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ARTIKELEN: C.J. de Poot - Dilemma's in de opsporing E.J. van der Torre en E.R. Muller - Het recherchevak; een institutionele benadering C.J.de Poot en P.J. van Koppen - Meten van recherchewerk F. van Tulder, P. Smit en S. Siero - Ophelderingspercentages als maatsaf voor prestaties? B.L. Mac Lean - Contact tussen O.M. en recherche door de jaren heen; de praktijk A.G. van Amelsvoort, H. Groenendaal en J. van Manen - Werkwijze bij het onderzoek op de Plaats Delict (PD) R.J. Bokhorst - De telefoontap in grote opsporingsonderzoeken 8. J. van der Schoor - Brains voor de recherche SAMENVATTING: In dit themanummer wordt een beeld geschetst van het veranderingsproces dat de recherche doormaakt. Er is voor gekozen  zowel wetenschappers als praktijkdeskundigen aan het woord te laten over hun visies op de organisatie en het dagelijks werk van de recherche

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Conforto térmico e desempenho de bezerras Girolando alojadas em abrigos individuais com diferentes coberturas

Esta pesquisa foi desenvolvida com o objetivo de caracterizar os efeitos do ambiente térmico nos índices de conforto, respostas fisiológicas e no desempenho de bezerras Girolando, alojadas em abrigos individuais cobertos com diferentes materiais. O experimento foi realizado entre janeiro e março de 2012, com duração de 56 dias, conduzido com 24 bezerras de composição genética 7/8 Holandês-Gir aos 15 dias de vida e com peso médio de 40,6 kg. Os tratamentos consistiram em três tipos de cobertura, palha de palmeira, telha de polímero reciclado e telha de fibrocimento, com 8 repetições. O delineamento experimental adotado foi o inteiramente casualizado com comparação entre médias pelo teste de Tukey (p < 0,05). A entalpia e a carga térmica radiante diferiram estatisticamente em todos os tratamentos sendo os menores valores apresentados pelos abrigos com cobertura de telha reciclada, 59,3 kJ kg-1 de ar seco e 444,8 W m-2, respectivamente. Não houve diferença significativa em nenhuma das variáveis fisiológicas estudadas, porém a frequência respiratória esteve elevada em todos os tratamentos sendo mais acentuada nos animais sob cobertura de fibrocimento (57,2 mov min-1) indicando mais suscetibilidade ao estresse térmico

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease