary north-eastern border in the early XX-th century. According to Komarov Botanical Institute Herbarium (LE) data, the secondary area of L. nigra in Russia is restricted to several findings in the Karelian Isthmus. Amelanchier spicata, the June berry, listed among the most aggressive plant invaders in European Russia, is dispersed by thrushes along roads in forests and then invades sorrel and horsetail-peatmoss spruce and pine forests on southern-boreal watersheds in Lisino Reserve, often as a gap-filling species. It is less common and abundant in secondary birch and aspen forests. In contrast to Lonicera nigra, it is infrequent and never abundant in riverine forests (See Table 4), the fact probably explained by difference in prevailing bird distributor species. A. spicata is never found in feathermoss pine forests on fluvial-glacial sand as well as in dwarfshrub-peatmoss pine bog forests. The invasion of this species in the reserve area probably took place after 1984-1987 when the species was not registered in forest communities of the area according to the author’s personal observations. In 2017, the activeness of A. spicata is low in all the forest types it inhabits, being compared to that of the dominant aboriginal species (See Table 5). As follows from the correlation analysis results, no one of the discussed invaders affects the projective cover of any of the native plant species in both protected areas significantly. Speaking of Amelanchier spicata, it is in fact far less aggressive than in the more southern areas of Central and Southern Russia where the species transforms forest communities actively and affects aboriginal field- and ground-layer plants negatively, even as far as to the extinction of some of the latter, as it is well-known from the literature on the subject. We are just at the beginning of the invasion process in the forests of the Russian North-West yet. The invasion of both species studied is likely to be connected with the climate change processes. The research reveals that a neglected adventive species, persisting long within a given area, may also suddenly become an aggressive invader (the case of Lonicera nigra). The invasion of adventive shrubs into the paludified forest communities, including those of the boreal peatmoss spruce forests which served as etalons of floristic stability quite recently, is also alarming.

Patients with coronary artery disease have multiple co-morbids that include dyslipidemia, hypertension, diabetes mellitus, smoking and physical inactivity. It has been seen that depression is another issue in these patients that need close attention. Studies have shown that it affects between 20% and 40% in patients with coronary artery disease (CAD) and have a higher prevalence than in general population.1 One of the study done by SS Bokhari et al.2 has shown a point prevalence of depression in CAD as 37% (31.3% males and 53.8% females). Numerous studies have shown that patients with CAD and depression have poor health outcomes.3 Depression in different aspects in Pakistani population after myocardial infarction,4 after PCI5 and in in-hospital patients with CAD6 were evaluated and found to have significant mental illness which co-relates with the results of other international studies. Keeping all the research studies American Heart Association wrote a scientific statement and endorsed depression as a risk factor for cardiac morbidity and mortality.7 Importance of depression screening as a part of myocardial infarction protocol for caring patients with Ischemic Heart Disease was seen in TRIUMPH trial (Translational Research Investigating Underlying Disparities in Acute Myocordial Infarction Patients Health Status)8 ENRICHD Trial (Enhancing Recovery in Coronary Heart Disease)9 use of citalopram or serlatine plus as clinical management was used for depressive symptoms with CAD in CREATE Trial (Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy).10 In Pakistan where prevalent of CAD is high i.e. one in 4 middle age adults,11 managing such patients are numerous that includes revascularization (Surgical and Interventional), drugs and treatment of modifiable and nonmodifiable risk factors. Despite all these efforts it’s a need of time to focus on diagnosing depression in CAD to improve outcomes. Depression screening should be conducted to identify these important risk factors and treated with drugs in reducing morbidity and mortality. References Lett HS, Blumenthal JA, Babyak MA, Sherwood A, Strauman T, Robins C, et al. Depression as a risk factor for coronary artery disease: evidence, mechanisms, and treatment. Psychosom Med. 2004;66:305-15. Bokhari SS, Samad AH, Hanif S, Hadique S, Cheema MQ, Fazal MAS, et al. Prevalence of depression in patients with coronary artery disease in a tertiary care hospital in Pakistan. J Pak Med Assoc. 2002;52(9):436-9. Jackson CA, Sudlow CLM, Mishra GD. Psychological Distress and Risk of Myocardial Infarction and Stroke in the 45 and Up Study. Circ Cardiovasc Qual Outcomes. 2018;11:e004500. Saeed H, Khan F, Mohsin SF, Qizilbash FH, Fraz TR, Jawed Q, et al. Pattern of Depression Among Patients of Myocardial Infarction in Karachi, Pakistan: A Cross-sectional Study. Cureus. 2018;10(8):e3199 Mujtaba SF, Sial JA, Karim M. Depression and Anxiety in patients undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome. Pak J Med Sci. 2020;36(5):1100-5. Khan SA, Azhar S, Asad SM, Iqbal A, Kousar R, Ahmad M, et al. Assessment of anxiety and depression in hospitalized cardiac patients of Faisalabad Institute of Cardiology, Pakistan. Trop J Pharm Res. 2016;15(11):2483-7 Lichtman JH, Froelicher ES, Blumenthal JA, Carney RM, Doering LV, Frasure-Smith N, et al. Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association. Circulation 2014;129:1350-69. Smolderen KG, Buchanan DM, Gosch K, Whooley M, Chan PS, Vaccarino V, et al. Depression Treatment and 1-Year Mortality Following Acute Myocardial Infarction: Insights from the TRIUMPH Registry. Circulation 2017;135:1681-9. Berkman LF, Blumenthal J, Burg M, Carney RM, Catellier D, Cowan MJ, et al. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA 2003;289:3106-16. Lespérance F, Frasure-Smith N, Koszycki D, Laliberté MA, van Zyl LT, Baker B, et al. Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. JAMA 2007;297:367-79. Jafar TH, Jafary FH, Jessani S, Chaturvedi N. Heart disease epidemic in Pakistan: women and men at equal risk. Am Heart J. 2005;150(2):221-6.

Introducción: El cáncer de próstata (CP) el segundo cáncer diagnosticado en hombres, con mayor incidencia a los 66 años. La obesidad, el tabaquismo, alcoholismo y antecedentes familiares de CP se han encontrado asociados al riesgo de metástasis. El objetivo del presente estudio fue medir la asociación entre factores y el estado metastásico en pacientes con CP en un centro único de referencia en Ecuador. Metodología: El presente estudio analítico, se realizó en el Hospital “Teodoro Maldonado Carbo”, en Guayaquil-Ecuador, en el período enero-diciembre del 2019. El cálculo muestral fue no probabilístico, tipo censo. Se incluyeron casos con CP. Las variables fueron: edad, PSA, escala de Gleason, presencia de metástasis, sintomatología, tabaquismo, obesidad y antecedentes. Se presenta Odds Ratio como medida de asociación con intervalo de confianza del 95% y valor P. Resultados: El estudio incluyó 363 pacientes, con edad promedio de 75.2 ± 9.6 años. El grupo con metástasis fue de 202 casos (55.65%). Metástasis ósea 32.5%, pulmonar 9.6%, ganglionar 8.8% y hepático 4.75%. En la sintomatología la más frecuente fue, disuria (44.4%); el 33.6% con polaquiuria, un 13.2% hematuria y 8.8% tenesmo. El estadio Gleason-9 OR=24.85 (IC 95% 1.47-419.8) P=0.0259. El nivel de PSA >19 ng/ml OR= 6.996 (IC 95% 2.68-18.29) P=0.0001. El tabaquismo OR=2.34 (IC 95% 1.52-3.60) P=0.0001. Fueron factores protectores el valor de PSA <19 ng/ml OR=0.082 (IC 95% 0.043-0.157) P<0.0001, acudir a consulta de Hipertensión arterial OR=0.33 (IC 95% 0.161-0.691) P=0.0032 y el estadío Gleason-6 OR=0.108 (IC 95% 0.0665-9.1736) P<0.0001. Conclusión: Los niveles de PSA >19 ng/ml y el estadio Gleason >9 se asocian a la presencia de metástasis en pacientes con CP. Recibido: Julio 14, 2022 Aceptado: Octubre 27, 2022 Publicado: Diciembre 2, 2022 Editor: Dra. Evelyn Valencia Espinoza. Introducción El cáncer de próstata es el segundo cáncer más diagnosticado en hombres alrededor del mundo, con mayor incidencia promedio a los 66 años [1]. En países desarrollados, el cáncer de próstata se diagnostica a edades más tempranas cuando este se confina a la glándula prostática, debido al uso del antígeno prostático específico (PSA) [2]. El antígeno prostático específico es proteína creada por el epitelio prostático, el cual, es específico de órgano, más no de cáncer, debido a que el mismo puede estar elevado en patologías como prostatitis, hiperplasia prostática benigna, entre otras. Sin embargo, es el mejor biomarcador hasta ahora para el diagnóstico temprano del cáncer de próstata. Según la American Academy of Family Physicians, se ha determinado que 3 de cada 10 hombres con elevado PSA, tienen un alto riesgo de sufrir de cáncer de próstata que va a depender de la edad y el nivel del PSA que se encuentre. Algunos estudios demuestran que las pruebas de rutina de PSA en hombres entre 55 a 66 años disminuyen la mortalidad por cáncer de próstata, de manera significativa. Sin embargo, la baja especificidad para Cáncer de Próstata de la prueba, hace que la interpretación de ella no sea concluyente [3]. La Escala de Gleason es un sistema de graduación que sirve, una vez establecido el diagnóstico de adenocarcinoma de próstata, para medir la agresividad histopatológica de la neoplasia [4]. Está plenamente establecido que la escala de Gleason, de acuerdo a los hallazgos histopatológicos del tumor, nos permite categorizar a los pacientes de una manera más precisa y de esta manera tener una idea clara del pronóstico de dicho paciente. Con estos antecedentes se estableció el objetivo de determinar los factores de riesgo asociados a metástasis en pacientes con cáncer de próstata en un centro de referencia regional en Guayaquil-Ecuador. Materiales y métodos Diseño del estudio El presente estudio es observacional-analítica. La fuente es retrospectiva. Área de estudio El estudio se realizó en el servicio de urología del Hospital de Especialidades “Teodoro Maldonado Carbo”, del Instituto Ecuatoriano de Seguridad Social, en Guayaquil-Ecuador. El período de estudio fue del 1ro de Enero del 2019 hasta el 31 de diciembre del 2019. Universo y muestra El universo fue conformado por todos los pacientes registrados en la institución. El cálculo del tamaño muestral fue no probabilístico, tipo censo, en donde se incluyeron todos los casos incidentes en el período de estudio. Participantes Se incluyeron casos de pacientes adultos diagnosticados con cáncer de próstata en quienes se contó con valoración de PSA y la escala de Gleason. Se excluyeron registros incompletos para el análisis. Variables Las variables fueron edad, PSA, escala de Gleason, presencia de metástasis, sintomatología, métodos diagnósticos. Procedimientos, técnicas e instrumentos. Los datos fueron recogidos de la historia clínica en un formulario diseñado exclusivamente para tal propósito. Los diagnósticos de CP se realizaron por punción aspiración por aguja fina (PAAF) guiada por ecografía. Las placas fueron leídas por Patólogos distintos. Se usó el sistema AS400 para la pesquisa de casos usando los diagnósticos codificados: C61. Evitación de sesgos Para garantizar la confiabilidad de la información los investigadores fueron entrenados sobre la recolección de los datos. Se usó una lista de doble chequeo para incluir los casos. Los datos fueron validados y curados por el investigador principal. Análisis estadístico Recopilada la información en una hoja electrónica Excel, se ingresó en una matriz de datos del software SPSS™ 22.0 (IBM, Chicago, USA). Se utilizó estadística descriptiva en base a frecuencias y porcentajes para las variables cualitativas y para las cuantitativas medidas de tendencia central. Se presenta Odds Ratio como medida de asociación con intervalo de confianza del 95% y valor P. Resultados El estudio incluyó 363 pacientes. Caracterización clínica Fueron 363 pacientes, con edad promedio de 75.2 ± 9.6 años. La edad mínima fue de 49 años, y la máxima de 98 años. Los pacientes con metástasis fueron 202 casos (55.65%). Con respecto al lugar de diseminación metastásica, se encontró mayor predilección a desarrollar metástasis ósea en el 32.5% de los pacientes, seguido de metástasis pulmonar con el 9.6%, metástasis ganglionar con el 8.8% y a nivel hepático 4.75% de los casos. En la sintomatología la más frecuente fue, disuria con el 44.4%; el 33.6% con polaquiuria, un 13.2% hematuria y 8.8% tenesmo. El estudio más frecuente utilizado, fue el eco prostático, con un 42.7%; la tomografía 20.4%), gammagrafía prostática 25.6%, la resonancia magnética con el 11.3%. Factores clínicos El 44.4% de los pacientes padecía alcoholismo, el 27.5% presentaba tabaquismo, el 23.1% eran consumidores de carnes y lácteos; otros hábitos poco frecuentes se relacionaron con el 4.7%; 0.3% no refería ningún hábito de importancia. Dentro de los antecedentes patológicos se evidenció que, 54.5% de los pacientes tenían antecedentes familiares de Cáncer de próstata, 29.2% presentaba obesidad y sobrepeso, en tercer lugar, con 9.9% de los pacientes padecía de hipertensión arterial y entre otros antecedentes asociados tenían un porcentaje del 5.5% (Tabla 1). De la totalidad de los evaluados, el 45.2% tuvieron Gleason 6, mientras que aquellos con valores en la Escala de Gleason de 10, alcanzaban el 1.4%. La medición del riesgo se presenta en la tabla 1. Se constituyeron factores de riesgo para el desarrollo de metástasis el tabaquismo, y el estadío clínico Gleason 7, 8 y 9, los valores de PSA en rangos de 19-49 ng/ml, de 50 a 99 ng/ml y 100-299 ng/ml. Se establecieron como factores de protección estadísticamente significativos al antecedente personal de Hiperplasia prostática benigna, a la condición de hipertensión arterial, al estadio clínico Gleason 6, al valor de PSA <19 ng/ml (Tabla 1). Discusión Al comparar el presente estudio con investigaciones previas se constató que la edad constituye un factor de riesgo no modificable para padecer cáncer prostático, según el Instituto Nacional de Cáncer en Estados Unidos, en su programa estadístico de Vigilancia, Epidemiología y Resultados (SEER) entre los años 2015-2019 se encontró una mayor incidencia de casos en los pacientes que tenían entre 70-74 años de edad [5], así también lo describió el trabajo de Leitzmann et al, en los años correspondientes a 2000-2008 donde la incidencia comienza a aumentar desde los 40-44 años de edad para llegar a su pico máximo de 984.8 pacientes por cada 100.000 hombres con edades entre 70-74 años [6], similarmente en este estudio el mínimo de edad fue 49 años en la población con un máximo de 98 y un media de 75.15 respectivamente. En cuanto a la distribución de regiones anatómicas donde se suele presentar la metástasis en el cáncer prostático; en primer lugar se determinó a los huesos (84%) en segundo lugar a nódulos linfáticos distantes (10.6%) y hepático (10.2%) [7] según un estudio conducido por Gandaglia et al. lo cual en similitud a este estudio el sitio más frecuente fue a nivel óseo con un 32.5% de todos los pacientes, seguido de la metástasis pulmonar con 9.6% y ganglionar 8.8%. A su vez Auz y Brito (2018) encontraron en su investigación realizada en el Hospital Solca Núcleo de Quito-Ecuador que incluyó a 1713 pacientes donde el sitio más frecuente de metástasis fue el óseo en un 82.25%, seguido del ganglionar linfático con 7.05% y luego 2.8% a nivel pulmonar [8]. En lo que corresponde a los hábitos de los pacientes, un 44.4% de pacientes en este estudio consumía de alcohol regularmente, mientras que el 27.5% consumía tabaco y el 23.1% eran consumidores de carnes y lácteos, lo cual se contrasta con el estudio de Auz y Brito (2018) detallado anteriormente donde 31.1% de los pacientes consumían alcohol regularmente y el 28.3% de los pacientes consumían tabaco al momento de diagnóstico, no se midieron datos en relación al consumo de lácteos y carnes rojas [8]. Un factor de riesgo no modificable muy importante fue la presencia de antecedentes familiares de cáncer de próstata en este estudio con un 54.5% de los pacientes lo cual en el trabajo de Auz y Brito (2018) solamente 9% tuvieron antecedentes familiares de cáncer prostático y un 23.2% de otros tipos de cánceres [23]. Según Barber et al. en su estudio se identificó que pacientes con historia familiar de cáncer prostático únicamente, tienen un riesgo aumentado del 68% de padecer lo mismo (95% CI 1.53-1.83) y un 72% de enfermedad letal [9]. Así también lo describió Powell IJ (2011) en su publicación que dice que hombres con relativos de primer grado (Padre, hermano, hijo) tienen un riesgo de desarrollar cáncer prostático que es aproximadamente del doble a la población general [10]. En el presente estudio 29.2% de los pacientes presentaba sobrepeso y 9.9% de los pacientes padecía hipertensión arterial, así mismo en el estudio de Möller et al. se encontró que un IMC alto (26) en comparación a 20-22 a la edad de 21 años fue asociada con riesgo menor de cáncer prostático letal o avanzado y Gleason 7 [11], también se habla sobre que de los componentes del síndrome metabólico incluyendo la hipertensión arterial ninguno tiene relación con el desarrollo de cáncer prostático [10]. Dentro de los síntomas más frecuentes en esta investigación se encontraron la disuria con un 44.4% de todos los pacientes, le siguió la polaquiuria (33.6%) y finalmente la hematuria (13.2%). De manera similar el estudio de Birtle et al. llevado a cabo entre los años 2000-2001 con bases de datos de la Asociación Británica de Cirujano Urológicos determinó que de 33 pacientes con cáncer metastásico de próstata con PSA <10 ng/ml 51% se presentó con síntomas urinarios y/o dolor pélvico, 21% presentó dolor óseo, 18% retención urinaria y 10% caquexia y malasia [12]. En el presente estudio de la totalidad de pacientes, 45.2% de ellos tuvieron puntajes de Gleason de 6 y en menor medida con 1.4% de los pacientes puntajes de Gleason 10, esto se puede comparar con el estudio de Thomsen et al. donde se encontró que altos puntajes en la escala de Gleason se relacionaron a la presencia de metástasis, así en ese estudio los pacientes que presentaron metástasis a distancia según la escala TNM (M1), 41% tenía un puntaje de Gleason 5, mientras que solo el 3% tenía Gleason 1 [13]. El método de imagen más utilizado en este estudio fue el de la ecografía prostática con un 42.7% y en menor medida la resonancia magnética con el 11.3%. En la investigación de Huang et al. se encontró que el uso de la Resonancia Magnética con el sistema PI-RADS v2 fue el sistema más preciso para predecir la metástasis a nódulos linfáticos en la zona pélvica, los pacientes con PI-RADs <5 fueron asociados con un riesgo muy bajo de metástasis ganglionar [14]. La ecografía prostática 3D se demostró un 84% de sensibilidad y 96% de especificidad para identificar extensión tumoral extra capsular macroscópica y fue capaz de identificar a 14/16 diseminaciones a la vesícula seminal según Mitterberger et al. en el año 2008 [15]. Finalmente con respecto a valoraciones de PSA que se presentaron en los pacientes diagnosticados con cáncer de próstata, se pudo evidenciar, que el 100% de los pacientes con PSA mayor de 500 ng/ml tuvo metástasis, así como el grupo de pacientes con 300-499 ng/ml PSA, a diferencia del grupo con menos de 19 ng/ml PSA donde solo el 40.6% tuvo metástasis, lo cual se puede comparar al estudio de Thomsen et al. donde de los pacientes con más de 400 ng/ml, el 64.9% presentó metástasis, le sigue el grupo con valores de 200-399 ng/ml donde el 54% desarrolló metástasis y al final el grupo con menos de 19 ng/ml tuvo solo al 1.45% de pacientes con metástasis, podemos así deducir que el valor de PSA es directamente proporcional al riesgo de metástasis, sin embargo, recomendamos tomar en cuenta más factores de riesgos de manera conjunta para una evaluación integral del paciente [13]. Conclusiones En orden de importancia estadística los factores asociados a metástasis en cáncer prostático son el estadio clínico Gleason 9 y 8, Los niveles de PSA entre 50 a 299 ng/ml, y el tabaquismo. Fueron factores protectivos el antecedente clínico de Hiperplasia Prostática benigna, hipertensión y el nivel de PSA <19 ng/ml. Nota del Editor La Revista Oncología Ecu permanece neutral con respecto a los reclamos jurisdiccionales en mapas publicados y afiliaciones institucionales. Agradecimientos Los autores agradecen a todas las personas de la Institución que colaboraron en el desarrollo de esta investigación. Información administrativa Abreviaturas APP: antecedentes patológicos personales. APF: Antecedentes patológicos familiares. HPB: hiperplasia prostática benigna. Ca: Cáncer. PSA: Antígeno prostático específico. OR: Odds ratio. IC: intervalo de confianza Archivos Adicionales Ninguno declarado por los autores. Fondos Los autores no recibieron ningún tipo de reconocimiento económico por este trabajo de investigación. Disponibilidad de datos y materiales Existe la disponibilidad de datos bajo solicitud al autor de correspondencia. No se reportan otros materiales. Contribuciones de los autores Emily Gabriela Chimbo Acuña: conceptualización, validación, visualización, metodología, administración de proyecto, escritura: revisión y edición. Karen Gabriela Valverde Zambrano: conceptualización, curación de datos, análisis formal, adquisición de fondos, investigación, recursos, software, redacción - borrador original. Iván Altamirano: conceptualización, curación de datos, análisis formal, adquisición de fondos, investigación, recursos, software. Todos los autores leyeron y aprobaron la versión final del manuscrito. Aprobación del comité de ética No aplica a estudios de bases de datos o historias clínicas. Consentimiento para publicación El presente estudio es un análisis de base de datos, no aplica para este tipo de estudio. Referencias Professionals S-O. EAU Guidelines: Prostate Cancer [Internet]. [citado 20 de octubre de 2021]. Disponible en: https://uroweb.org/guideline/prostate-cancer/#note_11 Barry MJ, Nelson JB. Patients Present with More Advanced Prostate Cancer since the USPSTF Screening Recommendations. J Urol. diciembre de 2015;194(6):1534-6. DOI: 1016/j.juro.2015.09.033 PMid: 26384450 Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardino PT, Flanigan RC, et al. Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6,630 men. J Urol. mayo de 1994;151(5):1283-90. DOI: 1016/S0022-5347(17)35233-3 PMid: 7512659 Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ, Recker F, Berenguer A, Määttänen L, Bangma CH, Aus G, Villers A, Rebillard X, van der Kwast T, Blijenberg BG, Moss SM, de Koning HJ, Auvinen A; ERSPC Investigators. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009 Mar 26;360(13):1320-8. DOI: 10.1056/NEJMoa0810084. Epub 2009 Mar 18. PMID: 19297566. Surveillance, Epidemiology, and End Results Program (SEER) of the National Cancer Institute. Fast Stats: An interactive tool for access to SEER cancer statistics. Bethesda, MD: SEER, National Cancer Institute; nd. Available from: www.seer.cancer.gov/faststats. Leitzmann MF, Rohrmann S. Risk factors for the onset of prostatic cancer: age, location, and behavioral correlates. Clin Epidemiol. 5 de enero de 2012;4:1 DOI: 2147/CLEP.S16747 PMid: 22291478 PMCid: PMC3490374 Gandaglia G, Abdollah F, Schiffmann J, Trudeau V, Shariat SF, Kim SP, et al. Distribution of metastatic sites in patients with prostate cancer: A population-based analysis. Prostate. febrero de 2014;74(2):210-6. DOI: 1002/pros.22742. PMid:24132735 Auz Fierro E, Brito Chasiluisa H. Factores relacionados con la supervivencia de pacientes con cancer de prostata en el hospital solca nucleo de quito durante el periodo 2003 - 2018. [Internet]. [Hospital Solca Nucleo de Quito]: Pontificia Universidad Católica del Ecuador; 2018. Disponible en: 22000 Barber L, Gerke T, Markt SC, Peisch SF, Wilson KM, Ahearn T, et al. Family History of Breast or Prostate Cancer and Prostate Cancer Risk. Clinical Cancer Research. 1 de diciembre de 2018;24(23):5910-7. DOI: 1158/1078-0432.CCR-18-0370. PMid: 30082473 PMCid: PMC6279573 Powell IJ. The precise role of ethnicity and family history on aggressive prostate cancer: a review analysis. Arch Esp Urol. 2011 Oct;64(8):711-9. PMID: 22052754; PMCID: PMC3859428. Möller E, Wilson KM, Batista JL, Mucci LA, Bälter K, Giovannucci E. Body size across the life course and prostate cancer in the Health Professionals Follow-up Study: Body size and prostate cancer. Int J Cancer. 15 de febrero de 2016;138(4):853-65. DOI: 1002/ijc.29842 PMid: 26355806 PMCid: PMC5042346 Birtle AJ, Freeman A, Masters JRW, Payne HA, Harland SJ, BAUS Section of Oncology Cancer Registry. Clinical features of patients who present with metastatic prostate carcinoma and serum prostate-specific antigen (PSA) levels < 10 ng/mL: the «PSA negative» patients. Cancer. 1 de diciembre de 2003;98(11):2362-7. DOI: 1002/cncr.11821 PMid: 14635070 Thomsen FB, Westerberg M, Garmo H, Robinson D, Holmberg L, Ulmert HD, et al. Prediction of metastatic prostate cancer by prostate-specific antigen in combination with T stage and Gleason Grade: Nationwide, population-based register study. PLoS One. 2020;15(1):e0228447. DOI: 1371/journal.pone.0228447 PMid: 31995611 PMCid: PMC6988964 Huang C, Song G, Wang H, Lin Z, Wang H, Ji G, et al. Preoperative PI-RADS Version 2 scores helps improve accuracy of clinical nomograms for predicting pelvic lymph node metastasis at radical prostatectomy. Prostate Cancer Prostatic Dis. marzo de 2020;23(1):116-26 DOI: 1038/s41391-019-0164-z PMid: 31383954 Mitterberger M, Pinggera GM, Pallwein L, Gradl J, Frauscher F, Bartsch G, et al. The value of three-dimensional transrectal ultrasonography in staging prostate cancer. BJU Int. julio de 2007;100(1):47-50. DOI: 1111/j.1464-410X.2007.06845.x PMid: 17433033.

