Literatura académica sobre el tema "Mil Luna[s] Park[s]"

PRODUTIVIDADE E QUALIDADE TECNOLÓGICA DA CANA-DE-AÇÚCAR SUBMETIDA A DIFERENTES LÂMINAS DE IRRIGAÇÃO E DOSES DE NITROGÊNIO ANDRÉA RAQUEL FERNANDES CARLOS DA COSTA1; MÁRIO MONTEIRO ROLIM2; DJALMA EUSÉBIO SIMÕES NETO3; MANASSÉS MESQUITA DA SILVA4; GERÔNIMO FERREIRA DA SILVA5 E ELVIRA MARIA RÉGIS PEDROSA6 1 Departamento de Engenharia Agrícola, UFRPE, Rua Dom Manuel de Medeiros, s/n, Dois Irmãos, CEP: 52171-900, Recife-PE, Brasil. E-mail: andrearaquel19@hotmail.com 2 Departamento de Engenharia Agrícola, UFRPE, Rua Dom Manuel de Medeiros, s/n, Dois Irmãos, CEP: 52171-900, Recife-PE, Brasil. E-mail: mariorolim10@uol.com.br 3 Estação Experimental de Cana-de-Açúcar, UFRPE, Rua Ângela Cristina C. P. de Luna, s/n, Novo, CEP: 55914-030, Carpina-PE, Brasil. E-mail: djalmasneto@hotmail.com 4 Departamento de Engenharia Agrícola, UFRPE, Rua Dom Manuel de Medeiros, s/n, Dois Irmãos, CEP: 52171-900, Recife-PE, Brasil. E-mail: manasses.ufrpe@gmail.com 5 Departamento de Engenharia Agrícola, UFRPE, Rua Dom Manuel de Medeiros, s/n, Dois Irmãos, CEP: 52171-900, Recife-PE, Brasil. E-mail: agrogefe@yahoo.com.br 6 Departamento de Engenharia Agrícola, UFRPE, Rua Dom Manuel de Medeiros, s/n, Dois Irmãos, CEP: 52171-900, Recife-PE, Brasil. E-mail: elvira.pedrosa@ufrpe.br 1 RESUMO Dentre os fatores de produção, a irrigação e a adubação nitrogenada destacam-se como fundamentais para o aumento de produtividade e qualidade da cana-de-açúcar, assim, objetivou-se avaliar a produtividade e a qualidade tecnológica da cana-de-açúcar (cana-planta) submetida a diferentes lâminas de irrigação e doses de nitrogênio. A pesquisa foi executada em Carpina-PE, na Estação Experimental de Cana-de-Açúcar pertencente a Universidade Federal Rural de Pernambuco. Os tratamentos consistiram, em quatro lâminas de irrigação (1498; 1614; 1739 e 1854 mm) e cinco doses de nitrogênio (0; 20; 40; 80 e 120 kg ha-1) arranjados em faixas e delineados em blocos ao acaso com quatro repetições. As diferentes lâminas de irrigação, associadas às doses crescentes de nitrogênio proporcionaram aumento no rendimento de colmos e açúcar. Os teores de sólidos solúveis e de fibra da cana-de-açúcar diminuíram com o aumento das lâminas de irrigação, independentemente das doses de nitrogênio aplicadas. Os maiores teores de açúcar teórico recuperável e de sacarose no colmo da cana-de-açúcar, foram obtidos com a aplicação da lâmina de 1498 mm associada com a dose de 20 kg ha-1 de nitrogênio. Palavras-chave: Saccharum spp., rendimento, atributos tecnológicos, irrigação, adubação nitrogenada. COSTA, A. R. F. C. da; ROLIM, M. M.; SIMÕES NETO, D. E.; SILVA, M. M. da; SILVA, G. F. da; PEDROSA, E. M. R. PRODUCTIVITY AND TECHNOLOGICAL QUALITY SUGARCANE SUBMITTED TO DIFFERENT WATER DEPTHS AND NITROGEN DOSES 2 ABSTRACT Among factors that affect production, irrigation and nitrogen fertilization stand out as fundamental to increase productivity and quality of sugarcane, thus, the objective of this study was to evaluate productivity and technological quality of sugarcane (cane-plant) submitted to different water depths and nitrogen doses. The research was carried out in Carpina-PE, at the Experimental Station of Sugarcane belonging to the Federal Rural University of Pernambuco. Treatments consisted of four irrigation depths (1498; 1614; 1739 and 1854 mm) and five nitrogen doses (0; 20; 40; 80 and 120 kg ha-1), arranged in strips and outlined in randomized blocks with four replications. The different irrigation depths associated with increasing doses of nitrogen provided an increase in yield of stalks and sugar. The soluble solids content and sugarcane fiber decreased with increasing water depths, regardless of the applied nitrogen doses. The highest levels of recoverable theoretical sugar and sucrose content in the cane sugarcane were obtained with the application of the 1498 mm irrigation depths associated with the dose of 20 kg ha-1 of nitrogen. Keywords: Saccharum spp., yield, technological attributes, irrigation, nitrogen fertilization.

