Supernova enrichment of planetary systems in low-mass star clusters

The presence and abundance of short lived radioisotopes (SLRs) $^{26}$Al and $^{60}$Fe in chondritic meteorites implies that the Sun formed in the vicinity of one or more massive stars that exploded as supernovae (SNe). Massive stars are more likely to form in massive star clusters ($>$1000 M$_{\odot}$) than lower mass clusters. However, photoevaporation of protoplanetary discs from massive stars and dynamical interactions with passing stars can inhibit planet formation in clusters with radii of $\sim$1 pc. We investigate whether low-mass (50 - 200 M$_{\odot}$) star clusters containing one or two massive stars are a more likely avenue for early Solar system enrichment as they are more dynamically quiescent. We analyse $N$-body simulations of the evolution of these low-mass clusters and find that a similar fraction of stars experience supernova enrichment than in high mass clusters, despite their lower densities. This is due to two-body relaxation, which causes a significant expansion before the first supernova even in clusters with relatively low (100 stars pc$^{-3}$) initial densities. However, because of the high number of low mass clusters containing one or two massive stars, the absolute number of enriched stars is the same, if not higher than for more populous clusters. Our results show that direct enrichment of protoplanetary discs from supernovae occurs as frequently in low mass clusters containing one or two massive stars (>20 M$_{\odot}$) as in more populous star clusters (1000 M$_\odot$). This relaxes the constraints on the direct enrichment scenario and therefore the birth environment of the Solar System

The Development and Transformation of Anglo-American Relations in Lawn Tennis around the Turn of the Twentieth Century

Anglo-American relations in tennis are a fascinating subject, particularly in the period of the late-19th/early-20th century, during which the developments seen both on and off court were reflective and indicative of broader societal shifts, as the US gradually replaced Britain as the world’s leading industrialized nation. The aims of this paper are to discuss how Anglo-American relations in lawn tennis shifted throughout this period, from when lawn tennis was “invented” in Britain to the onset of the Great War, and to contextualize these developments in the light of shifting geo-political/economic and cultural relations more generally between the two nations, alongside developments within sport and tennis more specifically. Shifts in the following areas are examined: attitudes toward and opinions of the relative standards of both American and British tennis players from the general public, correspondents and the media of the other nation, in terms of their overall rank and possibilities of success; and, attitudes from tennis officials toward the formal organization of competitions between players of both nations

Metabonomics and Intensive Care

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2016. Other selected articles can be found online at http://www.biomedcentral.com/collections/annualupdate2016. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901

Higher premorbid serum testosterone predicts COVID-19-related mortality risk in men.

Objective: Men are at greater risk from COVID-19 than women. Older, overweight men, and those with type 2 diabetes, have lower testosterone concentrations and poorer COVID-19-related outcomes. We analysed the associations of premorbid serum testosterone concentrations, not confounded by the effects of acute SARS-CoV-2 infection, with COVID-19-related mortality risk in men. Design: This study is a United Kingdom Biobank prospective cohort study of community-dwelling men aged 40-69 years. Methods: Serum total testosterone and sex hormone-binding globulin (SHBG) were measured at baseline (2006-2010). Free testosterone values were calculated (cFT). the incidence of SARS-CoV-2 infections and deaths related to COVID-19 were ascertained from 16 March 2020 to 31 January 2021 and modelled using time-stratified Cox regression. Results: In 159 964 men, there were 5558 SARS-CoV-2 infections and 438 COVID-19 deaths. Younger age, higher BMI, non-White ethnicity, lower educational attainment, and socioeconomic deprivation were associated with incidence of SARS-CoV-2 infections but total testosterone, SHBG, and cFT were not. Adjusting for potential confounders, higher total testosterone was associated with COVID-19-related mortality risk (overall trend P = 0.008; hazard ratios (95% CIs) quintile 1, Q1 vs Q5 (reference), 0.84 (0.65-1.12) Q2:Q5, 0.82 (0.63-1.10); Q3:Q5, 0.80 (0.66-1.00); Q4:Q5, 0.82 (0.75-0.93)). Higher SHBG was also associated with COVID-19 mortality risk (P = 0.008), but cFT was not (P = 0.248). Conclusions: Middle-aged to older men with the highest premorbid serum total testosterone and SHBG concentrations are at greater risk of COVID-19-related mortality. Men could be advised that having relatively high serum testosterone concentrations does not protect against future COVID-19-related mortality. Further investigation of causality and potential underlying mechanisms is warranted

Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF

© 2016 BMJ Publishing Group Ltd & British Thoracic Society.Rationale Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberrant proliferative responses. GSK2126458 is a novel, potent, PI3K/mammalian target of rapamycin (mTOR) inhibitor which has recently completed phase I trials in the oncology setting. Our aim was to establish a scientific and dosing framework for PI3K inhibition with this agent in IPF at a clinically developable dose. Methods We explored evidence for pathway signalling in IPF lung tissue and examined the potency of GSK2126458 in fibroblast functional assays and precision-cut IPF lung tissue. We further explored the potential of IPF patient-derived bronchoalveolar lavage (BAL) cells to serve as pharmacodynamic biosensors to monitor GSK2126458 target engagement within the lung. Results We provide evidence for PI3K pathway activation in fibrotic foci, the cardinal lesions in IPF. GSK2126458 inhibited PI3K signalling and functional responses in IPF-derived lung fibroblasts, inhibiting Akt phosphorylation in IPF lung tissue and BAL derived cells with comparable potency. Integration of these data with GSK2126458 pharmacokinetic data from clinical trials in cancer enabled modelling of an optimal dosing regimen for patients with IPF. Conclusions Our data define PI3K as a promising therapeutic target in IPF and provide a scientific and dosing framework for progressing GSK2126458 to clinical testing in this disease setting. A proof-ofmechanism trial of this agent is currently underway. Trial registration number NCT01725139, pre-clinical

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

Use of Ex Vivo Normothermic Perfusion for Quality Assessment of Discarded Human Donor Pancreases.

A significant number of pancreases procured for transplantation are deemed unsuitable due to concerns about graft quality and the associated risk of complications. However, this decision is subjective and some declined grafts may be suitable for transplantation. Ex vivo normothermic perfusion (EVNP) prior to transplantation may allow a more objective assessment of graft quality and reduce discard rates. We report ex vivo normothermic perfusion of human pancreases procured but declined for transplantation, with ABO-compatible warm oxygenated packed red blood cells for 1-2 h. Five declined human pancreases were assessed using this technique after a median cold ischemia time of 13 h 19 min. One pancreas, with cold ischemia over 30 h, did not appear viable and was excluded. In the remaining pancreases, blood flow and pH were maintained throughout perfusion. Insulin secretion was observed in all four pancreases, but was lowest in an older donation after cardiac death pancreas. Amylase levels were highest in a gland with significant fat infiltration. This is the first study to assess the perfusion, injury, as measured by amylase, and exocrine function of human pancreases using EVNP and demonstrates the feasibility of the approach, although further refinements are required.This study was financially supported by a grant from the Mason Medical Research Foundation.This is the author accepted manuscript. The final version is available via Wiley at http://onlinelibrary.wiley.com/doi/10.1111/ajt.13303/abstract

Optimising use of electronic health records to describe the presentation of rheumatoid arthritis in primary care: a strategy for developing code lists