Seven spot ladybird beetle, (Coccinella septempunctata) is a widely distributed natural enemy of soft-bodied insect pests especially aphids worldwide. Both the adult and larvae of this coccinellid beetle are voracious feeders and serve as a commercially available biological control agent around the globe. Different techniques are adopted to enhance the mass rearing and storage of this natural enemy by taking advantage of its natural ability to withstand under extremely low temperatures and entering diapause under unfavorable low temperature conditions. The key objective of this study was to develop a cost effective technique for enhancing the storage life and predatory potential of the larvae of C. septempunctata through cold storage in conjunction with the use of nuclear techniques, gamma radiations. Results showed that the host eating potential of larvae was enhanced as the cold storage duration was increased. Gamma irradiation further enhanced the feeding potential of larvae that were kept under cold storage. Different irradiation doses also affected the development time of C. septempuntata larvae significantly. Without cold storage, the lower radiation doses (10 and 25 GY) prolonged the developmental time as compared to un-irradiated larvae. Furthermore, the higher dose of radiation (50GY) increased the developmental time after removal from cold storage. This study first time paves the way to use radiation in conjunction with cold storage as an effective technique in implementation of different biological control approaches as a part of any IPM programs.Key wordGamma irradiations; cold storage, Coccinella septempunctata larvae; predatory potential; integrated pest management programme.INTRODUCTIONNuclear techniques such as gamma radiations have a vast application in different programmes of biological control including continuous supply of sterilized host and improved rearing techniques (Greany and Carpenter, 2000; Cai et al., 2017). Similarly irradiation can be used for sentinel-host eggs and larvae for monitoring survival and distribution of parasitoids (Jordão-paranhos et al., 2003; Hendrichs et al., 2009; Tunçbilek et al., 2009; Zapater et al., 2009; Van Lenteren, 2012). Also, at the production level, such technique may facilitate the management of host rearing, improve quality and expedite transport of product (Fatima et al., 2009; Hamed et al., 2009; Wang et al., 2009). Gamma irradiations can also be used to stop insect’s development to enhance host suitability for their use in different mass rearing programs (Celmer-Warda, 2004; Hendrichs et al., 2009; Seth et al., 2009). Development and survival of all insects have a direct connection with temperatures which in turn affect the physical, functional and behavioral adaptations (Ramløy, 2000). Many insects living in moderate regions can survive at low temperature by process of diapause. A temperature between 0 to 10oC may cause some insects to become sluggish and they only become active when the temperature is suitable. Such insects show greater adaptations to flexible temperature regimes for better survival. Many studies have reported this concept of cold-hardiness in insects in general (Bale, 2002; Danks, 2006) and specifically in coccinellid beetles over past years (Watanabe, 2002; Koch et al., 2004; Pervez and Omkar, 2006; Labrie et al., 2008; Berkvens et al., 2010). Using this cold hardiness phenomenon, many coccinellids have been studied for the effect of cold storage such as Coccinella undecimpunctata (Abdel‐Salam and Abdel‐Baky, 2000), Coleomegilla maculata (Gagné and Coderre, 2001) and Harmonia axyridis (Watanabe, 2002). This natural phenomenon, therefore, can be a helpful tool in developing low temperature stockpiling for improving mass-rearing procedures (Mousapour et al., 2014). It may provide a significant output in terms of providing natural enemies as and when required during pest infestation peaks (Venkatesan et al., 2000). Use of irradiation in conjunction with cold storage proves to be an effective technique in implementation of different biological control approaches as a part of any IPM programme. A study reported that the pupate of house fly, Musca domestica irradiated at dose of 500 Gy and can stored up to 2 months at 6°C for future use for a parasitoid wasp Spalangia endius rearing (Zapater et al., 2009). Similarly, when irradiated at 20 GY, parasitic wasps Cotesia flavipes were stored safely up to two months without deterioration of their parasitic potential (Fatima et al., 2009). Similarly, bio-control program of sugarcane shoot borer Chilo infescatellus proved successful through the use of irradiation combined with cold storage of its egg and larval parasitoids Trichogramma chilonis and C. flavipes (Fatima et al., 2009). Less mobile life stages such as larvae are of significance in any IPM strategy because they remain on target site for more time period as compared to adults. Therefore, use of predatory larvae is very promising in different biological control approaches because of their immediate attack on pests and more resistance to unfavorable environmental conditions than delicate egg stage. In addition, with their augmentation into fields, larval stage shows their presence for longer time than adult stage and their feeding potential is also satisfactory as that of adults. For the best utilization of these predators in the field and maximum impact of 3rd and 4th larval instars on prey, we should encourage late 2nd second instar larvae of predatory beetles in the fields as these instars have more feeding capacity due to increased size and ability to handle larger preys.In spite of higher significance, there is little information available about the effect of cold storage on the survival of larval instars of different ladybird beetles and its effect on their predatory potential. Very few studies report the use of cold storage for non-diapausing larval stage like for Semiadalia undecimnotata and only one study reported the short-term storage (up to two weeks) of 2nd and 3rd instar coccinellid, C. maculate, without any loss in feeding voracity of larvae after storage (Gagné and Coderre, 2001). The survival of 3rd and 4th larval instars of C. undecimpunctata for 7 days after storage at 5oC was reported in a study but the survival rate declined after 15-60 days of storage (Abdel‐Salam and Abdel‐Baky, 2000). As C. septempunctata is considered one of the voracious predators (Afroz, 2001; Jandial and Malik, 2006; Bilashini and Singh, 2009; Xia et al., 2018) and diapause is a prominent feature of this beetle and it may undergo facultative diapause under suitable laboratory conditions (Suleman, 2015). No information is available to date about the combined effect of cold storage and irradiation on the larval instars of this species.OBJECTIVES The objective of this study was to devise a cost effective technique for the cold storage and its effect on the subsequent predatory potential of the seven spotted ladybird beetle larvae in conjunction with the use of gamma radiations. Hypothesis of the study was that an optimum length of low temperature treatment for storage purpose would not affect the predation capacity of C. septempunctata larvae and their developmental parameters including survival and pupation will remain unaffected. Furthermore, use of gamma irradiation will have some additional effects on survival and feeding capacity of irradiated C. septempunctata larvae. Such techniques can be utilized in different biocontrol programs where short term storage is required. So these larvae can be successfully imparted in different IPM programs against sucking complex of insect pests as a component of biological control strategyMATERIALS AND METHODSPlant materials: Collection and rearing of C. septempunctata: Adult C. septempunctata were collected from the wheat crop (in NIAB vicinity and farm area) in the month of March during late winter and early in spring season 2016-2017. They were kept in plastic jars and were fed with brassica aphids. Under controlled laboratory conditions (25+2oC, 16h: 8h L:D and 65+5% R.H.), eggs of C. septempuctata were obtained and after hatching, larvae were also given brassica aphids as dietary source. Larvae of second instar were selected for this experiment (as the first instar is generally very weak and vulnerable to mortality under low temperatures). As the larvae approached second instar, they were separated for the experimentation. Irradiation of larvae at different doses: Irradiation of larvae was carried out by the irradiation source 137CS at Radiation laboratory, and the larvae were then brought back to the IPM laboratory, Plant Protection Division, Nuclear Institute for Agriculture and Biology (NIAB) Faisalabad. Radiation doses of 10 GY (Grey), 25 GY and 50 GY were used to treat the second instar larvae. There were three replicates for each treatment and five larvae per replicate were used. Control treatment was left un-irradiated.Cold storage of irradiated larvae: In present work, second instar C. septempunctata larvae were studied for storage at low temperature of 8oC. The larvae were kept at 8oC for 0, I and II weeks where week 0 depicts no cold treatment and this set of larvae was left under laboratory conditions for feeding and to complete their development. For larvae that were kept under cold storage for one week at 8°C, the term week I was devised. Similarly, week II denotes the larvae that remained under cold conditions (8°C) for two continuous weeks. Larvae were removed from cold storage in their respective week i.e., after week I and week II and were left under laboratory conditions to complete their development by feeding on aphids. Data collection: For recording the predatory potential of C. septempunctata larvae, 100 aphids were provided per larva per replicate on a daily basis until pupation as this number was more than their feeding capacity to make sure that they were not starved (personal observation). Observations were recorded for survival rate, developmental time and feeding potential. Data analysis: Data were statistically analysed by Statistical Software SPSS (Version 16.0). The data were subjected to normality check through the One-sample Kolmogorov-Smirnov test. Non normal data were transformed to normal data which were then used for all parametric variance tests. One-way and two-way analyses of variance were used. For comparison between variables, LSD test at α 0.05 was applied.RESULTSFeeding potential of irradiated larvae after removal from cold storage: Results showed an increase in the feeding potential of C. septempunctata larvae with increased cold storage duration. The feeding potential was significantly higher for the larvae that spent maximum length of time (week II) under cold storage conditions followed by week I and week 0. Gamma irradiations further enhanced the feeding potential of larvae that were kept under cold storage. When larvae were irradiated at 10 GY, the eating capacity of larvae increased significantly with the duration of cold storage. Similarly, larvae that were irradiated at 25 GY, showed increase in feeding potential on aphids as the time period of cold storage increased. The feeding potential of larvae that were irradiated at 50 GY, was again significantly increased with increase of cold storage duration. When different radiation doses were compared to week 0 of storage, there was a significant difference in feeding potential and larvae irradiated at 50 GY consumed the maximum numbers of aphids when no cold storage was done followed by larvae irradiated at 10 and 25 GY. With the other treatment, where larvae were kept under cold storage for one week (week I) the larvae irradiated at 50GY again showed the highest feeding potential. The feeding potential of irradiated larvae was again significantly higher than the un-irradiated larvae that were kept for two weeks (week II) under cold storage (table 1).Two-way ANOVA was performed to check the interaction between the different radiation doses and different lengths of storage durations for feeding potential of C. septempunctata larvae on aphids. The feeding potential of larvae irradiated at different doses and subjected to variable durations of cold storage were significantly different for both the radiation doses and cold storage intervals. Furthermore, the interaction between the radiation doses and storage duration was also significant meaning that the larvae irradiated at different doses with different length of cold storage were having significant variations in feeding levels (table 2).Developmental time of irradiated larvae after removal from cold storage: Significant difference was found in the development time of the larvae of C. septempunctata when irradiated at different doses at week 0 (without cold storage). The larvae irradiated at 10 GY took the maximum time for development and with the increase in irradiation dosage, from 25 to 50 GY, the time of development was shortened. The larvae irradiated at 50 GY had the same development time as the un-irradiated ones. When, the irradiated larvae were subjected to cold storage of one week duration (week I), their development time after removal from storage condition varied significantly. The larvae irradiated at 25 GY took the maximum time for development followed by larvae irradiated at 50 GY and 10 GY. There was an indication that the development time was extended for irradiated larvae as compared to un-irradiated larvae.Results also depicted a significant difference in the time taken by irradiated larvae to complete their development after taken out from cold storage of two weeks duration (week II). As the storage time of irradiated larvae increased, the development time was prolonged. Results showed that the larvae that were irradiated at 25 and 50 GY, took the maximum time to complete their development. With the prolonged duration of cold storage up to two weeks (week II), this difference of development time was less evident at lower doses (10 GY). The larvae irradiated at 10 GY showed a significant difference in their developmental duration after being taken out of cold storage conditions of the week 0, I and II. There was no difference in the developmental duration of larvae that were un-irradiated and subjected to different regimes of storage. Un-irradiated larvae were least affected by the duration of storage. With the increase in the storage time, a decrease in the developmental time was recorded. Larvae that were irradiated at 10 GY, took the maximum period to complete their development when no cold storage was done (week 0) followed by week I and II of cold storage. When the larvae irradiated at 25 GY were compared for their development time, there was again significant difference for week 0, I and II of storage duration. Maximum time was taken by the larvae for their complete development when removed from cold storage after one week (week I). With the increase in storage duration the time taken by larvae to complete their development after removal from cold storage reduced.When the larvae were removed after different lengths of cold storage duration i.e., week 0, week I and week II, there was a significant difference in the developmental time afterwards. Results have shown that the higher dose of radiation, increased the developmental time after removal from cold storage. The larvae irradiated at 50 GY took the longest time to complete their development after removal from cold storage (week I and week II) as compared the larvae that were not kept under cold storage conditions (week 0) (table 3).Interaction between the different radiation doses and different lengths of storage durations for development time of larvae were checked by two-way ANOVA. The development time of larvae irradiated at different doses and subjected to variable durations of cold storage were significantly different for both the doses and cold storage intervals. Furthermore, the interaction between the radiation doses and storage duration was also significant meaning that the larvae irradiated at different doses with different length of cold storage were having significant variations in development times (table 4). DISCUSSIONThe present research work indicates the possibility of keeping the larval instars of C. septempunctata under cold storage conditions of 8oC for a short duration of around 14 days without affecting its further development and feeding potential. Furthermore, irradiation can enhance the feeding potential and increase the development time of larval instars. This in turn could be a useful technique in mass rearing and field release programmes for biological control through larval instars. Usually temperature range of 8-10oC is an optimal selection of low temperature for storage as reported earlier for eggs two spotted ladybird beetle, Adalia bipunctata and the eggs of C. septempunctata (Hamalainen and Markkula, 1977), Trichogramma species (Jalali and Singh, 1992) and fairyfly, Gonatocerus ashmeadi (Hymenoptra; Mymaridae) (Leopold and Chen, 2007). However, a study reported more than 80% survival rate for the coccinellid beetle, Harmonia axyridis for up to 150 days at moderately low temperature of 3-6oC (Ruan et al., 2012). So there is great flexibility in coccinellid adults and larvae for tolerating low temperature conditions. After removal from cold storage, larvae showed better feeding potential with consumption of more aphids when compared to normal larvae that were not placed under low temperature conditions. This indicates that when the adult or immature insect stages are subjected to low temperature environment, they tend to reduce their metabolic activity for keeping them alive on the reserves of their body fats and sustain themselves for a substantial length of time under such cold environment. Hereafter, the larval instars that were in cold storage were behaving as if starved for a certain length of time and showed more hunger. This behavior of improved or higher feeding potential of stored larvae has been reported previously (Chapman, 1998). Hence, the feeding potential of C. septempunctata larvae significantly increased after cold storage. Gagné and Coderre (2001) reported higher predatory efficacy in larvae of C. maculata when stored at the same temperature as in the present study i.e., 8oC. Similarly, Ruan et al. (2012) showed that the multicolored Asian ladybug, H. axyridis, when stored under cold conditions, had more eating capacity towards aphids Aphis craccivora Koch than the individuals that were not stored. Such studies indicate that the higher feeding potential in insects after being subjected to low temperature environmental conditions could be due to the maintenance of their metabolism rate to a certain level while utilizing their energy reserves to the maximum extent (Watanabe, 2002).The individuals coming out from cold storage are therefore capable of consuming more pray as they were in a condition of starvation and they have to regain their energy loss through enhanced consumption. Furthermore, the starvation in C. septempunctata has previously been reported to affect their feeding potential (Suleman et al., 2017). In the present study, the larval development was delayed after returning to normal laboratory conditions. Cold storage affects the life cycle of many insects other than coccinellids. The cold storage of green bug aphid parasitoid, Lysiphlebus testaceipes Cresson (Hymenoptra; Braconidae) mummies increased the life cycle 3-4 times. Nevertheless, in current study the development process of stored larvae resumed quickly after taking them out and larvae completed their development up to adult stage. Similar kinds of results were reported for resumption of larval development after removal from cold storage conditions. Such studies only report satisfactory survival rates and development for a short duration of cold storage but as the length of storage is increased, it could become harmful to certain insects. Gagné and Coderre (2001) reported that cold storage for longer period (three weeks) proved fatal for almost 40% of larvae of C. maculata. Furthermore, in the same study, the feeding potential of C. maculata larvae was also affected beyond two weeks of cold storage due to the loss of mobility after a long storage period. Many studies have reported that longer durations of low temperature conditions can either damage the metabolic pathways of body cells or may increase the levels of toxins within the bodies of insects. Also, low temperature exposure for longer duration may cause specific interruptions in the insect body especially neuro-hormones responsible for insect development, which could be dangerous or even life threatening.Chen et al. (2004) also reported that the biological qualities of parasitized Bemisia tabaci pupae on population quality of Encarsia formosa were affected negatively with increase in cold storage duration. Similarly, the egg hatchability of green lacewing Chrysoperla carnea Stephen was lost completely beyond 18 days of cold storage (Sohail et al., 2019). However, in the present study the cold storage was done for maximum two weeks and it is to be regarded as a short term storage hence the survival rate was satisfactory. Longer periods of cold storage for larvae are not considered safe due to their vulnerable state as compared to adults which are hardier. Also 2nd instar larvae used in the present study for cold storage for being bigger in size and physical stronger than 1st instar. Abdel‐Salam and Abdel‐Baky (2000) reported that in C. undecimpunctata the cold storage of 3rd and 4th larval instars was higher and considered safer than early larval instars. The same study showed sharp decline in survival rate after two weeks and there was no survival beyond 30-60 days of cold storage. The present study showed that short term storage of the larvae of C. septempunctata could be done without any loss of their feeding potential or development so the quality of predator remained unaffected. Similar kind of work for many other insects had been reported previously where cold storage technique proved useful without deteriorating the fitness of stored insects. For example, the flight ability of reared codling moth Cydia pomonella Linnaeus remained unaffected after removal from cold storage (Matveev et al., 2017). Moreover, a sturdy reported that pupae of a parasitoid wasp Trichogramma nerudai (Hymenoptera; Trichogrammatidae) could be safely put in cold storage for above than 50 days (Tezze and Botto, 2004). Similarly, a technique of cold storage of non-diapausing eggs of black fly Simulium ornaturm Meigen was developed at 1oC. Another study reported safe storage of a predatory bug insidious flower bug Orius insidiosus for more than 10 days at 8°C (Bueno et al., 2014).In present study without cold storage, the lower doses of 10 and 25 GY prolonged the developmental time as compared to un-irradiated larvae and higher doses of irradiations in conjunction with cold storage again significantly prolonged the developmental time of larvae when returned to the laboratory conditions. Salem et al. (2014) also reported that Gamma irradiations significantly increased the duration of developmental stages (larvae and pupae) in cutworm, Agrotis ipsilon (Hufnagel). In another study, where endoparasitic wasps Glyptapanteles liparidis were evaluated with irradiated and non-irradiated gypsy moth Lymantria dispar larvae for oviposition, it was found that non-irradiated larvae had a shorter time to reach the adult stage as compared to irradiated larvae (Novotny et al., 2003). Both for higher doses with cold storage and lower doses without cold storage extended the larval duration of C. septempunctata. In another study when the parasitoid wasp Habrobracon hebetor was irradiated at the dose of 10 GY, it resulted in prolonged longevity (Genchev et al., 2008). In the same study, when another parasitoid Ventruria canescens was irradiated at lower doses of 4GY and 3 GY, it resulted in increased emergence from the host larvae, while gamma irradiations at the dose of 1 GY and 2 GY significantly stimulated the rate of parasitism (Genchev et al., 2008). The current study also indicated higher rates of predation in the form of increased feeding potential of larvae as a result of irradiations at lower doses.CONCLUSIONThe outcome of the current study shows that storage of 2nd instar C. septempunctata at low temperature of 8oC for a short duration of about 14 days is completely safe and could have broader application in different biocontrol programs. Such flexibility in storage duration can also assist in different mass rearing techniques and commercial uses. The combination of gamma radiation with low temperature cold storage could be a useful tool in developing different biological pest management programs against sucking insect pests. Incidence of periodic occurrence of both the target insect pests with their predatory ladybird beetles in synchrony is an important aspect that could be further strengthened by cold storage techniques. Therefore, short or long term bulk cold storage of useful commercial biocontrol agents and then reactivating them at appropriate time of pest infestation is a simple but an advantageous method in mass rearing programs. Increased feeding capacity of stored larvae is another edge and hence such larvae may prove more beneficial as compared to unstored larvae. Both cold storage and improved feeding of the C. septempuctata larvae can be utilized for implementation of IPM for many sucking insect pests of various crops, fruits and vegetables. Due to some constraints this study could not be continued beyond two weeks but for future directions, higher doses and longer duration periods could further elaborate the understanding and better application of such useful techniques in future IPM programmes on a wider scale. Also, some other predatory coccinellid beetle species can be tested with similar doses and cold storage treatments to see how effective this technique is on other species as well.ACKNOWLEDGMENTS We acknowledge the Sugarcane Research and Development Board for providing a research grant (No. SRDB/P/4/16) to carry out this research work. This paper is a part of research thesis entitled “Effect of gamma irradiation on storage and predatory potential of seven spotted lady bird beetle larvae” submitted to Higher Education Commission, Pakistan for the degree of M.Phil. Biological Sciences.CONFLICT OF INTERESTAuthors have no conflict of interest.REFERENCESAbdel‐Salam, A. and N. J. J. o. A. E. Abdel‐Baky, 2000. Possible storage of Coccinella undecimpunctata (Col., coccinellidae) under low temperature and its effect on some biological characteristics. 124(3‐4): 169-176.Afroz, S., 2001. Relative abundance of aphids and their coccinellid predators. Journal of aphidology, 15: 113-118.Bale, J., 2002. Insects and low temperatures: From molecular biology to distributions and abundance. Biological sciences, 357(1423): 849-862.Berkvens, N., J. S. Bale, D. Berkvens, L. Tirry and P. De Clercq, 2010. Cold tolerance of the harlequin ladybird Harmonia axyridis in europe. Journal of insect physiology, 56(4): 438-444.Bilashini, Y. and T. J. I. J. A. E. Singh, 2009. Studies on population dynamics and feeding potential of Coccinella septempunctata linnaeus in relation to Lipaphis erysimi (kaltenbach) on cabbage. Indian journal of applied entomology, 23: 99-103.Bueno, V. H. P., L. M. Carvalho and J. Van Lenteren, 2014. Performance of Orius insidiosus after storage, exposure to dispersal material, handling and shipment processes. Bulletin of insectology, 67(2): 175-183.Cai, P., X. Gu, M. Yao, H. Zhang, J. Huang, A. Idress, Q. Ji, J. Chen and J. Yang, 2017. The optimal age and radiation dose for Bactrocera dorsalis (Hendel)(Diptera: Tephritidae) eggs as hosts for mass-reared Fopius arisanus (Sonan)(Hymenoptera: Braconidae). Biological control, 108: 89-97.Celmer-Warda, K., 2004. Preliminary studies suitability and acceptability of irradiated host larvae Plodia interpunctella (Hubner) on larval parasitoids Venturia canescens (gravenhorst). Annals of warsaw agricultural university, horticulture (Landscape Architecture), 25: 67-73.Chapman, R. F., 1998. The insects: Structure and function. Cambridge university press.Chen, Q., L.-f. Xiao, G.-r. Zhu, Y.-s. LIU, Y.-j. ZHANG, Q.-j. WU and B.-y. XU, 2004. Effect of cold storage on the quality of Encarsia formosa Gahan. Chinese journal of biological control, 20(2): 107-109.Danks, H., 2006. Insect adaptations to cold and changing environments. The Canadian entomologist, 138(1): 1-23.Fatima, B., N. Ahmad, R. M. Memon, M. Bux and Q. Ahmad, 2009. Enhancing biological control of sugarcane shoot borer, Chilo infuscatellus (Lepidoptera: Pyralidae), through use of radiation to improve laboratory rearing and field augmentation of egg and larval parasitoids. Biocontrol science technology, 19(sup1): 277-290.Gagné, I. and D. Coderre, 2001. Cold storage of Coleomegilla maculata larvae. Biocontrol science technology, 11(3): 361-369.Genchev, N., N. Balevski, D. Obretenchev and A. Obretencheva, 2008. Stimulation effects of low gamma radiation doses on perasitoids Habrobracon hebetor and Ventruria canescens. Journal of Balkan ecology, 11: 99-102.Greany, P. D. and J. E. Carpenter, 2000. Årea-ide control of fruit flies and other insect pests: Importance. Joint proceedings of the International Conference on Årea-Wide Control of insect pests, May 28–June 2, 1998 and the Fifth International symposium on fruit flies of economi, June 1-5.Hamalainen, M. and M. Markkula, 1977. Cool storage of Coccinella septempunctata and Adalia bipunctata (Col., coccinellidae) eggs for use in the biological control in greenhouses. Annales agricultural fennicae, 16: 132-136.Hamed, M., S. Nadeem and A. Riaz, 2009. Use of gamma radiation for improving the mass production of Trichogramma chilonis and Chrysoperla carnea. Biocontrol science technology, 19(sup1): 43-48.Hendrichs, J., K. Bloem, G. Hoch, J. E. Carpenter, P. Greany and A. S. Robinson, 2009. Improving the cost-effectiveness, trade and safety of biological control for agricultural insect pests using nuclear techniques. Biocontrol science technology, 19(sup1): 3-22.Jalali, S. and S. Singh, 1992. Differential response of four Trichogramma species to low temperatures for short term storage. Entomophaga, 37(1): 159-165.Jandial, V. K. and K. Malik, 2006. Feeding potential of Coccinella septempunctata Linn. (Coccinellidae: Coleoptera) on mustard aphid, lipaphis erysimi kalt. And potato peach aphid, Myzus persicae sulzer. Journal of entomological research, 30(4): 291-293.Jordão-paranhos, B. A., J. M. Walder and N. T. Papadopoulos, 2003. A simple method to study parasitism and field biology of the parasitoid Diachasmimorpha longicaudata (Hymenoptera: Braconidae) on Ceratitis capitata (Diptera: Tephritidae). Biocontrol science technology, 13(6): 631-639.Koch, R. L., M. Carrillo, R. Venette, C. Cannon and W. D. Hutchison, 2004. Cold hardiness of the multicolored asian lady beetle (Coleoptera: Coccinellidae). Environmental entomology, 33(4): 815-822.Labrie, G., D. Coderre and E. Lucas, 2008. Overwintering strategy of multicolored asian lady beetle (Coleoptera: Coccinellidae): Cold-free space as a factor of invasive success. Annals of the entomological society of America, 101(5): 860-866.Leopold, R. and W.-l. Chen, 2007. Cold storage of the adult stage of Gonatocerus ashmeadi girault: The impact on maternal and progeny quality. In: Proceedings of the 2007 pierce’s disease research symposium, San Diego, CA. pp: 42-46.Matveev, E., J. Kwon, G. Judd and M. J. T. C. E. Evenden, 2017. The effect of cold storage of mass-reared codling moths (Lepidoptera: Tortricidae) on subsequent flight capacity. The Canadian entomologist, 149(3): 391-398.Mousapour, Z., A. Askarianzadeh and H. Abbasipour, 2014. Effect of cold storage of pupae parasitoid wasp, Habrobracon hebetor (say)(Hymenoptera: Braconidae), on its efficiency. Archives of phytopathology plant protection, 47(8): 966-972.Novotny, J., M. Zúbrik, M. L. McManus and A. M. Liebhold, 2003. Sterile insect technique as a tool for increasing the efficacy of gypsy moth biocontrol. Proceedings: Ecology, survey and management of forest insects GTR-NE-311, 311.Pervez, A. and Omkar, 2006. Ecology and biological control application of multicoloured asian ladybird, Harmonia axyridis: A review. Biocontrol science technology, 16(2): 111-128.Ramløy, U.-B., 2000. Aspects of natural cold tolerance in ectothermic animals. Human reproduction, 15(suppl_5): 26-46.Ruan, C.-C., W.-M. Du, X.-M. Wang, J.-J. Zhang and L.-S. Zang, 2012. Effect of long-term cold storage on the fitness of pre-wintering Harmonia axyridis (pallas). BioControl, 57(1): 95-102.Salem, H., M. Fouda, A. Abas, W. Ali and A. Gabarty, 2014. Effects of gamma irradiation on the development and reproduction of the greasy cutworm, Agrotis ipsilon (Hufn.). Journal of radiation research applied sciences, 7(1): 110-115.Seth, R. K., T. K. Barik and S. Chauhan, 2009. Interaction of entomopathogenic nematodes, Steinernema glaseri (Rhabditida: Steinernematidae), cultured in irradiated hosts, with ‘f1 sterility’: Towards management of a tropical pest, Spodoptera litura (fabr.)(Lepidoptera: Noctuidae). Biocontrol science technology, 19(sup1): 139-155.Sohail, M., S. S. Khan, R. Muhammad, Q. A. Soomro, M. U. Asif and B. K. Solangi, 2019. Impact of insect growth regulators on biology and behavior of Chrysoperla carnea (stephens)(Neuroptera: Chrysopidae). Ecotoxicology, 28(9): 1115-1125.Suleman, N., 2015. Heterodynamic processes in Coccinella septempunctata L. (Coccinellidae: Coleoptera): A mini review. Entomological science, 18(2): 141-146.Suleman, N., M. Hamed and A. Riaz, 2017. Feeding potential of the predatory ladybird beetle Coccinella septempunctata (Coleoptera; Coccinellidae) as affected by the hunger levels on natural host species. Journal of phytopathology pest management, 4: 38-47.Tezze, A. A. and E. N. Botto, 2004. Effect of cold storage on the quality of Trichogramma nerudai (Hymenoptera: Trichogrammatidae). Biological control, 30(1): 11-16.Tunçbilek, A. S., U. Canpolat and F. Sumer, 2009. Suitability of irradiated and cold-stored eggs of Ephestia kuehniella (Pyralidae: Lepidoptera) and Sitotroga cerealella (Gelechidae: Lepidoptera) for stockpiling the egg-parasitoid Trichogramma evanescens (Trichogrammatidae: Hymenoptera) in diapause. Biocontrol science technology, 19(sup1): 127-138.Van Lenteren, J. C., 2012. The state of commercial augmentative biological control: Plenty of natural enemies, but a frustrating lack of uptake. BioControl, 57(1): 1-20.Venkatesan, T., S. Singh and S. Jalali, 2000. Effect of cold storage on cocoons of Goniozus nephantidis muesebeck (Hymenoptera: Bethylidae) stored for varying periods at different temperature regimes. Journal of entomological research, 24(1): 43-47.Wang, E., D. Lu, X. Liu and Y. Li, 2009. Evaluating the use of nuclear techniques for colonization and production of Trichogramma chilonis in combination with releasing irradiated moths for control of cotton bollworm, Helicoverpa armigera. Biocontrol science technology, 19(sup1): 235-242.Watanabe, M., 2002. Cold tolerance and myo-inositol accumulation in overwintering adults of a lady beetle, Harmonia axyridis (Coleoptera: Coccinellidae). European journal of entomology, 99(1): 5-10.Xia, J., J. Wang, J. Cui, P. Leffelaar, R. Rabbinge and W. Van Der Werf, 2018. Development of a stage-structured process-based predator–prey model to analyse biological control of cotton aphid, Aphis gossypii, by the sevenspot ladybeetle, Coccinella septempunctata, in cotton. Ecological complexity, 33: 11-30.Zapater, M. C., C. E. Andiarena, G. P. Camargo and N. Bartoloni, 2009. Use of irradiated musca domestica pupae to optimize mass rearing and commercial shipment of the parasitoid spalangia endius (Hymenoptera: Pteromalidae). Biocontrol science technology, 19(sup1): 261-270.