O estudo teve como objetivo avaliar a qualidade microbiológica e físico-química e o potencial antioxidante e antimicrobiano de méis comerciais do Sertão nordestino do Brasil. A qualidade de trinta amostras de méis comerciais foi investigada por meio de análises microbiológicas e físico-químicas (cor, umidade, sólidos solúveis totais, acidez, índice de formaldeído, cinza, hidroximetilfurfural, diástase, Teste de Lund e condutividade elétrica). As amostras que atenderam à legislação nacional e internacional foram analisadas quanto a açúcares redutores, prolina, proteínas totais, atividade antioxidante e antibacteriana. Em todas as amostras de mel estudadas não foram detectados coliformes totais, E. coli, S. aureus, leveduras ou esporos de Clostridium. Contudo, apenas 26,67% das amostras estavam dentro dos parâmetros determinados pelos comitês normativos quanto à qualidade físico-química. Tanto a atividade antioxidante quanto a antimicrobiana foram determinadas e apresentaram os maiores teores para as amostras P9 e F9. A partir dos resultados é possível sugerir que as amostras de mel coletadas no Sertão nordestino apresentam qualidade microbiológica, potencial antimicrobiano e funcional. No entanto, é necessário que o produto atenda aos padrões físico-químicos para que seja utilizado com segurança na promoção da saúde humana. Estes dados direcionam políticas públicas à maximização da assistência técnica e transferência de tecnologia aos produtores do Sertão nordestino do Brasil, no intuito de melhorar a qualidade do mel para que atendam os padrões estabelecidos pelos comitês normativos. Palavras-chave: Apis mellifera. Produtos Apícolas. DPPH. Mel Multifloral. Polifenóis. Prolina. Salmonella typhi. Abstract The study aimed to evaluate the microbiological and physicochemical quality and the antioxidant and antimicrobial potential of commercial honeys from the northeastern Sertão of Brazil. The quality of thirty commercial honey samples was investigated through microbiological and physicochemical analyzes (color, moisture, total soluble solids, acidity, formaldehyde index, ash, hydroxymethylfurfural, diastasis, Lund test and electrical conductivity). Samples that complied with national and international legislation were analyzed for reducing sugars, proline, total proteins, antioxidant and antibacterial activity. In all honey samples studied, no total coliforms, E. coli, S. aureus, yeasts or Clostridium spores were detected. However, only 26.67% of the samples were within the parameters determined by the normative committees regarding the physical-chemical quality. Both antioxidant and antimicrobial activity were determined and showed the highest levels for samples P9 and F9. From the results it is possible to suggest that the honey samples collected in the north-eastern Sertão have microbiological quality, antimicrobial and functional potential. However, it is necessary that the product meets the physicochemical standards so that it can be used safely in the promotion of human health. These data direct public policies to maximize technical assistance and technology transfer to producers in the northeastern Sertão of Brazil, in order to improve the quality of honey so that they meet the standards established by the normative committees. Keywords: Apis mellifera. Bee Products. DPPH. Multifloral Honey. Polyphenols. Proline. Salmonella typhi.

Background: Cigarette smokers have a lower level of pulmonary function and physical fitness than non-smokers. Very little information is available for the short-term effects of smoking to lungs of asymptomatic smokers. Aims and Objectives: The main focus of this study is to evaluate short duration toxic consequences of smoking to the lungs of asymptomatic smokers through spirometry and 6 min walk test (6MWT). Materials and Methods: The present study is an observational cross-sectional study conducted in a tertiary care hospital which includes 160 individuals, 80 smokers and 80 non-smokers. The spirometric variables and 6MWT were performed to quantify smoking exposure. The whole statistics was analyzed using SPSS 21 and the mean between two groups was compared after applying standard Chi-square test. The means across more than 2 groups were compared after applying the standard analysis of variance (ANOVA) test. Results: Most of lung function parameter such as forced expiratory volume in 1 s (FEV1), FEV1%, FEV1/forced vital capacity % (FVC%), maximum mid-expiratory flow 25–75%, peak expiratory flow rate (PEFR), PEFR%, and maximum voluntary ventilation % is decreased significantly in asymptomatic smokers than non-smokers except FVC and FVC%. The 6MWT distance is also reduced gradually and significantly in asymptomatic smokers from 1–5 pack-years to 15–20 pack-years. Conclusion: Lung function parameters and 6MWT decreased significantly in asymptomatic smoker with increased quantum of pack-years. Therefore, early screening of high-risk smokers would lead to reduction of the clinical disease.

PRODUÇÃO DE MARACUJAZEIRO AMARELO NO SOLO COM CALCÁRIO E POTÁSSIO SOB IRRIGAÇÃO COM ÁGUA SALINA LOURIVAL FERREIRA CAVALCANTE1; CLODOALDO JÚNIOR OLIVEIRA SANTOS1; JOSÉ SIMPLÍCIO DE HOLANDA2; ANTONIO JOÃO DE LIMA NETO3; ANTÔNIO GUSTAVO DE LUNA SOUTO4 E TONY ANDRESON GUEDES DANTAS5 1 Universidade Federal da Paraíba, Departamento de Solos e Engenharia Rural, Rodovia BR 079 - Km 12, 58.397-000, Areia, PB, Brasil. E-mail: lofeca@cca.ufpb.br; agrosantos@bol.com.br 2 Empresa de Pesquisa Agropecuária do Rio Grande do Norte, Av. Eliza Branco Pereira dos Santos, s/nº, Parque das Nações, 59.158-160, Parnamirim, RN, Brasil. E-mail: simplicioemparn@rn.gov.br 3 Universidade Federal do Ceará, Departamento de Fitotecnia, Campus do Pici, Av. Mister Hull, 2977, Bloco 805, 60.356-001, Fortaleza, CE, Brasil. E-mail: limanetoagro@hotmail.com 4 Universidade Federal da Paraíba, Departamento de Fitotecnia e Ciências Ambientais, Rodovia BR 079 - Km 12, 58.397-000, Areia, PB, Brasil. E-mail: gusluso@hotmail.com 5 Instituto Federal de Educação, Ciência e Tecnologia do Ceará, Rodovia CE-187, s/n, Aeroporto, 62.320-000, Tianguá, CE, Brasil. E-mail: tony.dantas@ifce.edu.br 1 RESUMO O experimento foi conduzido no município de Coronel Ezequiel, Rio Grande do Norte, para avaliar os efeitos do calcário calcítico e doses de K2O, na forma de cloreto de potássio, nos