Journal articles on the topic '24.29 theatre studies: other'

BackgroundThe experience of art offers an emerging field in healthcare staff development, much of which is appropriate to the practice of palliative care. The workings of aesthetic learning interventions such as interactive theatre in relation to palliative and end of-life care staff development programmes are widely uncharted.AimTo investigate the use of aesthetic learning interventions used in palliative and end-of-life care staff development programmes.DesignScoping review.Data sourcesPublished literature from 1997 to 2015, MEDLINE, CINAHL and Applied Social Sciences Index and Abstracts, key journals and citation tracking.ResultsThe review included 138 studies containing 60 types of art. Studies explored palliative care scenarios from a safe distance. Learning from art as experience involved the amalgamation of action, emotion and meaning. Art forms were used to transport healthcare professionals into an aesthetic learning experience that could be reflected in the lived experience of healthcare practice. The proposed learning included the development of practical and technical skills; empathy and compassion; awareness of self; awareness of others and the wider narrative of illness; and personal development.ConclusionAesthetic learning interventions might be helpful in the delivery of palliative care staff development programmes by offering another dimension to the learning experience. As researchers continue to find solutions to understanding the efficacy of such interventions, we argue that evaluating the contextual factors, including the interplay between the experience of the programme and its impact on the healthcare professional, will help identify how the programmes work and thus how they can contribute to improvements in palliative care.References. 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Reflective practice: nursing ethics through story telling”,Nursing ethics1997; 4(2): 135–146.. Reilly J, Trial J, Piver D and Schaff P. Using Theatre to Increase Empathy Training in Medical Students,Journal for Learning through the Arts2012; 8(1).. Inske ep S and Lisco S. Alternative Clinical Nursing Experience in an Art Gallery.Nurse Educator2001; 26(3): 117--119.. Thompson T, van de Klee D, Lamont-Robinson, C and Duffin W. Out of Our Heads! Four perspectives on the curation of an on-line exhibition of medically themed artwork by UK medical undergraduates”,Medical Education Online 2010; 15.. Hickey D, Doyle C, Quinn S, O’Driscoll P, Patience D, Chittick K and Cliverd A. Catching’ the concept of spiritual care: implementation of an education programme”,International journal of palliative nursing2008; 14(8): 396–400.. Deloney LA and Graham CJ. 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The Power of Pretend: Using Simulation to Teach End-of-Life Care,Nurse Educator2009; 34(6): 276--280.. Gillis C. “Seeing the difference”: An interdisciplinary approach to death, dying, humanities, and medicine.Journal of Medical Humanities2006;27(2): 105–115.. Donovan T and Mercer D. Onward in my journey: preparing nurses for a new age of cancer care,Cancer nursing2003; 26(5) 400–404.. Fogarty CT. Fifty-five word stories: “small jewels” for personal reflection and teaching,Family medicine2010; 42(6): 400–402.. Foster W and Freeman E. Poetry in general practice education: perceptions of learners,Family Practice2008;25(4) 294–303.. Lillyman S, Gutteridge R and Berridge P. Using a storyboarding technique in the classroom to address end of life experiences in practice and engage student nurses in deeper reflection,Nurse Education in Practice2011; 11(3): 179–185.. Frei J, Alvarez S and Alexander M. Ways of Seeing: Using the Visual Arts in Nursing Education,Journal of Nursing Education2010; 49(12): 672--676.. Sherman DW, Matzo ML, Pitorak E, Ferrell BR and Malloy P. Preparation and care at the time of death: content of the ELNEC curriculum and teaching strategies,Journal for Nurses in Staff Development2005; 21(3): 93–102.. Franklin M. Acting on dilemmas in palliative care,Nursing times2001; 97(49): 37–38.. Epner DE and Baile WF. Difficult conversations: teaching medical oncology trainees communication skills one hour at a time,Academic Medicine2014; 89(4): 578–584.. Shannon SE, Long-Sutehall T and Coombs M. Conversations in end-of-life care: communication tools for critical care practitioners,Nursing in critical care.2011; 16(3): 124–130.. Deci EL and Ryan RM.Intrinsic motivation and self-determination in human behaviour. New York: Plenum Press, 1985.. Wee B, Hillier R, Coles C, Mountford B, Sheldon F and Turner P. 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During the course of the 21th century, there appeared trends and schools that characterised European theatrical practice as a whole, and yet the functioning of the academic discipline would traverse different paths in small-language cultures, especially those that fell under Soviet power, than the rest of the continent did. We associate the emergence of theatre studies as an academic discipline with the emerging concept of performativity, as seen in Erika Fischer-Lichte’s impactful paper. “However, the discovery of the performative dates back to the beginning of this century. It resulted, among other things, in the birth of a new academic discipline – theatre studies.” (Erika Fischer-Lichte, „From Text to Performance: The Rise of Theatre Studies as an Academic Discipline in Germany”, Theatre Research International 24, No. 2. [1999]: 168–178, 168.) From the vantage point of the hundred-year-long history of German theatre studies, this statement is undeniably inspiring, since on the one hand, it allows us to glimpse the shared characteristics of performance culture at the beginning of the century, from Craig through Appia to Stanislavski, and on the other, it lets us note that decades later, the language theory research beginning with Austen derives inspiration from a completely different experiential platform when it comes to the performative character of language (and not that of bodily processes.) However, in small-language cultures we perceive a different academic practice, therefore in this paper we follow the structure of scholarship born of the discovery, experience and naming of performativity, until the solidification of Sovietised academic practices in the 1960s.

As an extension of our studies on the antitumour properties of various hemocyanins, we sought to compare the antiproliferative effects of hemocyanins derived from two snail species: Helix lucorum (HlH) and Helix aspersa (HaH). This is the first report on the antitumour effects of HaH. We hypothesized that HaH has antitumour effects not only against bladder cancer, as previously shown with other hemocyanins, but also on other cancer cell lines. The antiproliferative properties of the mentioned hemocyanins were investigated in vitro on the following human cell lines: bladder cancer (CAL-29 and T-24), ovarian cancer (FraWü), acute monocytic leukemia (THP-1), prostate cancer (DU-145), glioma cancer (LN-18), and Burkitt’s lymphoma (Daudi). The properties of HaH were compared to those of HlH, keyhole limpet hemocyanin (KLH), and two positive controls (doxorubicin and mitomycin C). An antiproliferative effect of the total molecule and one structural subunit of HaH, bc-HaH, against both bladder cancer cell lines, T-24 and CAL-29, was observed. The cytotoxic effect of HaH ranged between 15% and 60% among the other tested cell lines. The endotoxin contamination did not affect the efficacy of HaH. Therefore, HlH and HaH could be appropriate for more detailed investigations of their use as antitumour agents for the studied cancers.

The year 2022 marks the 100th anniversary of Juri Lotman’s birth. On this occasion, I propose to return to one of Lotman’s concepts, namely that of frame. The term was proposed in The structure of the artistic text (1970/1977), in the traditional understanding of a limit that separates a text produced in any kind of medium from extra-textual structures (other texts) or non-text (real-life contexts). This notion of frame comes close to its understanding in literary studies, as well as the theory and philosophy of art and should not be confused with a well-known concept of frame propagated in AI Studies (Minsky 1975; Petöfi 1976) and which refers to a global cognitive pattern of storing common-sense knowledge about particular concepts and situations in memory. Lotman returned to the discussion of the textual frame in Universe of the mind (1990), mainly in application to the fine arts. He also elaborated there a more inclusive concept of boundary (proposed in Lotman 1984/2005) as a demarcation of the semiosphere and of its internal subsystems, which necessitates constant translations between particular codes and languages. Lotman dubbed transgressions of textual borders transcoding, which in contemporary parlance is a clear manifestation of transmediality. Therefore, I propose to analyse the concept of frame in relation to Intermedial Studies (cf. Elleström, 2014). Such crossings of boundaries between different media/modes/modalities are simultaneously creative and potentially confusing, in that they display a semiotic collision of artistic codes and require a heightened processing effort on the part of the addressee. My vantage point is basically semiotic, with the focus of interest going less to verbal texts and more to the issues of frame in the visual arts. Semiotic considerations on the problem of boundaries are complemented with brief phenomenologically-oriented ponderings on aesthetic and cognitive import of framing devices (Crowther, 2009) that emphasize their antithetical function as: a) devices with their own artistic value, even complementing the text vs. b) “defences against the exterior” and hindrances to creative liberty. First, I turn to two areas of interest of Lotman himself: 1) the extension of artistic media in Baroque art and 2) collages, which I treat as transmediality through surface. Lotman perceived collages as a collision of the fictitious with the real, referring to their doubly figurative nature (metonymical and metaphorical). Next, I complement this discussion with examples taken from 20th-century painting and sculpture, e.g. Spatialism, Minimalism, and Hyperrealism. Of particular interest is the situation in which the frame becomes a text commenting on its content or plays a metatextual function. Another game worthy of attention is embedding of frames. The discussion closes with the case of transmedial effects between painting and theatre, illustrated by Polish painter and stage-director Tadeusz Kantor’s theatrical experiments in Cracovian Cricot 2 Theatre: a) Velázquez’s Infanta Margarita entering Kantor’s self-portraits and a photo-portrait frame in the performance Today is my birthday (1990); b) Kantor stepping out of the frame of his own self-portrait on the illusory boundary between real life, painting and theatre. The article posits to treat frame and multiple ways of transgressing it as an integrational phenomenon that opens a path for further interdisciplinary studies across the borders of artistic semiotics, Intermedial Studies, literary theorizing and the theory and philosophy of art.