The study Effect of a strategy of a supraglottic airway device versus tracheal intubation during out-of-hospital cardiac arrest on functional outcome: the AIRWAYS-2 randomised clinical trial Benger JR, Kirby K, Black S, Brett SJ, Clout M, Lazaroo MJ, Nolan JP, Reeves BC, Robinson M, Scott LJ, Smartt H, South A, Stokes EA, Taylor J, Thomas M, Voss S, Wordsworth S, Rogers CA Published on 28 August 2018 JAMA 2018;320:779-91 This study was funded by the National Institute for Health Research Health Technology Assessment Programme (project number 12/167/102). To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000686/new-airway-device-as-good-as-tracheal-tube-for-resuscitation-out-of-hospita

The available photographs of the Classes of 1928 and 1929 are confusing because they not only bear the same date (1929) but are also composed of individual shots of the graduates rather than the customary group photograph. An answer to the riddle was provided by the presence of J A Thorburn (a member of the Class of 1927) who was a 'super' and qualified in 1928, in the one photograph, together with MC Robinson who also graduated in 1928. The photograph dated 1929 on which 4 graduates and the Dean, Prof. Dr P J du Toit, appear is that of the Class of 1928.The other photograph dated 1929 in which the Dean is absent is therefore dated correctly. Concise descriptions are given of the life histories of the nine graduates. Their careers show considerable variation. Only one of them spent his entire career at the Onderstepoort Research Institute as a very eminent research scientist and professor, and two became well-known professors at the Onderstepoort Faculty. Two were in municipal service for most of their careers and a third ended up working for a municipal authority after spending some time in England and at the Onderstepoort Research Institute. Two spent virtually their entire careers in the field as state veterinarians and a third farmed for most of his career, although he also dabbled in private practice and managed one of the provincial game parks in Natal (now KwaZulu-Natal) for some time. Four served in the South African Veterinary Corps during World War II.