componentes de produção do maracujazeiro amarelo e no aumento da salinidade do solo provocado pela irrigação com água salina de 3,6 dS m-1 durante o período da aridez e na lixiviação dos sais do ambiente radicular das plantas promovida pelas águas do período chuvoso. Os tratamentos foram dispostos em delineamento em blocos casualizados usando arranjo fatorial 3 × 2, referente as doses de calcário de 1,4; 2,5 e 3,6 t ha-1, 80 e 160 kg ha-1 de K2O na forma de cloreto de potássio. Pelos resultados, a irrigação com água salina (3,6 dS m-1), em comparação com dados da literatura de plantas irrigadas com água de boa qualidade, não comprometeu a capacidade produtiva do maracujazeiro amarelo. Dentre os tratamentos, a combinação de 80 kg ha-1 de K2O com 3,6 t ha-1 de calcário calcítico proporcionou os maiores valores de massa média dos frutos, produção por planta e produtividade da cultura. Apesar da alta salinidade da água de irrigação elevar o caráter salino do solo no ambiente radicular das plantas durante o período da estiagem, as águas do período chuvoso e as condições físicas do solo proporcionam a lixiviação dos sais e possibilitam o uso de água com restrições salinas na agricultura. Palavras-chave: Passiflora edulis, calagem, lixiviação de sais CAVALCANTE, L. F.; SANTOS, C. J. O.; HOLANDA, J. S.; LIMA NETO, A. J.; SOUTO, A. G. L.; DANTAS, T. A. G. YELLOW PASSION FRUIT PLANTS PRODUCTION ON SOIL WITH LIME AND POTASSIUM UNDER IRRIGATION WITH SALINE WATER 2 ABSTRACT The experiment was carried out in Coronel Ezequiel county, Rio Grande do Norte, Brazil, in order to evaluate the effects of limestone and chloride potassium in production components of yellow passion fruit plants and soil salinity, caused by irrigation with saline water of 3.6 dS m-1 during the dry season, and salt leaching of the soil promoted by waters of the rainy season. Treatments were arranged in randomized blocks using factorial design of 3 × 2, referring to three levels of limestone, 1.4, 2.5 and 3.6 t ha-1 and two potassium levels, 80 and 160 kg ha-1 in potassium chloride form. According to present results, irrigation with saline water (3.6 dS m-1), in comparison with data from the literature about plants irrigated with non-saline water, did no compromise the productive capacity of yellow passion fruit. Among the treatments, the combination of 80 kg ha-1 of K2O with 3.6 t ha-1 of limestone provided the fruits production with more mean mass, yield per plant and crop yield. Although the high salinity of the irrigation water increases the soil saline character on root environment of the plants during the dry season, the rainy season waters and the soil physical conditions provide the salt leaching and allow the use of water with saline restrictions in agriculture. Keywords: Passiflora edulis, liming, salt lixiviation

Botryotinia fuckeliana de Bary (anamorph Botrytis cinerea Pers.) is an ubiquitous plant pathogen causing gray mold disease on more than 200 crops grown in the field or in greenhouses. Eucalyptus seedlings originating from three different greenhouses showing stem lesions were submitted to the Gulf Coast Research and Education Center Disease Clinic in June 2012. Ten single spore isolates of B. cinerea were obtained and tested for sensitivity using spore germination and germ tube elongation assays described previously (4). Fungicides tested were pyraclostrobin at 100 μg/ml (Cabrio, BASF, Research Triangle Park, NC), thiophanate-methyl at 100 μg/ml (Topsin-M, UPI, King of Prussia, PA), fenhexamid at 1 and 50 μg/ml (Elevate, Arysta Life Sciences, Cary, NC), fludioxonil at 0.1 and 10 μg/ml (Medallion, Syngenta Crop Protection, Research Triangle Park, NC), and iprodione at 5 and 50 μg/ml (Rovral, Bayer CropScience, Greensboro, NC) on 1% malt extract agar (MEA, 10 g malt extract and 15 g agar), and to cyprodinil at 1 and 25 μg/ml (Vanguard, Syngenta Crop Protection) on 0.5% sucrose agar (4). Sensitivity to the succinate dehydrogenase inhibitors (SDHIs) boscalid at 5 μg/ml (Endura, BASF), penthiopyrad at 1 and 3 μg/ml (Fontelis, DuPont Crop Protection, Willington, DE), and fluopyram at 3 μg/ml (Luna Privilege, Bayer CropScience) was evaluated on yeast bacto acetate agar (YBA) (3). The discriminatory dose for boscalid was adapted from (2) whereas those used for penthiopyrad and fluopyram were developed in this study. Isolates were grown on malt yeast extract agar for 7 to 10 days and spore suspensions were prepared in sterile distilled water and diluted to 106 conidia/ml. Respective media in 9-cm petri dishes were seeded with 7-μl droplets from each isolate allowing testing for all isolates on one plate. Two plates were used for each fungicide and sensitivity tests were repeated twice. Germination and germ tube growth were assessed microscopically after 16 to 24 h incubation at 22°C. The frequency of isolates resistant to two, three, and four fungicides was 90, 60, and 10%, respectively. Nine isolates (90%) were resistant to thiophanate-methyl and pyraclostrobin, simultaneously, whereas six (60%) and two isolates (20%) were resistant to boscalid and fenhexamid, respectively. All boscalid-resistant isolates were also resistant to pyraclostrobin and thiophanate-methyl, but one fenhexamid-resistant isolate was sensitive to the other three fungicides. Eight isolates that germinated at 5 μg/ml iprodione but not at 50 μg/ml were considered sensitive. All isolates were sensitive to the SDHIs penthiopyrad and fluopyram as well as to cyprodinil and fludioxonil. To our knowledge, this is the first report of resistance to pyraclostrobin, thiophanate-methyl, fenhexamid, and boscalid in B. cinerea from eucalyptus seedlings in Florida. The absence of resistance to fludioxonil and iprodione is likely because these fungicides are not registered in nurseries as well as fluopyram and penthiopyrad which were developed only recently. Management practices should be developed to limit the selection and spread of additional resistant populations in eucalyptus nurseries as has occurred in Florida strawberries where multi-fungicide resistance is widespread (1). References: (1) A. Amiri et al. Plant Dis. 97:393, 2013. (2) M. Leroch et al. Appl. Environ. Microbiol. 79:159, 2013. (3) G. Stammler and J. Speakman. J. Phytopathol. 154:508, 2006. (4) R. W. S. Weber and M. Hahn. J. Plant Dis. Prot. 118:17, 2011.

Arsenic and Protein Expression: It might help to know the mechanism of As toxicity is described Introduction One of the largest public health problems at present is the drinking of water containing levels of Inorg-As that are known to be carcinogenic. The chronic ingestion of Inorg-As can results in skin cancer, urinary bladder cancer, lungs cancer, kidneys cancer, liver cancer, and cancer of other human organs 1-6. The molecular mechanisms of the carcinogenicity and toxicity of inorganic arsenic are not well understood 7–9. Many mechanisms of arsenic toxicity and carcinogenicity have been suggested 1, 7, 10 including chromosome abnormalities 11, oxidative stress 12, 13, altered growth factors 14, cell proliferation 15, altered DNA repair 16, altered DNA methylation patterns 17, inhibition of several key enzymes 18, gene amplification 19 etc. Some of these mechanisms result in alterations in protein expression. Proteomics is a powerful tool developed to enhance the study of complex biological system 20. This technique has been extensively employed to investigate the proteome response of cells to drugs and other diseases 21, 22. A proteome analysis of the Na-As (III) response in cultured lung cells found in vitro oxidative stress-induced apoptosis 23. In one of the study, hamsters were exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days and several protein spots were over expressed and several were under expressed in the livers and urinary bladders of hamsters (Fig.) 24, 25. Hamsters were exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days. The control hamsters were given tap water. The spot pairs of (A) equally expressed, (B) overexpressed, and (C) under expressed proteins in the liver tissues were shown. The amount of the protein is proportional to the volume of the protein peak. Transgelin was down-regulated, and GST-pi was up-regulated in the urinary bladder tissues of hamsters. In the liver tissues ornithine aminotransferase (OAT) was up-regulated, and senescence marker protein 30 (SMP 30), and fatty acid binding protein (FABP) were down-regulated. Down-regulation of transgelin has been noted in the urinary bladders of rats having bladder outlet obstruction 26. Ras-dependent and Ras-independent mechanisms can cause the down regulation of transgelin in human breast and colon carcinoma cell lines and patient-derived tumor samples 27. The loss of transgelin expression has been found in prostate cancer cells 28 and in human colonic neoplasms 29. It has been suggested that the loss of transgelin expression may be an important early event in tumor progression and a diagnostic marker for cancer development 26-29. Figure. Three-dimentional simulation of over-and under expressed protein spots in the livers of hamsters using Decyder software. Over-expression of GST-pi has been found in colon cancer tissues 30. Strong expression of GST-pi also has been found in gastric cancer 31, malignant melanoma 32, lung cancer 33, breast cancer 34 and a range of other human tumors 35. GST-pi has been up-regulated in transitional cell carcinoma of human urinary bladder 36. OAT has a role in regulating mitotic cell division and it is required for proper spindle assembly in human cancer cell 37. Ornithine amino transferase knockdown in human cervical carcinoma and osteosarcoma cells by RNA interference blocks cell division and causes cell death 37. It has been suggested that ornithine amino transferase has a role in regulating mitotic cell division and it is required for proper spindle assembly in human cancer cells 37. SMP 30 expressed mostly in the liver. By stimulating membrane calcium-pump activity it protects cells against various injuries 38. High levels of saturated, branched chain fatty acids are deleterious to cells and resulting in lipid accumulation and cytotoxicity. FABP expression has protected the cells against branched chain saturated fatty acid 39. Proteomics would be a powerful tool to know the unknown cellular mechanisms of arsenic toxicity in humans. References. NRC (National Research Council). (2001). Arsenic in Drinking Water. Update to the 1999 Arsenic in Drinking Water Report. National Academy Press, Washington, DC. Chen, C. J., Chen, C. , Wu, M. M., Kuo, T. L. (1992). Cancer potential in liver, lung, bladder, and kidney due to ingested inorganic arsenic in drinking water. Br. J. Cancer 66, 888-892. Hopenhayn-Rich, C., M.L. Biggs, A. Fuchs, et al. 1996. Bladder cancer mortality with arsenic in drinking water in Argentina. Epidemiology 7: 117–124. International Agency for Research on Cancer. (1987). In IARC Monograph on the Evaluation of Carcinogenicity Risk to Humans. 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The model of Late Pleistocene-Holocene sequence stratigraphy of the subaqueous Red River delta and the adjacent shelf is proposed by interpretation of high-resolution seismic documents and comparison with previous research results on Holocene sedimentary evolution on the delta plain. Four units (U1, U2, U3, and U4) and four sequence stratigraphic surfaces (SB1, TS, TRS and MFS) were determined. The formation of these units and surfaces is related to the global sea-level change in Late Pleistocene-Holocene. SB1, defined as the sequence boundary, was generated by subaerial processes during the Late Pleistocene regression and could be remolded partially or significantly by transgressive ravinement processes subsequently. The basal unit U1 (fluvial formations) within incised valleys is arranged into the lowstand systems tract (LST) formed in the early slow sea-level rise ~19-14.5 cal.kyr BP, the U2 unit is arranged into the early transgressive systems tract (E-TST) deposited mainly within incised-valleys under the tide-influenced river to estuarine conditions in the rapid sea-level