'Education, education, education' : legal, moral and clinical

This article brings together Professor Donald Nicolson's intellectual interest in professional legal ethics and his long-standing involvement with law clinics both as an advisor at the University of Cape Town and Director of the University of Bristol Law Clinic and the University of Strathclyde Law Clinic. In this article he looks at how legal education may help start this process of character development, arguing that the best means is through student involvement in voluntary law clinics. And here he builds upon his recent article which argues for voluntary, community service oriented law clinics over those which emphasise the education of students

Influence Of Kir Genes And Their Hla Ligands In Susceptibility To Dengue In A Population From Southern Brazil

Killer cell immunoglobulin-like receptors (KIR) form a group of regulatory molecules that specifically recognise human leukocyte antigen (HLA) class I molecules, modulating the cytolytic activity of natural killer cells. The purpose of this study was to investigate the influence of KIR genes and their class I HLA ligands in susceptibility to dengue fever in a population from southern Brazil through a case-control study. One hundred four subjects with confirmed diagnoses of dengue participated in this study, along with a control group of 172 individuals from the same geographic area. HLA and KIR genotyping was performed by polymerase chain reaction with sequence-specific oligonucleotide probes (PCR-SSOP) and with sequence-specific primer (PCR-SSP) techniques, respectively. Data analysis showed significant differences for the KIR2DS1 (54.8% vs 40.7%, P=0.03), KIR2DS5 (50.0% vs 36.0%, P=0.03) and KIR2DL5 (76.0% vs 56.4%, P=0.001) genes. With regard to KIR-ligand pairs, positive associations with dengue were observed in KIR3DS1-Bw4 (45.2% vs 29.7%, P=0.01), KIR3DL1-Bw4 (80.7% vs 65.1%, P<0.001), KIR2DL1-C2 (75.0% vs 62.2%, P=0.03) and KIR2DS1-C2 (40.4% vs 25.6%, P=0.01) interactions, and a negative association in KIR2DL3-C1/C1 (18.2% vs 33.1%, P = 0.01). Furthermore, the analysis of KIR haplogroups showed a possible protective factor against dengue fever in individuals with the AA genotype. Taken together, these results suggest the existence of genetic predisposition to dengue fever in the population from southern Brazil. © 2013 John Wiley & Sons A/S.826397404Guzman, M.G., Kouri, G., Dengue and dengue hemorrhagic fever in the Americas: lessons and challenges (2003) J Clin Virol, 27, pp. 1-13(2012) Dengue and Severe Dengue, , http://www.who.int/mediacentre/factsheets/fs117/en/, WHO. Geneva: World Health Organization, Available at:Martina, B.E., Koraka, P., Osterhaus, A.D., Dengue virus pathogenesis: an integrated view (2009) Clin Microbiol Rev, 22, pp. 564-581Halstead, S.B., Observations related to pathogenesis of dengue hemorrhagic fever (1970) Yale J Biol Med, 42, pp. 350-360Rosen, L., La pathogenèse de la dengue hemorragique: discussion critique des hypothèses Actuelles (1986) Bull Soc Pathol, 79, pp. 342-349Whitehorn, J., Farrar, J., Dengue (2010) Br Med Bull, 95, pp. 161-173Pelak, K., Need, A.C., Fellay, J., Copy number variation of KIR genes influences HIV-1 control (2011) PLoS Biol, 9, pp. e1001208Alter, G., Martin, M.P., Teigen, N., Differential natural killer cell-mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes (2007) J Exp Med, 204, pp. 3027-3036Marangon, A.V., Silva, G.F., Verdichio de Moraes, C.F., KIR genes and their human leukocyte antigen ligands in the progression to cirrhosis in patients with chronic hepatitis C (2011) Hum Immunol, 72, pp. 1074-1078Rauch, A., Laird, R., McKinnon, E., Influence of inhibitory killer immunoglobulin-like receptors and their HLA-C ligands on resolvinghepatitis C virus infection (2007) Tissue Antigens, 69, pp. 237-240Méndez, A., Granda, H., Meenagh, A., Study of KIR genes in tuberculosis patients (2006) Tissue Antigens, 68, pp. 386-389Franceschi, D.A., Mazini, O.S., Rudnick, C.C., Association between killer-cell immunoglobulin-like receptor genotypes and leprosy in Brazil (2008) Tissue Antigens, 72, pp. 478-482Suto, Y., Ishikawa, Y., Kasahara, M., Gene arrangement of the killer cell inhibitory receptor family on human chromosome 19q13.4 detected by fiber-FISH (1998) Immunogenetics, 48, pp. 235-241Green, S., Pichyangkul, S., Vaughn, D.W., Early CD69 expression on peripheral blood lymphocytes from children with dengue hemorrhagic fever (1999) J Infect Dis, 180, pp. 1429-1435Vilches, C., Parham, P., KIR: diverse, rapidly evolving receptors of innate and adaptive immunity (2002) Annu Rev Immunol, 20, pp. 217-251Parham, P., Killer cell immunoglobulin-like receptor diversity: balancing