Abstract Background Ensovibep is a multi-specific DARPin (designed ankyrin repeat protein) antiviral in clinical development for treatment of COVID-19. In the Phase 2 EMPATHY study, ensovibep demonstrated greater viral load decline versus placebo. Here we report (1) the efficacy of ensovibep in patients with and without anti-SARS-CoV-2 antibodies at baseline and (2) SARS-CoV-2 mutation emergence data with treatment. Methods Eligible ambulatory patients with ≥2 COVID-19 symptoms (onset within 7 days) and positive SARS-CoV-2 rapid antigen test on day of dosing, were randomized (1:1:1:1) to ensovibep (600, 225 or 75 mg) or placebo as single, IV infusion. Chemiluminescent immunoassays were used for antibody detection (SARS-CoV-2 S1/S2 IgG and SARS-CoV-2 IgM). A pre-specified subgroup analysis was performed based on baseline anti-SARS-CoV-2 antibody status. Analysis of changes in viral genome from baseline to post baseline was performed to evaluate treatment-emergent mutations. Results Of the patients analyzed, 48.5% had anti-SARS-CoV-2 antibodies at baseline. Baseline log10 SARS-CoV-2 viral load (mean ±SD) was similar across groups [ensovibep (all doses) 6.5 ±1.5, placebo 6.2 ±1.5]; &gt; 90% were infected with the Delta (B.1.617.2) variant. SARS-CoV-2 viral load reduction up to Day 8 showed similar effects in favor of ensovibep compared with placebo regardless of the presence of anti-SARS-CoV-2 antibodies (Figure 1). Patients in ensovibep 75 mg, 600 mg, and placebo groups had comparable incidences of emergent mutations, with a higher incidence in the 225 mg group. Based on analysis of 70% of the expected viral sequencing data, two mutations in the key binding residues of ensovibep were observed (Y489H and F486L) in a total of three patients treated with ensovibep. These patients either cleared virus by Day 8 or mutations were transient (occurred at a single time point but not later in the course of infection). Figure 1Forest plot of estimated treatment differences and associated 95% confidence intervals in time-weighted change from baseline in log10 SARS-CoV-2 viral load through Day 8 by subgroups for the presence of anti-SARS-CoV-2 antibodies (SARS-CoV-2 S1/S2 IgG and/or SARS-CoV-2 IgM) at baseline. Conclusion Ensovibep effectively reduces SARS-CoV-2 viral load regardless of the presence of anti-SARS-CoV-2 antibodies at baseline. Furthermore, there were no emerging mutations of concern, indicating that a single dose administration of ensovibep is associated with minimal selective pressure. Disclosures Marc Bonten, MD, PhD, Astra-Zeneca: Advisor/Consultant|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Novartis: Advisor/Consultant Richa Chandra, MD, Novartis Pharmaceuticals Corporation: Employee Damodaran Solai Elango, MD, Novartis Healthcare Pvt Ltd: Employee Pierre Fustier, PhD, Molecular Partners AG: Employee Kinfemichael Gedif, PhD, Novartis Pharmaceuticals Corporation: Employee Susana Goncalves, MD, Novartis Pharma AG: Employee Awawu Igbinadolor, MD, Novartis: Awawu Igbinadolor reports financial support from different pharmaceutical companies and organizations Jeff Kingsley, DO, MBA, CPI, FACRP, Centricity Research: Other Charles G. Knutson, PhD, Novartis Institutes for BioMedical Research: Employee Petra Kukkaro, PhD, Novartis Pharma AG: Employee Nagalingeswaran Kumarasamy, MD, Novartis: Nagalingeswaran Kumarasamy reports financial support from different pharmaceutical companies and organizations Philippe Legenne, MD, Molecular Partners AG: Employee Martha Mekebeb-Reuter, MD, Novartis: Martha Mekebeb-Reuter reports financial support from different pharmaceutical companies and organizations Krishnan Ramanathan, MD, Novartis Pharma AG: Employee Evgeniya Reshetnyak, PhD, Novartis Pharmaceuticals Corporation: Employee Michael Robinson, PhD, Novartis Institute for Tropical Disease: Employee Jennifer Rosa, MD, Novartis: Jennifer Rosa reports financial support from different pharmaceutical companies and organizations Marianne Soergel, MD, Molecular Partners AG: Employee Vaia Stavropoulou, PhD, Molecular Partners AG: Employee Nina Stojcheva, PhD, Molecular Partners AG: Employee Michael T. Stumpp, PhD, Molecular Partners AG: Employee Andreas Tietz, MD, Novartis Pharma AG: Employee Xiaojun Zhao, PhD, Novartis Institutes for BioMedical Research: Employee Zhaojie Zhang, PhD, 8. Novartis Institutes for BioMedical Research: Employee.

Abstract Resources currently available to the scientific community that may be of interest for endocrinology research are described briefly here. More information is available through The Endocrine Society Home Page (http://www.endo-society.org) or the information provided below. Human Tissue Resources NCI - Cooperative Human Tissue Network (CHTN) The NCI Cooperative Human Tissue Network provides normal, benign, pre-cancerous, and cancerous human tissue to the scientific community for biomedical research. Specimens are collected according to the investigator’s individual protocol. Information routinely provided with the specimens includes pathology reports and histological characterization. Contact the CHTN Web site at http://www-chtn.ims.nci.nih.gov, or Ms. Marianna Bledsoe, National Cancer Institute, (301) 496-7147; e-mail: mb80s@nih.gov. NCI - Cooperative Breast Cancer Tissue Resource (CBCTR) The NCI Cooperative Breast Cancer Tissue Resource can provide researchers with access to over 9,000 formalin-fixed, paraffin-embedded primary breast cancer tissues, with associated pathologic, clinical, and outcome data. All specimens are evaluated for pathologic diagnosis by CBCTR pathologists using standard diagnostic criteria. The collection is particularly well suited for validation studies of diagnostic and prognostic markers. Researchers can search an online database to determine whether the resource specimens and data meet their needs. Contact CBCTR’s Web site at: http://www-cbctr.ims.nci.nih.gov, or Ms. Sherrill Long, Information Management Services, Inc., (301) 984-3445; e-mail: sherrill@ims.nci.nih.gov. NCI - NAPBC Breast Cancer Specimen and Data Information System The NCI Breast Cancer Specimen and Data Information System, available on the World Wide Web at http://www-napbc.ims.nci.nih.gov, contains a listing of institutions that can provide access to breast cancer specimens and/or data to biomedical researchers. NCI - AIDS and Cancer Specimen Bank (ACSB) The AIDS and Cancer Specimen Bank provides qualified researchers with tissue, cell, blood, and fluid specimens, as well as clinical data from patients with AIDS and cancer. The specimens and clinical data are available for research studies, particularly those that translate basic research findings to clinical application. Contact the ACSB Web site (http://acsb.ucsf.edu/), Dr. Ellen Feigal, National Cancer Institute at (301) 496-6711; e-mail: ef30d@nih.gov; or Dr. Jodi Black, e-mail: jb377x@nih.gov. NCI - Breast, Ovarian, and Colorectal Cancer Family Registries (CFRs) The Cancer Family Registries includes two international registries: the Cancer Family Registry for Breast Cancer Studies (Breast CFR) and the Cancer Family Registry for Colorectal Cancer Studies (Colon CFR). The Breast CFR provides family history information, biological specimens, and epidemiologic and clinical data from clinic-based and population-based families at risk for breast and ovarian cancers. The Breast CFR infrastructure is particularly suited to support interdisciplinary and translational breast cancer research. Similarly, the Colon CFR collection includes family history information, epidemiologic and clinical data, and related biological specimens from individuals with colorectal cancer and their families. The colon CFR is a resource for population- and clinic-based translational research in the genetic epidemiology of colorectal cancer. For information on these registries, contact the CFR Web site (http://epi.grants.cancer.gov/cfr.html) or Dr. Daniela Seminara, National Cancer Institute, (301) 496-9600; e-mail: seminard@mail.nih.gov. NCI - Specimen Resource Locator The NCI Specimen Resource Locator (http://cancer.gov/specimens) is a database that helps researchers locate specimens for research. The database includes resources such as tissue banks and tissue procurement systems with access to normal, benign, precancerous, and/or cancerous human tissue covering a wide variety of organ sites. Researchers specify the types of specimens, number of cases, preservation methods, and associated data they require. The Locator will search the database and return a list of tissue resources most likely to meet their requirements. When no match is obtained, the researcher is referred to the NCI Tissue Expediter (http://www-cdp.ims.nci.nih.gov/expediter.html; e-mail: tissexp@mail.nih.gov). The Tissue Expediter is a scientist who can help match researchers with appropriate resources or identify appropriate collaborators when those are necessary. NIDDK - Biologic Samples from Diabetic Study Foundation A portion (1/3) of all stored nonrenewable samples (plasma, serum, urine) from subjects enrolled in the Diabetes Control and Complications Trial (DCCT) is available for use by the scientific community to address questions for which these samples may be invaluable. Announcements for using this resource appear in the NIH Guide for Grants and Contracts periodically. Inquiries may be addressed to: Catherine C. Cowie, Ph.D., Director, Type I Diabetes Clinical Trials Program, NIDDK, 6707 Democracy Blvd., Room 691, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20814-9692. Phone: (301) 594-8804; fax: (301) 480-3503; e-mail: cowiec@extra.niddk.nih.gov. NICHD - Brain and Tissue Bank for Developmental Disorders The purpose of the Bank is to collect, preserve, and distribute human tissues to investigators interested in autism and developmental disorders; normal tissues may be available for other research purposes. Further information can be obtained at: www.btbank.org. The contact persons are H. Ron Zielke or Sally Wisniewsky, University of Maryland (1-800-847-1539) and Carol Petito or Stephanie Lojko, University of Miami (1-800-592-7246). NCRR - National Disease Research Interchange (NDRI) The Human Tissue and Organ Resource is a collaborative agreement between NCRR, NEI, NIAID, NIDDK, the NIH Office of Rare Diseases, and NDRI that provides normal and diseased human tissues and organs for biomedical laboratory research. Specimens are collected according to protocols designed by each researcher and within the necessary time frame. Sources include autopsies, eye banks, surgical procedures, and organ procurement programs. For further information, consult the NDRI Web site (www.ndri.com) or contact Ms. Sally Strickler at NDRI, 1889 John F. Kennedy Boulevard, 6th Floor, Philadelphia, PA 19103. Phone: (215) 557-7361; fax: (215) 557-7154; e-mail: sstrickler@ndri.com. NCRR - Islet Cell Resource Center (ICRs) A collaborative agreement between NCRR, NIDDK, JDRFI, and several academic islet isolation centers has been established to provide transplant-grade human pancreatic islets for clinical and basic research protocols. Information on submitting requests for islets can be obtained from Richard A. Knazek, M.D., Division of Clinical Research, NCRR, NIH, 6705 Rockledge Drive, Bethesda, MD 20892. Phone (301) 435-0790; fax (301) 480-3661; e-mail: richardk@ncrr.nih.gov. NIA - SWAN Repository (longitudinal, multiethnic study of women at midlife including the menopausal transition) The SWAN Repository is a biologic specimen bank of the Study of Women’s Health Across the Nation (SWAN). The SWAN cohort was recruited in 1996/7 and consists of 3302 African-American, Caucasian, Chinese-American, Hispanic, and Japanese-American women. The SWAN Repository contains blood and urine specimens from each study participant’s annual visit, at which time medical and health history, psychosocial measures, biological measures, and anthropometric data is also collected. In addition, a subset of participants provide urine samples over the length of one menstrual cycle each year. All of these samples are in the SWAN Repository and are available to researchers who wish to study the midlife and menopausal transition. A DNA sample repository for SWAN is in the early stages of development. To learn more about the SWAN Repository and how to apply to use SWAN Repository specimens, contact the Web site at http://www.swanrepository.com or Dr. MaryFran Sowers, University of Michigan, School of Public Health, Epidemiology Dept., (734) 936-3892; e-mail: mfsowers@umich.edu. Human and Animal Cell and Biologic Reagent Resources NIDDK - National Hormone and Peptide Program The National Hormone and Peptide Program (NHPP) offers peptide hormones and their antisera, tissues (rat hypothalami), and miscellaneous reagents to qualified investigators. These reagents are supplied for research purposes only, not for therapeutic, diagnostic, or commercial uses. These materials are procured or donated through programs supported primarily by Dr. A. F. Parlow of the Harbor-UCLA Medical Center, Research and Education Institute, Torrance, CA; the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); and the Center for Population Research of the National Institute of Child Health and Human Development (CPR, NICHD). A more complete description of resources within this program is provided in The Endocrine Society journals. Direct scientific-technical inquiry to NHPP Scientific Director, Dr. Al Parlow, at phone: (310) 222-3537; fax: (310) 222-3432; e-mail: parlow@humc.edu. Visit the NHPP Web site at http://www.humc.edu/hormones. NICHD - National Hormone and Pituitary Program (see NIDDK listing) Following is a list of reagents currently available through the resources of NICHD: Androgen receptor and peptide antigen Recombinant monkey (cynomologus) and baboon luteinizing hormone Follicle-stimulating hormone and antisera NIA - Aging Cell Repository To facilitate aging research on cells in culture, the NIA provides support for the Aging Cell Repository located at the Coreill Institute for Medical Research in Camden, NJ. The Aged Cell Bank provides fibroblast, lymphoblastoid, and differentiated cell lines from a wide range of human age-related conditions and other mammalian species, as well as DNA from a limited subset of cell lines. For further information, the Aged Cell Bank catalog can be accessed at http://locus.umdnj.edu/nia or contact Dr. Robert Johnson at 1-800-752-3805. NCRR - Various Cell Repositories NCRR maintains the following cell repository resources: American Type Culture Collection (ATCC), National Cell Culture Center. Further information regarding these resources may be obtained through the NCRR Home Page (http://www.ncrr.nih.gov). Animal Resources NIA - Aging Rodent Resources NIA maintains both rat and mouse colonies for use by the scientific community. The animals available range in age from 1 to 36 months. A repository of fresh-frozen tissue from the NIA aged rodent colonies is under development. The NIA also maintains a colony of calorically restricted rodents of selected genotypes, which are available to the scientific community. For further information, please refer to the Aged Rodent information handbook at http://www.nih.gov/nia/research/rodent.htm or contact Dr. Nancy Nadon, Office of Biological Resources and Resource Development, NIA. Phone: (301) 496-0181; fax: (301) 402-0010; e-mail: nadonn@nia.nih.gov. NCRR - Mutant Mouse Regional Resource Centers The Mutant Mouse Regional Resource Center (MMRRC) serves as a repository of genetically altered mice for the biomedical research community. Currently composed of four regional centers and an informatics coordinating center, this national network imports, rederives, and maintains submitted mutant mouse strains. The network also preserves, characterizes (phenotypically and genotypically), and redistributes selected mouse models to the scientific research community, among other activities. Further information can be obtained from the Web site at http://www.mmrrc.org, or from Franziska Grieder, D.V.M., Ph.D., NCRR; phone (301) 435-0744; e-mail: griederf@ncrr.nih.gov. NCRR - Regional Primate Research Centers The Regional Primate Centers are a unique national network of nonhuman primate research and resource centers for biomedical and behavioral investigations. These centers provide the appropriate environment and resources for the development and study of nonhuman primate models essential for clinical and basic research on human health problems and disease processes. Further information may be obtained from the notice, Procedures for Accessing Regional Primate Research Centers, published in the NIH Guide for Grants and Contracts, at http://grants.nih.gov/grants/guide/notice-files/not97-014.html, or from Jerry A. Robinson, Ph.D., Director, Regional Primate Research Centers and AIDS Animal Models Program, National Center for Research Resources. Phone: (301) 435-0744; fax: (301) 480-3819; e-mail: jerryR@ep.ncrr.nih.gov. NIA - Nonhuman Primates, Aging Set-Aside Colony NIA maintains approximately 200 nonhuman primates (M. mulatta) at four Regional Primate Research Centers (see above) for conducting research on aging. These animals range in age from 18 to 35 years. While these animals are predominantly reserved for non-invasive research, exceptions can be made to this policy. For further information, please contact Dr. Nancy Nadon, Office of Biological Resources and Resource Development, NIA. Phone: (301) 496-0181; fax: (301) 402-0010; e-mail: nadonn@nia.nih.gov. NCRR - Various Animal Resources NCRR maintains the following animal resources: Animal Models and Genetic Stocks, Chimpanzee Biomedical Research Program, NIH Animal Genetic Resource, and the Specific Pathogen Free Macaque Breeding and Research Program. Further information regarding these resources may be obtained through the NCRR Home Page (http://www.ncrr.nih.gov). Miscellaneous Resources NCRR - National Gene Vector Laboratories (NGVLs) A collaborative agreement between NIH and several academic centers has been established to produce and distribute gene vectors for use in Phase I and II clinical gene therapy protocols. The vector types include retrovirus, lentivirus, adenovirus, adeno-associated virus, and herpesvirus. Specific toxicology studies of these vectors can also be performed by the NGVLs. Requests for vector production and toxicology studies should be directed to Ms. Lorraine Rubin, NGVL Project Coordinator, Indiana University School of Medicine. Phone: (317) 274-0448; fax: (317) 278-2262; e-mail: lrubin@iupui.edu; Web site: http://www.ngvl.org/.

Despite now long-standing recognition of the value and importance of the scholarship of teaching and learning, questions continue to be raised about how to satisfy the hybrid responsibilities of teaching and research. The key message of this paper is that instructor-researchers, educational developers, and research ethics personnel should consider two key guidance documents in tandem: the Society for Teaching and Learning in Higher Education’s statement on Ethical Principles in University Teaching (Murray, Gillese, Lennon, Mercer, & Robinson, 1996) and the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, & Social Sciences and Humanities Research Council of Canada, 2014). Together these documents provide much needed guidance for teaching and researching ethically. Bien que la valeur et l’importance de l’avancement des connaissances en enseignement et en apprentissage soient reconnues depuis longtemps, on continue à se poser des questions pour savoir comment satisfaire les doubles responsabilités d’enseignement et de recherche. Le message principal de cet article est que les instructeurs-chercheurs, les conseillers pédagogiques et le personnel d’éthique de la recherche devraient prendre en considération deux documents principaux d’orientation en tandem : la déclaration de la Société pour l’avancement de la pédagogie dans l’enseignement supérieur sur les « Principes éthiques dans l’enseignement universitaire » (Ethical Principles in University Teaching - Murray, Gillese, Lennon, Mercer, & Robinson, 1996) et « Énoncé de politique des trois Conseils : Éthique de la recherche avec des êtres humains » (Conseil de recherches en sciences humaines du Canada, Conseil de recherches en sciences naturelles et en génie du Canada, & Instituts de recherche en santé du Canada, 2014). Ensemble, ces documents fournissent une orientation utile pour enseigner et mener des recherches de manière éthique.

Abstract STUDY QUESTION Are reproductive, metabolic or psychological health profiles of women with clinically diagnosed polycystic ovary syndrome (PCOS) different from those with undiagnosed PCOS? SUMMARY ANSWER Obtaining a clinical diagnosis of PCOS is strongly linked to the experience of fertility problems, but not clinical depression or poor metabolic health, although these were highly prevalent in women with PCOS irrespective of when they were diagnosed. WHAT IS KNOWN ALREADY PCOS is an endocrine disorder that is relative common, but heterogeneous in presentation. This may impact on the pathways to diagnosis and timely treatment. STUDY DESIGN, SIZE, DURATION A cross-sectional analysis of a community-based cohort of 974 women, established retrospectively when women were around 30 years of age. PARTICIPANTS/MATERIALS, SETTING, METHODS In this cohort of women born in Adelaide, South Australia, half of women who met the Rotterdam criteria for PCOS were previously undiagnosed. We compared women with prior clinical diagnosis of PCOS, those diagnosed through participation in this research, and the remainder in the cohort. Sociodemographic characteristics, reproductive, metabolic and psychological health, including medical conditions and medications were considered. Logistic regression was undertaken to identify independent predictors of prior clinical diagnosis. MAIN RESULTS AND THE ROLE OF CHANCE There were 56 women with a prior clinical diagnosis of PCOS (5.7%) and a further 64 (6.6%) were undiagnosed until study entry. The great majority of women with a prior diagnosis of PCOS reported having had problems with periods (95%) and excess body hair (63%). Corresponding proportions for women undiagnosed until study participation were slightly lower (81% and 45%, respectively). Although the proportion of women attempting or achieving pregnancy was similar across all groups, those with a prior diagnosis of PCOS were four times more likely to have reported difficulties becoming pregnant than those undiagnosed (odds ratio = 4.05, 95% CI 1.74–9.45) and frequently sought medical assistance. Metabolic problems were higher in both PCOS groups compared to women without PCOS. In both PCOS groups, the prevalence of clinical depression was 50% higher than in those with no PCOS (P = 0.021). LIMITATIONS, REASONS FOR CAUTION The number of women who were diagnosed with PCOS both prior to and during the study limited statistical power available to detect modest differences between the PCOS groups. Some women in the group classified as not having PCOS may have remained undiagnosed, but any bias from this source would contribute to more conservative findings. WIDER IMPLICATIONS OF THE FINDINGS Findings reinforce the need for early detection of PCOS symptoms from adolescence, ensuring timely diagnosis and appropriate health care. The high prevalence of depression among clinically diagnosed and undiagnosed women with PCOS suggests this is a feature of the condition and supports recent recommendations in the international PCOS guidelines to screen all women with PCOS for depression and anxiety. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a project grant (2017) from the National Health and Medical Research Council of Australia (NHMRC) Centre for Research Excellence in Polycystic Ovary Syndrome (Grant ID APP1078444). R.C.F. and J.C.A. were supported by Robinson Research Institute Lloyd Cox Career Development Fellowships (2018). Establishment of the cohort was funded by an NHMRC Strategic Award No. 465455, a Career Development Award in Population Health (No. 349548) and the Australian Research Council (Future Fellowship FT100101018) awarded to M.J.D. All authors declared no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