The purpose of this study is to provide an overview of the application of tax management at PT. XYZ as a shipping company and know the effectiveness of this strategy. The object of this research is Article 29 Income Tax which is the remainder of the Income Tax Payable in the tax year or in other words accrued income tax. Income Tax Article 29 occurs if the tax payable for a tax year is greater than the tax credit, then the tax deficit payable must be paid before the annual notification letter is submitted. The PPh credit includes PPh Articles 21, 22, 23, 24 and 25 on the legal basis of Law no. 36 of 2008. This study uses a qualitative descriptive analysis method, namely by collecting data through literature studies and interviews. Keywords: PPH 29; Shipping Company; Tax Planning Abstrak Tujuan penelitian ini adalah untuk memberikan gambaran mengenai penerapan manajemen pajak pada PT. XYZ sebagai perusahaan pelayaran serta mengetahui keefektifan dari strategi tersebut. Objek penelitian ini adalah Pajak Penghasilan Pasal 29 yang merupakan sisa dari PPh Terutang dalam tahun pajak atau dengan kata lain pajak penghasilan yang masih harus dibayar. Pajak Penghasilan Pasal 29 terjadi jika pajak yang terutang untuk suatu tahun pajak lebih besar dari kredit pajak, maka defisit pajak yang terutang harus dilunasi sebelum surat pemberitahuan tahunan disampaikan. Kredit PPh meliputi PPh Pasal 21, 22, 23, 24 dan 25 dengan dasar hukum UU No. 36 Tahun 2008. Penelitian ini menggunakan metode analisis deskriptif kualitatif yaitu dengan mengumpulkan data melalui studi literatur dan wawancara. Kata kunci: PPH 29,; Perencanaan Pajak; Perusahaan Pelayaran

ObjectivesThis study aimed to compare and evaluate any differences in clinical and radiological outcomes between three surgical techniques of cranio-cervical decompression (CCD) in adults with symptomatic Chiari malformation type I (CM1).DesignRetrospective review using the theatre management system (ORSOS) and records of the patients who underwent CCD for CM1 from January 2011 to January 2018.SubjectsPatients over 16 years of age who underwent CCD secondary to CM1 diagnosed by clinical and radiological criteria.MethodsPatients were divided in three cohorts according the operative technique used: an extradural osteo-ligamentous decompression (BD), BD plus dural opening either without duroplasty (DOWD) or with watertight augmentative duroplasty (DOPD). The primary clinical outcome was measured by utilizing the Chicago Chiari Outcome Scale (CCOS). Syrinx outcome was measured on post-op MRI. Statistical analysis was performed using IBM SPSS 24 with α=0.05.ResultsFifty-two adults underwent fifty-three CCD: 7 BD, 29 DOWD, 17 DOPD. Median follow-up was 12 months (IQR 6–23). Patients who underwent BD or DOPD had a shorter median hospital stay (6 days) than DOWD (11 days). Median CCOS was lower following DOWD (13) compared to BD (14) and DOPD (15). Post-operative complications were higher in DOWD (51.7%) compared to DOPD (17.5%).ConclusionsBetter clinical outcomes, lower complication risk and shorter duration of hospital stay were associated with DOPD. Prospective randomized studies could confirm these findings.

PURPOSE: Previous literature on dancers and athletes has shown a large impact of eating disorders (EDs) on these individuals, but there is limited research on EDs affecting non-dance performing artists (i.e., musicians, actors, etc.). This systematic review aimed to identify and evaluate the literature on EDs in non-dance performing artists. METHODS: A systematic review of the literature was performed on 24 databases, using search terms related to EDs and non-dance performing artists. All results from the databases were systematically screened for inclusion and exclusion criteria. RESULTS: The initial search returned 86,383 total articles, which after screening and removal of duplicates and irrelevant papers yielded 129 results. After screening the 129 full-text results for eligibility, 10 studies met criteria for inclusion: 6 papers addressed EDs in musicians, and 4 papers addressed EDs in theatre performers. Most studies used questionnaires and body mass index (BMI) as diagnostic tools for EDs. Most were small-scale studies and participants were mostly students. Because of the studies’ heterogeneity and varying quality, the results obtained were often contradictory and questionable. CONCLUSIONS: Although there has been a lot of literature in dancers, we found relatively few studies associating EDs with other performing artists, and most were inconsistent in their information.

Multiple observational studies have demonstrated that psoriasis is associated with nephropathy; however, the renal involvement in psoriasis remains largely a matter of debate. The current study was designed to investigate if psoriatic patients are at increased risk of renal abnormalities, in absence of any other comorbidities. Forty patients (11 women, 29 men, mean age 44.9 ± 15.45 years) with moderate to severe chronic plaque type psoriasis who were not under systemic therapy and 40 age- and gender-matched control subjects were enrolled in the study. Patients and controls with history of diabetes, hypertension, and chronic renal disease were excluded. Urinalysis by dipstick and microscopic evaluation and 24 h proteinuria and albuminuria were measured in all patients and controls. Patients with psoriasis and controls were not significantly different with respect to the prevalence of abnormal urinalysis (7.5% versus 5%, P = 1.0), mean 24 h proteinuria (70.40 ± 24.38 mg/24 h versus 89.40 ± 26.78 mg/24 h, P = 0.30), and albuminuria (14.15 ± 8.12 mg/24 h versus 16.62 ± 8.21 mg/24 h, P = 0.18). The presence of abnormal urinalysis was not more common in patients with psoriasis than in controls. Our study demonstrated that psoriatic patients without any other comorbidities are not at increased risk of kidney disease.

This article raises the problem of the international activities of the Cadet Party from 1906 to 1917. During this period, the Cadets were at the head of the foreign policy activities of the State Duma from the first to the fourth convocations. Firstly, the reason is that the cadets had a developed network of personal and professional contacts with Western politicians and journalists; secondly, they formulated their own vision of foreign policy, and were also ideologically close to the political elite of England and France. The Cadet Party used its international authority in two directions: on the one hand, this increased the party’s authority within the Russian society; on the other hand, Russia was drawing closer to its allies in the Entente. In this rapprochement, it is not so much the geopolitical aspect that is important as the establishment of horizontal ties between the societies of these countries, which allows building long-term friendly relations. This was the main feature of the activities of the Cadets – they did not have government powers, their activities did not lead to the conclusion of agreements, but it influenced public opinion both in Russia and abroad.

Suicide is the leading cause of death among young men aged 15–29 in Greenland, but few epidemiological studies have described this problem. We aimed to summarise descriptive epidemiological studies of suicide in young men in Greenland compared with other demographic groups in Denmark and Greenland to inform future suicide prevention strategy. We searched PubMed, PsycINFO, and Embase using an agreed search strategy to identify English-language papers describing suicide epidemiology in Greenlandic men aged 15–29. We followed PRISMA guidelines in screening and appraising eligible publications. Eight articles fulfilled inclusion criteria of 64 meeting search criteria. Findings covering 1970–2011 supported a dramatic rise in suicide rates in Greenlandic men aged 15–24 from 1976, who remained the highest-ranking demographic group over 1976–2011 compared with men and women of all age groups in Denmark and Greenland. Highest rates recorded were almost 600 per 100,000 per year in men aged approximately 20–23 over 1977–1986. No studies described suicide epidemiology after 2011, and no studies described risk factors for suicide in young men. Given the very high suicide rates recorded for young men over 1976–2011, such studies will be essential for informing the development and evaluation of appropriate preventive interventions.

Abstract. Galanin, a 29 amino acid peptide, inhibits insulin and somatostatin secretion from the isolated, perfused dog pancreas. To assess the nature of the influences of galanin on the endocrine pancreas, we examined the effects of porcine galanin and six different galanin analogues at the equimolar concentration of 1 nmol/l on the hormone release from the isolated, perfused dog pancreas. It was found that galanin2–29 (by 75 ± 4%), like the native galanin1–29 (by 90 ± 3%) potently inhibited insulin secretion (p < 0.001). In contrast, galanin3–29 did not significantly affect insulin secretion. This indicates that removal of the two N-terminal amino acids markedly reduces the potency of galanin. Also, the replacement of the amino acid number 2 (Trp) by Tyr or Phe was followed by a loss of the insulin lowering effect of galanin at this dose level. Likewise, galanin 10–29 had no significant effect on insulin secretion. In contrast, the C-terminally deleted galanin1–15 significantly inhibited insulin secretion (by 24 ± 5%; p < 0.01), though with a lower potency than did native galanin (p < 0.05). Consequently, the C-terminal end of galanin is also of importance for the effect. Somatostatin secretion was inhibited by galanin (p < 0.001), but not by any of the other investigated peptides. Glucagon secretion was not affected by galanin. It is concluded that the two N-terminal amino acids of galanin are essential for the inhibitory action on the insulin secretion. The removal of the N-terminal Gly residue decreases the action of galanin on insulin secretion to a much smaller extent than does the removal of, in addition, the Trp residue. However, the remainder of the molecule seems necessary for full potency. It is also concluded that the inhibition by galanin of somatostatin secretion seems to require the entire molecule.

Greenhouse and growth chamber studies were conducted to determine conditions for infection of the fungal pathogenColletotrichum truncatum(Schw.) Andrus and Moore on Florida beggarweed (Desmodium tortuosum(Sw.) DC. # DEDTO and to determine the host specificity of this fungus. Optimum conditions for disease development were 14 to 16 h incubation in 100% relative humidity (RH) at 24 to 29 C. Control of Florida beggarweed with 105to 107C. truncatumspores/ml was greatest in the cotyledon stage and decreased with plant age. Ten of 18Desmodiumspecies tested were susceptible to the Florida beggarweed isolate ofC. truncatumbut 13 other plant species and varieties were resistant and 61 were immune.

