Parallel-propagating Fluctuations at Proton-kinetic Scales in the Solar Wind are Dominated by Kinetic Instabilities

We use magnetic helicity to characterise solar wind fluctuations at proton-kinetic scales from Wind observations. For the first time, we separate the contributions to helicity from fluctuations propagating at angles quasi-parallel and oblique to the local mean magnetic field, $\mathbf{B}_0$. We find that the helicity of quasi-parallel fluctuations is consistent with Alfv\'en-ion cyclotron and fast magnetosonic-whistler modes driven by proton temperature anisotropy instabilities and the presence of a relative drift between $\alpha$-particles and protons. We also find that the helicity of oblique fluctuations has little dependence on proton temperature anisotropy and is consistent with fluctuations from the anisotropic turbulent cascade. Our results show that parallel-propagating fluctuations at proton-kinetic scales in the solar wind are dominated by proton temperature anisotropy instabilities and not the turbulent cascade. We also provide evidence that the behaviour of fluctuations at these scales is independent of the origin and macroscopic properties of the solar wind.Comment: Accepted for publication in ApJL. 6 Pages, 3 figures, 1 tabl

SBML qualitative models: a model representation format and infrastructure to foster interactions between qualitative modelling formalisms and tools

Background: Qualitative frameworks, especially those based on the logical discrete formalism, are increasingly used to model regulatory and signalling networks. A major advantage of these frameworks is that they do not require precise quantitative data, and that they are well-suited for studies of large networks. While numerous groups have developed specific computational tools that provide original methods to analyse qualitative models, a standard format to exchange qualitative models has been missing. Results: We present the Systems Biology Markup Language (SBML) Qualitative Models Package (“qual”), an extension of the SBML Level 3 standard designed for computer representation of qualitative models of biological networks. We demonstrate the interoperability of models via SBML qual through the analysis of a specific signalling network by three independent software tools. Furthermore, the collective effort to define the SBML qual format paved the way for the development of LogicalModel, an open-source model library, which will facilitate the adoption of the format as well as the collaborative development of algorithms to analyse qualitative models. Conclusions: SBML qual allows the exchange of qualitative models among a number of complementary software tools. SBML qual has the potential to promote collaborative work on the development of novel computational approaches, as well as on the specification and the analysis of comprehensive qualitative models of regulatory and signalling networks

CD or not CD, that is the question - a digital interobserver agreement study in coeliac disease

OBJECTIVE: Coeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of IgA tTG and haemoglobin (Hb) data improves the inter-observer agreement of diagnosis.DESIGN: We undertook a large study of the concordance in histological examination of duodenal biopsies using digitised WSIs in an entirely virtual reporting setting. Our study was organised in two phases: in phase one, 13 pathologists independently classified 100 duodenal biopsies (40 normal; 40 CD; 20 indeterminate enteropathy) in the absence of any clinical or laboratory data. In phase two, the same pathologists examined the (re-anonymised) WSIs with the inclusion of IgA tTG and Hb data.RESULTS: We found the mean probability of two observers agreeing in the absence of additional data to be 0.73 (±0.08) with a corresponding Cohen's kappa of 0.59 (±0.11). We further showed that the inclusion of additional data increased the concordance to 0.80 (±0.06) with a Cohen's kappa coefficient of 0.67 (±0.09).CONCLUSION: We showed that the addition of serological data significantly improves the quality of CD diagnosis. However, the limited inter-observer agreement in CD diagnosis using digitised WSIs, even after the inclusion of IgA tTG and Hb data, indicates the important of interpreting duodenal biopsy in the appropriate clinical context. It further highlights the unmet need for an objective means of reproducible duodenal biopsy diagnosis, such as the automated analysis of WSIs using AI.<br/

Atlas of the clinical genetics of human dilated cardiomyopathy

[Abstract] Aim. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results. In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion. This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.Hôpitaux de Paris; PHRC AOM0414

The challenge of contributing to policy making in primary care: The gendered experiences and strategies of nurses

This paper explores nurses' experiences as members of primary care organisations set up to develop and commission health services for local communities. Nurses, alongside GPs and other health professionals, were given a place on the governing bodies (boards) of Local Health Groups - a move widely welcomed by the nursing profession as long overdue recognition of the important contribution nurses and nursing could bring to the policy arena. Nurse board members faced a number of challenges in their attempts to contribute to and influence local health policy. This ethnographic study (which involved non-participant observation of 33 board meetings and interviews with 29 board members including nurses) suggests that medical authority and control, and hierarchical power relations between doctors and nurses on the board, were seen by nurses as significant obstacles to their participation in this new policy arena. In response to their perceived lack of power and subordinate status, nurses employed a number of strategies to negotiate their participation as board members - these included 'getting it right', 'achieving the right balance', 'self-presentation' and 'unassertiveness'. These strategies reflected and reproduced gendered identities and relations of power and raise important questions regarding the influence of nurses and nursing within policy making. © 2010 The Author. Sociology of Health & Illness © 2010 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Assumption without representation: the unacknowledged abstraction from communities and social goods

We have not clearly acknowledged the abstraction from unpriceable “social goods” (derived from communities) which, different from private and public goods, simply disappear if it is attempted to market them. Separability from markets and economics has not been argued, much less established. Acknowledging communities would reinforce rather than undermine them, and thus facilitate the production of social goods. But it would also help economics by facilitating our understanding of – and response to – financial crises as well as environmental destruction and many social problems, and by reducing the alienation from economics often felt by students and the public

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Returns on investment in wild dog management-beef production in the South Australian Arid Lands

Beef cattle producers in Australia have reported an increase in calf losses as a result of wild dog attacks in recent years. However, while control measures may reduce calf losses from wild dog attacks, they may also reduce attacks on kangaroos. Thus, wild dog control measures may inadvertently increase kangaroo competition with cattle for grazing vegetation, which is potentially costly for graziers. In this study the net returns to beef production from investments in wild dog controls in a case study area—omitting the social and environmental effect of wild dogs—is assessed. The case study area for this study includes the natural resource management district groups of Marla–Oodnadatta and Marree–Innamincka, in the South Australian Arid Lands. A bioeconomic livestock model is developed to estimate the benefits of South Australian wild dog control programs to reduce calf losses. A decision to control wild dogs will depend on the magnitude of the benefits of wild dog management relative to the costs of increased kangaroo competition for grazing vegetation. Results indicate that the decision to implement wild dog control—based solely on the net benefits from beef production—will vary with changes in the rate of increase in calf deaths, the extent of kangaroo competition for grazing vegetation and the net value of livestock