Background Research using electronic health records (EHRs) relies heavily on coded clinical data. Due to variation in coding practices, it can be difficult to aggregate the codes for a condition in order to define cases. This paper describes a methodology to develop ‘indicator markers’ found in patients with early rheumatoid arthritis (RA); these are a broader range of codes which may allow a probabilistic case definition to use in cases where no diagnostic code is yet recorded. Methods We examined EHRs of 5,843 patients in the General Practice Research Database, aged ≥30y, with a first coded diagnosis of RA between 2005 and 2008. Lists of indicator markers for RA were developed initially by panels of clinicians drawing up code-lists and then modified based on scrutiny of available data. The prevalence of indicator markers, and their temporal relationship to RA codes, was examined in patients from 3y before to 14d after recorded RA diagnosis. Findings Indicator markers were common throughout EHRs of RA patients, with 83.5% having 2 or more markers. 34% of patients received a disease-specific prescription before RA was coded; 42% had a referral to rheumatology, and 63% had a test for rheumatoid factor. 65% had at least one joint symptom or sign recorded and in 44% this was at least 6-months before recorded RA diagnosis. Conclusion Indicator markers of RA may be valuable for case definition in cases which do not yet have a diagnostic code. The clinical diagnosis of RA is likely to occur some months before it is coded, shown by markers frequently occurring ≥6 months before recorded diagnosis. It is difficult to differentiate delay in diagnosis from delay in recording. Information concealed in free text may be required for the accurate identification of patients and to assess the quality of care in general practice

Explaining the human resource management preferences of employees: A study of Chinese workers

The forces of globalization, technology and the differences or similarities in institutional systems place substantial pressure on convergence and divergence in HRM practices. Moreover, local customs and the responses from employees also pose serious constraints on the degree of convergence or divergence (Rowley and Benson 2002). In other words, there is what might be termed an upward influence coming from the employees. Although companies may benchmark HRM ‘best practices’, the actual adoption and success of these practices depends, to a large extent, on perceptions and acceptance from employees. However, the opinions of non-managerial employees have been largely neglected in the studies of HRM (Cooke 2009; Legge 1995; Guest 2002; Edgar and Geare 2005; Qiao, Khilji and Wang 2009). Cooke (2009), after reviewing studies on HRM in China published between 1998 and 2007 in major business and management journals, reported that two-thirds of the studies had collected data from managers and most of them relied on managers as the sole source for information. Since the information has mainly been provided by managers, there is the potential for bias because feedback from the managers probably reflects the ideal or ‘best practices’ of HRM that those managers want to implement, rather than the actual HR policies or practices being used in the organization. Thus Cooke (2009, p.19) argued that ‘unless we can broaden our research catchment to include views from the widest range of stakeholders, particularly the employees, our understanding of HRM in China remains partial, from management’s lens’. This study explores the HR preferences of Chinese employees, both non-managerial and managerial ones, based on a sample of 2852 questionnaires from companies in China. A number of questions are explored. For example, what do they think of a ‘promotion-from-within’ policy? Do they prefer an individual-based bonus or a group-based bonus? Do they prefer a ‘downward performance appraisal method’ or a ‘multi-source performance appraisal method’? The research findings shows a strong ‘group orientation’ and a great emphasis on ‘soft factors’ such as seniority, loyalty and connections in many HRM areas. The debate on whether Chinese HRM will converge or diverge towards the Western models is still ongoing. Many argue that there could be further convergence towards the Western practices because globalization may place substantial pressure on firms to standardize practices and policies (see Chen, Lawler and Bae 2005). Others argue that HRM is highly context specific in which institutional and cultural forces have enduring influences (see Rowley and Cooke 2010), which indicates a divergent perspective. The third group supports a ‘cross-vergence’ view which argues that there will be signs of convergence in certain areas but Chinese HRM will keep its ‘Chinese characteristics’ (Cooke 2005, 2010; Yeung, Warner and Rowley 2008; Warner 2009a, b). This study supports the ‘cross-vergence’ perspective. It is argued that certain areas of Chinese HRM are converging to the Western model, but the influence of traditional Chinese personnel practices remains strong. A ‘group orientation’, a major emphasis on ‘soft factors’ and a trade union presence is likely to remain as the three main features of Chinese HRM in the long-term