ABSTRACT A murine model of intratracheally induced histoplasmosis was used to evaluate a new triazole antifungal agent, Schering (SCH) 56592, for treatment of histoplasmosis. MICs were determined for SCH 56592, amphotericin B, and itraconazole by testing yeast-phase isolates from 20 patients by a macrobroth dilution method. The MICs at which 90% of the isolates are inhibited were for 0.019 μg/ml for SCH 56592, 0.5 μg/ml for amphotericin B, and ≤0.019 μg/ml for itraconazole. Survival studies were done on groups of 10 B6C3F1 mice with a lethal inoculum of 105. All mice receiving 5, 1, or 0.25 mg of SCH 56592 per kg of body weight per day, 2.5 mg of amphotericin B per kg every other day (qod), or 75 mg of itraconazole per kg per day survived to day 29. Only 44% of mice receiving 5 mg of itraconazole/kg/day survived to day 29. Fungal burden studies done in similar groups of mice with a sublethal inoculum of 104showed a reduction in CFUs and Histoplasma antigen levels in lung and spleen tissue in animals treated with 2 mg of amphotericin B/kg qod, 1 mg of SCH 56592/kg/day, and 75 mg of itraconazole/kg/day, but not in those treated with lower doses of the study drugs (0.2 mg of amphotericin B/kg qod, 0.1 mg of SCH 56592/kg/day, or 10 mg of itraconazole/kg/day). Serum drug concentrations were measured 3 and 24 h after the last dose in mice (groups of five to seven mice), each treated for 7 days with SCH 56592 (10 and 1 mg/kg/day) and itraconazole (75 and 10 mg/kg/day). Mean levels measured by bioassay were as follows: SCH 56592, 10 mg/kg/day (2.15 μg/ml at 3 h and 0.35 μg/ml at 24 h); SCH 56592, 1 mg/kg/day (0.54 μg/ml at 3 h and none detected at 24 h); itraconazole, 75 mg/kg/day (22.53 μg/ml at 3 h and none detected at 24 h); itraconazole, 10 mg/kg/day (1.33 μg/ml at 3 h and none detected at 24 h). Confirmatory results were obtained by high-pressure liquid chromatography assay. These studies show SCH 56592 to be a promising candidate for studies of treatment of histoplasmosis in humans.

Context: Hip pain from femoroacetabular impingement (FAI) can impair health-related quality of life (HRQL) but can be treated via hip arthroscopy techniques. Objective: To systematically assess the HRQL outcomes after arthroscopic management of FAI. Date Sources: Three online databases (EMBASE, PubMed, and Ovid [MEDLINE]) were searched for relevant literature from database inception until June 2018 and screened by 2 reviewers independently and in duplicate. Study Selection: Level I to IV English studies that investigated HRQL outcomes after hip arthroscopy were included. Data for generic and hip-specific HRQL outcomes were collected. Mean differences were plotted in a forest plot when possible. Study Design: Systematic review. Level of Evidence: Level 4. Results: A total of 29 studies were included for assessment. Of the 6476 patients (6959 hips), the mean age was 32 years (range 9-79 years) and 50.7% were female. Significant improvements were reported in all studies assessing generic HRQL outcomes, including the 12-Item Short Form Health Survey (range of mean postoperative scores, 82.2-89.8), and EuroQOL-5D scores (range of mean postoperative scores, 0.74-0.87) between 12 and 24 months postoperatively. Significant improvements were similarly identified in the hip-specific HRQL outcomes scores, with the majority of studies also reporting improvement between 12 and 24 months postoperatively. Mean improvement in International Hip Outcome Tool–33 scores from preoperative values to postoperative values ranged from 22.7 to 43.2 ( I2 = 44%), for studies with follow-up between 12 and 24 months. Conclusion: Hip arthroscopy can lead to significant improvement in generic and hip-specific HRQL outcomes at 12 to 24 months postoperatively in patients with FAI who do not have advanced hip osteoarthritis. Confirmatory, high-quality, prospective studies are warranted to compare this observed improvement with other treatment modalities for FAI and to determine long-term outcomes.

Objective: To analyze the results of different surgical modalities for patients undergoing rectal tumor resection. Methods: A systematic literature review of texts published in databases in the last 10 years was carried out. Results: 84 results were found and 29 studies made up the corpus: 11 exclusively evaluated robotic surgery (Group I), 12 compared robotic surgery and laparoscopic surgery (Group II); four compared robotic surgery, laparoscopic surgery and open surgery (Group III); two address robotic surgery, but deal with rectal tumor resection procedures in conjunction with the resection of liver metastases (Group IV). Conclusion: 24 studies (82.8%) evaluated robotic surgery as the most favorable for the treatment of rectal cancer, three studies (10.3%) considered robotic surgery equivalent to laparoscopic and two studies (6.9%) judged laparoscopic superior to robotic surgery. Among the differentials of robotic surgery for patients undergoing the procedure, the following stand out: mortality rates below other types of surgery, significant reduction in surgical trauma, lower rate of urinary retention and loss of sphincter control.

This meta-analysis examined the relationship between moral identity and moral emotions drawing on 57 independent studies. Moral identity was significantly associated with moral emotions, r = .32, p < .01, 95% confidence interval [CI: .27, .36]. Effect sizes were moderated by the type of moral emotion. Studies reporting other-regarding emotions (sympathy, empathy, and compassion) had the largest effect sizes ( r = .41), while negative other-evaluative emotions (moral anger, contempt, and disgust) had the smallest ( r = .16). Self-evaluative and other-evaluative positive emotions had intermediate effect sizes ( r values between .29 and .32). The type of emotion measure also was a significant moderator, with trait measures of emotion ( r = .38) correlating more strongly with moral identity than state measures ( r = .24). Effect sizes did not differ for the type of moral identity measure being used, publication status, or cultural origin of the study sample. The results of this meta-analysis demonstrate a robust empirical connection between moral identity and moral emotions, which confirms the multifaceted role of moral identity in moral functioning.

Abstract. A total of 209 events of quasi-monochromatic atmospheric gravity waves (QMGWs) were acquired over 5 years of gravity waves (GWs) observation in southern Brazil. The observations were made by measuring the OH (hydroxyl radical) emission using an all-sky imager hosted by the Southern Space Observatory (SSO) coordinated by the National Institute for Space Research at São Martinho da Serra (RS) (29.44° S, 53.82° W). Using a two-dimensional fast-Fourier-Transform-based spectral analysis, it has been shown that the QMGWs have horizontal wavelengths of 10–55 km, periods of 5–74 min, and phase speeds up to 100 m s−1. The waves exhibited clear seasonal dependence on the propagation direction with anisotropic behavior, propagating mainly toward the southeast during the summer and autumn seasons and mainly toward the northwest during the winter. On the other hand, the propagation directions in the spring season exhibited a wide range from northwest to south. A complementary backward ray-tracing result revealed that the significant factors contributing to the propagation direction of the QMGWs are their source locations and the dynamics of the background winds per season. Three case studies in winter were selected to investigate further the propagation dynamics of the waves and determine their possible source location. We found that the jet stream associated with the cold front and their interaction generated these three GW events.

ObjectiveTo report the presenting syndromes and to determine whether pretreatment criteria of Hashimoto encephalopathy (HE) predict response to steroids.MethodsWe assessed symptoms and steroid responsiveness in 24 patients with pretreatment criteria of HE, including (1) subacute onset of cognitive impairment, psychiatric symptoms, or seizures; (2) euthyroid status or mild hypothyroidism; (3) serum thyroid peroxidase antibodies (TPOAb) >200 IU/mL; (4) absent neuronal antibodies in serum/CSF; and (5) no other etiologies. Additional studies included determination of TPOAb (>200 IU/mL) in 74 patients with criteria of possible autoimmune encephalitis (AE) without neuronal antibodies and 205 patients with different neuroimmunologic diseases, psychosis, or new-onset refractory status epilepticus (NORSE). Serum antibodies to the amino (ΝΗ2)-terminal of α-enolase (NH2-α-enolaseAb) were examined in the indicated 24 patients and 13 controls.ResultsThe 24 patients (14 women) with suspected HE had a median age of 48 years (range 8–79 years). Four syndromes were identified: psychiatric (7, 29%), encephalopathy (7, 29%), NORSE-like (6, 25%), and limbic encephalitis (4, 17%). Only 6 of 19 (31.6%) patients completely responded to steroids. The frequency of TPOAb in the 74 patients with possible AE (6 of 74, 8.1%) was similar to that of the 205 controls (17 of 205, 8.2%; p = 0.84). NH2-α-enolaseAb were identified in 1 of 24 suspected HE cases and 1 of 13 controls.ConclusionCurrent pretreatment criteria of HE do not predict steroid responsiveness. The detection of TPOAb across all control groups reveals their poor disease-specificity. NH2-α-enolaseAb did not help in the diagnosis of HE. These findings imply a redefinition of HE that requires a systematic exclusion of antibody-mediated encephalitis.

Abstract Twenty-nine of 172 patients (17%) who received an allogeneic bone marrow transplant (BMT) from histocompatible sibling donors for hematologic malignancies were mixed hematopoietic chimeras; ie, they had a mixture of donor and host hematopoietic or lymphohematopoietic cells at greater than or equal to 14 days after transplantation. Twenty- four of the 29 mixed chimeras (83%) have remained in continuous complete remission for up to 116 months (greater than 9 years) following BMT. Four of the 29 patients (14%) have had recurrent leukemia, and 7 of the 29 (24%) have had moderate or severe graft-v- host disease (GVHD). Twelve of these 29 patients have persisted as stable mixed chimeras for greater than or equal to 2 years after BMT, whereas other patients converted to all donor-type hematopoiesis. The incidence of mixed chimerism was independent of the pretransplant regimen, the donor or recipient age (less than 20 v greater than 20 years), remission status (first complete remission of acute leukemia and first chronic phase of chronic myelocytic leukemia v later stages of disease), and type of leukemia. Our data indicate that mixed hematopoietic chimerism is not rare after BMT for hematologic malignancies and that its presence is compatible with long-term disease- free survival. Prospective studies of mixed chimerism after BMT are warranted to achieve better understanding of its biologic importance.

Twenty-nine of 172 patients (17%) who received an allogeneic bone marrow transplant (BMT) from histocompatible sibling donors for hematologic malignancies were mixed hematopoietic chimeras; ie, they had a mixture of donor and host hematopoietic or lymphohematopoietic cells at greater than or equal to 14 days after transplantation. Twenty- four of the 29 mixed chimeras (83%) have remained in continuous complete remission for up to 116 months (greater than 9 years) following BMT. Four of the 29 patients (14%) have had recurrent leukemia, and 7 of the 29 (24%) have had moderate or severe graft-v- host disease (GVHD). Twelve of these 29 patients have persisted as stable mixed chimeras for greater than or equal to 2 years after BMT, whereas other patients converted to all donor-type hematopoiesis. The incidence of mixed chimerism was independent of the pretransplant regimen, the donor or recipient age (less than 20 v greater than 20 years), remission status (first complete remission of acute leukemia and first chronic phase of chronic myelocytic leukemia v later stages of disease), and type of leukemia. Our data indicate that mixed hematopoietic chimerism is not rare after BMT for hematologic malignancies and that its presence is compatible with long-term disease- free survival. Prospective studies of mixed chimerism after BMT are warranted to achieve better understanding of its biologic importance.

This article provides a national estimate of wife rape and various other types of sexual coercion by a spouse or intimate partner. Findings from a 1997 national probability sample revealed that 34% of women were victims of some type of sexual coercion with a husband or partner in their lifetime. Of these women, 10% experienced rape by a current partner. This rate increased to 13% when only victims of rape by a current husband were included, which is consistent with previous studies on wife rape. Other findings reveal that women had unwanted sex with a current spouse or partner in return for a partner’s spending money on them (24%), because they thought it was their “duty” (43%), after a romantic situation (29%), after the partner begged and pleaded with them (26%), and after their partner said things to bully them (9%). The importance of examining a continuum of sexual coercion is discussed and findings are compared and contrasted with other prevalence rates for sexual coercion in marriage.

Abstract Dasatinib (SPRYCEL®) is a highly potent BCR-ABL inhibitor, with 325-fold higher potency than imatinib and a 16-fold higher potency than nilotinib in vitro. Across a series of phase II and III trials with more than 2 years of follow-up, dasatinib has demonstrated durable efficacy in patients with CML following resistance, suboptimal response, or intolerance to imatinib. Qualitative and quantitative assessment of BCR-ABL transcripts by RT-PCR is the most sensitive method for assessing minimal residual disease in patients with CML. In the treatment of patients with CML in the first-line setting, achievement of a major molecular response (MMR) within 18 months of therapy is considered to be clinically important. Here, molecular responses to dasatinib in patients with CML-CP following resistance, suboptimal response, or intolerance to imatinib were analyzed using data from two phase II studies (CA180-013 [START-C], -017 [START-R]) and a phase III dose-optimization study (CA180-034). BCR-ABL mRNA levels were determined in peripheral blood samples using real-time quantitative PCR and results were standardized using the international scale. A MMR was defined as a reduction of BCR-ABL transcripts to ≤ 0.1%. Samples were assayed at one of four laboratories (Mannheim, Germany; Adelaide, Australia; or Seattle, USA for −013 and −017; and Wallingford, USA for −034). Of 1,158 patients with CML-CP who were randomized to (017) or treated with (013/034) dasatinib, 1,067 had a molecular assessment and were included in the analysis. After 3, 6, 12, and 24 months of follow-up, a MMR was achieved by 12%, 22%, 35%, and 40%, respectively, of all patients analyzed. The 24-month MMR rate among patients who had achieved or maintained a complete cytogenetic response was 72%. In patients with imatinib resistance/suboptimal response (n=829), overall MMR rates after 3, 6, 12, and 24 months were 10%, 18%, 29%, and 34%, respectively, and in patients with imatinib intolerance (n=238), MMR rates were 22%, 37%, 55%, and 63%, respectively. In patients treated during the 034 study with dasatinib 100 mg once daily, which is associated with fewer key side effects, MMR rates at different time points were similar to rates with other dose schedules (24-month MMR: 100 mg QD, 36%; other schedules, 38%). Among all patients who achieved a MMR, median time to MMR was 5.7 months (6.0 months with 100 mg QD), and after 18 months, 92% of responding patients were without loss of MMR (88% with 100 mg QD). Overall, the results of this analysis demonstrate that high rates of MMR are rapidly achieved in patients with CML-CP treated with dasatinib following resistance, suboptimal response, or intolerance to imatinib. Table Major molecular response (%) Follow-up (months) 3 6 12 24 All analyzed patients (n=1067) 12 22 35 40 Resistant/suboptimal response (n=829) 10 18 29 34 Intolerant (n=238) 22 37 55 63 Phase II studies (013/017) (n=467) 17 27 39 44 Resistant (n=373) 13 21 31 35 Intolerant (n=94) 33 50 69 78 Phase III dose-optimization study (034) (n=600) 9 19 32 38 Resistant/suboptimal response (n=456) 7 16 27 33 Intolerant (n=144) 15 29 46 54 Response by dose schedule 100 mg QD (n=154) 7 18 29 36 70 mg BID (n=146) 9 18 32 38 140 mg QD (n=144) 13 22 32 38 50 mg BID (n=156) 7 17 34 38

SUMMARYAims – Service user involvement in mental health service development and research is becoming more common in countries like the UK. USA and Canada. This systematic review of the international scientific literature has been carried out to assess the stage of development of mental health service users involvement in research. Method – Systematic review of any research project actively involving service users in any part of the research process. Results – Thirty-five studies met the inclusion and exclusion criteria and were included in the systematic review. Nine studies used quantitative techniques, 24 used qualitative techniques and two studies used both quantitative and qualitative techniques. While three studies were user-led, in three other studies the users were simply consulted but did not have any active role in the research. The remaining 29 studies were based on a collaboration between service users and professional researchers. Conclusions – The involvement of mental health service users in the research process is feasible both in quantitative and qualitative research studies. The involvement of service users in research has a number of benefits; such research requires more accurate planning and more time than the traditional research.Declaration of Interest: none.

Aims Arthroplasty skills need to be acquired safely during training, yet operative experience is increasingly hard to acquire by trainees. Virtual reality (VR) training using headsets and motion-tracked controllers can simulate complex open procedures in a fully immersive operating theatre. The present study aimed to determine if trainees trained using VR perform better than those using conventional preparation for performing total hip arthroplasty (THA). Patients and Methods A total of 24 surgical trainees (seven female, 17 male; mean age 29 years (28 to 31)) volunteered to participate in this observer-blinded 1:1 randomized controlled trial. They had no prior experience of anterior approach THA. Of these 24 trainees, 12 completed a six-week VR training programme in a simulation laboratory, while the other 12 received only conventional preparatory materials for learning THA. All trainees then performed a cadaveric THA, assessed independently by two hip surgeons. The primary outcome was technical and non-technical surgical performance measured by a THA-specific procedure-based assessment (PBA). Secondary outcomes were step completion measured by a task-specific checklist, error in acetabular component orientation, and procedure duration. Results VR-trained surgeons performed at a higher level than controls, with a median PBA of Level 3a (procedure performed with minimal guidance or intervention) versus Level 2a (guidance required for most/all of the procedure or part performed). VR-trained surgeons completed 33% more key steps than controls (mean 22 (sd 3) vs 12 (sd 3)), were 12° more accurate in component orientation (mean error 4° (sd 6°) vs 16° (sd 17°)), and were 18% faster (mean 42 minutes (sd 7) vs 51 minutes (sd 9)). Conclusion Procedural knowledge and psychomotor skills for THA learned in VR were transferred to cadaveric performance. Basic preparatory materials had limited value for trainees learning a new technique. VR training advanced trainees further up the learning curve, enabling highly precise component orientation and more efficient surgery. VR could augment traditional surgical training to improve how surgeons learn complex open procedures. Cite this article: Bone Joint J 2019;101-B:1585–1592

AbstractBackgroundPost operative radiographs following total joint arthroplasty are requested as part of routine follow up in many institutions. These studies have a significant cost to the local departments, in terms of financial and clinic resources, however, previous research has suggested they may not alter the course of the patients treatment. The purpose of this study was to assess the significance of elective post operative radiographs on changes in management of patients who underwent total joint arthroplasty.MethodAll patients who underwent total knee arthroplasty and total hip arthroplasty at a District General Hospital from 2019 to 2020 were included. Data was collected retrospectively from medical records and radiograph requests. Alterations to clinical management based on radiographic findings were reviewed in clinic letters.ResultsA total of 227 Total joint arthroplasty were retrieved. With 111(49%) total hip arthroplasty and 116 (51%) total knee arthroplasty. 54 were excluded due to having no clinical follow up and 173 met inclusion criteria. 56 (32%) had their post operative elective radiograph, while 93 (53.8%) patients had none. There were no abnormalities detected from the elective radiographs and none of the patients returned to the theatre. 24 patients (13%) presented with symptoms and had non-elective radiographs, 16 (67%) did not have any interventions and 8 (4.6%) required intervention and were taken to theatre. Discussion: Not performing these radiographs saves time, cost, and prevents unnecessary radiation exposure. In our institution, a 2-view joint radiograph costs £29 and takes roughly 15 minutes. This does not include indirect costs of additional clinic time and patient waiting time. In the larger context, the cost associated with elective radiographs is significant and our data suggests that routine post-operative radiographs are not beneficial as part of standard post-operative protocol for asymptomatic patients. However, performing imaging remains beneficial for patients who re-present with symptoms.ConclusionRoutine elective post-operative joint radiographs did not detect any true abnormalities. Information from elective radiographs has no clinical significance and did not change management. Therefore, this study recommends that there is no rationale requesting elective post-operative joint radiographs.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Neuropeptide Y (NPY) is increasingly considered to be involved in the central regulation of energy balance. Our previous studies suggest that hypothalamic NPY neurons of the arcuatoparaventricular (ARC-PVN) projection are inhibited in association with the marked increases in brown adipose tissue (BAT) thermogenesis and uncoupling protein (UCP) gene expression in rats exposed to cold. We therefore hypothesized that the NPYergic ARC-PVN system would be activated in a thermoneutral environment, when energy expenditure falls to a minimum, and that this activation could mediate the fall in BAT activity. We measured regional hypothalamic NPY concentrations, hypothalamic NPY receptor binding, and NPY mRNA together with UCP mRNA levels in rats exposed to thermoneutrality (29 degrees C) for 24 h. At thermoneutrality, UCP mRNA levels fell to 42% of those in controls maintained at 22 degrees C, but there were no significant changes in hypothalamic NPY or NPY mRNA levels or in NPY receptor binding. We conclude that the fall in UCP mRNA expression occurring under short-term thermoneutral condition is mediated by neuroendocrine mechanisms other than increased activity of hypothalamic NPY neurons.

Abstract Background. In chronic myeloid leukemia (CML), achievement of optimal responses by time point has improved long-term outcomes. In IRIS study, patients who achieved major molecular response (MMR) at 18 months had event-free survival (EFS) benefit, compared to those who achieved complete cytogenetic response (CCyR) without MMR. However, the best treatment for these patients is still not confirmed. By the previous studies, sustaining standard-dose of imatinib (IM) is expected to yield less than 20 percent of additive MMR. In this study, we investigated the efficacy of nilotinib (NIL) versus high-dose IM versus sustaining standard-dose IM for CCyR patients with suboptimal molecular response to frontline IM therapy. Methods. Early chronic phase (CP) CML patients who have achieved CCyR but no MMR after at least 18 months and up to 24 months ( 18 to 24 months) on first-line IM therapy at a daily dose of 400 mg were divided into 3 treatment groups; NIL 400mg BID (800 mg/day; group 1) vs IM 400 mg BID (800 mg/day; group 2) vs IM 400mg QD (400mg/day; group 3). Group 1 and 2 patients were selected in RE-NICE multicenter study and group 3 patients were selected with the same inclusion criteria of RE-NICE. The efficacy endpoints are MMR rate by 12 months and MMR rate and undetectable molecular residual disease (UMRD) rates by 36 months. Safety profiles of each group were compared. Patients showing lack of response (lack of complete hematologic response (CHR) at 6 months, increasing WBC, no major cytogenetic response (MCyR) at 24 months), loss of response (loss of CHR or MCyR) or intolerance to treatment were allowed to switch to other treatment. Results. With a data cut-off date of 17 Jul 2014, a total of 83 patients were evaluated; 29 patients in NIL group (group 1), 29 patients in high-dose IM group (group 2) and 25 patients in standard-dose IM group (group 3). With a median follow-up of 36 months (range, 1-63), all patients in group 1 remained in nilotinib treatment, 17 patients in group 2 switched to NIL 400mg BID due to intolerance (n=4) and lack of response (no MMR; n=13). In group 3, with a median follow-up of 71 months (range, 6-132), 15 patients switched to other treatment due to intolerance (n=5) and lack of response (no MMR; n=10). Up to now, all patients in three groups have maintained CCyR without progression or resistance. 10 in 29 (35%), 8 in 29 (28%) and 5 in 25 (20%) patients achieved MMR by 12 months, and 20 in 29 (69%), 15 in 29 (51%) and 11 in 25 (44%) patients achieved MMR by 36 months in group 1, group 2 and group 3 respectively. Overall, 3 patients in group 1 (3/29, 10%) achieved confirmed UMRD. Overall 3 years probability of MMR was significantly higher in group 1 than the other two groups (67.8% vs 41.0% vs 40.4%, group 1, 2, 3 respectively, group 1 vs 2, P=0.089, group 1 vs 3, P=0.035, group 2 vs 3, P=0.614). Compare to other groups, the patients in group 2 showed higher toxicities, such as leukopenia, anemia, thrombocytopenia, edema, fatigue, dyspnea and hypophosphatemia. Conclusions. Nilotinib 400mg twice daily treatment showed better efficacy than high-dose or same standard-dose imatinib for the treatment of patients who have suboptimal molecular response to initial standard-dose imatinib. Additionally, a switch to nilotinib in suboptimal molecular responder to imatinib would also be preferable option in terms of tolerability. Updated data with longer follow-up duration will be presented in the meeting. Disclosures No relevant conflicts of interest to declare.

Background: Despite the high rate of HIV infections, there is still high rate of early unprotected sex, unintended pregnancy, and unsafe abortions especially among unmarried adolescent girls and young women (AGYW) 10-24 years of age in sub Saharan Africa. AGYW face challenges in accessing health care, contraception needs, and power to negotiate safer sex. This study aimed to estimate the rate of pregnancy among AGYW aged 10-24, 10-19 and 15-19 years in the Southern African Development Community (SADC) economic region. Methods: A systematic review and meta-analysis was used to describe the prevalence of pregnancy among AGYW in 15 SADC member countries between January 2007 and December2017. The articles were extracted from PubMed/MEDLINE, African Index Medicus, and other reports. They were screened and reviewed according to PRISMA methodology to fulfil study eligibility criteria. Results: The overall regional weighted pregnancy prevalence among AGYW 10-24 years of age was 25% (95% CI: 21% to 29%). Furthermore, sub-population 10-19 years was 22% (95% CI:19% to 26%) while 15-19 years was 24% (18% to 30%). There was a significant heterogeneity detected between the studies (I=99.78%, P < 0.001), even within individual countries. Conclusion: The findings revealed a high pregnancy rate among AGYW in the SADC region. This prompts the need to explore innovative research and programs expanding and improving sexual and reproductive health communication to reduce risk and exposure of adolescents to early planned, unplanned and unwanted pregnancies, SRHR challenges, access to care, HIV/STIs, as well as other risk strategies.

Guided by systematic studies on Melpomene, we tested the monophyly of the genus by analyzing sequences of cpDNA (atpβ, rbcL) and morphological characters for 24 of the 29 recognized species. The atpβ data did not yield any resolution of the investigated group. The other data sets each supported the monophyly of the genus, as did all data combined, and indicate it to be sister to the Lellingeria apiculata group as proposed in previous studies. While the morphologically distinct M. leptostoma and M. gracilis are basal lineages with long branch lengths, most of the relationships within the core genus are weakly supported and have very short branch lengths. This indicates a recent radiation of the genus in the northern Andes, its center of diversity, apparently under the influence of the fast up lift of the mountain range and of glacial fluctuations of the vegetation zones, with subsequent dispersals to the Guyana Highlands, the Brazilian shield, and Africa.

Background: Antibiotics alone are often insufficient to treat recurrent C. difficile infection (rCDI) because they have no activity against C. difficile spores that germinate within a disrupted microbiome. SER-109, an investigational, oral, microbiome therapeutic comprised of purified Firmicutes spores, was designed to reduce rCDI through microbiome repair. We report an integrated efficacy analysis through week 24 for SER-109 from phase 3 studies, ECOSPOR III and ECOSPOR IV. Methods: ECOSPOR III was a randomized, placebo-controlled phase 3 trial conducted at 56 US or Canadian sites that included 182 participants with ≥2 CDI recurrences, confirmed via toxin EIA testing. Participants were stratified by age (<65 years or ≥65 years) and antibiotic regimen (vancomycin, fidaxomicin) and were randomized 1:1 to placebo or SER-109 groups. ECOSPOR IV was an open-label, single-arm study conducted at 72 US or Canadian sites including 263 participants with rCDI enrolled in 2 cohorts: (1) rollover participants from ECOSPOR III who experienced on-study recurrence diagnosed by toxin EIA (n = 29) and (2) participants with ≥1 CDI recurrence (diagnosed by PCR or toxin EIA), inclusive of the current episode (n = 234). In both studies, the investigational product was administered orally as 4 capsules over 3 consecutive days following symptom resolution after standard-of-care antibiotics. The primary efficacy end point was rCDI (recurrent toxin-positive diarrhea requiring treatment) through week 8. Other end points included CDI recurrence rates and safety through 24 weeks. Results: These 349 participants received at least 1 dose of SER-109 in ECOSPOR III or ECOSPOR IV (mean age 64.2; 68.8% female). Overall, 77 participants (22.1%) enrolled with their first CDI recurrence. Four participants received blinded SER-109 in ECOSPOR III followed by a second dose of open-label SER-109 in ECOSPOR IV. Overall, the proportion of participants who received any dose of SER-109 with rCDI at week 8 was 9.5% (33 of 349; 95% CI, 6.6 %–13.0%), and the CDI recurrence rate remained low through 24 weeks (15.2%, 53 of 349; 95% CI, 11.6%–19.4%), corresponding to sustained clinical response rates of 90.5% (95% CI, 87.0%–93.4%) and 84.8% (95% CI, 80.6%–88.4%), respectively (Fig. 1). Most rollover participants (25 of 29, 86.2%) were from the placebo arm; 13.8% had rCDI by week 8. Conclusions: In this integrated analysis, the rates of rCDI were low and durable in participants who received the investigational microbiome therapeutic SER-109, with sustained clinical response rates of 90.5% and 84.8% at weeks 8 and 24, respectively. These data further support the potential benefit of microbiome repair with SER-109 following antibiotics for rCDI to prevent recurrence in high-risk patients.Financial support: This study was funded by Seres Therapeutics.Disclosure: None

We studied the frequency, causes, and predictors of adverse events in 624 patients who had completed treatment for acute lymphoblastic leukemia (ALL) in three consecutive total therapy studies (VII, IX, and X, 1972 to 1983). Event-free survival in study X was significantly better overall than that in studies VIII and IX (P less than .0001 by the log-rank test). In study X, 75% of the patients were electively taken off therapy, compared with 54% in studies VIII and IX. However, the risks of having an adverse event during the first 5 years after completion of therapy were remarkably similar: 22% (95% confidence interval, 17% to 29%) in study X versus 24% (20% to 29%) in studies VIII and IX. Bone marrow, testicular, and CNS relapses accounted for the majority of failures in both groups (85% in study X and 92% in studies VIII and IX). Late adverse events consisted largely of hematologic relapses and the development of solid tumors. Black race (P = .001) and leukemia without an anterior mediastinal mass (P = .05) were associated with an increased risk of failure after completion of treatment in the two earlier clinical trials, whereas a lower leukemic cell DNA content (DNA index less than 1.16) was the only predictor of late treatment failure in the more recent trial (P = .019). None of the other presenting features that were examined (eg, age, leukocyte count, and sex) had value as predictors of late failure. Thus, improved treatment altered the impact of specific prognostic factors and the distribution of sites of relapse, but it did not significantly affect the risk of delayed failure.