signals in the natural killer cell response (2004) Immunol Lett, 92, pp. 11-13Uhrberg, M., Parham, P., Wernet, P., Definition of gene content for nine common group B haplotypes of the Caucasoid population: KIR haplotypes contain between seven and eleven KIR genes (2002) Immunogenetics, 54, pp. 221-229Carrington, M., Norman, P., The KIR gene cluster (2003) US Natl Library Med, , http://www.ncbi.nlm.nih.gov/books/bookres.fcgi/mono_003/ch1d1.pdf, Available at:Long, E.O., Rajagopalan, S., HLA class I recognition by killer cell Ig-like receptors (2000) Semin Immunol, 12, pp. 101-108Vales-Gomez, M., Reyburn, H., Strominger, J., Molecular analyses of the interactions between human NK receptors and their HLA ligands (2000) Hum Immunol, 61, pp. 28-38Kulkarni, S., Martin, M.P., Carrington, M., The Yin and Yang of HLA and KIR in human disease (2008) Semin Immunol, 20, pp. 343-352Bashirova, A.A., Martin, M.P., McVicar, D.W., Carrington, M., The killer immunoglobulin-like receptor gene cluster: tuning the genome for defense (2006) Annu Rev Genomics Hum Genet, 7, pp. 277-300Probst, C.M., Bompeixe, E.P., Pereira, N.F., HLA polymorphism and evaluation of European, African, and Amerindian contribution to the white and mulatto populations from Paraná, Brazil (2000) Hum Biol, 72, pp. 597-617John, S.W., Weitzner, G., Rozen, R., Scriver, C.R., A rapid procedure for extracting genomic DNA from leukocytes (1990) Nucleic Acids Res, 192, p. 408Cardozo, D.M., Guelsin, G.A., Clementino, S.L., Extração de DNA a partir de sangue humano coagulado para aplicação nas técnicas de genotipagem de antígenos leucocitários humanos e de receptores semelhantes à imunoglobulina (2009) Rev Soc Bras Med Trop, 42, pp. 651-656(1998) ASHI Standards for Histocompatibility Testing, 1998 Membership Directory, , ASHI. Lenexa, Kansas: American Society for Histocompatibility and ImmunogeneticsRudnick, C.C., Guelsin, G.A., Marangon, A.V., Franceschi, D.A., Sell, A.M., Visentainer, J.E., Otimização de metodologia para o estudo de genes KIR (2010) J Bras Patol Med Lab, 46, pp. 215-224Yindom, L.M., Forbes, R., Aka, P., Killer-cell immunoglobulin-like receptors and malaria caused by Plasmodium falciparum in The Gambia (2012) Tissue Antigens, 79, pp. 104-113Pydi, S.S., Sunder, S.R., Venkatasubramanian, S., Kovvali, S., Jonnalagada, S., Valluri, V.L., Killer cell immunoglobulin like receptor gene association withtuberculosis (2013) Hum Immunol, 74, pp. 85-92Luszczek, W., Manczak, M., Cislo, M., Gene for the activating natural killer cell receptor, KIR2DS1, is associated with susceptibility to psoriasis vulgaris (2004) Hum Immunol, 65, pp. 758-766Suzuki, Y., Hamamoto, Y., Ogasawara, Y., Genetic polymorphisms of killer cell immunoglobulin-like receptors are associated with susceptibility to psoriasis vulgaris (2004) J Invest Dermatol, 122, pp. 1133-1136Augusto, D.G., Lobo-Alves, S.C., Melo, M.F., Pereira, N.F., Petzl-Erler, M.L., Activating KIR and HLA Bw4 ligands are associated to decreased susceptibility to pemphigus foliaceus, an autoimmune blistering skin disease (2012) PLoS ONE, 7, pp. e39991Diaz-Pena, R., Vidal-Castineira, J.R., Alonso-Arias, R., Association of the KIR3DS1*013 and KIR3DL1*004 alleles with susceptibility to ankylosing spondylitis (2010) Arthritis Rheum, 62, pp. 1000-1006Karabon, L., Jedynak, A., Giebel, S., KIR/HLA gene combinations influence susceptibility to B-cell chronic lymphocytic leukemia and the clinical course of disease (2011) Tissue Antigens, 78, pp. 129-138Stern, M., Opelz, G., Döhler, B., Hess, C., Natural killer-cell receptor polymorphisms and posttransplantation non-Hodgkin lymphoma (2010) Blood, 115, pp. 3960-3965Middleton, D., Vilchez, J.R., Cabrera, T., Analysis of KIR gene frequencies in HLA class I characterized bladder, colorectal and laryngeal tumours (2007) Tissue Antigens, 69, pp. 220-226Wauquier, N., Padilla, C., Becquart, P., Leroy, E., Vieillard, V., Association of KIR2DS1 and KIR2DS3 with fatal outcome in Ebola virus infection (2010) Immunogenetics, 62, pp. 767-771Zhi-Ming, L., Yu-Lian, J., Zhao-Lei, F., Polymorphisms of killer cell immunoglobulin-like receptor gene: possible association with susceptibility to or clearance of hepatitis B virus infection in Chinese Han population (2007) Croat Med, 6, pp. 800-806Carr, W.H., Pando, M.J., Parham, P., KIR3DL1 polymorphisms that affect NK cell inhibition by HLA-Bw4 ligand (2005) J Immunol, 175, pp. 5222-5229Khakoo, S.I., Thio, C.L., Martin, M.P., HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection (2004) Science, 305, pp. 872-874Gazit, R., Garty, B.Z., Monselise, Y., Expression of KIR2DL1 on the entire NK cell population: a possible novel immunodeficiency syndrome (2004) Blood, 103, pp. 1965-196

Comparison of extensive and intensive pig production systems in Uruguay in terms of ethologic, physiologic and meat quality parameters

[EN] The objective of this work is to characterize two contrasting systems of fattening pigs in Uruguay. A total of 96 pigs (average 41.7 kg) were divided into eight groups of 12 animals, representing two production systems: (IN) pigs confined in pens of 12 m2 or (OUT) kept in plots with field shelters and access to pasture. Behavioral observations were performed by scan sampling at 5-minute intervals, three times a day during weeks 6, 8, 10 and 12 of the experiment. Aggressions were also observed at the end of the experimental period. Blood samples were taken for cortisol analysis and other physiological parameters, during growth period and slaughter and meat quality characteristics were assessed after slaughter. Differences were found in carcass characteristics, wherein IN presented a higher dorsal fat. These animals presented an overall lower activity and spent less time resting, with a stable pattern throughout the day. In OUT, pigs usually rested at midday hours, more active in the morning and afternoon. The number of total reciprocal aggressions in the observation period was 4.2±3.7 for IN and 2.3±2.2 for OUT. Cortisol levels and biochemical profile did not show evidence of important problems in the animals. Welfare is not compromised in any of the systems, although higher levels of cortisol and aggressions could be indicating some stress problems in the confinement system. Meat characteristics in OUT were considered better than in IN from a nutritional point of view.Blumetto, O.; Calvet Sanz, S.; Estellés Barber, F.; Villagrá García, A. (2013). Comparison of extensive and intensive pig production systems in Uruguay in terms of ethologic, physiologic and meat quality parameters. REVISTA BRASILEIRA DE ZOOTECNIA-BRAZILIAN JOURNAL OF ANIMAL SCIENCE. 42(7):521-529. doi:10.1590/S1516-35982013000700009S52152942

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)