Legal, medical and lay understanding of embryos in Portugal: alignment with biology?

Pretende-se contribuir para o debate em torno dos processos de circulação de conhecimentos e sentidos entre especialistas e “leigos” no que concerne ao estatuto dos embriões humanos em Portugal. Reflete-se sobre as expectativas e preocupações manifestadas quanto à confiança, qualidade, segurança e eficácia das tecnologias médicas de reprodução assistida. O estudo assenta na realização de entrevistas individuais, com vistas a explorar as complexidades, similitudes e diferenças entre as visões e os valores de juristas, médicos e casais envolvidos em tratamentos de fertilização in vitro. Trata-se de uma análise qualitativa em um estudo de caso. Se os juristas e os médicos enquadram o estatuto dos embriões em categorias de índole biológica, técnica e/ou jurídico-legal, já os casais estabelecem com os mesmos diversas relações ontológicas de índole moral, afetiva e social, pelo que estes podem ser representados como seres éticos face à biologização médico-legal dos embriões.Our aim is to contribute towards the debate about the processes through which knowledge and meanings regarding the status of human embryos circulate among experts and laymen in Portugal. Expectations and concerns expressed regarding the reliability, quality, safety and efficacy of medical technologies for assisted reproduction were assessed. This study is based on data from individual interviews that sought to explore the complexities, similarities and differences among the views and values of jurists, doctors and couples involved in in vitro fertilization treatments. It consists of a qualitative analysis on a case study. If jurists and doctors frame the status of embryos as categories of a biological, technical and/or legal nature, couples establish between themselves a variety of ontological relationships of a moral, affective and social nature. Through these, they can be represented as ethical beings, thus contrasting with the medical-legal biologization of the embryos.To the jurists, doctors and women and men who we interviewed and who shared with us their views and experiences, our sincere thanks. We also thank Helena Lima and Filomena Louro (Scientific Editing Programme, University of Minho) for the translation of the Portuguese text into English; and the revision of David George Elliff. The authors thank the Foundation for Science and Technology (Portuguese Ministry of Science, Technology and Higher Education) for the financial support for this research, through a PhD fellowship (SFRH/BD/10396/2002) and a post-doctoral fellowship (SFRH/BPD/47020/2008).info:eu-repo/semantics/publishedVersio

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