ObjectiveTo assess the methodological quality of pre-market clinical studies performed on medical devices (MDs), including in-vitro diagnostic (IVD) MDs, in Europe.DesignObservational cross-sectional study.SettingA large German ethics committee.MaterialsFrom the consecutive sample of study applications between March 2010 and December 2013, we selected MD study applications requiring approval by an ethics committee and the competent federal authority. These included pre-market studies on devices that had not yet received a CE (Conformité Européenne) mark or had previously been CE marked for a different indication. Also included were post-CE studies requiring federal authority approval because the study entailed additional invasive or otherwise burdensome components.Primary and secondary outcome measuresBesides the design of the studies, we assessed the planned sample size, study duration and other aspects.Results122 study applications were analysed: 98 (80%) concerned therapeutic rather than diagnostic devices and 84 (69%) were pre-market studies. The proportion of studies on class I, IIa, IIb and III devices was 10%, 15%, 28% and 39%, respectively. 10 studies (8%) investigated IVD MDs. A randomised controlled trial (RCT) was planned in 70 (57%) of the 122 applications; studies with non-randomised control groups (n=23; 19%) or without controls (n=29; 24%) were less common. In the sub-group of pre-market studies on therapeutic devices, the proportion of RCTs was 66% (43/65). The median sample size was 120 participants or samples (IQR 53–229). The median study duration was 24 (14–38) months. 87 studies (71%) considered at least one patient-relevant outcome. 12 (17%) and 37 (53%) of the 70 RCTs applied a fully or partially blinded design, respectively.ConclusionA large proportion of MD studies in Germany apply a randomised controlled design, thus contradicting the industry argument that RCTs on MDs are commonly infeasible.

Fecal samples from 76 of 83 apparently healthy small Indian mongooses (Urva auropunctata) were PCR positive with circovirus/cyclovirus pan-rep (replicase gene) primers. In this case, 30 samples yielded high quality partial rep sequences (~400 bp), of which 26 sequences shared maximum homology with cycloviruses from an arthropod, bats, humans or a sheep. Three sequences exhibited maximum identities with a bat circovirus, whilst a single sequence could not be assigned to either genus. Using inverse nested PCRs, the complete genomes of mongoose associated circoviruses (Mon-1, -29 and -66) and cycloviruses (Mon-20, -24, -32, -58, -60 and -62) were determined. Mon-1, -20, -24, -29, -32 and -66 shared <80% maximum genome-wide pairwise nucleotide sequence identities with circoviruses/cycloviruses from other animals/sources, and were assigned to novel circovirus, or cyclovirus species. Mon-58, -60 and -62 shared maximum pairwise identities of 79.90–80.20% with human and bat cycloviruses, which were borderline to the cut-off identity value for assigning novel cycloviral species. Despite high genetic diversity, the mongoose associated circoviruses/cycloviruses retained the various features that are conserved among members of the family Circoviridae, such as presence of the putative origin of replication (ori) in the 5′-intergenic region, conserved motifs in the putative replication-associated protein and an arginine rich region in the amino terminus of the putative capsid protein. Since only fecal samples were tested, and mongooses are polyphagous predators, we could not determine whether the mongoose associated circoviruses/cycloviruses were of dietary origin, or actually infected the host. To our knowledge, this is the first report on detection and complete genome analysis of circoviruses/cycloviruses in the small Indian mongoose, warranting further studies in other species of mongooses.

Three brief studies were conducted by the IBM Boca Raton Human Factors department to investigate user expectations and preferences regarding power switches. In the first study, 24 IBM employees were surveyed by showing them a power supply with a paddle switch in front. The results indicated that if the power switch was mounted vertically, 100% of the sample expected UP to be ON. When the switch was mounted horizontally on the front, 25% of the sample expected LEFT to be ON, and the other 75% expected RIGHT to be ON. Ninety IBM employees participated in the second study. The purpose of this study was to investigate the way people expect a rocker switch to work when it is located on the side of the machine. Overall, 46% of the sample expected the switch AWAY from the operator to be ON, and 54% expected the switch TOWARD the operator to be ON. In the third study, 49 IBM employees responded to a mailed questionnaire, and 24 participants from a temporary employment agency completed the same questionnaire. The results for the six items were: 1. For UP/DOWN switch: UP=ON: 97%, DOWN=ON: 03% 2. For LEFT/RIGHT switch: LEFT=ON:29%, RIGHT=ON:71% 3. For AWAY/TOWARD switch: AWAY=ON:52%, TOWARD=ON:48% 4. Style preference (IBM Employees), (Agency Personnel) UP/DOWN:94% UP/DOWN:58% LEFT/RIGHT:02% LEFT/RIGHT:29% AWAY/TOWARD:04% AWAY/TOWARD:13% 5. Location preference: FRONT:72%, SIDE:25%, BACK:03% 6. Side preference: LEFT:10%, RIGHT:90% Since it appears that virtually 100% of users have the same expectation regarding the operation of a vertical power switch, designers should avoid using other power switch orientations. This is not a critical design issue, but it is better to design machines the way that users expect them to work.

Tools for predicting growth of Staphylococcus aureus, Salmonella, and Escherichia coli O157:H7 (THERM; temperature history evaluation for raw meats) have been developed using ground pork and sausage. THERM tools have been tested with three types of pork sausage but not with other pork products or during sequential temperature abuse periods. We conducted inoculation studies (five strains each of S. aureus and/or Salmonella plus E. coli O157:H7) with simulated cooling of warm sausages, in-process warming of bratwurst, isothermal temperature abuse of pork frankfurter batter, and two sequential periods of 13, 15.6, or 21.1°C temperature abuse of breakfast sausage, natural (additive-free) chops, and enhanced (phosphate solution–injected) loins. In sequential temperature abuse studies, a temperature abuse period (≤24 h) occurred before and after either refrigeration (5°C for 24 h), or freezing (−20°C for 24 h) and thawing (24 h at 5°C). Pathogen growth predictions from THERM developed using ground pork and sausage were compared with experimental results of 0 to 3.0 log CFU of growth. Across all temperature abuse conditions, qualitative predictions (growth versus no growth) made using the pork tool (n = 133) and the sausage tool (n = 115) were accurate (51 and 50%, respectively), fail-safe (44 and 50%), or fail-dangerous (5 and 0%). Quantitative predictions from the two tools were accurate (29 and 22%, respectively), fail-safe (59 and 73%), or fail-dangerous (12 and 5%). Pathogen growth was greater during the second sequential temperature abuse period but not significantly so (P &gt; 0.05). Both THERM tools provide useful qualitative predictions of pathogen growth in pork products during isolated or sequential temperature abuse events.

The article contains the notes pro memoria about A. P. Kazhdan’s studies of manuscripts, his achievements and losses in this field. The first case is the episode of the describing by young A. Kazhdan the collection of Greek manuscripts in the former Lenin State Library, now – Russian State Library. The next point is connected with manuscript copy-book by N. Novosadsky, that contained texts of many literary works of Eustathius of Thessalonice, Michael Rhetor (“of Thessalonice”) and other Byzantine authors, copied in El Escorial. They were used by A. Kazhdan himself and by his students in their studies. The last episode con-cerns the case of prohibit for A. Kazhdan to visit Athos and research some manuscripts, even while he visited Grece with a group of colleagues. Those three cases contribute to our un-derstanding of not only the biography of A. P. Kazhdan, but also of the history of Byzantine studies in the USSR and the Russian historiography of the second half of the 20th century in general.

PURPOSE N-(phosphonacetyl)-L-aspartic acid (PALA) is a pyrimidine synthesis inhibitor that modulates fluorouracil (FU) cytotoxicity. Two previous studies of patients with colorectal carcinoma documented complete response (CR) and partial response (PR) rates of 40% and 43% using weekly low-dose PALA followed by a 24-hour FU infusion. We investigated whether comparable results could be obtained with biochemical modulation by low-dose PALA using bolus instead of infusional FU. PATIENTS AND METHODS Forty-five patients without prior chemotherapy who had advanced colorectal carcinoma were treated with PALA 250 mg/m2 followed 24 hours later by bolus FU at three dose levels, 600, 700, 800 mg/m2, repeated weekly for 6 weeks followed by a 2-week break. RESULTS The CR and PR rate was 15 of 43 patients or 35% (95% confidence interval [CI], 21% to 49%), with an overall median survival of 18 months. Grade 3 or 4 diarrhea was the major toxicity observed in 24% of patients receiving FU at 700 mg/m2 and in 43% of patients receiving 800 mg/m2. Hematologic toxicity was observed only with an FU dose of 800 mg/m2, and 29% (four of 14) of patients developed grade 4 leukopenia. We also noted the development of ascites in six patients, mild hyperbilirubinemia in 16 patients, and a decreased albumin level in 22 patients; these abnormalities occurred more frequently in responding patients. CONCLUSIONS The observed response rate, median survival, and toxicity in this study are similar to those obtained with PALA plus infusional FU and with other methods of FU modulation. Larger phase III studies are needed to compare bolus FU/PALA regimens with other PALA and non-PALA-containing combinations. Our future focus will be attenuate this regimen's toxicity while maintaining or improving its response rates and survival.