Abstract Resources currently available to the scientific community that may be of interest for endocrinology research are described briefly here. More information is available through The Endocrine Society Home Page (http://www.endo-society.org) or the information provided below. HUMAN TISSUE RESOURCES NCI - Cooperative Human Tissue Network (CHTN) The NCI Cooperative Human Tissue Network (CHTN) provides normal, benign, precancerous, and cancerous human tissue to the scientific community for biomedical research. Specimens are collected according to the investigator’s individual protocol. Information provided with the specimens includes routine histopathologic and demographic data. Contact the CHTN Web site at http://www-chtn.ims.nci.nih.gov, or 1-866-GO2-CHTN (1-866-462-2486). NCI - Cooperative Breast Cancer Tissue Resource (CBCTR) The NCI Cooperative Breast Cancer Tissue Resource (CBCTR) can provide researchers with access to over 9,000 cases of formalin-fixed, paraffin-embedded primary breast cancer specimens, with associated pathologic, clinical, and outcome data. All specimens are evaluated for pathologic diagnosis by CBCTR pathologists using standard diagnostic criteria. The collection is particularly well suited for validation studies of diagnostic and prognostic markers. Researchers can search an online database to determine whether the resource specimens and data meet their needs. Contact CBCTR’s Web site at: http://www-cbctr.ims.nci.nih.gov, or Ms. Sherrill Long, Information Management Services, Inc., (301) 984-3445; e-mail: longs@imsweb.com. NCI - Cooperative Prostate Cancer Tissue Resource (CPCTR) The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) can provide researchers with access to paraffin-embedded and frozen prostate cancer tissues with associated clinical and outcome data. The collection is particularly useful for validation studies of diagnostic and prognostic markers. Questions about the resource should be directed to ASK-CPCTR-L@LIST.NIH.GOV. Additional information can be obtained from CPCTR’s Web site at http://www.prostatetissues.org, or by contacting Ms. Sherrill Long, Information Management Services, Inc., (301) 984-3445; e-mail: longs@imsweb.com. NCI - AIDS and Cancer Specimen Resource (ACSR) The AIDS and Cancer Specimen Resource (ACSR) provides qualified researchers with tissue, cell, blood, and fluid specimens, as well as clinical data from patients with AIDS and cancer. The specimens and clinical data are available for research studies, particularly those that translate basic research findings to clinical application. Contact the ACSR Web site (http://acsr.ucsf.edu/), or Dr. Jodi Black, (301) 402-6293; e-mail: jb377x@nih.gov. NCI - Breast, Ovarian, and Colorectal Cancer Family Registries (CFRs) The Cancer Family Registries (CFRs) include two international registries: the Cancer Family Registry for Breast Cancer Studies (Breast CFR) and the Cancer Family Registry for Colorectal Cancer Studies (Colon CFR). The Breast CFR provides family history information, biological specimens, and epidemiologic and clinical data from clinic-based and population-based families at risk for breast and ovarian cancers. The Breast CFR infrastructure is particularly suited to support interdisciplinary and translational breast cancer research. Similarly, the Colon CFR collection includes family history information, epidemiologic and clinical data, and related biological specimens from individuals with colorectal cancer and their families. The colon CFR is a resource for population- and clinic-based translational research in the genetic epidemiology of colorectal cancer. For information on these registries, contact the CFR Web site (http://epi.grants.cancer.gov/cfr.html) or (301) 496-9600. NCI - Specimen Resource Locator The NCI Specimen Resource Locator (http://cancer.gov/specimens) is a database that helps researchers locate specimens for research. The database includes resources such as tissue banks and tissue procurement systems with access to normal, benign, precancerous, and/or cancerous human tissue covering a wide variety of organ sites. Researchers specify the types of specimens, number of cases, preservation methods, and associated data they require. The Locator will search the database and return a list of tissue resources most likely to meet their requirements. When no match is obtained, the researcher is referred to the NCI Tissue Expediter [(301) 496-7147; e-mail: tissexp@mail.nih.gov]. The Tissue Expediter is a scientist who can help match researchers with appropriate resources or identify appropriate collaborators when those are necessary. NIDDK - Biologic Samples from Diabetic Study Foundation A portion (1/3) of all stored nonrenewable samples (plasma, serum, urine) from subjects enrolled in the Diabetes Control and Complications Trial (DCCT) is available for use by the scientific community to address questions for which these samples may be invaluable. Announcements for using this resource appear in the NIH Guide for Grants and Contractsperiodically. Inquiries may be addressed to: Catherine C. Cowie, Ph.D., Director, Type I Diabetes Clinical Trials Program, NIDDK, 6707 Democracy Blvd., Room 691, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20814-9692. Phone: (301) 594-8804; fax: (301) 480-3503; e-mail: cowiec@extra.niddk.nih.gov. NICHD - Brain and Tissue Bank for Developmental Disorders The purpose of the Bank is to collect, preserve, and distribute human tissues to investigators interested in autism and developmental disorders; normal tissues may be available for other research purposes. Further information can be obtained at: www.btbank.org. The contact persons are H. Ron Zielke or Sally Wisniewsky, University of Maryland (1-800-847-1539), and Carol Petito or Stephanie Lojko, University of Miami (1-800-592-7246). NCRR - Human Tissues and Organs Resource (HTOR) The Human Tissues and Organs Resource (HTOR) cooperative agreement supports a procurement network developed by the National Disease Research Interchange (NDRI), a not-for-profit organization. By collaborating with various medical centers, hospitals, pathology services, eye banks, tissue banks, and organ procurement organizations, HTOR provides a wide variety of human tissues and organs—both diseased and normal—to researchers for laboratory studies. Such samples include tissues from the central nervous system and brain; cardiovascular system; endocrine system; eyes, bone, and cartilage. For further information, consult the NDRI Web site (www.ndri.com) or contact Ms. Sally Strickler at NDRI, 1880 John F. Kennedy Boulevard, 6th Floor, Philadelphia, PA 19103. Phone: (800) 222-6374, ext. 227; fax: (215) 557-7154; e-mail: sstrickler@ndri.com. NCRR - Islet Cell Resource (ICR) With support from NCRR, 10 Islet Cell Resource (ICR) centers isolate, purify, and characterize human pancreatic islets for subsequent transplantation into patients with type I diabetes. The ICR centers procure whole pancreata and acquire relevant data about donors; improve islet isolation and purification techniques; distribute islets for use in approved clinical protocols; and perfect the methods of storage and shipping. In this way, the centers optimize the viability, function, and availability of islets and help clinical researchers capitalize on the recently reported successes in islet transplantation. Information on submitting requests for islet cells can be obtained from Richard A. Knazek, M.D., Division of Clinical Research, NCRR, NIH, 6705 Rockledge Drive, Bethesda, MD 20892. Phone (301) 435-0790; fax (301) 480-3661; e-mail: richardk@ncrr.nih.gov. NIA - SWAN Repository (longitudinal, multiethnic study of women at midlife including the menopausal transition) The SWAN Repository is a biologic specimen bank of the Study of Women’s Health Across the Nation (SWAN). The SWAN cohort was recruited in 1996/7 and consists of 3302 African-American, Caucasian, Chinese-American, Hispanic, and Japanese-American women. The SWAN Repository contains blood and urine specimens from each study participant’s annual visit, at which time medical and health history, psychosocial measures, biological measures, and anthropometric data are also collected. In addition, a subset of participants provide urine samples over the length of one menstrual cycle each year. All of these samples are in the SWAN Repository and are available to researchers who wish to study the midlife and menopausal transition. A DNA sample repository for SWAN is in development. To learn more about the SWAN Repository and how to apply to use SWAN Repository specimens, contact the Web site at http://www.swanrepository.com or Dr. MaryFran Sowers, University of Michigan, School of Public Health, Epidemiology Dept., (734) 936-3892; e-mail: mfsowers@umich.edu. HUMAN AND ANIMAL CELL AND BIOLOGIC REAGENT RESOURCES NIDDK - National Hormone and Peptide Program The National Hormone and Peptide Program (NHPP) offers peptide hormones and their antisera, tissues (rat hypothalami), and miscellaneous reagents to qualified investigators. These reagents are supplied for research purposes only, not for therapeutic, diagnostic, or commercial uses. These materials can be obtained from Dr. A. F. Parlow of the Harbor-UCLA Medical Center, Research and Education Institute, Torrance, CA. A more complete description of resources within this program is provided in The Endocrine Society journals. Direct scientific-technical inquiry to NHPP Scientific Director, Dr. Al Parlow, at phone: (310) 222-3537; fax: (310) 222-3432; e-mail: parlow@humc.edu. Visit the NHPP Web site at http://www.humc.edu/hormones. NICHD - National Hormone and Pituitary Program (see NIDDK listing) Following is a list of reagents currently available through the resources of NICHD: Androgen receptor and peptide antigen Recombinant monkey (cynomolgus) and baboon luteinizing hormone and follicle-stimulating hormone and antisera NIA - Aging Cell Bank To facilitate aging research on cells in culture, the NIA provides support for the Aging Cell Bank located at the Coriell Institute for Medical Research in Camden, NJ. The Aged Cell Bank provides fibroblast, lymphoblastoid, and differentiated cell lines from a wide range of human age-related conditions and other mammalian species, as well as DNA from a limited subset of cell lines. For further information, the Aged Cell Bank catalog can be accessed at http://locus.umdnj.edu/nia or contact Dr. Donald Coppock at 1-800-752-3805. NCRR - Various Cell Repositories NCRR maintains the following cell repository resources: American Type Culture Collection, National Cell Culture Center, National Stem Cell Resource, and the Yeast Genetic Stock Center. Further information regarding these resources may be obtained through the NCRR Web site at: www.ncrr.nih.gov/ncrrprog/cmpdir/BIOLOG.asp. ANIMAL RESOURCES NIA - Aging Rodent Resources NIA maintains both rat and mouse colonies for use by the scientific community. The animals available range in age from 1 to 36 months. A repository of fresh-frozen tissue from the NIA aged rodent colonies is stocked with tissue from mouse and rat strains, including caloric-restricted BALB/c mice. The NIA also maintains a colony of calorically restricted rodents of selected genotypes, which are available to the scientific community. For further information, please refer to the Aged Rodent information handbook at http://www.nih.gov/nia/research/rodent.htm or contact Dr. Nancy Nadon, Office of Biological Resources and Resource Development, NIA. Phone: (301) 496-0181; fax: (301) 402-5597; e-mail: rodents@nia.nih.gov. NCRR - Mutant Mouse Regional Resource Centers (MMRRC) The Mutant Mouse Regional Resource Center (MMRRC) Program consists of centers that collectively operate as a one-stop shop to serve the biomedical research community. Investigators who have created select mutant mouse models may donate their models to an MMRRC for broad dissemination to other investigators who request them for noncommercial research investigations related to human health, disease, and treatments. The NCRR Division of Comparative Medicine (DCM) supports the MMRRCs, which are electronically linked through the MMRRC Informatics Coordinating Center (ICC) to function as one facility. The ICC, located at The Jackson Laboratory in Bar Harbor, ME, provides database and other informatics support to the MMRRC to give the research community a single entry point to the program. Further information can be obtained from the Web site at http://www.mmrrc.org, or from Franziska Grieder, D.V.M., Ph.D., Division of Comparative Medicine, NCRR. Phone (301) 435-0744; fax: (301) 480-3819; e-mail: griederf@ncrr.nih.gov. NCRR - Induced Mutant Mouse Resource (IMR) The Induced Mutant Mouse Resource (IMR) at The Jackson Laboratory provides researchers with genetically engineered mice (transgenic, targeted mutant, retroviral insertional mutant, and chemically induced mutant mice). The function of the IMR is to select, import, cryopreserve, maintain, and distribute these important strains of mice to the research community. To improve their value for research, the IMR also undertakes genetic development of stocks, such as transferring mutant genes or transgenes to defined genetic backgrounds and combining transgenes and/or targeted mutations to create new mouse models for research. Over 800 mutant stocks have been accepted by the IMR. Current holdings include models for research on cancer, immunological and inflammatory diseases, neurological diseases and behavioral disorders, cardiovascular diseases, developmental disorders, metabolic and other diseases, reporter (e.g. GFP) and recombinase (e.g. cre/loxP) strains. About 8 strains a month are being added to the IMR holdings. A list of all strains may be obtained from the IMR Web site: www.jax.org/resources/documents/imr/. Online submission forms are also available on that site. All mice can be ordered by calling The Jackson Laboratory’s Customer Service Department at 1-800-422-MICE or (207) 288-5845 or by faxing (207) 288-6150. NIDDK - Mouse Metabolic Phenotyping Centers The mission of the Mouse Metabolic Phenotyping Centers is to provide the scientific community with standardized, high-quality metabolic and physiologic phenotyping services for mouse models of diabetes, diabetic complications, obesity, and related disorders. Researchers can ship mice to one of the four Centers (University of Cincinnati, University of Texas Southwestern Medical Center, Vanderbilt University, and Yale University) and obtain on a fee-for-service basis a range of complex exams used to characterize mouse metabolism, blood composition, energy balance, eating and exercise, organ function and morphology, physiology, and histology. Many tests are done in living animals and are designed to elucidate the subtle hallmarks of metabolic disease. Information, including a complete list of available tests, can be found at www.mmpc.org, or contact Dr. Maren R. Laughlin, NIDDK, at (301) 594-8802; e-mail: Maren.Laughlin@nih.gov; or Dr. Kristin Abraham, NIDDK, at (301) 451-8048; e-mail: abrahamk@extra.niddk.nih.gov. NCRR - National Primate Research Centers (NPRCs) National Primate Research Centers (NPRCs)* are a network of eight highly specialized facilities for nonhuman primates (NHP) research. Funded by grants through NCRR’s Division of Comparative Medicine (DCM), each center, staffed with experienced research and support staff, provides the appropriate research environment to foster the development of NHP models of human health and disease for biomedical investigations. The NPRCs are affiliated with academic institutions and are accessible to eligible biomedical and behavioral investigators supported by research project grants from the National Institutes of Health and other sources. Further information may be obtained from the notice, Procedures for Accessing Regional Primate Research Centers, published in the NIH Guide for Grants and Contracts at http://grants2.nih.gov/grants/guide/notice-files/not97-014.html, or from Jerry A. Robinson, Ph.D., Director, National Primate Research Centers and AIDS Animal Models Program, Division of Comparative Medicine, NCRR. Phone: (301) 435-0744; fax: (301) 480-3819; e-mail: JerryR@ncrr.nih.gov. *The National Primate Research Centers were formerly called Regional Primate Research Centers. The name was changed in April 2002 to reflect the expanded role of the centers. NIA - Nonhuman Primates, Aging Set-Aside Colony NIA maintains approximately 200 nonhuman primates (M. mulatta) at four National Primate Research Centers (see above) for conducting research on aging. These animals range in age from 18 to 35 years. While these animals are predominantly reserved for non-invasive research, exceptions can be made to this policy. For further information, please contact Dr. Nancy Nadon, Office of Biological Resources and Resource Development, NIA. Phone: (301) 496-0181; fax: (301) 402-0010; e-mail: nadonn@nia.nih.gov. NIA - Obesity, Diabetes and Aging Animal Resource (ODAAR) The NIA supports a colony of aged rhesus macaques, many of which are obese and/or diabetic. This is a long-term colony of monkeys housed at the University of Maryland. They have been extensively and longitudinally characterized for general health variables, blood chemistry, food intake, and body weight. Diabetic monkeys are tested daily for urine glucose and ketone levels, and prediabetic monkeys are tested weekly. Data for some of the monkeys extends as far back as 15 years. This unique resource is available for collaborative studies. ODAAR has a significant amount of stored tissue collected at necropsy and stored blood collected longitudinally. Serial blood collection or tissue collection at necropsy can also be performed prospectively. Testing and imaging can also be performed on the monkeys. Inquiries regarding collaborative studies using the ODAAR colony should be directed to: Barbara C. Hansen, Ph.D., Director, Obesity and Diabetes Research Center, University of Maryland, 10 South Pine St., Baltimore, MD 21201-1192, Phone: (410) 706-3168; fax: (410) 706-7540; e-mail: bchansen@aol.com. NCRR - Various Animal Resources NCRR maintains the following animal resources: Animal Models and Genetic Stocks, Chimpanzee Biomedical Research Program, NIH Animal Genetic Resource, and the Specific Pathogen Free Macaque Breeding and Research Program. Further information regarding these and other resources may be obtained through the NCRR Web site at www.ncrr.nih.gov/comparative_med.asp. MISCELLANEOUS RESOURCES NCRR - National Gene Vector Laboratories (NGVLs) The National Gene Vector Laboratories (NGVLs), with core funding from NCRR, serve as a resource for researchers to obtain adequate quantities of clinical-grade vectors for human gene transfer protocols. The vector types include retrovirus, lentivirus, adenovirus, adeno-associated virus, and herpes-virus. The NGVLs consist of three vector production centers at: Baylor College of Medicine; City of Hope National Medical Center and Beckman Research Institute; and Indiana University, which also serves as the Coordinating Center for all the laboratories. Two additional laboratories conduct toxicology studies for NGVL-approved investigators. These laboratories are located at the Southern Research Institute and the University of Florida. Additional information about the process for requesting vector production and/or pharmacology/toxicology support should be directed to Ms. Lorraine Rubin, NGVL Project Coordinator, Indiana University School of Medicine. Phone: (317) 274-4519; fax: (317) 278-4518; e-mail: lrubin@iupui.edu. The NGVL Coordinating Center at Indiana University also hosts a Web site: http://www.ngvl.org/. NCRR - General Clinical Research Centers (GCRCs) The General Clinical Research Centers (GCRCs) are a national network of 80 centers that provide optimal settings for medical investigators to conduct safe, controlled, state-of-the-art in-patient and out-patient studies of both children and adults. GCRCs also provide infrastructure and resources that support several career development opportunities. Investigators who have research project funding from the National Institutes of Health (NIH) and other peer-reviewed sources may apply to use GCRCs. Because the GCRCs support a full spectrum of patient-oriented scientific inquiry, researchers who use these centers can benefit from collaborative, multidisciplinary research opportunities. To request access to a GCRC facility, eligible investigators should initially contact a GCRC program director, listed in the National Center for Research Resources (NCRR) Clinical Research Resources Directory (www.ncrr.nih.gov/ncrrprog/clindir/crdirectory.asp). Further information can be obtained from Anthony R. Hayward, M.D., Director, Division of Clinical Research, National Center for Research Resources at NIH. Phone: (301) 435-0790; e-mail: haywarda@ncrr.nih.gov.

Abstract Resources currently available to the scientific community that may be of interest for endocrinology research are described briefly here. More information is available through The Endocrine Society Home Page (http://www.endo-society.org) or the information provided below. HUMAN TISSUE RESOURCES NCI - Cooperative Human Tissue Network (CHTN) The NCI Cooperative Human Tissue Network (CHTN) provides normal, benign, precancerous, and cancerous human tissue to the scientific community for biomedical research. Specimens are collected according to the investigator’s individual protocol. Information provided with the specimens includes routine histopathologic and demographic data. Contact the CHTN Web site at http://www-chtn.ims.nci.nih.gov, or 1-866-GO2-CHTN (1-866-462-2486). NCI - Cooperative Breast Cancer Tissue Resource (CBCTR) The NCI Cooperative Breast Cancer Tissue Resource (CBCTR) can provide researchers with access to over 9,000 cases of formalin-fixed, paraffin-embedded primary breast cancer specimens, with associated pathologic, clinical, and outcome data. All specimens are evaluated for pathologic diagnosis by CBCTR pathologists using standard diagnostic criteria. The collection is particularly well suited for validation studies of diagnostic and prognostic markers. Researchers can search an online database to determine whether the resource specimens and data meet their needs. Contact CBCTR’s Web site at: http://www-cbctr.ims.nci.nih.gov, or Ms. Sherrill Long, Information Management Services, Inc., (301) 984-3445; e-mail: longs@imsweb.com. NCI - Cooperative Prostate Cancer Tissue Resource (CPCTR) The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) can provide researchers with access to paraffin-embedded and frozen prostate cancer tissues with associated clinical and outcome data. The collection is particularly useful for validation studies of diagnostic and prognostic markers. Questions about the resource should be directed to ASK-CPCTR-L@LIST.NIH.GOV. Additional information can be obtained from CPCTR’s Web site at http://www.prostatetissues.org, or by contacting Ms. Sherrill Long, Information Management Services, Inc., (301) 984-3445; e-mail: longs@imsweb.com. NCI - AIDS and Cancer Specimen Resource (ACSR) The AIDS and Cancer Specimen Resource (ACSR) provides qualified researchers with tissue, cell, blood, and fluid specimens, as well as clinical data from patients with AIDS and cancer. The specimens and clinical data are available for research studies, particularly those that translate basic research findings to clinical application. Contact the ACSR Web site (http://acsr.ucsf.edu/), or Dr. Jodi Black, (301) 402-6293; e-mail: jb377x@nih.gov. NCI - Breast, Ovarian, and Colorectal Cancer Family Registries (CFRs) The Cancer Family Registries (CFRs) include two international registries: the Cancer Family Registry for Breast Cancer Studies (Breast CFR) and the Cancer Family Registry for Colorectal Cancer Studies (Colon CFR). The Breast CFR provides family history information, biological specimens, and epidemiologic and clinical data from clinic-based and population-based families at risk for breast and ovarian cancers. The Breast CFR infrastructure is particularly suited to support interdisciplinary and translational breast cancer research. Similarly, the Colon CFR collection includes family history information, epidemiologic and clinical data, and related biological specimens from individuals with colorectal cancer and their families. The colon CFR is a resource for population- and clinic-based translational research in the genetic epidemiology of colorectal cancer. For information on these registries, contact the CFR Web site (http://epi.grants.cancer.gov/cfr.html) or (301) 496-9600. NCI - Specimen Resource Locator The NCI Specimen Resource Locator (http://cancer.gov/specimens) is a database that helps researchers locate specimens for research. The database includes resources such as tissue banks and tissue procurement systems with access to normal, benign, precancerous, and/or cancerous human tissue covering a wide variety of organ sites. Researchers specify the types of specimens, number of cases, preservation methods, and associated data they require. The Locator will search the database and return a list of tissue resources most likely to meet their requirements. When no match is obtained, the researcher is referred to the NCI Tissue Expediter [(301) 496-7147; e-mail: tissexp@mail.nih.gov]. The Tissue Expediter is a scientist who can help match researchers with appropriate resources or identify appropriate collaborators when those are necessary. NIDDK - Biologic Samples from Diabetic Study Foundation A portion (1/3) of all stored nonrenewable samples (plasma, serum, urine) from subjects enrolled in the Diabetes Control and Complications Trial (DCCT) is available for use by the scientific community to address questions for which these samples may be invaluable. Announcements for using this resource appear in the NIH Guide for Grants and Contracts periodically. Inquiries may be addressed to: Catherine C. Cowie, Ph.D., Director, Type I Diabetes Clinical Trials Program, NIDDK, 6707 Democracy Blvd., Room 691, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20814-9692. Phone: (301) 594-8804; fax: (301) 480-3503; e-mail: cowiec@extra.niddk.nih.gov. NICHD - Brain and Tissue Bank for Developmental Disorders The purpose of the Bank is to collect, preserve, and distribute human tissues to investigators interested in autism and developmental disorders; normal tissues may be available for other research purposes. Further information can be obtained at: www.btbank.org. The contact persons are H. Ron Zielke or Sally Wisniewsky, University of Maryland (1-800-847-1539), and Carol Petito or Stephanie Lojko, University of Miami (1-800-592-7246). NCRR - Human Tissues and Organs Resource (HTOR) The Human Tissues and Organs Resource (HTOR) cooperative agreement supports a procurement network developed by the National Disease Research Interchange (NDRI), a not-for-profit organization. By collaborating with various medical centers, hospitals, pathology services, eye banks, tissue banks, and organ procurement organizations, HTOR provides a wide variety of human tissues and organs—both diseased and normal—to researchers for laboratory studies. Such samples include tissues from the central nervous system and brain; cardiovascular system; endocrine system; eyes, bone, and cartilage. For further information, consult the NDRI Web site (www.ndri.com) or contact Ms. Sally Strickler at NDRI, 1880 John F. Kennedy Boulevard, 6th Floor, Philadelphia, PA 19103. Phone: (800) 222-6374, ext. 227; fax: (215) 557-7154; e-mail: sstrickler@ndri.com. NCRR - Islet Cell Resource (ICR) With support from NCRR, 10 Islet Cell Resource (ICR) centers isolate, purify, and characterize human pancreatic islets for subsequent transplantation into patients with type I diabetes. The ICR centers procure whole pancreata and acquire relevant data about donors; improve islet isolation and purification techniques; distribute islets for use in approved clinical protocols; and perfect the methods of storage and shipping. In this way, the centers optimize the viability, function, and availability of islets and help clinical researchers capitalize on the recently reported successes in islet transplantation. Information on submitting requests for islet cells can be obtained from Richard A. Knazek, M.D., Division of Clinical Research, NCRR, NIH, 6705 Rockledge Drive, Bethesda, MD 20892. Phone (301) 435-0790; fax (301) 480-3661; e-mail: richardk@ncrr.nih.gov. NIA - SWAN Repository (longitudinal, multiethnic study of women at midlife including the menopausal transition) The SWAN Repository is a biologic specimen bank of the Study of Women’s Health Across the Nation (SWAN). The SWAN cohort was recruited in 1996/7 and consists of 3302 African-American, Caucasian, Chinese-American, Hispanic, and Japanese-American women.144.9.4215http://www.swanrepository.com or Dr. MaryFran Sowers, University of Michigan, School of Public Health, Epidemiology Dept., (734) 936-3892; e-mail: mfsowers@umich.edu. HUMAN AND ANIMAL CELL AND BIOLOGIC REAGENT RESOURCES NIDDK - National Hormone and Peptide Program The National Hormone and Peptide Program (NHPP) offers peptide hormones and their antisera, tissues (rat hypothalami), and miscellaneous reagents to qualified investigators. These reagents are supplied for research purposes only, not for therapeutic, diagnostic, or commercial uses. These materials can be obtained from Dr. A. F. Parlow of the Harbor-UCLA Medical Center, Research and Education Institute, Torrance, CA. A more complete description of resources within this program is provided in The Endocrine Society journals. Direct scientific-technical inquiry to NHPP Scientific Director, Dr. Al Parlow, at phone: (310) 222-3537; fax: (310) 222-3432; e-mail: parlow@humc.edu. Visit the NHPP Web site at http://www.humc.edu/hormones. NICHD - National Hormone and Pituitary Program (see NIDDK listing) Following is a list of reagents currently available through the resources of NICHD: Androgen receptor and peptide antigen Recombinant monkey (cynomolgus) and baboon luteinizing hormone and follicle-stimulating hormone and antisera NIA - Aging Cell Bank To facilitate aging research on cells in culture, the NIA provides support for the Aging Cell Bank located at the Coriell Institute for Medical Research in Camden, NJ. The Aged Cell Bank provides fibroblast, lymphoblastoid, and differentiated cell lines from a wide range of human age-related conditions and other mammalian species, as well as DNA from a limited subset of cell lines. For further information, the Aged Cell Bank catalog can be accessed at http://locus.umdnj.edu/nia or contact Dr. Donald Coppock at 1-800-752-3805. NCRR - Various Cell Repositories NCRR maintains the following cell repository resources: American Type Culture Collection, National Cell Culture Center, National Stem Cell Resource, and the Yeast Genetic Stock Center. Further information regarding these resources may be obtained through the NCRR Web site at: www.ncrr.nih.gov/ncrrprog/cmpdir/BIOLOG.asp. ANIMAL RESOURCES NIA - Aging Rodent Resources NIA maintains both rat and mouse colonies for use by the scientific community. The animals available range in age from 1 to 36 months. A repository of fresh-frozen tissue from the NIA aged rodent colonies is stocked with tissue from mouse and rat strains, including caloric-restricted BALB/c mice. The NIA also maintains a colony of calorically restricted rodents of selected genotypes, which are available to the scientific community. For further information, please refer to the Aged Rodent information handbook at http://www.nih.gov/nia/research/rodent.htm or contact Dr. Nancy Nadon, Office of Biological Resources and Resource Development, NIA. Phone: (301) 496-0181; fax: (301) 402-5597; e-mail: rodents@nia.nih.gov. NCRR - Mutant Mouse Regional Resource Centers (MMRRC) The Mutant Mouse Regional Resource Center (MMRRC) Program consists of centers that collectively operate as a one-stop shop to serve the biomedical research community. Investigators who have created select mutant mouse models may donate their models to an MMRRC for broad dissemination to other investigators who request them for noncommercial research investigations related to human health, disease, and treatments. The NCRR Division of Comparative Medicine (DCM) supports the MMRRCs, which are electronically linked through the MMRRC Informatics Coordinating Center (ICC) to function as one facility. The ICC, located at The Jackson Laboratory in Bar Harbor, ME, provides database and other informatics support to the MMRRC to give the research community a single entry point to the program. Further information can be obtained from the Web site at http://www.mmrrc.org, or from Franziska Grieder, D.V.M., Ph.D., Division of Comparative Medicine, NCRR. Phone (301) 435-0744; fax: (301) 480-3819; e-mail: griederf@ncrr.nih.gov. NCRR - Induced Mutant Mouse Resource (IMR) The Induced Mutant Mouse Resource (IMR) at The Jackson Laboratory provides researchers with genetically engineered mice (transgenic, targeted mutant, retroviral insertional mutant, and chemically induced mutant mice). The function of the IMR is to select, import, cryopreserve, maintain, and distribute these important strains of mice to the research community. To improve their value for research, the IMR also undertakes genetic development of stocks, such as transferring mutant genes or transgenes to defined genetic backgrounds and combining transgenes and/or targeted mutations to create new mouse models for research. Over 800 mutant stocks have been accepted by the IMR. Current holdings include models for research on cancer, immunological and inflammatory diseases, neurological diseases and behavioral disorders, cardiovascular diseases, developmental disorders, metabolic and other diseases, reporter (e.g. GFP) and recombinase (e.g. cre/loxP) strains. About 8 strains a month are being added to the IMR holdings. A list of all strains may be obtained from the IMR Web site: www.jax.org/resources/documents/imr/. Online submission forms are also available on that site. All mice can be ordered by calling The Jackson Laboratory’s Customer Service Department at 1-800-422-MICE or (207) 288-5845 or by faxing (207) 288-6150. NIDDK - Mouse Metabolic Phenotyping Centers The mission of the Mouse Metabolic Phenotyping Centers is to provide the scientific community with standardized, high-quality metabolic and physiologic phenotyping services for mouse models of diabetes, diabetic complications, obesity, and related disorders. Researchers can ship mice to one of the four Centers (University of Cincinnati, University of Texas Southwestern Medical Center, Vanderbilt University, and Yale University) and obtain on a fee-for-service basis a range of complex exams used to characterize mouse metabolism, blood composition, energy balance, eating and exercise, organ function and morphology, physiology, and histology. Many tests are done in living animals and are designed to elucidate the subtle hallmarks of metabolic disease. Information, including a complete list of available tests, can be found at www.mmpc.org, or contact Dr. Maren R. Laughlin, NIDDK, at (301) 594-8802; e-mail: Maren.Laughlin@nih.gov; or Dr. Kristin Abraham, NIDDK, at (301) 451-8048; e-mail: abrahamk@extra.niddk.nih.gov. NCRR - National Primate Research Centers (NPRCs) National Primate Research Centers (NPRCs)* are a network of eight highly specialized facilities for nonhuman primates (NHP) research. Funded by grants through NCRR’s Division of Comparative Medicine (DCM), each center, staffed with experienced research and support staff, provides the appropriate research environment to foster the development of NHP models of human health and disease for biomedical investigations. The NPRCs are affiliated with academic institutions and are accessible to eligible biomedical and behavioral investigators supported by research project grants from the National Institutes of Health and other sources. Further information may be obtained from the notice, Procedures for Accessing Regional Primate Research Centers, published in the NIH Guide for Grants and Contracts at http://grants2.nih.gov/grants/guide/notice-files/not97-014.html, or from Jerry A. Robinson, Ph.D., Director, National Primate Research Centers and AIDS Animal Models Program, Division of Comparative Medicine, NCRR. Phone: (301) 435-0744; fax: (301) 480-3819; e-mail: JerryR@ncrr.nih.gov. *The National Primate Research Centers were formerly called Regional Primate Research Centers. The name was changed in April 2002 to reflect the expanded role of the centers. NIA - Nonhuman Primates, Aging Set-Aside Colony NIA maintains approximately 200 nonhuman primates (M. mulatta) at four National Primate Research Centers (see above) for conducting research on aging. These animals range in age from 18 to 35 years. While these animals are predominantly reserved for non-invasive research, exceptions can be made to this policy. For further information, please contact Dr. Nancy Nadon, Office of Biological Resources and Resource Development, NIA. Phone: (301) 496-0181; fax: (301) 402-0010; e-mail: nadonn@nia.nih.gov. NIA - Obesity, Diabetes and Aging Animal Resource (ODAAR) The NIA supports a colony of aged rhesus macaques, many of which are obese and/or diabetic. This is a long-term colony of monkeys housed at the University of Maryland. They have been extensively and longitudinally characterized for general health variables, blood chemistry, food intake, and body weight. Diabetic monkeys are tested daily for urine glucose and ketone levels, and prediabetic monkeys are tested weekly. Data for some of the monkeys extends as far back as 15 years. This unique resource is available for collaborative studies. ODAAR has a significant amount of stored tissue collected at necropsy and stored blood collected longitudinally. Serial blood collection or tissue collection at necropsy can also be performed prospectively. Testing and imaging can also be performed on the monkeys. Inquiries regarding collaborative studies using the ODAAR colony should be directed to: Barbara C. Hansen, Ph.D., Director, Obesity and Diabetes Research Center, University of Maryland, 10 South Pine St., Baltimore, MD 21201-1192, Phone: (410) 706-3168; fax: (410) 706-7540; e-mail: bchansen@aol.com. NCRR - Various Animal Resources NCRR maintains the following animal resources: Animal Models and Genetic Stocks, Chimpanzee Biomedical Research Program, NIH Animal Genetic Resource, and the Specific Pathogen Free Macaque Breeding and Research Program. Further information regarding these and other resources may be obtained through the NCRR Web site at www.ncrr.nih.gov/comparative_med.asp. MISCELLANEOUS RESOURCES NCRR - National Gene Vector Laboratories (NGVLs) The National Gene Vector Laboratories (NGVLs), with core funding from NCRR, serve as a resource for researchers to obtain adequate quantities of clinical-grade vectors for human gene transfer protocols. The vector types include retrovirus, lentivirus, adenovirus, adeno-associated virus, and herpes-virus. The NGVLs consist of three vector production centers at: Baylor College of Medicine; City of Hope National Medical Center and Beckman Research Institute; and Indiana University, which also serves as the Coordinating Center for all the laboratories. Two additional laboratories conduct toxicology studies for NGVL-approved investigators. These laboratories are located at the Southern Research Institute and the University of Florida. Additional information about the process for requesting vector production and/or pharmacology/toxicology support should be directed to Ms. Lorraine Rubin, NGVL Project Coordinator, Indiana University School of Medicine. Phone: (317) 274-4519; fax: (317) 278-4518; e-mail: lrubin@iupui.edu. The NGVL Coordinating Center at Indiana University also hosts a Web site: http://www.ngvl.org/. NCRR - General Clinical Research Centers (GCRCs) The General Clinical Research Centers (GCRCs) are a national network of 80 centers that provide optimal settings for medical investigators to conduct safe, controlled, state-of-the-art in-patient and out-patient studies of both children and adults. GCRCs also provide infrastructure and resources that support several career development opportunities. Investigators who have research project funding from the National Institutes of Health (NIH) and other peer-reviewed sources may apply to use GCRCs. Because the GCRCs support a full spectrum of patient-oriented scientific inquiry, researchers who use these centers can benefit from collaborative, multidisciplinary research opportunities. To request access to a GCRC facility, eligible investigators should initially contact a GCRC program director, listed in the National Center for Research Resources (NCRR) Clinical Research Resources Directory (www.ncrr.nih.gov/ncrrprog/clindir/crdirectory.asp). Further information can be obtained from Anthony R. Hayward, M.D., Director, Division of Clinical Research, National Center for Research Resources at NIH. Phone: (301) 435-0790; e-mail: haywarda@ncrr.nih.gov.

Abstract STUDY QUESTION Could changes in transforming growth factor β (TGFβ) signalling during foetal ovary development alter the expression of polycystic ovary syndrome (PCOS) candidate genes leading to a predisposition to PCOS? SUMMARY ANSWER TGFβ signalling molecules are dynamically expressed during foetal ovary development and TGFβ1 inhibits expression of the androgen receptor (AR) and 7 (INSR, C8H9orf3, RAD50, ERBB3, NEIL2, IRF1 and ZBTB16) of the 25 PCOS candidate genes in foetal ovarian fibroblasts in vitro, whilst increasing expression of the AR cofactor TGFβ-induced transcript 1 (TGFB1I1 or Hic5). WHAT IS KNOWN ALREADY The ovarian stroma arises from the mesonephros during foetal ovary development. Changes in the morphology of the ovarian stroma are cardinal features of PCOS. The ovary is more fibrous and has more tunica and cortical and subcortical stroma. It is not known why this is and when this arises. PCOS has a foetal origin and perhaps ovarian stroma development is altered during foetal life to determine the formation of a polycystic ovary later in life. PCOS also has a genetic origin with 19 loci containing 25 PCOS candidate genes. In many adult tissues, TGFβ is known to stimulate fibroblast replication and collagen deposition in stroma, though it has the opposite effect in the non-scaring foetal tissues. Our previous studies showed that TGFβ signalling molecules [TGFβs and their receptors, latent TGFβ binding proteins (LTBPs) and fibrillins, which are extracellular matrix proteins that bind LTBPs] are expressed in foetal ovaries. Also, we previously showed that TGFβ1 inhibited expression of AR and 3 PCOS candidate genes (INSR, C8H9orf3 and RAD50) and stimulated expression of TGFB1I1 in cultured foetal ovarian fibroblasts. STUDY DESIGN, SIZE, DURATION We used Bos taurus for this study as we can ethically collect foetal ovaries from across the full 9-month gestational period. Foetal ovaries (62–276 days, n = 19) from across gestation were collected from pregnant B. taurus cows for RNA-sequencing (RNA-seq) analyses. Foetal ovaries from B. taurus cows were collected (160–198 days, n = 6) for culture of ovarian fibroblasts. PARTICIPANTS/MATERIALS, SETTING, METHODS RNA-seq transcriptome profiling was performed on foetal ovaries and the data on genes involved in TGFβ signalling were extracted. Cells were dispersed from foetal ovaries and fibroblasts cultured and treated with TGFβ1. The effects of TGFβ regulation on the remaining eight PCOS candidate genes not previously studied (ERBB3, MAPRE1, FDFT1, NEIL2, ARL14EP, PLGRKT, IRF1 and ZBTB16) were examined. MAIN RESULTS AND THE ROLE OF CHANCE Many TGFβ signalling molecules are expressed in the foetal ovary, and for most, their expression levels increased accross gestation (LTBP1/2/3/4, FBN1, TGFB2/3, TGFBR2/3 and TGFB1I1), while a few decreased (FBN3, TGFBR3L, TGFBI and TGFB1) and others remained relatively constant (TGFBRAP1, TGFBR1 and FBN2). TGFβ1 significantly decreased expression of PCOS candidate genes ERBB3, NEIL2, IRF1 and ZBTB16 in cultured foetal ovarian fibroblasts. LARGE SCALE DATA The FASTQ files, normalized data and experimental information have been deposited in the Gene Expression Omnibus (GEO) accessible by accession number GSE178450. LIMITATIONS, REASONS FOR CAUTION Regulation of PCOS candidate genes by TGFβ was carried out in vitro and further studies in vivo are required. This study was carried out in bovine where foetal ovaries from across all of the 9-month gestational period were available, unlike in the human where it is not ethically possible to obtain ovaries from the second half of gestation. WIDER IMPLICATIONS OF THE FINDINGS From our current and previous results we speculate that inhibition of TGFβ signalling in the foetal ovary is likely to (i) increase androgen sensitivity by enhancing expression of AR, (ii) increase stromal activity by stimulating expression of COL1A1 and COL3A1 and (iii) increase the expression of 7 of the 25 PCOS candidate genes. Thus inhibition of TGFβ signalling could be part of the aetiology of PCOS or at least the aetiology of polycystic ovaries. STUDY FUNDING/COMPETING INTEREST(S) Funding was received from Adelaide University China Fee Scholarship (M.L.), Australian Research Training Program (R.A.) and the Faculty of Health and Medical Science Divisional Scholarship (R.A.), Adelaide Graduate Research Scholarships (R.A. and N.A.B.), Australia Awards Scholarship (M.D.H.), Robinson Research Institute Career Development Fellowship (K.H.) and Building On Ideas Grant (K.H.), National Health and Medical Research Council of Australia Centre for Research Excellence in the Evaluation, Management and Health Care Needs of Polycystic Ovary Syndrome (N.A.B., M.D.H. and R.J.R.; GTN1078444) and the Centre for Research Excellence on Women’s Health in Reproductive life (R.A., R.J.R. and K.H.; GTN1171592) and the UK Medical Research Council (R.A.A.; grant no. G1100357). The funders did not play any role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors of this manuscript have nothing to declare and no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

