Torture at Times: Waterboarding in the Media

The current debate over waterboarding has spawned hundreds of newspaper articles in the last two years alone. However, waterboarding has been the subject of press attention for over a century. Examining the four newspapers with the highest daily circulation in the country, we found a significant and sudden shift in how newspapers characterized waterboarding. From the early 1930s until the modern story broke in 2004, the newspapers that covered waterboarding almost uniformly called the practice torture or implied it was torture: The New York Times characterized it thus in 81.5% (44 of 54) of articles on the subject and The Los Angeles Times did so in 96.3% of articles (26 of 27). By contrast, from 2002-2008, the studied newspapers almost never referred to waterboarding as torture. The New York Times called waterboarding torture or implied it was torture in just 2 of 143 articles (1.4%). The Los Angeles Times did so in 4.8% of articles (3 of 63). The Wall Street journal characterized the practice as torture in just 1 of 63 articles (1.6%). USA Today never called waterboarding torture or implied it was torture. In addition, the newspapers are much more likely to call waterboarding torture if a country other than the United States is the perpetrator. In The New York Times, 85.8% of articles (28 of 33) that dealt with a country other than the United States using waterboarding called it torture or implied it was torture while only 7.69% (16 of 208) did so when the United States was responsible. The Los Angeles Times characterized the practice as torture in 91.3% of articles (21 of 23) when another country was the violator, but in only 11.4% of articles (9 of 79) when the United States was the perpetrator

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

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

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

Assessing local building cultures for resilience & development: A practical guide for community-based assessment

International audienceThe development of a set of tools to enhance appreciation of local practices developed by communities regarding settlements and risks is an initiative that aims to promote context-based strategies for responding efficiently and adequately to habitat improvement and vulnerability reduction needs. This guide offers a methodological and operational support for decision-making and practices towards approaches and actions deeply rooted in local contexts. It is a practical tool that provides detailed explanation on planning, preparing and undertaking field assessments of local practices related to habitat and risks. It refers to a participatory approach suitable for, and adapted to, various geographical, cultural and risk-prone areas. By supporting habitat assessment in all its different aspects, it also fosters links between programmes, providing clues and keys to define and implement coherent projects including income generating activities, livelihood, health and other related sectors. The necessary investment to be taken into account in project planning to achieve the basic step described in this booklet will result in huge savings, as logistical issues will be drastically reduced during the project implementation. It is a worthwhile investment that will lead to decisions ensuring more benefits to the affected communities, including a long-term enhancement of their resilience capacityCet ouvrage s'adresse aux responsables de projets et aux preneurs de décisions. L'auteur explique tout d'abord la démarche de projet respectueuse des cultures constructives. L'auteur présente ensuite une méthode d'évaluation des cultures constructives locales et expose l'importance de celle-ci dans un proje

High pathogenicity avian influenza (H5N1) in northern gannets: global spread, clinical signs, and demographic consequences

During 2021 and 2022 High Pathogenicity Avian Influenza (HPAI) killed thousands of wild birds across Europe and North America, suggesting a change in infection dynamics and a shift to new hosts, including seabirds. Northern Gannets (Morus bassanus) appeared especially severely impacted, but a detailed account of the data available is required to help understand how the virus spread across the metapopulation, and the ensuing demographic consequences. Accordingly, we analyse information on confirmed and suspected HPAIV outbreaks across most North Atlantic Gannet colonies and for the largest colony (Bass Rock, UK), provide impacts on population size, breeding success, and preliminary results on apparent adult survival and serology. Unusually high numbers of dead Gannets were first noted at colonies in Iceland during April 2022. Outbreaks in May occurred in many Scottish colonies, followed by colonies in Canada, Germany and Norway. By the end of June, outbreaks had occurred in colonies in Canada and the English Channel. Outbreaks in 12 UK and Ireland colonies appeared to follow a clockwise pattern with the last infected colonies recorded in late August/September. Unusually high mortality was recorded at 40 colonies (75% of global total colonies). Dead birds testing positive for HPAIV H5N1 were associated with 58% of these colonies. At Bass Rock, the number of occupied nest sites decreased by at least 71%, breeding success declined by ~66% compared to the long-term UK mean and the resighting of marked individuals suggested that apparent adult survival between 2021 and 2022 could have been substantially lower than the preceding 10-year average. Serological investigation detected antibodies specific to H5 in apparently healthy birds indicating that some Gannets recover from HPAIV infection. Further, most of these recovered birds had black irises, suggestive of a phenotypic indicator of previous infection. Untangling the impacts of HPAIV infection from other challenges faced by seabirds is key to establishing effective conservation strategies for threatened seabird populations as the likelihood of further epizootics increases, due to increasing habitat loss and the industrialization of poultry production