Human Neurobrucellosis with Intracerebral Granuloma Caused by a Marine Mammal Brucella spp.

We present the first report of community-acquired human infections with marine mammal–associated Brucella spp. and describe the identification of these strains in two patients with neurobrucellosis and intracerebral granulomas. The identification of these isolates as marine mammal strains was based on omp2a sequence and amplification of the region flanking bp26

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes

The roles of specialisation and evidence-based practice in inter-professional jurisdictions : a qualitative study of stroke services in England, Sweden and Poland

This paper investigates how the concepts of clinical specialisation and evidence influence the jurisdictional power of doctors, nurses and therapists involved in stroke care in Sweden, England and Poland. How stroke care has become a distinct specialism across Europe and the role that evidence has played in this development are critically analysed. Five qualitative case studies were undertaken across the three countries, consisting of 119 semi-structured interviews with a range of healthcare workers. The informants were purposively selected and their perspectives of evidence-based practice (EBP) within stroke care were explored. The data were analysed through thematic content analysis. The two key themes that emerged from the data were the health professionals' degrees of EBP and specialisation. The results illustrate how the two concepts of clinical specialisation and evidence are interrelated and work together to influence the different professions' degree of professional jurisdiction. It is concluded that doctors' professional dominance gives them full jurisdiction in stroke care and that nurses' and therapists' degrees of jurisdiction is dependent on their ability to specialise

Integrative Analysis of Epigenetic Modulation in Melanoma Cell Response to Decitabine: Clinical Implications

Decitabine, an epigenetic modifier that reactivates genes otherwise suppressed by DNA promoter methylation, is effective for some, but not all cancer patients, especially those with solid tumors. It is commonly recognized that to overcome resistance and improve outcome, treatment should be guided by tumor biology, which includes genotype, epigenotype, and gene expression profile. We therefore took an integrative approach to better understand melanoma cell response to clinically relevant dose of decitabine and identify complementary targets for combined therapy. We employed eight different melanoma cell strains, determined their growth, apoptotic and DNA damage responses to increasing doses of decitabine, and chose a low, clinically relevant drug dose to perform whole-genome differential gene expression, bioinformatic analysis, and protein validation studies. The data ruled out the DNA damage response, demonstrated the involvement of p21Cip1 in a p53-independent manner, identified the TGFβ pathway genes CLU and TGFBI as markers of sensitivity to decitabine and revealed an effect on histone modification as part of decitabine-induced gene expression. Mutation analysis and knockdown by siRNA implicated activated β-catenin/MITF, but not BRAF, NRAS or PTEN mutations as a source for resistance. The importance of protein stability predicted from the results was validated by the synergistic effect of Bortezomib, a proteasome inhibitor, in enhancing the growth arrest of decitabine in otherwise resistant melanoma cells. Our integrative analysis show that improved therapy can be achieved by comprehensive analysis of cancer cells, identified biomarkers for patient's selection and monitoring response, as well as targets for improved combination therapy

A Decade of Incorporating Social Sciences in the Integrated Marine Biosphere Research Project (IMBeR): Much Done, Much to Do?

Successful management and mitigation of marine challenges depends on cooperation and knowledge sharing which often occurs across culturally diverse geographic regions. Global ocean science collaboration is therefore essential for developing global solutions. Building effective global research networks that can enable collaboration also need to ensure inter- and transdisciplinary research approaches to tackle complex marine socio-ecological challenges. To understand the contribution of interdisciplinary global research networks to solving these complex challenges, we use the Integrated Marine Biosphere Research (IMBeR) project as a case study. We investigated the diversity and characteristics of 1,827 scientists from 11 global regions who were attendees at different IMBeR global science engagement opportunities since 2009. We also determined the role of social science engagement in natural science based regional programmes (using key informants) and identified the potential for enhanced collaboration in the future. Event attendees were predominantly from western Europe, North America, and East Asia. But overall, in the global network, there was growing participation by females, students and early career researchers, and social scientists, thus assisting in moving toward interdisciplinarity in IMBeR research. The mainly natural science oriented regional programmes showed mixed success in engaging and collaborating with social scientists. This was mostly attributed to the largely natural science (i.e., biological, physical) goals and agendas of the programmes, and the lack of institutional support and push to initiate connections with social science. Recognising that social science research may not be relevant to all the aims and activities of all regional programmes, all researchers however, recognised the (potential) benefits of interdisciplinarity, which included broadening scientists’ understanding and perspectives, developing connections and interlinkages, and making science more useful. Pathways to achieve progress in regional programmes fell into four groups: specific funding, events to come together, within-programme-reflections, and social science champions. Future research programmes should have a strategic plan to be truly interdisciplinary, engaging natural and social sciences, as well as aiding early career professionals to actively engage in such programmes.This publication resulted in part from support from the U.S. National Science Foundation (Grant OCE-1840868) to the Scientific Committee on Oceanic Research (SCOR)

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Technically advanced and SF6-free 145 kV blue GIS

SF6, the most commonly used arc extinguishing and insulating gas in gas-insulated switchgears (GIS), is a greenhouse gas with high global warming potential, requiring careful handling throughout its life cycle. In order to reduce the GIS-related global warming impact, innovative solutions using alternative gases have been developed by different manufacturers, especially the blue GIS from Siemens – available for 145 kV / 40 kA / 3150 A – with clean air insulation and vacuum switching technology shows many technical advantages