Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Paternity testing and the biological determination of fatherhood

The introduction, availability, and marketing of a transparent and decisive method for determining genetic connections, while irrefutably solving the issue of biological paternity has posed new challenges about the precise constitution and meaning of fatherhood. This article presents the results of a qualitative study of the experience of paternity testing specifically from the perspective of men who were tested or who were unsure of paternity. It presents data on these men's own perceptions of fatherhood. What the study found was that, while biology mattered and the testing was important to men, it did not always solve important issues around fathering and nongenetic ties

The making and breaking of paternity secrets in donor insemination

This paper analyses the complex issues faced by regulators of the infertility treatment industry in response to the social and technological changes that heralded a new openness in knowledge about genetics, paternity and the concomitant need for donor offspring to know their genetic origins. The imperative for full information about their donor and biological father, who contributed to their creation and half of their genome, was an outcome unanticipated by the architects of the donor insemination programme. Genetic paternity testing realised the possibility of fixed and certain knowledge about paternity. This paper outlines medicine’s role in the formation of normative families through the use of donor insemination. Extending information from an Australian study on the use of DNA paternity testing, it analyses what the social and scientific changes that have emerged and gained currency in the last several decades mean for the new ‘openness’ and the role of paternity testing in this context. It concludes with recommendations about how to deal with the verification of paternity in linking donor conceived adult children to their donor

Surgical sterilisation : medical power, women\u27s knowledge

An exploration of women\u27s experience of tubal ligation and the social context in which their contraceptive decision making occurs. This study gives priority to women\u27s knowledge about their own bodies and investigates how women negotiate contraceptive risks, the information provision process, the outcome of tubal ligation in terms of side-effects and the medical responses to women\u27s reporting of their problems. It makes recommendations about the information women should have to meet the requirement of an informed consent when accepting contraceptive surgery

Paternity secrets: why women don't tell

This paper reports findings from a study on paternity testing.1 Through an analysis of in-depth interviews with women from across Australia, some of whom were themselves uncertain of paternity, the study unveils their experiences of the making and keeping of a secret that became increasingly difficult to confess. In disclosing themes and commonalities in women’s accounts of their paternity secrets, it highlights the shared nature of the dilemma. At the same time, the differential and exceptional experiences of women in nonconventional and coercive relationships illustrate the precarious position of some women in relation to paternity uncertainty. Using a “moral panics” framework, the paper examines the way in which the activity of these women has been constructed as a widespread social problem encapsulated in the notions of paternity fraud and misattributed paternity. It then discusses the implications of this construction for the making of family policy based on reactivity to a moral panic

The failure of DNA forensic testing: a case study of the 2009 Australian bushfire disaster

Within science and technology studies there is a vast literature on the manner in which public inquiries and official investigations manage the political fallout and the failures of socio-technical systems in the wake of a disaster. This paper uses a case study example of public and media inquiry into the 2009 bushfires in Victoria, Australia to demonstrate how the sole reliance on biological, physical and genetic factors in victim identification unnecessarily delayed the reconciliation process and exacerbated the personal and social distress to families. In particular it analyses how, despite the lack of success in identifying bushfire victims using “gold standard” forensic technologies, including DNA testing, there was relatively little critique of the forensic process. Where dissatisfaction threatened to overflow as a result of brief media coverage of the unnecessary delays in returning the dead to their families, it was quickly contained. Many victims were ultimately identified through geo-location and e-witness accounts, but these were not sought nor considered valid until scientific methods failed. Earlier recognition of the value of these accounts and knowledge of the limitations of forensic technologies in a catastrophic fire disaster would have expedited the reconciliation process, allowing the bodies of victims to be returned to their families in a timely manner

Mental health and workplace bullying: the role of power, professions and 'on the job' training

Study of the professions, and the process of professionalisation as an occupational strategy, has mainly concentrated on investigating structures of power, rather than individual and deliberate use of power. This chapter provides a microanalysis of power relations by examining professional power and hierarchy in interpersonal relations within the workplace. It makes links across the spectrum of workplaces in which bullying occurs - from those where physical intimidation and threat of violence is experienced, to the professions and quasi-professions where legitimate power becomes the vehicle for invisible bullying practices. Arguably, it is within the professions that bullying occurs in its most rarefied form and, to understand the phenomenon, I argue that we should closely examine instances of workplace bullying where there is no one tangible or definable act but clearly an ongoing threat to an individual worker's health and safety. In particular, I explore the positionality of the traditional professions within new organisational structures. The paper concludes with recommendations for the promotion of mental health at work that focus on both environmental and individual strategies

The incidental discovery of non-paternity through genetic carrier screening: an exploration of lay attitudes

With advances in genetic medicine, paternity is increasingly being determined by genetic rather than social markers. In this article, the author examines the complex nature of paternity and the way in which it has been constructed socially, legally, and medically. She then presents the results from an empirical study on public attitudes toward genetic testing and paternity. In particular, she examines lay attitudes toward an ethical dilemma posed by the incidental discovery of nonpaternity during the process of genetic testing for a recessively inherited disease. She concludes the article by drawing attention to the potential problems inherent in the intervention of genetic medicine into family relationships