Comprehensive annotation of the Parastagonospora nodorum reference genome using next-generation genomics, transcriptomics and proteogenomics

Parastagonospora nodorum, the causal agent of Septoria nodorum blotch (SNB), is an economically important pathogen of wheat (Triticum spp.), and a model for the study of necrotrophic pathology and genome evolution. The reference P. nodorum strain SN15 was the first Dothideomycete with a published genome sequence, and has been used as the basis for comparison within and between species. Here we present an updated reference genome assembly with corrections of SNP and indel errors in the underlying genome assembly from deep resequencing data as well as extensive manual annotation of gene models using transcriptomic and proteomic sources of evidence (https://github.com/robsyme/Parastagonospora_nodorum_SN15). The updated assembly and annotation includes 8,366 genes with modified protein sequence and 866 new genes. This study shows the benefits of using a wide variety of experimental methods allied to expert curation to generate a reliable set of gene models

Phenotypic characterisation of regulatory T cells in dogs reveals signature transcripts conserved in humans and mice

Regulatory T cells (Tregs) are a double-edged regulator of the immune system. Aberrations of Tregs correlate with pathogenesis of inflammatory, autoimmune and neoplastic disorders. Phenotypically and functionally distinct subsets of Tregs have been identified in humans and mice on the basis of their extensive portfolios of monoclonal antibodies (mAb) against Treg surface antigens. As an important veterinary species, dogs are increasingly recognised as an excellent model for many human diseases. However, insightful study of canine Tregs has been restrained by the limited availability of mAb. We therefore set out to characterise CD4+CD25high T cells isolated ex vivo from healthy dogs and showed that they possess a regulatory phenotype, function, and transcriptomic signature that resembles those of human and murine Tregs. By launching a cross-species comparison, we unveiled a conserved transcriptomic signature of Tregs and identified that transcript hip1 may have implications in Treg function

Pan-cancer deconvolution of tumour composition using DNA methylation

The nature and extent of immune cell infiltration into solid tumours are key determinants of therapeutic response. Here, using a DNA methylation-based approach to tumour cell fraction deconvolution, we report the integrated analysis of tumour composition and genomics across a wide spectrum of solid cancers. Initially studying head and neck squamous cell carcinoma, we identify two distinct tumour subgroups: ‘immune hot’ and ‘immune cold’, which display differing prognosis, mutation burden, cytokine signalling, cytolytic activity and oncogenic driver events. We demonstrate the existence of such tumour subgroups pan-cancer, link clonal-neoantigen burden to cytotoxic T-lymphocyte infiltration, and show that transcriptional signatures of hot tumours are selectively engaged in immunotherapy responders. We also find that treatment-naive hot tumours are markedly enriched for known immune-resistance genomic alterations, potentially explaining the heterogeneity of immunotherapy response and prognosis seen within this group. Finally, we define a catalogue of mediators of active antitumour immunity, deriving candidate biomarkers and potential targets for precision immunotherapy

Youth unemployment and active labor market policies in Europe

Since the economic crisis in 2008, European youth unemployment rates have been persistently high at around 20% on average. The majority of European countries spends significant resources each year on active labor market programs (ALMP) with the aim of improving the integration prospects of struggling youths. Among the most common programs used are training courses, job search assistance and monitoring, subsidized employment, and public work programs. For policy makers, it is of upmost importance to know which of these programs work and which are able to achieve the intended goals – may it be the integration into the first labor market or further education. Based on a detailed assessment of the particularities of the youth labor market situation, we discuss the pros and cons of different ALMP types. We then provide a comprehensive survey of the recent evidence on the effectiveness of these ALMP for youth in Europe, highlighting factors that seem to promote or impede their effectiveness in practice. Overall, the findings with respect to employment outcomes are only partly promising. While job search assistance (with and without monitoring) results in overwhelmingly positive effects, we find more mixed effects for training and wage subsidies, whereas the effects for public work programs are clearly negative. The evidence on the impact of ALMP on furthering education participation as well as employment quality is scarce, requiring additional research and allowing only limited conclusions so far

Training Evaluation in a Learning Organization and Online Training Through the E-booklet Contribution of Game Theory and Shapley Value

International audienc

Implementation of infection control best practice in intensive care units throughout Europe: a mixed-method evaluation study

BACKGROUND: The implementation of evidence-based infection control practices is essential, yet challenging for healthcare institutions worldwide. Although acknowledged that implementation success varies with contextual factors, little is known regarding the most critical specific conditions within the complex cultural milieu of varying economic, political, and healthcare systems. Given the increasing reliance on unified global schemes to improve patient safety and healthcare effectiveness, research on this topic is needed and timely. The 'InDepth' work package of the European FP7 Prevention of Hospital Infections by Intervention and Training (PROHIBIT) consortium aims to assess barriers and facilitators to the successful implementation of catheter-related bloodstream infection (CRBSI) prevention in intensive care units (ICU) across several European countries. METHODS: We use a qualitative case study approach in the ICUs of six purposefully selected acute care hospitals among the 15 participants in the PROHIBIT CRBSI intervention study. For sensitizing schemes we apply the theory of diffusion of innovation, published implementation frameworks, sensemaking, and new institutionalism. We conduct interviews with hospital health providers/agents at different organizational levels and ethnographic observations, and conduct rich artifact collection, and photography during two rounds of on-site visits, once before and once one year into the intervention. Data analysis is based on grounded theory. Given the challenge of different languages and cultures, we enlist the help of local interpreters, allot two days for site visits, and perform triangulation across multiple data sources. Qualitative measures of implementation success will consider the longitudinal interaction between the initiative and the institutional context. Quantitative outcomes on catheter-related bloodstream infections and performance indicators from another work package of the consortium will produce a final mixed-methods report. CONCLUSION: A mixed-methods study of this scale with longitudinal follow-up is unique in the field of infection control. It highlights the 'Why' and 'How' of best practice implementation, revealing key factors that determine success of a uniform intervention in the context of several varying cultural, economic, political, and medical systems across Europe. These new insights will guide future implementation of more tailored and hence more successful infection control programs

Distinct microRNA signatures in human lymphocyte subsets and enforcement of the naive state in CD4+ T cells by the microRNA miR-125b.

MicroRNAs are small noncoding RNAs that regulate gene expression post-transcriptionally. Here we applied microRNA profiling to 17 human lymphocyte subsets to identify microRNA signatures that were distinct among various subsets and different from those of mouse lymphocytes. One of the signature microRNAs of naive CD4+ T cells, miR-125b, regulated the expression of genes encoding molecules involved in T cell differentiation, including IFNG, IL2RB, IL10RA and PRDM1. The expression of synthetic miR-125b and lentiviral vectors encoding the precursor to miR-125b in naive lymphocytes inhibited differentiation to effector cells. Our data provide an 'atlas' of microRNA expression in human lymphocytes, define subset-specific signatures and their target genes and indicate that the naive state of T cells is enforced by microRNA