Purpose. Studies of the growth and survival of Oriental river prawn (Macrobrachium nipponense) larvae depending on water temperature and salinity during cultivation. Methodology. Experimental studies were carried out at the Aquatic Department of Aquatic Bioresources and Aquaculture of the Odesa State Ecological University in 2020-2021. Brood Oriental river prawns (Macrobrachium nipponense) were caught in the lower Dniester river and placed into a 0.8 m3 RAS. The larvae were stocked in separate aquariums with automatically maintained specified temperature regime. The first series of experiments in fresh water investigated the influence of water temperatures of 20–22, 22–24, 24–26, and 28–31°C on the growth of shrimp larvae (from the 1st stage to the Pl stage). Cultivation in water with a salinity of 5, 7, 12 ‰ was carried out at a temperature of 20–22, 22–24, 28–31 °C. Ten prawn larvae were measured daily under a binocular microscope (MBS-10) using an eyepiece-micrometer. The stage of larval development and the survival rate were determined. Water salinity was determined using an ATAGO-100 refractometer, and an Azha-101M thermal oximeter was used to determine the oxygen content in water. Statistical processing of data was carried out in Microsoft Excel. Findings. It was established that at a temperature of 24–26°C, the duration of the transition from one stage of larval development to another in Oriental river prawn (Macrobrachium nipponense) increased as the larvae grew and developed. It lasted 4–5 days in the first stages (1-3), then stages from 6 to 9 days in the later stages. High temperature stimulated the growth of larvae and accelerated their development. In fresh water at a temperature of 29–31°C, the length of postlarvae (Pl) reached 6.69±1.15 mm in 28 days of rearing. Cultivation at high temperature resulted in a significant variation in larval sizes (from 4.4 to 8.6 mm CV–25,27). At lower temperatures (25-27, 22-24 and 20-22°C), the average sizes of prawn postlarvae were smaller (5.83±0.78, 4.56±0.15, 4.43±0.15), and the survival rates increased (46, 49 and 54%, respectively). Survival of larvae was inversely dependent on temperature r = –0.89. It was minimal (32%) at a temperature of 29–31°C. The higher the growing temperature, the lower the output of postlarvae. Water salinity, like temperature, significantly affected the growth, survival and size uniformity of postlarvae. In water with a salinity of 5‰, postlarvae reached their maximum length (6.56±0.15 mm) at a temperature of 29-31 °C. At temperatures of 20-22 and 22-24 °C, the size of the postlarvae did not reliably differ among themselves. The maximum survival of postlarvae (52%) was noted at a temperature of 22-24°. Regardless of water temperature, salinity of 5‰ ensured high uniformity of larvae size (CV: 6.11–9.09). At a salinity of 7‰, the maximum length of postlarvae was reached at a temperature of 29-31oC, and the highest survival rate of prelarvae (34%) was noted at a temperature of 20-22oC. The size of the larvae and their survival at other growing temperature conditions did not differ significantly (Р<95). A salinity of 7‰ also ensured the uniformity of postlarvae sizes (CV: 6.12-8.97). At a salinity of 12‰, high water temperature stimulated the growth of larvae with relative uniformity of their linear sizes, but in all variants of the experiment the survival rate of postlarvae was very low (4–9%). Originality. Experimental data on the growth and survival of larvae of the Oriental river prawn (Macrobrachium nipponense) depending on temperature and salinity are presented for the first time. The influence of the salinity of the environment on the size uniformity of the larvae was established. Practical value. The obtained results can be used for the development and improvement of methods of artificial reproduction and cultivation of the Oriental river prawn (Macrobrachium nipponense) under controlled conditions in recirculation aquaculture systems (RAS).

The purpose of this study was to analyze the screening rates and examination results of the national dental screening program for infants and children since its initiation. Data for this study were obtained from the annual health screening statistical yearbook of the National Health Insurance Service. The investigation focused on the screening rate according to year, age, and region, as well as examination results from 2008 to 2021. The study revealed a general increase in screening rates over the years, with a simultaneous decrease observed as the age of the subjects increased. Regional variations in screening rates were observed, with the highest and lowest rates in Sejong and Jeonbuk, respectively. Analysis of examination results revealed an increasing proportion of subjects requiring treatment as they aged. From 2008 to 2013, less than 15% of subjects aged 18 - 24 and 18 - 29 months required treatment, whereas over 30% required treatment in the remaining age groups. Between 2014 and 2021, the proportion of subjects in the 18 - 29 month age group requiring treatment remained under 15%, but it exceeded 40% in the other age groups. In conclusion, active participation in national dental screening for infants and children is crucial to improving oral health outcomes.

There is a lack of guidance for developing progression criteria (PC) within feasibility studies. We describe a process for co-producing PC for an ongoing feasibility study. Patient contributors, clinicians and researchers participated in discussions facilitated using the modified Nominal Group Technique (NGT). Stage one involved individual discussion groups used to develop and rank PC for aspects of the trial key to feasibility. A second stage involving representatives from each of the individual groups then discussed and ranked these PC. The highest ranking PC became the criteria used. At each stage all members were provided with a brief education session to aid understanding and decision-making. Fifty members (15 (29%) patients, 13 (25%) researchers and 24 (46%) clinicians) were involved in eight initial groups, and eight (two (25%) patients, five (62%) clinicians, one (13%) researcher) in one final group. PC relating to eligibility, recruitment, intervention and outcome acceptability and loss to follow-up were co-produced. Groups highlighted numerous means of adapting intervention and trial procedures should ‘change’ criteria be met. Modified NGT enabled the equal inclusion of patients, clinician and researcher in the co-production of PC. The structure and processes provided a transparent mechanism for setting PC that could be replicated in other feasibility studies.

Cross-linked guar gum microparticles of curcumin were prepared for controlled release by emulsion gelation method using glutaraldehyde as cross-linking agent. Morphology and surface characteristics of the formulations were assessed by scanning electron microscopy. Particle size of the guar gum microparticles was determined by optical microscopy. The mean particle size ranged from 82 to 250 μ. The % drug loading was found to be in the range of 20 to 51% while the percentage encapsulation efficiency was ranging between 29 to 86%. FT-IR and DSC studies revealed the compatibility of the drug with the polymer. Formulation CGMP3 exhibited maximum % EE of 84%, In vitro drug-release studies were performed in simulated gastric fluid (without enzymes) for 2 h followed by simulated intestinal fluid (without enzymes) for 6 h and continued for 24 h. Formulation CGMP3 exhibited relatively more sustained release profile than the other formulations. All formulations of 1.5% guar gum (CGMP2, CGMP3 and CGMP4) have shown retarded release than 1.0 % guar gum formulations (CGMP6, CGMP7 and CGMP8). Optimal glutaraldehyde concentration was found to be 2%. The optimized formulation subjected to stability studies was found to be stable when observed for particle size and drug content.

4080 Background: SP1049C (a block co-polymer incorporating doxorubicin) has demonstrated broad in vitro activity and superior anti-tumour activity in 9/9 in vivo animal tumour models compared to doxorubicin. Methods: Chemotherapy- or radiotherapy-naïve patients with measurable, inoperable, recurrent or metastatic adenocarcinoma of the oesophagus; KP ≥60; normal cardiac LVEF; adequate swallowing and adequate renal, hepatic and bone marrow function were eligible. SP1049C 75mg/m2 IV 30-minute infusion was given q3w, for up to 6 cycles. Radiological response was assessed after cycles 2, 4 and 6. Upon disease progression (PD) patients were offered standard chemotherapy. QoL (by QLQ-C30 and QLQ-OES24 questionnaires), toxicity, disease-related symptoms and cardiac function were also prospectively assessed. Results: From February 2002 to December 2004, 21 patients (all male), median age 62 years (range 38–78) with stage 3 (n = 1) of stage IV (n = 20) disease were enrolled. Response rate (WHO criteria) in 19 patients eligible for efficacy analysis (radiologically re-assessed after ≥2 cycles of treatment) included: PR 9/19 (47%), SD (8/19) 42% and PD (2/19) 11% by investigator assessment (confirmed PR 41%, unconfirmed PR 12% and SD 29% by independent review, RECIST criteria). One responding patient underwent salvage resection of a pT2N0 (Stage 2A) tumour. All patients are evaluable for toxicity. Toxicity (Gd 1–2/3–4, by patient) included: neutropaenia 24%/62%, leucopaenia 19%/29%, anaemia 38%/5% and thrombocytopaenia 9.5%/0% (resulting in 9 (43%) patients being dose-reduced to 55 mg/m2 at cycle 2), nausea 81%/19%, vomiting 62%/24%, anorexia 52.4%/14%, lethargy 81%/14%, febrile neutropaenia -/29%, mucositis 48%/5%, and Gd 1–2 alopecia in 67%. Grade I cardiotoxicity (fall in LVEF by 10–19% from baseline, CTC v2.0) was seen in 4 (19%) patients. The median overall survival (all patients) is 10 months; four patients received 2nd-line chemotherapy. Conclusions: SP1049C appears to have activity in monotherapy in this patient group and combination studies with other active agents are warranted. [Table: see text]

Abstract AFM24 is a first-in-class, tetravalent, bispecific ICE® that binds to EGFR on tumor cells and CD16A on natural killer (NK) cells and macrophages, inducing antibody-mediated cytotoxicity and antibody-mediated phagocytosis, respectively. Preclinical in vitro and in vivo studies have demonstrated AFM24 can induce killing of EGFR+ solid tumor cell lines, independently of EGFR mutational status; toxicology testing in cynomolgus monkeys revealed a favorable safety profile. An ongoing phase 1/2a study (NCT04259450) is evaluating the safety, efficacy, immunogenicity, pharmacokinetic (PK) and pharmacodynamic responses of AFM24 in patients with locally advanced or metastatic, treatment refractory solid tumors that are known to express EGFR. AFM24 is administered intravenously Q1W until disease progression, intolerable toxicity, investigator’s discretion or patient withdrawal. As of 29 Oct 2021, 29 patients (median [range] age 58 [29-81] years; number of prior therapies 4 [2-8]), predominantly with colorectal- (CRC, 16/29; 10 KRAS mutant) and non-small cell lung cancer (NSCLC, 7/29; 6 EGFR mutant), were treated with AFM24 across six dose levels (14-480 mg flat). The median number of AFM24 doses administered was 8, range 1-29. The most frequently reported (≥20% of patients) AFM24-related treatment-emergent adverse events (TEAEs) were infusion-related reactions (IRR, 20/29), nausea (7/29) and headache (6/29). There were no on-study deaths; two patients had serious TEAEs (one Grade 3 IRR and one Grade 2 hypoxia) and five patients had transient and reversible Grade 3-4 TEAEs (two Grade 3 IRRs, one Grade 3 hypertension, three ≥Grade 3 lymphocytopenia) attributed to AFM24, respectively. There was one dose-limiting toxicity at 40 mg (Grade 3 IRR). Best objective response was stable disease in 8/24 response-evaluable patients; three patients had stable disease for ≥4 months (two CRC, one NSCLC). Dose-proportional PK between 320 and 480 mg indicated saturation of target-mediated elimination. CD16A receptor occupancy (CD16ARO) on circulating blood cells was correlated with exposure and seemed to level off at 480 mg. Estimated intra-tumoral AFM24 concentrations and CD16ARO were in the range associated with maximum tumor cell killing in vitro. TNF-α, IFN-γ and IL-10 increased over time; other cytokines including IL-6 showed only transient increases. AFM24 has a well-managed safety profile and shows pharmacodynamic activity at doses of 320-480 mg. In parallel to continued dose escalation, expansion in disease specific cohorts has been launched at 480 mg. Other studies are evaluating AFM24 in combination with atezolizumab, and in combination with autologous NK cells holding the potential to activate the innate immune response to fight EGFR+ cancer. Citation Format: Anthony El-Khoueiry, Juanita Lopez, Omar Saavedra, Mark Awad, Jacob Thomas, Crescens Tiu, Elena Garralda, Bettina Rehbein, Gabriele Hintzen, Kerstin Pietzko, Christa Raab, Erich Rajkovic, Paulien Ravenstijn, Michael Emig. A phase 1/2a first-in-human study of AFM24, a CD16A/epidermal growth factor (EGFR) bispecific Innate Cell Engager (ICE®), in patients with locally advanced or metastatic EGFR-expressing solid tumors: Preliminary findings from the dose-escalation phase [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT149.

