Use of whole-genus genome sequence data to develop a multilocus sequence typing tool that accurately identifies Yersinia isolates to the species and subspecies levels

The genus Yersinia is a large and diverse bacterial genus consisting of human-pathogenic species, a fish-pathogenic species, and a large number of environmental species. Recently, the phylogenetic and population structure of the entire genus was elucidated through the genome sequence data of 241 strains encompassing every known species in the genus. Here we report the mining of this enormous data set to create a multilocus sequence typing-based scheme that can identify Yersinia strains to the species level to a level of resolution equal to that for whole-genome sequencing. Our assay is designed to be able to accurately subtype the important human-pathogenic species Yersinia enterocolitica to whole-genome resolution levels. We also report the validation of the scheme on 386 strains from reference laboratory collections across Europe. We propose that the scheme is an important molecular typing system to allow accurate and reproducible identification of Yersinia isolates to the species level, a process often inconsistent in nonspecialist laboratories. Additionally, our assay is the most phylogenetically informative typing scheme available for Y. enterocolitica

Homogeneity and Heterogeneity as Situational Properties: Producing – and Moving Beyond? – Race in Post-Genomic Science

In this article, we explore current thinking and practices around the logics of difference in gene–environment interaction research in the post-genomic era. We find that scientists conducting gene–environment interaction research continue to invoke well-worn notions of racial difference and diversity, but use them strategically to try to examine other kinds of etiologically significant differences among populations. Scientists do this by seeing populations not as inherently homogeneous or heterogeneous, but rather by actively working to produce homogeneity along some dimensions and heterogeneity along others in their study populations. Thus we argue that homogeneity and heterogeneity are situational properties – properties that scientists seek to achieve in their study populations, the available data, and other aspects of the research situation they are confronting, and then leverage to advance post-genomic science. Pointing to the situatedness of homogeneity and heterogeneity in gene–environment interaction research underscores the work that these properties do and the contingencies that shape decisions about research procedures. Through a focus on the situational production of homogeneity and heterogeneity more broadly, we find that gene–environment interaction research attempts to shift the logic of difference from solely racial terms as explanatory ends unto themselves, to racial and other dimensions of difference that may be important clues to the causes of complex diseases

Progressive age-associated activation of JNK associates with conduction disruption in the aged atrium.

Connexin43 (Cx43) is critical for maintaining electrical conduction across atrial muscle. During progressive aging cardiac conduction slows and becomes susceptible to disruption, predisposing to arrhythmias. Changes in Cx43 protein expression, or its phosphorylation status, can instigate changes in the conduction of the cardiac action potential. Our study investigated whether increased levels of activated c-jun N-terminal kinase (JNK) is the mechanism responsible for the decline of Cx43 protein and intercellular communication during progressive aging. We examined right atrial muscle from guinea pigs between 1 day and 38 months of age. The area of the intercalated disc increased with age concurrent with a 75% decline in total C43 protein expression and spatial re-organisation of the remaining protein. An age-dependent increase in activated-JNK correlated with a rise in phosphorylated Cx43. The data also correlated with slowing of the action potential conduction velocity across the right atria from 0.38±0.01 m/s at 1 month of age to 0.30±0.01 m/s at 38 months of age. The JNK activator anisomycin increased levels of activated JNK in myocytes and reduced Cx43 protein expression paralleling the aging effect The JNK inhibitor SP600125, was found to eradicate almost all trace of Cx43 protein from the intercalating discs. We conclude that in vivo activation of JNK increases with age leading to the loss of Cx43 protein from atrial myocytes. This progressive loss results in impaired conduction and is likely to contribute to the increasing risk of atrial arrhythmias with advancing age

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Patterns of adherence to and compliance with the Portuguese smoke-free law in the leisure-hospitality sector