rise ~14.5-9 cal.kyr BP, the U3 unit is arranged into the late transgressive systems tract (L-TST) deposited widely on the continental shelf in the fully marine condition during the late sea-level rise ~9-7 cal.kyr BP, and the U4 unit represents for the highstand systems tract (HST) with clinoform structure surrounding the modern delta coast, extending to the water depth of 25-30 m, developed by sediments from the Red River system in ~3-0 cal.kyr BP.ReferencesBadley M.E., 1985. Practical Seismic Interpretation. International Human Resources Development Corporation, Boston, 266p.Bergh G.D. V.D., Van Weering T.C.E., Boels J.F., Duc D.M, Nhuan M.T, 2007. Acoustical facies analysis at the Ba Lat delta front (Red River delta, North Vietnam. Journal of Asian Earth Science, 29, 532-544.Boyd R., Dalrymple R., Zaitlin B.A., 1992. Classification of Elastic Coastal Depositional Environments. Sedimentary Geology, 80, 139-150.Catuneanu O., 2002. Sequence stratigraphy of clastic systems: concepts, merits, and pitfalls. Journal of African Earth Sciences, 35, 1-43.Catuneanu O., 2006. Principles of Sequence Stratigraphy. Elsevier, Amsterdam, 375p.Catuneanu O., Abreu V., Bhattacharya J.P., Blum M.D., Dalrymple R.W., Eriksson P.G., Fielding C.R., Fisher W.L., Galloway W.E., Gibling M.R., Giles K.A., Holbrook J.M., Jordan R., Kendall C.G. St. C., Macurda B., Martinsen O.J., Miall A.D., Neal J.E., Nummedal D., Pomar L., Posamentier H.W., Pratt B.R., Sarg J.F., Shanley K.W., Steel R. J., Strasser A., Tucker M.E., Winker C., 2009. Towards the standardization of sequence stratigraphy. Earth-Science Reviews, 92, 1-33.Catuneanu O., Galloway W.E., Kendall C.G. St C., Miall A.D., Posamentier H.W., Strasser A. and Tucker M.. E., 2011. Sequence Stratigraphy: Methodology and Nomenclature. Newsletters on Stratigraphy, 44(3), 173-245.Coleman J.M and Wright L.D., 1975. Modern river deltas: variability of processes and sand bodies. In: Broussard M.L (Ed), Deltas: Models for exploration. Houston Geological Society, Houston, 99-149.Doan Dinh Lam, 2003. History of Holocene sedimentary evolution of the Red River delta. PhD thesis in Vietnam, 129p (in Vietnamese).Duc D.M., Nhuan M.T, Ngoi C.V., Nghi T., Tien D.M., Weering J.C.E., Bergh G.D., 2007. Sediment distribution and transport at the nearshore zone of the Red River delta, Northern Vietnam. Journal of Asian Earth Sciences, 29, 558-565.Dung B.V., Stattegger K., Unverricht D., Phach P.V., Nguyen T.T., 2013. Late Pleistocene-Holocene seismic stratigraphy of the Southeast Vietnam Shelf. Global and Planetary Change, 110, 156-169.Embry A.F and Johannessen E.P., 1992. T-R sequence stratigraphy, facies analysis and reservoir distribution in the uppermost Triassic-Lower Jurassic succession, western Sverdrup Basin, Arctic Canada. In: Vorren T.O., Bergsager E., Dahl-Stamnes O.A., Holter E., Johansen B., Lie E., Lund T.B. (Eds.), Arctic Geology and Petroleum Potential. Special Publication. Norwegian Petroleum Society (NPF), 2, 121-146.Funabiki A., Haruyama S., Quy N.V., Hai P.V., Thai D.H., 2007. Holocene delta plain development in the Song Hong (Red River) delta, Vietnam. Journal of Asian Earth Sciences, 30, 518-529.General Department of Land Administration., 1996. Vietnam National Atlas. General Department of Land Administration, Hanoi, 163p.Hanebuth T.J.J. and Stattegger K., 2004. Depositional sequences on a late Pleistocene-Holocene tropical siliciclastic shelf (Sunda shelf, Southeast Asia). Journal of Asian Earth Sciences, 23, 113-126.Hanebuth T.J.J., Voris H.K.., Yokoyama Y., Saito Y., Okuno J., 2011. Formation and fate of sedimentary depocenteres on Southeast Asia’s Sunda Shelf over the past sea-level cycle and biogeographic implications. Eath-Science Reviews, 104, 92-110.Hanebuth T., Stattegger K and Grootes P. M., 2000. Rapid flooding of the Sunda Shelf: a late-glacial sea-level record. Science, 288, 1033-1035.Helland-Hansen W and Gjelberg, J.G., 1994. Conceptual basis and variability in sequence stratigraphy: a different perspective. Sedimentary Geology, 92, 31-52.Hori K., Tanabe S., Saito Y., Haruyama S., Nguyen V., Kitamura., 2004. Delta initiation and Holocene sea-level change: example from the Song Hong (Red River) delta, Vietnam. Sedimentary Geology, 164, 237-249.Hunt D. and Tucker M.E., 1992. Stranded parasequences and the forced regressive wedge systems tract: deposition during base-level fall. Sedimentology Geology, 81, 1-9.Hunt D. and Tucker M.E., 1995. Stranded parasequences and the forced regressive wedge systems tract: deposition during base-level fall-reply. Sedimentary Geology, 95, 147-160.Lam D.D. and Boyd W.E., 2000. Holocene coastal stratigraphy and model for the sedimentary development of the Hai Phong area in the Red River delta, north Vietnam. Journal of Geology (Series B), 15-16, 18-28.Lieu N.T.H., 2006. Holocene evolution of the Central Red River Delta, Northern Vietnam. PhD thesis of lithological and mineralogical in Germany, 130p.Luu T.N.M., Garnier J., Billen G., Orange D., Némery J., Le T.P.Q., Tran H.T., Le L.A., 2010. Hydrological regime and water budget of the Red River Delta (Northern Vietnam). Journal of Asian Earth Sciences, 37, 219-228.Mather S.J., Davies J., Mc Donal A., Zalasiewicz J.A., and Marsh S., 1996. The Red River Delta of Vietnam. British Geological Survey Technical Report WC/96/02, 41p.Mathers S.J. and Zalasiewicz J.A.,1999. Holocene sedimentary architecture of the Red River delta, Vietnam. Journal of Coastal Research, 15, 314-325.Milliman J.D. and Mead R.H., 1983. Worldwide delivery of river sediment to the oceans. Journal of Geology, 91, 1-21.Milliman J.D and Syvitski J.P.M., 1992. Geomorphic/tectonic control of sediment discharge to the Ocean: the importance of small mountainous rivers. Journal of Geology, 100, 525-544.Mitchum Jr. R.M., Vail P.R., 