07–173Anderson, Carolyn (U Strathclyde, UK; carolyn.anderson@strath.ac.uk), Early communication strategies: Using video analysis to support teachers working with preverbal pupils. British Journal of Special Education (Blackwell) 33.3 (2006), 114–120.07–174Bowers, Anthony (Ningbo U Technology, China), Presentation of an Australian–Chinese joint venture program in China. EA Journal (English Australia) 23.1 (2006), 24–34.07–175Bralich, Philip A. (Georgia State U, USA), The new SAT and fundamental misunderstandings about grammar teaching. English Today (Cambridge University Press) 22.3 (2006), 61–64.07–176Carless, D. (Hong Kong U, China; dcarless@hkucc.hku.hk), Collaborative EFL teaching in primary schools. ELT Journal (Oxford University Press) 60.4 (2006), 328–335.07–177Chen, Runyi (South China Normal U, China) & Hird, Bernard, Codeswitching in EFL group work in China. Language, Culture and Curriculum (Multilingual Matters) 19.2 (2006), 208–219.07–178Cushıon, Steve (London Metropolitan U, UK), What does CALL have to offer computer science and what does computer science have to offer CALL?Computer Assisted Language Learning (Routledge/Taylor & Francis) 19.2–3 (2006), 193–242.07–179Fidler, S. (National Education Institute, Slovenia; soca.fidler@guest.arnes.si), Awakening to languages in primary school. ELT Journal (Oxford University Press) 60.4 (2006), 346–354.07–180Gillies, Robyn M. (U Queensland, Australia), Teachers' and students' verbal behaviours during cooperative and small-group learning. British Journal of Educational Psychology (British Psychological Society) 76.2 (2006), 271–287.07–181Glew, Paul J. (U Western Sydney, Australia; aul.glew@coverdale.nsw.edu.au), A perspective on ELICOS in an independent school. EA Journal (English Australia) 23.1 (2006), 14–23.07–182Goh, Christine & Yusnita Taib (Nanyang U, Singapore), Metacognitive instruction in listening for young learners. ELT Journal (Oxford University Press) 60.3 (2006), 222–232.07–183Hémard, Domınıque (London Metropolitan U, UK), Design issues related to the evaluation of learner–computer interaction in a web-based environment: Activities v. tasks.Computer Assisted Language Learning (Routledge/Taylor & Francis) 19.2–3 (2006), 261–276.07–184Howard, Elizabeth R., Igone Arteagoitia, Mohammed Louguit, Valerie Malabonga & Dorry M. Kenyon (Centre for Applied Linguistics, Washington DC, USA), The development of the English Developmental Contrastive Spelling Test: A tool for investigating Spanish influence on English spelling development. TESOL Quarterly 40.2 (2006), 399–420.07–185Labbo, Linda D. (U Georgia, USA), Literacy pedagogy and computer technologies: Toward solving the puzzle of current and future classroom practices. Australian Journal of Language and Literacy (Australian Literacy Educators' Association) 29.3 (2006), 199–209.07–186Lau, Kit-ling (Chinese U Hong Kong), Implementing strategy instruction in Chinese language classes: A school-based Chinese reading strategy instruction programme. Educational Research (Routledge/Taylor & Francis) 48.2 (2006), 195–209.07–187Littlemore, Jeannette & Graham Low (U Birmingham, UK), Metaphoric competence, second language learning, and communicative language ability. Applied Linguistics (Oxford University Press) 27.2 (2006), 268–294.07–188Liu, Ping (California State U, USA), Community-based Chinese schools in Southern California: A survey of teachers. Language, Culture and Curriculum (Multilingual Matters) 19.2 (2006), 237–247.07–189Mackey, A. (Georgetown U, USA), Feedback, noticing and instructed second language learning. Applied Linguistics (Oxford University Press) 27.3 (2006), 405–430.07–190McPake, Joanna (U Stirling, UK) & Jo Arthur, Scots in contemporary social and educational context. Language, Culture and Curriculum (Multilingual Matters) 19.2 (2006), 155–170.07–191Rodgers, Daryl M. (U Illinois, USA; dmrodger@uiuc.edu), Developing content and form: Encouraging evidence from Italian content-based instruction. The Modern Language Journal (Blackwell) 90.3 (2006), 373–386.07–192Santos, Denise (U Reading, UK; d.m.d.santos@reading.ac.uk) & Branca Falabella Fabrício, The English lesson as a site for the development of critical thinking. TESL-EJ (http://www.tesl-ej.org) 10.2 (2006), 23 pp.07–193Schmid, E. Cutrim (U of Education Heidelberg, Germany), Investigating the use of interactive whiteboard technology in the English language classroom through the lens of a critical theory of technology. Computer Assisted Language Learning (Routledge/Taylor & Francis) 19.1 (2006), 47–62.07–194Stephens, Meredith (Matsuyama U, Japan), The use and abuse of Japanese in the university English class. The Language Teacher (Japan Association for Language Teaching) 30.8 (2006), 13–18.07–195Stoller, Fredricka L. (Northern Arizona U, USA), Bradley Horn, William Grabe & Marin S. Robinson, Evaluative review in materials development. Journal of English for Academic Purposes (Elsevier) 5.3 (2006), 174–192.07–196Timuçin, Metin (Sakarya U, Turkey; mtimucin@sakarya.edu.tr), Implementing CALL in an EFL context. ELT Journal (Oxford University Press) 60.3 (2006), 262–271.07–197Ward, Monıca (Dublin City U, Ireland), Using software design methods in CALL. Computer Assisted Language Learning (Routledge/Taylor & Francis) 19.2–3 (2006), 129–147.

Indigenous cross-cultural training has been around since the 1980s. It is often seen as a way to increase the skills and competency of staff engaged in providing service to Indigenous clients and customers, teaching Indigenous students within universities and schools, or working with Indigenous communities (Fredericks and Bargallie, “Indigenous”; “Which Way”). In this article we demonstrate how such training often exposes power, whiteness, and concepts of an Indigenous “other”. We highlight how cross-cultural training programs can potentially provide a setting in which non-Indigenous participants can develop a deeper realisation of how their understandings of the “other” are formed and enacted within a “white” social setting. Revealing whiteness as a racial construct enables people to see race, and “know what racism is, what it is not and what it does” (Bargallie, 262). Training participants can use such revelations to develop their racial literacy and anti-racist praxis (Bargallie), which when implemented have the capacity to transform inequitable power differentials in their work with Indigenous peoples and organisations.What Does the Literature Say about Cross-Cultural Training? An array of names are used for Indigenous cross-cultural training, including cultural awareness, cultural competency, cultural responsiveness, cultural safety, cultural sensitivity, cultural humility, and cultural capability. Each model takes on a different approach and goal depending on the discipline or profession to which the training is applied (Hollinsworth). Throughout this article we refer to Indigenous cross-cultural training as “cultural competence” or “cultural awareness” and discuss these in relation to their application within higher education institutions. While literature on health and human services programs in Australia, Canada, New Zealand, and other nation states provide clear definitions of terms such as “cultural safety”, cultural competence or cultural awareness is often lacking a concise and consistent definition.Often delivered as a half day or a one to two-day training course, it is unrealistic to think that Indigenous cultural competence can be achieved through one’s mere attendance and participation. Moreover, when courses centre on “cultural differences” and enable revelations about those differences they are in danger of presenting idealised notions of Indigeneity. Cultural competence becomes a process through which an Indigenous “other” is objectified, while very little is offered by way of translating knowledge and skills into practice when working with Indigenous peoples.What this type of learning has the capacity to do is oversimplify and reinforce racism and racist stereotypes of Indigenous peoples and Indigenous cultures. What is generally believed is that if non-Indigenous peoples know more about Indigenous peoples and cultures, relationships between Indigenous and non-Indigenous peoples will somehow improve. The work of Goenpul scholar Aileen Moreton-Robinson is vital to draw on here, when she asks, has the intellectual investment in defining our cultural differences resulted in the valuing of our knowledges? Has the academy become a more enlightened place in which to work, and, more important, in what ways have our communities benefited? (xvii)What is revealed in a range of studies – whether centring on racism and discrimination or the ongoing disparities across health, education, incarceration, employment, and more – is that despite forty plus years of training focused on understanding cultural differences, very little has changed. Indigenous knowledges continue to be devalued and overlooked. Everyday and structural racisms shape everyday experiences for Indigenous employees in Australian workplaces such as the Australian Public Service (Bargallie) and the Australian higher education sector (Fredericks and White).As the literature demonstrates, the racial division of labour in such institutions often leaves Indigenous employees languishing on the lower rungs of the employment ladder (Bargallie). The findings of an Australian university case study, discussed below, highlights how power, whiteness, and concepts of “otherness” are exposed and play out in cultural competency training. Through their exposure, we argue that better understandings about Indigenous Australians, which are not based on culture difference but personal reflexivity, may be gained. Revealing What Was Needed in the Course’s Foundation and ImplementationThis case study is centred within a regional Australian university across numerous campuses. In 2012, the university council approved an Aboriginal and Torres Strait Islander strategy, which included a range of initiatives, including the provision of cross-cultural training for staff. In developing the training, a team explored the evidence as it related to university settings (Anning; Asmar; Butler and Young; Fredericks; Fredericks and Thompson; Kinnane, Wilks, Wilson, Hughes and Thomas; McLaughlin and Whatman). This investigation included what had been undertaken in other Australian universities (Anderson; University of Sydney) and drew on the recommendations from earlier research (Behrendt, Larkin, Griew and Kelly; Bradley, Noonan, Nugent and Scales; Universities Australia). Additional consultation took place with a broad range of internal and external stakeholders.While some literature on cross-cultural training centred on the need to understand cultural differences, others exposed the problems of focusing entirely on difference (Brach and Fraser; Campinha-Bacote; Fredericks; Spencer and Archer; Young). The courses that challenged the centrality of cultural difference explained why race needed to be at the core of its training, highlighting its role in enabling discussions of racism, bias, discrimination and how these may be used as means to facilitate potential individual and organisational change. This approach also addressed stereotypes and Eurocentric understandings of what and who is an Indigenous Australian (Carlson; Gorringe, Ross and Forde; Hollinsworth; Moreton-Robinson). It is from this basis that we worked and grew our own training program. Working on this foundational premise, we began to separate content that showcased the fluidity and diversity of Indigenous peoples and refrained from situating us within romantic notions of culture or presenting us as an exotic “other”. In other words, we embraced work that responded to non-Indigenous people’s objectified understandings and expectations of us. For example, the expectation that Indigenous peoples will offer a Welcome to Country, performance, share a story, sing, dance, or disseminate Indigenous knowledges. While we recognise that some of these cultural elements may offer enjoyment and insight to non-Indigenous people, they do not challenge behaviours or the nature of the relationships that non-Indigenous people have with Aboriginal and Torres Strait Islander peoples (Bargallie; Fredericks; Hollinsworth; Westwood and Westwood; Young).The other content which needed separating were the methods that enabled participants to understand and own their standpoints. This included the use of critical Indigenous studies as a form of analysis (Moreton-Robinson). Critical race theory (Delgado and Stefancic) was also used as a means for participants to interrogate their own cultural positionings and understand the pervasive nature of race and racism in Australian society and institutions (McLaughlin and Whatman). This offered all participants, both non-Indigenous and Indigenous, the opportunity to learn how institutional racism operates, and maintains discrimination, neglect, abuse, denial, and violence, inclusive of the continued subjugation that exists within higher education settings and broader society.We knew that the course needed to be available online as well as face-to-face. This would increase accessibility to staff across the university community. We sought to embed critical thinking as we began to map out the course, including the theory in the sections that covered colonisation and the history of Indigenous dispossession, trauma and pain, along with the ongoing effects of federal and state policies and legislations that locates racism at the core of Australian politics. In addition to documenting the ongoing effects of racism, we sought to ensure that Indigenous resistance, agency, and activism was highlighted, showing how this continues, thus linking the past to the contemporary experiences of Indigenous peoples.Drawing on the work of Bargallie we wanted to demonstrate how Aboriginal and Torres Strait Islander peoples experience racism through systems and structures in their everyday work with colleagues in large organisations, such as universities. Participants were asked to self-reflect on how race impacts their day-to-day lives (McIntosh). The final session of the training focused on the university’s commitment to “Closing the Gap” and its Reconciliation Action Plan (RAP). The associated activity involved participants working individually and in small groups to discuss and consider what they could contribute to the RAP activities and enact within their work environments. Throughout the training, participants were asked to reflect on their personal positioning, and in the final session they were asked to draw from these reflections and discuss how they would discuss race, racism and reconciliation activities with the governance of their university (Westwood and Westwood; Young).Revelations in the Facilitators, Observers, and Participants’ Discussions? This section draws on data collected from the first course offered within the university’s pilot program. During the delivery of the in-person training sessions, two observers wrote notes while the facilitators also noted their feelings and thoughts. After the training, the facilitators and observers debriefed and discussed the delivery of the course along with the feedback received during the sessions.What was noticed by the team was the defensive body language of participants and the types of questions they asked. Team members observed how there were clear differences between the interest non-Indigenous participants displayed when talking about Aboriginal and Torres Strait Islander peoples and a clear discomfort when they were asked to reflect on their own position in relation to Indigenous people. We noted that during these occasions some participants crossed their arms, two wrote notes to each other across the table, and many participants showed discomfort. When the lead facilitator raised this to participants during the sessions, some expressed their dislike and discomfort at having to talk about themselves. A couple were clearly unhappy and upset. We found this interesting as we were asking participants to reflect and talk about how they interpret and understand themselves in relation to Indigenous people and race, privilege, and power.This supports the work of DiAngelo who explains that facilitators can spend a lot of time trying to manage the behaviour of participants. Similarly, Castagno identifies that sometimes facilitators of training might overly focus on keeping participants happy, and in doing so, derail the hard conversations needed. We did not do either. Instead, we worked to manage the behaviours expressed and draw out what was happening to break the attempts to silence racial discussions. We reiterated and worked hard to reassure participants that we were in a “safe space” and that while such discussions may be difficult, they were worth working through on an individual and collective level.During the workshop, numerous emotions surfaced, people laughed at Indigenous humour and cried at what they witnessed as losses. They also expressed anger, defensiveness, and denial. Some participants revelled in hearing answers to questions that they had long wondered about; some openly discussed how they thought they had discovered a distant Aboriginal relative. Many questions surfaced, such as why hadn’t they ever been told this version of Australian history? Why were we focusing on them and not Aboriginal people? How could they be racist when they had an Aboriginal friend or an Aboriginal relative?Some said they felt “guilty” about what had happened in the past. Others said they were not personally responsible or responsible for the actions of their ancestors, questioning why they needed to go over such history in the first place? Inter-woven within participants’ revelations were issues of racism, power, whiteness, and white privilege. Many participants took a defensive stance to protect their white privilege (DiAngelo). As we worked through these issues, several participants started to see their own positionality and shared this with the group. Clearly, the revelation of whiteness as a racial construct was a turning point for some. The language in the group also changed for some participants as revelations emerged through the interrogation and unpacking of stories of racism. Bargallie’s work exploring racism in the workplace, explains that “racism”, as both a word and theme, is primarily absent in conversations amongst non-Indigenous colleagues. Despite its entrenchment in the dialogue, it is rarely, if ever addressed. In fact, for many non-Indigenous people, the fear of being accused of racism is worse than the act of racism itself (Ahmed; Bargallie). We have seen this play out within the media, sport, news bulletins, and more. Lentin describes the act of denying racism despite its existence in full sight as “not racism”, arguing that its very denial is “a form of racist violence” (406).Through enhancing racial literacy, Bargallie asserts that people gain a better understanding of “what racism is, what racism is not and how race works” (258). Such revelations can work towards dismantling racism in workplaces. Individual and structural racism go hand-in-glove and must be examined and addressed together. This is what we wanted to work towards within the cultural competency course. Through the use of critical Indigenous studies and critical race theory we situated race, and not cultural difference, as central, providing participants with a racial literacy that could be used as a tool to challenge and dismantle racism in the workplace.Revelations in the Participant Evaluations?The evaluations revealed that our intention to disrupt the status quo in cultural competency training was achieved. Some of the discussions were difficult and this was reflected in the feedback. It was valuable to learn that numerous participants wanted to do more through group work, conversations, and problem resolution, along with having extra reading materials. This prompted our decision to include extra links to resource learning materials through the course’s online site. We also opted to provide all participants with a copy of the book Indigenous Australia for Dummies (Behrendt). The cost of the book was built into the course and future participants were thankful for this combination of resources.One unexpected concern raised by participants was that the course should not be “that hard”, and that we should “dumb down” the course. We were astounded considering that many participants were academics and we were confident that facilitators of other mandatory workplace training, for example, staff Equal Employment Opportunity (EEO), Fire Safety, Risk Management, Occupational Health and Safety, Discrimination and more, weren’t asked to “dumb down” their content. We explained to the participants what content we had been asked to deliver and knew their responses demonstrated white fragility. We were not prepared to adjust the course and dumb it down for white understandings and comfortabilities (Leonardo and Porter).Comments that were expected included that the facilitators were “passionate”, “articulate”, demonstrated “knowledge” and effectively “dealt with issues”. A couple of the participants wrote that the facilitators were “aggressive” or “angry”. This however is not new for us, or new to other Aboriginal women. We know Aboriginal women are often seen as “aggressive” and “angry”, when non-Indigenous women might be described as “passionate” or “assertive” for saying exactly the same thing. The work of Aileen Moreton-Robinson in Australia, and the works of numerous other Aboriginal women provide evidence of this form of racism (Fredericks and White; Bargallie; Bond). Internationally, other Indigenous women and women of colour document the same experiences (Lorde). Participants’ assessment of the facilitators is consistent with the racism expressed through racial microaggression outside of the university, and in other organisations. This is despite working in the higher education sector, which is normally perceived as a more knowledgeable and informed environment. Needless to say, we did not take on these comments.The evaluations did offer us the opportunity to adjust the course and make it stronger before it was offered across the university where we received further evaluation of its success. Despite this, the university decided to withdraw and reallocate the money to the development of a diversity training course that would cover all equity groups. This meant that Aboriginal and Torres Strait Islander peoples would be covered along with sexual diversity, gender, disability, and people from non-English speaking backgrounds. The content focused on Aboriginal and Torres Strait Islander peoples was reduced to one hour of the total course. Including Aboriginal and Torres Strait Islander peoples in this way is not based on evidence and works to minimise Indigenous Australians and their inherent rights and sovereignty to just another “equity group”. Conclusion We set out to develop and deliver a cross-cultural course that was based on evidence and a foundation of 40 plus years’ experience in delivering such training. In addition, we sought a program that would align with the university’s Reconciliation Action Plan and the directions being undertaken in the sector and by Universities Australia. Through engaging participants in a process of critical thinking centring on race, we developed a training program that successfully fostered self-reflection and brought about revelations of whiteness.Focusing on cultural differences has proven ineffective to the work needed to improve the lives of Indigenous Australian peoples. Recognising this, our discussions with participants directly challenged racist and negative stereotypes, individual and structural racism, prejudices, and white privilege. By centring race over cultural difference in cultural competency training, we worked to foster self-revelation within participants to transform inequitable power differentials in their work with Indigenous peoples and organisations. The institution’s disbandment and defunding of the program however is a telling revelation in and of itself, highlighting the continuing struggle and importance of placing additional pressure on persons, institutions, and organisations to implement meaningful structural change. ReferencesAhmed, Sara. On Being Included: Racism and Diversity in Institutional Life. Duke University Press, 2012.Anderson, Ian. “Advancing Indigenous Health through Medical Education”. Focus on Health Professional Education: A Multi-Disciplinary Journal 13.1 (2011): 1-12.Anning, Beres. “Embedding an Indigenous Graduate Attribute into University of Western Sydney’s Courses”. Australian Journal of Indigenous Education 39 (2010): 40-52.Asmar, Christine. Final Report on the Murrup Barak of Indigenous Curriculum, Teaching and Learning at the University of Melbourne, 2010-2011. Murrup Barak – Melbourne Institute for Indigenous Development, University of Melbourne, 2011.Bargallie, Debbie. Unmasking The Racial Contract: Everyday Racisms and the Impact of Racial Microaggressions on “Indigenous Employees” in the Australian Public Service. Aboriginal Studies Press, 2020. Behrendt, Larissa. Indigenous Australia for Dummies. Wiley Publishing, 2010.Behrendt, Larissa, Steven Larkin, Robert Griew, Robert, and Patricia Kelly. Review of Higher Education Access and Outcomes for Aboriginal and Torres Strait Islander People: Final Report. Department of Employment, Education and Workplace Relations, 2012.Brach, Cindy, and Irene Fraser. “Can Cultural Competency Reduce Racial and Ethnic Health Disparities? A Review and Conceptual Model”. Medical Care Research and Review 57.sup 1 (2000): 181-217.Bond, Chelsea. “When the Object Teaches: Indigenous Academics in Australian Universities”. Right Now 14 (2014). <http://rightnow.org.au/opinion-3/when-the-object-teaches-indigenous-academics-in-australian-universities/>.Bradley, Denise, Peter Noonan, Helen Nugent, and Bill Scales. Review of Australian Higher Education. Australian Government, 2008.Butler, Kathleen, and Anne Young. Indigenisation of Curricula – Intent, Initiatives and Implementation. Canberra: Tertiary Education Quality and Standards Agency, 2009. 20 Apr. 2020 <http://www.teqsa.gov.au/news-publications/publications>.Campinha-Bacote, Josepha. “A Model and Instrument for Addressing Cultural Competence in Health Care”. Journal of Nursing Education 38.5 (1999): 203-207.Carlson, Bronwyn. The Politics of Identity – Who Counts as Aboriginal Today? Canberra: Aboriginal Studies Press, 2016.Delgado, Richard, and Jean Stefancic. Critical Race Theory: An Introduction. New York University Press, 2001.DiAngelo, Robin. “Nothing to Add: A Challenge to White Silence in Racial Discussions”. Understanding and Dismantling Privilege 11.1 (2012). <http://www.wpcjournal.com/article/view/10100/Nothing%20to%20add%3A%20A%20Challenge%20to%20White%20Silence%20in%20Racial%20Discussions>.Frankenburg, Ruth. White Women, Race Matters: The Social Construction of Whiteness. Minneapolis: University of Minnesota Press, 1993.Fredericks, Bronwyn. “The Need to Extend beyond the Knowledge Gained in Cross-Cultural Awareness Training”. The Australian Journal of Indigenous Education 37.S (2008): 81-89.Fredericks, Bronwyn, and Debbie Bargallie. “An Indigenous Cultural Competency Course: Talking Culture, Care and Power”. In Cultural Competence and the Higher Education Sector: Perspectives, Policies and Practice, eds. Jack Frawley, Gabrielle Russell, and Juanita Sherwood, Springer Publications, 295-308. <https://link.springer.com/book/10.1007%2F978-981-15-5362-2>.Fredericks, Bronwyn, and Debbie Bargallie. “‘Which Way? Talking Culture, Talking Race’: Unpacking an Indigenous Cultural Competency Course”. International Journal of Critical Indigenous Studies 9.1 (2016): 1-14.Fredericks, Bronwyn, and Marlene Thompson. “Collaborative Voices: Ongoing Reflections on Cultural Competency and the Health Care of Australian Indigenous People”. Journal of Australian Indigenous Issues 13.3 (2010): 10-20.Fredericks, Bronwyn, and Nereda White. “Using Bridges Made by Others as Scaffolding and Establishing Footings for Those That Follow: Indigenous Women in the Academy”. Australian Journal of Education 62.3 (2018): 243–255.Gorringe, Scott, Joe Ross, and Cressida Fforde. Will the Real Aborigine Please Stand Up? Strategies for Breaking the Stereotypes and Changing the Conversation. AIATSIS Research Discussion Paper No. 28. Australian Institute of Aboriginal and Torres Strait Islander Studies (AIATSIS), 2011.Hollinsworth, David. “Forget Cultural Competence: Ask for an Autobiography”. Social Work Education: The International Journal 32.8 (2013): 1048-1060.hooks, bell. Feminist Theory: From Margin to Centre. London: Pluto Press, 2000.Kinnane, Stephen, Judith Wilks, Katie Wilson, Terri Hughes, and Sue Thomas. Can’t Be What You Can’t See: The Transition of Aboriginal and Torres Strait Islander Students into Higher Education. Final report to the Australian Government Office for Learning and Teaching. Canberra: Office of Learning and Teaching, 2014.Lentin, Alana. “Beyond Denial: ‘Not Racism’ as Racist Violence”. Continuum 32.1 (2018): 1-15.Leonardo, Zeus, and Ronald L. Porter. “Pedagogy of Fear: Toward a Fanonian Theory of ‘Safety’ in Race Dialogue”. Race Ethnicity and Education 13.2 (2010): 139-157.Lorde, Audrey. Sister Outsider: Essays and Speeches. Crossing Press, 1984.McIntosh, Peggy. White Privilege and Male Privilege: A Personal Account of Coming to See Correspondences through Work in Women's Studies. Wellesley College, Center for Research on Women, 1988.McLaughlin, Juliana, and Sue Whatman. “The Potential of Critical Race Theory in Decolonizing University Curricula”. Asia Pacific Journal of Education 31.4 (2011): 365-377.Moreton-Robinson, Aileen. The White Possessive: Property, Power, and Indigenous Sovereignty. University of Minnesota Press, 2015.Sargent, Sara E., Carol A. Sedlak, and Donna S. Martsolf. “Cultural Competence among Nursing Students and Faculty”. Nurse Education Today 25.3 (2005): 214-221.Sherwood, Juanita, and Tahnia Edwards. “Decolonisation: A Critical Step for Improving Aboriginal health”. Contemporary Nurse 22.2 (2016): 178-190.Spencer, Caroline, and Frances L. Archer. “Surveys of Cultural Competency in Health Professional Education: A Literature Review”. Journal of Emergency Primary Health Care 6.2 (2008): 17.Universities Australia. National Best Practice Framework for Indigenous Cultural Competency in Australian Universities. Universities Australia, 2011. <http://www.universitiesaustralia.edu.au/lightbox/1312>.University of Sydney. National Centre for Cultural Competence, 2016. <http://sydney.edu.au/nccc/>.Westwood, Barbara, and Geoff Westwood. “Aboriginal Cultural Awareness Training: Policy v. Accountability – Failure in Reality”. Australian Health Review 34 (2010): 423-429.Young, Susan. “Not Because It’s a Bloody Black Issue! Problematics of Cross Cultural Training”. In Unmasking Whiteness: Race Relations and Reconciliation, ed. Belinda McKay, 204-219. Queensland Studies Centre, University of Queensland Press, 1999.

This single and critical case study evaluated a faith-based natural family planning program's salient features using a framework on implementation fidelity. Multiple focus group discussions were conducted, with three groups of stakeholders (n=100), to gather qualitative data on their knowledge and experience of the program. Overall, the findings showed that the program primarily adhered to the essential elements of implementation fidelity, such as content, frequency, duration, and coverage prescribed by its designers. Three lessons were drawn to address some issues that have influenced the degree of fidelity in which the program was implemented. The first is the need to secure adequate and sustained human and financial resources. The second is the need to strengthen its partnership with government and non-government organizations that have provided them with much-needed assistance. Finally, there is also the need to provide extensive training, materials, and support to its service providers to preserve their morale and interest. Other faith-based organizations may hold this case as an indicator of how and why an NFP program works and the extent to which the need for family planning can be met adapted to their local conditions and needs. References Arbuckle, Gerald A. Refounding the Church: Dissent for Leadership. Quezon City: Claretian Publications. 1993. Arevalo, Marcos. "Expanding the Availability and improving the delivery of natural family planning services and fertility awareness education: providers' perspectives. Adv Contracept. Jun-Sep 1997; 13(2-3):275-81. Arévalo, Marcos, Victoria Jennings, and Irit Sinai. "Efficacy of a new method of family planning: the Standard Days Method." Contraception 65, no. 5 (2002): 333-338.Arévalo, Marcos, Irit Sinai, and Victoria Jennings. "A fixed formula to define the fertile window of the menstrual cycle as the basis of a simple method of natural family planning." Contraception 60, no. 6 (1999): 357-360. Atun, Jenna (2013). Religiosity and Contraceptive Use among Filipino Youth. Philippine Center for Population and Development. (2013) Accessed April 15, 2019, from http://www.pcpd.ph/.../religiosity-and-contraceptive-use- Authority, P. S. ICF Philippines national demographic and health survey 2017. Quezon City, Philippines, and Rockville, Maryland, USA: PSA and ICF, 2018. Authority, Philippine Statistics. "Philippine statistics authority." Accessed from Philippine Statistics Authority Web site: https://psa. gov. ph/vegetable-root-crops-main/tomato (2018). Authority, P. S. “Philippine statistics authority.” Accessed July 20, 2019, from Philippine Statistics Authority Web site: https://psa. gov. ph/vegetable-root-crops-main/tomato.(2016) Authority, P. S. “ICF Philippines national demographic and health survey.” Quezon City, Philippines, and Rockville, Maryland, USA: PSA and ICF, 2017. Bamber, John, Stella Owens, Heino Schonfeld, Deborah Ghate, and Deirdre Fullerton. "Effective Community Development Programmes: a review of the international evidence base." (2010). Barden-O'Fallon, Janine. "Availability of family planning services and quality of counseling by faith-based organizations: a three-country comparative analysis." Reproductive health, 14, no. 1 (2017): 57. Baskarada, Sasa. "Qualitative case study guidelines." The Qualitative Report 19, no. 40 (2014): 1-25. Accessed July 25, 2019, from http://www.nova.edu/ssss/QR/QR19/baskarada24.pdf Beaubien, Louis, and Daphne Rixon. "Key performance indicators in co-operatives: directions and principles." Journal of Co-operative Studies 45, no. 2 (2012): 5-15. Booker, Victoria K., June Grube Robinson, Bonnie J. Kay, Lourdes Gutierrez Najera, and Genevieve Stewart. "Changes in empowerment: Effects of participation in a lay health promotion program." Health Education & Behavior 24, no. 4 (1997): 452-464. Breitenstein, Susan M., Deborah Gross, Christine A. Garvey, Carri Hill, Louis Fogg, and Barbara Resnick. "Implementation fidelity in community‐based interventions." Research in nursing & health 33, no. 2 (2010): 164-173. Carroll, Christopher, Malcolm Patterson, Stephen Wood, Andrew Booth, Jo Rick, and Shashi Balain. "A conceptual framework for implementation fidelity." Implementation Science 2, no. 1 (2007): 40. Casterline, J.B., A.E. Perez & A.E. Biddlecom. “Factors Affecting Unmet Need for FP in the Philippines," “Studies in Family Planning, (1997). (3):173-191. Accessed November 02, 2019, from http://www.jstor.org/stable/2137886. Catholic Bishops' Conference of the Philippines. (2011). Guiding Principles of Population Control. Accessed September 27, 2019, from www.cbcponline.net/ Catholic Church. Bishops' Conference of the Philippines. (1992). Acts and Decrees of the Second Plenary Council of the Philippines. Catholic Bishops' Conference of the Philippines. Catholic Bishops' Conference of the Philippines. (1990). A Pastoral Letter on the Population Control Activities of the Philippine Government and Planned Parenthood Association. Accessed November 24, 2019, from cbcponline.net/v2/?p=324. Cleland, John, and Kazuyo Machiyama. "Unmet need for family planning: past achievements and remaining challenges." In Seminars in reproductive medicine, vol. 33, no. 01, pp. 011-016. Thieme Medical Publishers, 2015. Costello, Marilou P., and John B. Casterline. "Fertility decline in the Philippines: current status, prospects." asdf (2009): 479. Creel, Liz C., Justine V. Sass, and Nancy V. Yinger. "Overview of quality of care in reproductive health: definitions and measurements of quality." New Perspectives on Quality of Care 1 (2002): 1-8. Cronin Jr, J. Joseph, Michael K. Brady, and G. Tomas M. Hult. "Assessing the effects of quality, value, and customer satisfaction on consumer behavioral intentions in service environments." Journal of retailing 76, no. 2 (2000): 193-218. Crous, M. "Quality service delivery through customer satisfaction." (2006). D’Arcy, Catherine, Ann Taket, and Lisa Hanna. "Implementing empowerment-based Lay Health Worker programs: a preliminary study." Health promotion international 34, no. 4 (2019): 726-734. Dane, Andrew V., and Barry H. Schneider. "Program integrity in primary and early secondary prevention: are implementation effects out of control?" Clinical psychology review 18, no. 1 (1998): 23-45. David, Clarissa C., and Jenna Mae L. Atun. "Factors affecting fertility desires in the Philippines." Social Science Diliman 10, no. 2 (2014).Accessed August 12, 2019, from jounals.upd.edu.ph/index.php/socialsciencediliman/article/viewFile/4407/3999. Ewerling, F., Victora, C. G., Raj, A., Coll, C. V., Hellwig, F., & Barros, A. J. (2018). Demand for family planning satisfied with modern methods among sexually active women in low-and middle-income countries: who is lagging? Reproductive health, 15(1). (2018): 42. Francisco, J.M. “Letting the Texts of RH Speak for themselves: (Dis) continuity andCounterpoint in CBCP Statements.” Philippine Studies: Historical and Ethnographic Viewpoints, 223. (2015). Accessed October 17, 2019, from www.philippinestudies.net. Franta, Benjamin, Hilly Ann Roa-Quiaoit, Dexter Lo, and Gemma Narisma. "Climate Disasters in the Philippines." (2016). Fehring, Richard Jerome, Mary Schneider, and Kathleen Raviele. "Pilot evaluation of an Internet‐based natural family planning education and service program." Journal of Obstetric, Gynecologic & Neonatal Nursing 40, no. 3 (2011): 281-291. Glickman, Norman J., and Lisa J. Servon. "More than bricks and sticks: Five components of community development corporation capacity." Housing Policy Debate 9, no. 3 (1998): 497-539. Gomez, Fausto, B., OP. “The Role of Priests in Natural Family Planning." Boletin Ecclesiastico de Filipinas, LXXII, (1996): 163. Gribble, James N. "The standard days' method of family planning: a response to Cairo." International family planning perspectives 29, no. 4 (2003): 188-191. Guida, Maurizio, Giovanni A. Tommaselli, Massimiliano Pellicano, Stefano Palomba, and Carmine Nappi. "An overview on the effectiveness of natural family planning." Gynecological Endocrinology 11, no. 3 (1997): 203-219.Hasson, Henna. "Systematic evaluation of implementation fidelity of complex interventions in health and social care." Implementation Science 5, no. 1 (2010): 67. Infantado, R. B. "Main-streaming NFP into the Philippines' Department of Health: opportunities and challenges." Advances in Contraception 13, no. 2-3 (1997): 249-254. Institute for Reproductive Health. Faith-based organizations as partners in family planning: Working together to improve family well-being. Washington, DC: Georgetown University. (2011). Accessed February 11, 2019, from http://www.ccih.org/FBOs_as_Partners_in_FP_Report.pdf. Ledesma, Antonio. J. “All-NFP: A Way Forward.” Philippine Daily Inquirer (2012). Accessed August 04, 2019, from https://opinion.inquirer.net/35848/all-nfp-a-way-forward#ixzz5zAroo0oo Ledesma, Antonio. J. “Al-Natural Family Planning: Going beyond the RH Bill.” Accessed April 15, 2019, from https://archcdo.wordpress.com/ Lundgren, Rebecka, Jeannette Cachan, and Victoria Jennings. "Engaging men in family planning services delivery: experiences introducing the Standard Days Method® in four countries." World health & population 14, no. 1 (2012): 44. Lundgren, Rebecka I., Mihira V. Karra, and Eileen A. Yam. "The role of the Standard Days Method in modern family planning services in developing countries." The European Journal of Contraception & Reproductive Health Care 17, no. 4 (2012): 254-259.Mikolajczyk, Rafael T., Joseph B. Stanford, and Martina Rauchfuss. "Factors influencing the choice to use modern natural family planning." Contraception 67, no. 4 (2003): 253-258. Orbeta, Aniceto., Jr. “Poverty, Fertility Preferences, and Family Planning Practice in the Philippines.” Philippine Journal of Development, 129. (2006). Accessed October 25, 2019, from https://ideas.repec.org/p/phd/dpaper/dp_2005-22.html.July Orbeta, Aniceto Jr. “Poverty, vulnerability, and family size: evidence from the Philippines (No. 68). (2005). Asian Development Bank. Orbeta Jr, Aniceto, and Ernesto M. Pernia. Population Growth and Economic Development in the Philippines: What Has Been the Experience and What Must Be Done? No. 1999-22. PIDS Discussion Paper Series, 1999. Rufo, Aries. “The church pays lip service to natural family planning.” Rappler (2011). Accessed October 01, 2019, from https://news.abs-cbn.com/-depth/12/04/11/church-pays-lip-service-natural-family-planning. Schivone, Gillian B., and Paul D. Blumenthal. "Contraception in the developing world: special considerations." In Seminars in reproductive medicine, vol. 34, no. 03, pp. 168-174. Thieme Medical Publishers, 2016. Seidman, M. "Requirements for NFP service delivery: an overview." Advances in Contraception 13, no. 2-3 (1997): 241-247. Selak, Anne. “What the Church Owes Families.” La Croix International (2020) Accessed October 24, 2020, from https://www.commonwealmagazine.org/what-church-owes-families. Sinai, Irit, Rebecka Lundgren, Marcos Arévalo, and Victoria Jennings. "Fertility awareness-based methods of family planning: predictors of correct use." International family planning perspectives (2006): 94-100. Smoley, Brian A., and Christa M. Robinson. "Natural family planning." American family physician 86, no. 10 (2012): 924-928. Stanford, Joseph B., Janis C. Lemaire, and Poppy B. Thurman. "Women's interest in natural family planning." Journal of Family Practice 46 (1998): 65-72. Tommaselli, G. A., M. Guida, S. Palomba, M. Pellicano, and C. Nappi. "The importance of user compliance on the effectiveness of natural family planning programs." Gynecological endocrinology 14, no. 2 (2000): 81-89. Van de Vusse, Leona, Lisa Hanson, Richard J. Fehring, Amy Newman, and Jaime Fox. "Couples' views on the effects of natural family planning on marital dynamics." Journal of Nursing Scholarship 35, no. 2 (2003): 171-176. Vidal, Avis C. “Faith-based organizations in Community Development. (2001) Accessed January 28, 2020, from www.huduser.org/publications/pdf/faith-based.pdf. Walker, Christopher, and Mark Weinheimer. "The performance of community development systems: A report to the National Community Development Initiative." Washington, DC: Urban Institute (1996). Weldon, Elizabeth, Karen A. Jehn, and Priti Pradhan. "Processes that mediate the relationship between a group goal and improved group performance." Journal of personality and social psychology 61, no. 4 (1991): 555. World Health Organization, "Family Planning Contraception Methods," June 22, 2020. Accessed August 08, 2020, from https://www.who.int/news-room/fact-sheets/detail/family-planning-contraception. World Health Organization. "Building from common foundations: the World Health Organization and faith-based organizations in primary healthcare." (2008). World Health Organization. “Health topics: family planning.” (1988). Accessed September 24, 2020, from http://www.who.int/topics/family_planning/en/. World Health Organization. (1988). Natural family planning: a guide to the provision of services. Accessed August 27, 2019, from https://apps.who.int/iris/handle/10665/39322.Yin, Robert K. "Case study research: Design and methods 4th edition." In the United States: Library of Congress Cataloguing-in-Publication Data. 2009.