e17525 Background: Outcomes of pediatric and adult cancer pts have improved more than outcomes of AYA pts. Reduced access of AYA pts to clinical trials may partially account for this. Methods: The 10 cancers of highest annual incidence for pts ages 15-29 were identified using the 2005-09 SEER data base and searched on ClinicalTrials.gov (2012/OCT/27) using restriction terms “recruiting”, “intervention studies”, “Canada-Ontario”, and “Adult (18-65)”. Among trials identified, variables compared were sponsor (industry; not industry), intent (curative; palliative; other), endpoints (survival; disease control-adverse event; other), previous therapy (none; other), age (max < 29; max>29 but <50; max>50), intervention (drug; RT+/-drug; other) and randomized design (yes; no). Comparisons used a 2-tailed Fisher’s exact test. Results: We identified 139 trials, including (incidence rank order in bracket): breast-41 (8), non Hodgkin’s lymphoma-36 (4), CNS-30 (6) and acute lymphoblastic leukemia (ALL)-21[10]. There were 45 trials available for the other 6 indications; some trials permitted multiple indications. Most common features were non-industry sponsorship (58%), palliative intent (65%), disease control-adverse event primary endpoint (82%), not restricted to 1st line therapy (76%), max age>50 (69%), drug-only intervention (78%) and non-randomized design (56%). Among all trials, those with an age restriction did not significantly differ from trials with an age maximum of >50. Industry sponsorship was associated with fewer non-drug-only trials (2% vs. 36%; p<0.0001), curative trials (12% vs. 41%; p=0.0002) and age-restricted trials (10% vs. 48%; p<0.0001). CNS and ALL trials were more likely to restrict age eligibility (60% vs. 13%; p<0.0001 for CNS; 52% vs. 18%; p<0.0001 for ALL) and have non-industry sponsorship (90% vs. 49%; p<0.0001 for CNS; 76% vs. 24%; p=0.09 for ALL). Conclusions: Availability of clinical trials for Ontario AYA pts is very heterogeneous and no correlation is seen between AYA cancer-type incidence and number of trials. While CNS cancers and ALL appear unique, access and characteristics of trials for other AYA pts appear to relate to determinants associated with older patients.

Pre- and postductal transcutaneous oxygen tension (tcPo2) was measured in 23 preterm infants with hyaline membrane disease to estimate the degree of right to left ductal shunting. The study was done during the first 24 hours of life and the data were recorded continuously. The studies were 11.9 ± 4.0-hours long, (mean ± SD) and the difference between the pre- and postductal tcPo2 (ΔTcPo2) was measured every 100 seconds. Of 9,872 determinations, the ΔtcPo2 was ≤15 mm Hg in 90.1%, 16 to 29 mm Hg in 9.3%, and ≥ 30 mm Hg in 0.6%. It was concluded that large differences between pre- and postductal oxygen tension are rare in infants with hyaline membrane disease. The results of this and other published data suggest that it is unlikely that measurement of Pao2 in the descending aorta or tcPo2 below the ductus places infants at an increased risk of having retinopathy of prematurity develop.

We retrospectively reviewed our experience with 24 patients in the treatment of advanced recurrent squamous cell carcinoma of the head and neck, using salvage surgery and intraoperative iodine 125 (125I) implantation. Surgical complications and survival results were compiled and compared with those of other studies. The long-term effect of 125I on the carotid artery was evaluated by ultrasound We had a major complication rate of 21 % and an overall complication rate of 50%. Our 2-year overall and determinate survivals were=29% and 50%, respectively. Within the survival group, carotid ultrasounds were obtained to evaluate the long-term effect of I All ultrasounds obtained at least 1 year from the time of treatment showed minimal or no change from the contralateral side We conclude that intraoperative 125I and salvage surgery are an acceptable treatment for recurrent squamous cell carcinoma with minimal complication and effect on the carotid artery.

The knowledge on health service use, systematic follow-up, and support for families bereaved by suicide remains scarce. This scoping review includes studies from 2010 to March 2022 that investigate the follow-up and support offered by health services, peer support services, and other resources available (e.g., internet-based resources) for families bereaved by suicide. We followed the scoping review framework provided by the Johanna Briggs Institute and performed a double-blinded screening process using Covidence. Data were extracted by four researchers and a thematic analysis was performed to summarize the results. The PRISMA Extension for Scoping reviews was used for reporting results. Of 2385 studies screened by title, 190 by abstract, and 93 by full-text reading, we included 63 original articles of which 24, 29 and 10 were quantitative, qualitative, or mixed-methods studies, respectively. The review shows that we have some knowledge about the need for, and experiences with, health services and support resources for immediate family members bereaved by suicide, but a lack of knowledge about their help-seeking behaviour, patient pathways, systematic follow-up, coordination between services, and long-term outcomes. We need more longitudinal observational studies of health service use and patient trajectories for people bereaved by suicide.

Abstract The entry of the generic drugs on the market was an impressive development of the pharmaceutical industry and due to their lower prices also a decrease in the cost price for the treatment of patients. The difference in price (sometimes even 50%) between generics and original and different response to therapy sometimes raised serious questions related to their therapeutic equivalence. The scientific community is increasingly interested in this aspect, with studies (in vitro and on patients) demonstrated statistically significant differences in terms of differences generic / original drug. In this context, the aim of our study was to assess the in vitro cytotoxic activity of oxaliplatin (original and generic drug) on DLD-1 cell lines, HT-29, and carboplatin cytotoxic activity (and the reference molecule from Santa Cruz Biotechnology) on cell line A2780. Cell viability was evaluated using the MTT assay. Regarding the cell line DLD-1, IC50 values of generics was lower than the original after exposure for 24 hours to oxaliplatin but after 48 hours of exposure were not statistically significant differences. HT-29 line has a higher resistance to chemotherapy compared with oxaliplatin, the IC 50 values after 48 hours of exposure are higher than those for the line DLD-1. IC50 values are confirmed by morphological analysis of cells. Regarding carboplatin were not recorded statistically significant differences between the two generic drugs tested. Although other studies reported differences between generic and branded drugs in terms of hypersensibility reactions, adverse effects and efficacity, we cannot extrapolate our findings to the patients. Further studies on patients are neeeded for a better evaluation of the efficacity of generic vs. original drugs.

So far, no versatile set of reference genes for normalizing real-time polymerase chain reaction data has been identified. Numerous studies focusing the selection of reference genes for specific purposes frequently fail to elaborate a suitable selection strategy. In a number of such studies, the stage of selecting reference genes is ignored due to either its high cost or other reasons. As a result, the normalization of data is carried out using genes, which have previously shown their effectiveness under other, sometimes completely different, experimental conditions. In this work, we aim to study variations in the level of mRNA expression of several genes, some of which are commonly used to normalize RT-PCR data. As special conditions, modeling of rat liver fibrosis with thioacetamide was used.In our experiment, when considering the process of fibrogenesis as a whole, the optimal reference genes were found to be hes1 and sdha. However, when focusing on specific stages of fibrosis, a pair of genes should be selected depending on the stability indicators. At the initial fibrogenesis stages, sdha and hprt can be used. The hes1 gene is suitable as a reference gene, when the average Cq value of the target genes is approximately 29 cycles (as in hes1). Hes1 should be used with care when working in the Cq ranges of target genes of 26–29 and above 30, since the error is likely to increase. Following the same principle, the optimum Cq value for the sdha gene was observed to be 27, although the Cq range of 24–27 is also acceptable. At the same time, when working in the Cq range of above 28, the use of sdha may be associated with an increase in calculation errors.

Among numerous other immune-mediated diseases, glomerulonephritis has also been suspected to be an extrahepatic manifestation of HEV infection. In this prospective study, we tested 108 patients with glomerulonephritis and 108 age- and sex-matched healthy controls at the University Hospital Hamburg Eppendorf, Hamburg, Germany, for anti-HEV IgG (Wantai test) as a marker for previous HEV exposure. A total of 24 patients (22%) tested positive for anti-HEV IgG. Males tended to be more frequently anti-HEV IgG positive (29%) in comparison to females (16%). However, this does not reach statistical significance (p = 0.07). Anti-HEV IgG positive patients were older in comparison to negative patients (mean 53 vs. 45 years, p = 0.05). The kidney function seems to be slightly decreased in anti-HEV IgG positive patients in comparison to and anti-HEV IgG negative patients basing on creatinine (p = 0.04) and glomerular filtration rate (GFR) (p = 0.05). Slightly higher values of bilirubin could be found in IgG positive patients (p = 0.04). Anti-HEV-IgG seropositivity rate (22%) in glomerulonephritis patients, did not differ significantly in comparison to an age- and sex-matched control cohort of healthy blood donors (31/108 positive, 29%). A total of 2/2 patients with membranoproliferative glomerulonephritis (MPGN) tested anti-HEV IgG positive (p = 0.002 in comparison to glomerulonephritis patients with other subtypes). In conclusion, our findings indicate that previous HEV exposure in a region where GT3 is endemic is not associated with glomerulonephritis in general. However, the subgroup of MPGN patients should be investigated in future studies. Furthermore, future studies are needed to investigate whether the observed association between anti-HEV IgG positivity and reduced GFR in glomerulonephritis patients is HEV associated or is an age-related effect.