1977. Seismic stratigraphy and global changes of sea-level. Part 7: stratigraphic interpretation of seismic reflection patterns in depositional sequences. In: Payton C.E. (Ed.), Seismic Stratigraphy-Applications to Hydrocarbon Exploration, A.A.P.G. Memoir, 26, 135-144.Nguyen T.T., 2017. Late Pleistocene-Holocene sedimentary evolution of the South East Vietnam Shelf, PhD thesis (in Vietnamese), Hanoi University of Science, Vietnam, 169p.Nummedal D., Riley G.W., Templet P.T., 1993. High-resolution sequence architecture: a chronostratigraphic model based on equilibrium profile studies. In: Posamentier H.W., Summerhayes C.P., Haq B.U., Allen G.P. (Eds.), Sequence stratigraphy and Facies Associations. International Association of Sedimentologists Special Publication, 18, 55-58.Posamentier H.W. and Allen G.P., 1999. Siliciclastic sequence stratigraphy: concepts and applications. SEPM Concepts in Sedimentology and Paleontology, 7, 210p.Posamentier H.W., Jervey M.T. and Vail P.R., 1988. Eustatic controls on clastic deposition I-Conceptual framework. Sea-level changes-An Integrated Approach, The Society of Economic Paleontologists and Mineralogist. SEPM Special Publication, 42, 109-124.Reineck H.E., Singh I.B., 1980. Depositional sedimentary environments with reference to terrigenous clastics. Springer-Verlag Berlin Heidelberg New York, 551p. Ross K., 2011. Fate of Red River Sediment in the Gulf of Tonkin, Vietnam. Master Thesis. North Carolina State University, 91p.Saito Y., Katayama H., Ikehara K., Kato Y., Matsumoto E., Oguri K., Oda M., Yumoto M. 1998. Transgressive and highstand systems tracts and post-glacial transgression, the East China Sea. Sedimentary Geology, 122, 217-232.Stattegger K., Tjallingii R., Saito Y., Michelli M., Nguyen T.T., Wetzel A., 2013. Mid to late Holocene sea-level reconstruction of Southeast Vietnam using beachrock and beach-ridge deposits. Global and Planetary Change, 110, 214-222.Tanabe S., Hori K., Saito Y., Haruyama S., Doanh L.Q., Sato Y., Hiraide S., 2003a. Sedimentary facies and radiocarbon dates of the Nam Dinh-1 core from the Song Hong (Red River) delta, Vietnam. Journal of Asian Earth Sciences, 21, 503-513.Tanabe S., Hori K., Saito Y., Haruyama S., Phai V.V., Kitamura A., 2003b. Song Hong (Red River) delta evolution related to millennium-scale Holocene sea-level changes. Quaternary Science Reviews, 22(21-22), 2345-2361.Tanabe S., Saito Y., Lan V.Q., Hanebuth T.J.J., Lan N.Q., Kitamura A., 2006. Holocene evolution of the Song Hong (Red River) delta system, northern Vietnam. 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Abstract Background: Relapsed/Refractory diffuse large B-cell lymphoma (DLBCL) patients had a poor prognosis, especially those relapsing within 12 months of completion therapy. Clinically, there is a need to identify and target pathways associated with acquired treatment resistance. Using rituximab-chemotherapy resistant DLBCL cell lines generated in our laboratory, we demonstrated the acquirement of rituximab resistance is associated with changes in the cell cycle distribution (S phase arrest) and expression of cell cycle regulatory proteins (cyclin B, CDC2, CDK7, Wee1, checkpoint kinase 1 [CHK1] and checkpoint kinase 2 [CHK2]). CHK1 and 2 are serine/threonine kinases that control: 1) G2/M phase transition in response of DNA damage, 2) stabilization of DNA replication fork and 3) coordinate the mitosis. Inhibition of CHKs is an attractive strategy in cancer medicine. CHK1 inhibitors are been studied in phase I clinical trials in solid tumor malignancies (i.e. breast, pancreas or lung cancer). We hypothesized that CHK inhibition by Prexasertib has effective anti-tumor activity in DLBCL pre-clinical models. Methods: We used a panel of DLBCL cell lines including rituximab sensitive (Raji, RL, DHL4, DHL6, TMD8, RIVA, and U2932), rituximab resistant (Raji 4RH and RL 4RH), and double hit DLBCL (DOH2, ROS50 and VAL). In addition, experiments were conducted in primary tumor cells isolated from lymphoma patients. Cells were exposed to prexasertib alone or in combination with chemotherapy agents. Cell viability were determined by Presto Blue assay. IC50 was calculated by Graphpad software and coefficient of synergy was calculated using the CalcuSyn software. Subsequently, cells were expose to prexasertib and changes in cell cycle distribution and apoptosis were determined by propidium iodide staining (Pi), annexing V/PI staining and by Caspase3/7 activity detection assay. Changes in mitochondrial potential were determined by DiOC6 staining. Induction of DNA double strain break was investigated by western blot probed with phosphory-H2A.X antibody. At molecular basis, downstream pathway activities ( Mcl-1, phosphor-GSK3β, phosphory-H3, and wee1) were determined by western blot. Results: Prexasertib exhibited a dose dependent anti-lymphoma activity in all all cell lines tested including DHL cell lines. The IC50 of the cells ranged from 11nM to 2.8uM at 72 hours. Additive/synergistic effects were observed by combining prexasertib and doxorubicin, etoposide, vincristine, gemcitabine and proteasome inhibitors. At the dosage of 10nM and 25nM, prexasertib induced cell cycle arrest at G2/M phase. It also induced low membrane potential, caspse3/7 activation and apoptosis in all DLBCL cell lines. Interestingly, western blot also showed CHK inhibitor at 10nM was able to reduce Mcl-1 and p-GSK 3beta. Conclusion: Our data suggests that targeting checkpoint kinase is a promising therapeutic strategy in the lymphoma, including in double hit lymphoma pre-clinical models. In vivo studies are planned. Our data supports the clinical development of prexasertib in DLBCL. (Supported by Roswell Park Cancer Institute Alliance Foundation Grant) Disclosures No relevant conflicts of interest to declare.

Abstract Background. DNA methylation is a key epigenetic process involved in development, aging, and cancer. Mutations in DNMT3A and TET2 in the hematopoietic stem cell compartment lead to increased self-renewal. In addition to mutations in ASXL1, collectively, these DTA mutations are recognized as an aging phenomenon, known as the most common Clonal hematopoiesis of Indeterminate Potential (CHIP) mutations and alone are not predictive of increased risk for hematopoietic malignancy. Recently, DNMT3A mutations in donor hematopoietic cells were suggested to be associated with enhanced T-cell activity in allografted patients. Additionally, role of DNMT3A mutations in creating a proinflammatory state in cardiovascular disease setting and associated elevation of T-cell markers in the myocardium have been recently explored (Sano S et al. Circ Res. 2018). Since an inflamed tumor microenvironment is associated with improved immune checkpoint inhibitors (CPI) activity, we sought to determine the impact of CHIP (a proinflammatory state) on response to CPI and CPI's effects on clonal dynamics. Additionally, while classical chemotherapy (CTX) can create selective external pressure providing survival advantage to mutant stem cells, the selective pressure of T-cell activating therapies on hematopoietic stem cells is unclear. Methods. To study the relationship between CHIP and CPI, we used paired peripheral-blood samples taken before and after treatment with CPI therapy in patients (pts) with melanoma (MEL; n= 32) and non-small cell lung cancer (NSCLC; n=109). Serial samples (or post CPI samples) were evaluable in 5 MEL pts and 6 NSCLC pts. Error-corrected sequencing of a targeted panel of genes recurrently mutated in clonal hematopoiesis (CH) was performed on peripheral blood genomic DNA. Statistical comparisons between baseline and serial sample VAFs were performed using two-sided fisher's exact test, with a p < 0.05 considered significant. Results. In both the MEL and NSCLC cohort, baseline samples were collected before extensive therapy exposure. 90% (29/32) of the MEL cohort had no CTX or targeted therapy prior to the baseline sample; 28% (9/32) had prior radiotherapy (RT). 10% (11/109) of the NSCLC cohort samples had prior CTX, but only 2 of these were treated for more than 1 month before sample collection. CH was frequent in these minimally pre-treated patient samples; 28.1% (9/32) and 37.6% (41/109) of the baseline MEL and NSCLC samples, respectively. As expected, DTA mutations were the most common events in these cohorts. Samples with CH were from patients of older age, but had normal hematological parameters with exception of increased RDW (p=0.022). Primary tumor responses in this cohort were defined as durable (receipt of ≥12 CPI cycles) or not durable (<12 cycles). DNMT3Amut patients (VAF ≥1%, n=5) had more durable responses, i.e. higher median number of CPI cycles (21 cycles, range:10-40) compared to non-DNMT3Amut pts (7 cycles, range:1-13; p= NS). Additionally, pts with larger DNMT3Amut clones (figure 1- MEL cohort) tended to receive higher numbers of CPI cycles. In the serial sample analysis, we observed that mutations in DNMT3A and TET2 increased in size with longer CPI exposures (Figure 2, MEL cohort); pts 2, 3 and 5 received 13, 15 and 18 CPI cycles respectively, while pt 4 with the most notable clonal expansion in DNMT3A received 40 CPI cycles. All serial samples in MEL cohort showed a statistically significant change in VAF from baseline. In the serial sample analysis of NSCLC pts, we observed that those with ≥ 3 months of CPI exposure demonstrated decreases in clone size for non-DTA gene mutations such as SRCAP, STK11 and TPM1 (Table 1), but increases or stability in DNMT3A and TET2 mutations (Table 1). However, this VAF increase in DNMT3A and TET2 mutations in NSCLC cohort was not statistically significant. Conclusions. In this small cohort of pts with MEL and NSCLC, the presence of DNMT3A/TET2 CH was associated with longer checkpoint inhibitor exposure and increased allelic frequency over time. These findings need further validation in larger cohorts and delineation of the relationship between DTA mutations such as DNMT3A and enhanced immune activity. Acknowledgement: Data and samples for this study were provided by the Data Bank and BioRepository (DBBR), which is funded by the National Cancer Institute (P30 CA016056) and is a Roswell Park Cancer Institute Cancer Center Support Grant shared resource. Figure 1 Figure 1. Disclosures Griffiths: Taiho Oncology: Consultancy, Honoraria; Alexion Pharmaceuticals: Consultancy, Research Funding; Novartis: Honoraria; Boston Biomedical: Consultancy; Astex Pharmaceuticals: Honoraria, Research Funding; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Apellis Pharmaceuticals: Research Funding; Genentech: Research Funding; Takeda Oncology: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Hassane: Tempus Labs, Inc: Current Employment. Guzman: SeqRx: Consultancy; BridgeMedicines: Consultancy; Cellectis: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees. Wang: Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; Genentech: Membership on an entity's Board of Directors or advisory committees; Kite Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; Kura Oncology: Consultancy, Honoraria, Other: Advisory board, steering committee, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Other: Advisory Board; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Other: Advisory Board; Mana Therapeutics: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Other: Advisory Board, Speakers Bureau; Stemline Therapeutics: Consultancy, Honoraria, Other: Advisory board, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Advisory board; DAVA Oncology: Consultancy, Speakers Bureau; Rafael Pharmaceuticals: Other: Data safety monitoring committee; Gilead: Consultancy, Honoraria, Other: Advisory board; Daiichi Sankyo: Consultancy, Honoraria, Other: Advisory board; PTC Therapeutics: Consultancy, Honoraria, Other: Advisory board; Genentech: Consultancy; MacroGenics: Consultancy.

During cardio-pulmonary bypass (CPB), Heparin inhibits EXa (EXal), thrombin and platelet activity and is also reported to induce fibrinolysis. Eragmin (Erag) has 25% thrombin inhibition capacity as related to that of Heparin (Hep). An in_vitro study was performed to compare Frag with Hep by circulating blood in a pure artificial system. In 20 experiments, 400 ml of freshly collected blood with Frag or Hep were recycled for 2 h. HLM was primed with 400 ml of Ringeracetate. Blood sampling: donor, blood pack and every 20 min from the oxygenator. V_a£i£ble£/jassay/:ACT/Hemochron/5 APTT , TT and NT/Nyegaard/;FXaI, FVIII and ATIiT t"ATA)/amydolytic/; AT 111 (ATAg) and vWF/IEP/;Plasminogen (Pig) and albumine/immuno-diffusion/;FDP/Wellcome/;Platelet function/Adeplat S/;Fibrinogen (Fbg)/clottable/;Hemolysis (HL)/photometric/; (β -Thromboglobulin ((βTG)/RTA/;EVF, Hb, platelet count (PC) and Leucocyte count (LC)/ conventional). Corrections for hemo-/plasma dilutions were calculated. Dosages (n): Frag: 750 (1), 1500 (3), 2100 (4), 2500 (4) FXal-U (U); Hep: 1000 (3), 1500 (6) IU clinical level. Clotting only occurred at Frag 750 (1) and 1500 (2) U, when ACT, APTT, FVIII, Fbg and ATA were significantly lowered. Generally, PC fell 75% during the recycling, while PF was constant'∼20% and (βTG increased. Neither presence of FDP nor Pig consumption were detected. FXal, ACT, APTT, TT and NT were dose dependent for both drugs. ATA was directly dose-related to Frag but inversely to Hep. LC decreased with the Frag-dose but inversely to that of Hep. HL increased generally. Several proteins increased (clotting excl): Fbg 30%, ATAg 25%, ATA 45?o and vWF 60%. Conclusions. Prevention of clotting required about the double dosage of Frag. Shortened ACT and APTT predicted clotting while the levels of FXal, TT and NT did not. Thus, an effective thrombin inhibition is needed under this conditions. Consumptions of FVIII, Fbg and ATA but no further drop in PC at clotting, indicate weak platelet aggregation involvement. Absence of fibrinolytic signs supports that the fibrinolysis seen at CPB, is not a genuine effect of Hep (or Frag). Increases in some proteins may be caused by cytolysis. The rise in vWF is probably due to release from platelet surfaces.