CIEC – Research Centre on Child Studies, UM (FCT R&D 317)Background: In 2008, the Portuguese smoke-free law came into effect including partial bans in the leisure-hospitality (LH) sector. The objective of the study is to assess the prevalence of smoking control policies (total ban, smoking permission and designated smoking areas) adopted by the LH sector in Portugal. The levels of noncompliance with each policy are investigated as well as the main factors associated with smoking permission and noncompliance with the law. Methods: Cross-sectional study conducted between January 2010 and May 2011. A random sample of venues was selected from the Portuguese LH sector database, proportionally stratified according to type, size and geographical area. All venues were assessed in loco by an observer. The independent effects of venues’ characteristics on smoking permission and the level of noncompliance with the law were explored using logistic regression. Results: Overall, 1.412 venues were included. Total ban policy was adopted by 75.9% of venues, while 8.4% had designated smoking areas. Smoking ban was more prevalent in restaurants (85.9%). Only 29.7% of discos/bars/pubs opted for complete ban. Full or partial smoking permission was higher in discos/bar/pubs (OR = 7.37; 95%CI 4.87 to 11.17). Noncompliance with the law was higher in venues allowing smoking and lower in places with complete ban (33.6% and 7.6% respectively, p, 0.001). Discos/bars/pubs with full smoking permission had the highest level of noncompliance (OR = 3.31; 95%CI 1.40 to 7.83). Conclusions: Our findings show a high adherence to smoking ban policy by the Portuguese LH sector. Nonetheless, one quarter of the venues is fully or partially permissive towards smoking, with the discos/bars/pubs considerably contributing to this situation. Venues with smoking permission policies were less compliant with the legislation. The implementation of a comprehensive smoke-free law, without any exceptions, is essential to effectively protect people from the second hand smoke.The work is part of a large Epidemiological Study on the Portuguese Tobacco Control Policy, developed by the Instituto de Medicina Preventiva da Faculdade de Medicina de Lisboa and supported, in its preliminary part, by the Direccao Geral da Saude (DGS) and, in the second part, by the national funding institution Fundacao para a Ciencia e Tecnologia (FCT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Centile charts for birthweight for gestational age for Scottish singleton births

<p>Abstract</p> <p>Background</p> <p>Centile charts of birthweight for gestational age are used to identify low birthweight babies. The charts currently used in Scotland are based on data from the 1970s and require updating given changes in birthweight and in the measurement of gestational age since then.</p> <p>Methods</p> <p>Routinely collected data of 100,133 singleton births occurring in Scotland from 1998–2003 were used to construct new centile charts using the LMS method.</p> <p>Results</p> <p>Centile charts for birthweight for sex and parity groupings were constructed for singleton birth and compared to existing charts used in Scottish hospitals.</p> <p>Conclusion</p> <p>Mean birthweight has been shown to have increased over recent decades. The differences shown between the new and currently used centiles confirm the need for more up-to-date centiles for birthweight for gestational age.</p

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Risk Factors for Colonization with Extended-Spectrum β-Lactamase–producing Bacteria and Intensive Care Unit Admission

Coexisting conditions and previous antimicrobial drug exposure predict colonization

Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease

We identify an intronic deletion in VANGL1 that predisposes to renal injury in high risk populations through a kidney-intrinsic process. Half of all SLE patients develop nephritis, yet the predisposing mechanisms to kidney damage remain poorly understood. There is limited evidence of genetic contribution to specific organ involvement in SLE.(1,2) We identify a large deletion in intron 7 of Van Gogh Like 1 (VANGL1), which associates with nephritis in SLE patients. The same deletion occurs at increased frequency in an indigenous population (Tiwi Islanders) with 10-fold higher rates of kidney disease compared with non-indigenous populations. Vangl1 hemizygosity in mice results in spontaneous IgA and IgG deposition within the glomerular mesangium in the absence of autoimmune nephritis. Serum transfer into B cell-deficient Vangl1(+/-) mice results in mesangial IgG deposition indicating that Ig deposits occur in a kidney-intrinsic fashion in the absence of Vangl1. These results suggest that Vangl1 acts in the kidney to prevent Ig deposits and its deficiency may trigger nephritis in individuals with SLE