As a student undertaking a Longitudinal Integrated Clerkship (LIC)1 based in a GP practice in a rural community in the North of Scotland, I have been lucky to be given responsibility and my own clinic lists. Every day I conduct consultations that change my practice: the challenge of clinically applying the theory I have studied, controlling a consultation and efficiently exploring a patient's problems, empathising with and empowering them to play a part in their own care2 – and most difficult I feel – dealing with the vast amount of uncertainty that medicine, and particularly primary care, presents to both clinician and patient. I initially consulted with a lady in her 60s who attended with her husband, complaining of severe lower back pain who was very difficult to assess due to her pain level. Her husband was understandably concerned about the degree of pain she was in. After assessment and discussion with one of the GPs, we agreed some pain relief and a physio assessment in the next few days would be a practical plan. The patient had one red flag, some leg weakness and numbness, which was her ‘normal’ on account of her multiple sclerosis. At the physio assessment a few days later, the physio felt things were worse and some urgent bloods were ordered, unfortunately finding raised cancer and inflammatory markers. A CT scan of the lung found widespread cancer, a later CT of the head after some developing some acute confusion found brain metastases, and a week and a half after presenting to me, the patient sadly died in hospital. While that was all impactful enough on me, it was the follow-up appointment with the husband who attended on the last triage slot of the evening two weeks later that I found completely altered my understanding of grief and the mourning of a loved one. The husband had asked to speak to a Andrew MacFarlane Year 3 ScotGEM Medical Student 2 doctor just to talk about what had happened to his wife. The GP decided that it would be better if he came into the practice - strictly he probably should have been consulted with over the phone due to coronavirus restrictions - but he was asked what he would prefer and he opted to come in. I sat in on the consultation, I had been helping with any examinations the triage doctor needed and I recognised that this was the husband of the lady I had seen a few weeks earlier. He came in and sat down, head lowered, hands fiddling with the zip on his jacket, trying to find what to say. The GP sat, turned so that they were opposite each other with no desk between them - I was seated off to the side, an onlooker, but acknowledged by the patient with a kind nod when he entered the room. The GP asked gently, “How are you doing?” and roughly 30 seconds passed (a long time in a conversation) before the patient spoke. “I just really miss her…” he whispered with great effort, “I don’t understand how this all happened.” Over the next 45 minutes, he spoke about his wife, how much pain she had been in, the rapid deterioration he witnessed, the cancer being found, and cruelly how she had passed away after he had gone home to get some rest after being by her bedside all day in the hospital. He talked about how they had met, how much he missed her, how empty the house felt without her, and asking himself and us how he was meant to move forward with his life. He had a lot of questions for us, and for himself. Had we missed anything – had he missed anything? The GP really just listened for almost the whole consultation, speaking to him gently, reassuring him that this wasn’t his or anyone’s fault. She stated that this was an awful time for him and that what he was feeling was entirely normal and something we will all universally go through. She emphasised that while it wasn’t helpful at the moment, that things would get better over time.3 He was really glad I was there – having shared a consultation with his wife and I – he thanked me emphatically even though I felt like I hadn’t really helped at all. After some tears, frequent moments of silence and a lot of questions, he left having gotten a lot off his chest. “You just have to listen to people, be there for them as they go through things, and answer their questions as best you can” urged my GP as we discussed the case when the patient left. Almost all family caregivers contact their GP with regards to grief and this consultation really made me realise how important an aspect of my practice it will be in the future.4 It has also made me reflect on the emphasis on undergraduate teaching around ‘breaking bad news’ to patients, but nothing taught about when patients are in the process of grieving further down the line.5 The skill Andrew MacFarlane Year 3 ScotGEM Medical Student 3 required to manage a grieving patient is not one limited to general practice. Patients may grieve the loss of function from acute trauma through to chronic illness in all specialties of medicine - in addition to ‘traditional’ grief from loss of family or friends.6 There wasn’t anything ‘medical’ in the consultation, but I came away from it with a real sense of purpose as to why this career is such a privilege. We look after patients so they can spend as much quality time as they are given with their loved ones, and their loved ones are the ones we care for after they are gone. We as doctors are the constant, and we have to meet patients with compassion at their most difficult times – because it is as much a part of the job as the knowledge and the science – and it is the part of us that patients will remember long after they leave our clinic room. Word Count: 993 words References 1. ScotGEM MBChB - Subjects - University of St Andrews [Internet]. [cited 2021 Mar 27]. Available from: https://www.st-andrews.ac.uk/subjects/medicine/scotgem-mbchb/ 2. Shared decision making in realistic medicine: what works - gov.scot [Internet]. [cited 2021 Mar 27]. Available from: https://www.gov.scot/publications/works-support-promote-shared-decisionmaking-synthesis-recent-evidence/pages/1/ 3. Ghesquiere AR, Patel SR, Kaplan DB, Bruce ML. Primary care providers’ bereavement care practices: Recommendations for research directions. Int J Geriatr Psychiatry. 2014 Dec;29(12):1221–9. 4. Nielsen MK, Christensen K, Neergaard MA, Bidstrup PE, Guldin M-B. Grief symptoms and primary care use: a prospective study of family caregivers. BJGP Open [Internet]. 2020 Aug 1 [cited 2021 Mar 27];4(3). Available from: https://bjgpopen.org/content/4/3/bjgpopen20X101063 5. O’Connor M, Breen LJ. General Practitioners’ experiences of bereavement care and their educational support needs: a qualitative study. BMC Medical Education. 2014 Mar 27;14(1):59. 6. Sikstrom L, Saikaly R, Ferguson G, Mosher PJ, Bonato S, Soklaridis S. Being there: A scoping review of grief support training in medical education. PLOS ONE. 2019 Nov 27;14(11):e0224325.