Microdevices for extensional rheometry of low viscosity elastic liquids : a review

Extensional flows and the underlying stability/instability mechanisms are of extreme relevance to the efficient operation of inkjet printing, coating processes and drug delivery systems, as well as for the generation of micro droplets. The development of an extensional rheometer to characterize the extensional properties of low viscosity fluids has therefore stimulated great interest of researchers, particularly in the last decade. Microfluidics has proven to be an extraordinary working platform and different configurations of potential extensional microrheometers have been proposed. In this review, we present an overview of several successful designs, together with a critical assessment of their capabilities and limitations

High Levels of Sediment Contamination Have Little Influence on Estuarine Beach Fish Communities

While contaminants are predicted to have measurable impacts on fish assemblages, studies have rarely assessed this potential in the context of natural variability in physico-chemical conditions within and between estuaries. We investigated links between the distribution of sediment contamination (metals and PAHs), physico-chemical variables (pH, salinity, temperature, turbidity) and beach fish assemblages in estuarine environments. Fish communities were sampled using a beach seine within the inner and outer zones of six estuaries that were either heavily modified or relatively unmodified by urbanization and industrial activity. All sampling was replicated over two years with two periods sampled each year. Shannon diversity, biomass and abundance were all significantly higher in the inner zone of estuaries while fish were larger on average in the outer zone. Strong differences in community composition were also detected between the inner and outer zones. Few differences were detected between fish assemblages in heavily modified versus relatively unmodified estuaries despite high concentrations of sediment contaminants in the inner zones of modified estuaries that exceeded recognized sediment quality guidelines. Trends in species distributions, community composition, abundance, Shannon diversity, and average fish weight were strongly correlated to physico-chemical variables and showed a weaker relationship to sediment metal contamination. Sediment PAH concentrations were not significantly related to the fish assemblage. These findings suggest that variation in some physico-chemical factors (salinity, temperature, pH) or variables that co-vary with these factors (e.g., wave activity or grain size) have a much greater influence on this fish assemblage than anthropogenic stressors such as contamination

General practitioners' satisfaction with and attitudes to out-of-hours services

BACKGROUND: In recent years, Dutch general practitioner (GP) out-of-hours service has been reorganised into large-scale GP cooperatives. Until now little is known about GPs' experiences with working at these cooperatives for out-of-hours care. The purpose of this study is to gain insight into GPs' satisfaction with working at GP cooperatives for out-of-hours care in separated and integrated cooperatives. METHODS: A GP cooperative separate from the hospital Accident and Emergency (A&E) department, and a GP cooperative integrated within the A&E department of another hospital. Both cooperatives are situated in adjacent geographic regions in the South of the Netherlands. One hundred GPs were interviewed by telephone; fifty GPs working at the separated GP cooperative and fifty GPs from the integrated GP cooperative. Opinions on different aspects of GP cooperatives for out-of-hours care were measured, and regression analysis was performed to investigate if these could be related to GP satisfaction with out-of-hours care organisation. RESULTS: GPs from the separated model were more satisfied with the organisation of out-of-hours care than GPs from the integrated model (70 vs. 60 on a scale score from 0 to 100; P = 0.020). Satisfaction about out-of-hours care organisation was related to opinions on workload, guarantee of gatekeeper function, and attitude towards out-of-hours care as being an essential part of general practice. Cooperation with medical specialists was much more appreciated at the integrated model (77 vs. 48; P < 0.001) versus the separated model. CONCLUSION: GPs in this study appear to be generally satisfied with the organisation of GP cooperatives for out-of-hours care. Furthermore, GPs working at the separated cooperative seem to be more satisfied compared to GPs working at the integrated cooperative

The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer

Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al

Prediction of Thrombectomy Functional Outcomes using Multimodal Data

Recent randomised clinical trials have shown that patients with ischaemic stroke {due to occlusion of a large intracranial blood vessel} benefit from endovascular thrombectomy. However, predicting outcome of treatment in an individual patient remains a challenge. We propose a novel deep learning approach to directly exploit multimodal data (clinical metadata information, imaging data, and imaging biomarkers extracted from images) to estimate the success of endovascular treatment. We incorporate an attention mechanism in our architecture to model global feature inter-dependencies, both channel-wise and spatially. We perform comparative experiments using unimodal and multimodal data, to predict functional outcome (modified Rankin Scale score, mRS) and achieve 0.75 AUC for dichotomised mRS scores and 0.35 classification accuracy for individual mRS scores.Comment: Accepted at Medical Image Understanding and Analysis (MIUA) 202

Evidence based post graduate training. A systematic review of reviews based on the WFME quality framework

<p>Abstract</p> <p>Background</p> <p>A framework for high quality in post graduate training has been defined by the World Federation of Medical Education (WFME). The objective of this paper is to perform a systematic review of reviews to find current evidence regarding aspects of quality of post graduate training and to organise the results following the 9 areas of the WFME framework.</p> <p>Methods</p> <p>The systematic literature review was conducted in 2009 in Medline Ovid, EMBASE, ERIC and RDRB databases from 1995 onward. The reviews were selected by two independent researchers and a quality appraisal was based on the SIGN tool.</p> <p>Results</p> <p>31 reviews met inclusion criteria. The majority of the reviews provided information about the training process (WFME area 2), the assessment of trainees (WFME area 3) and the trainees (WFME area 4). One review covered the area 8 'governance and administration'. No review was found in relation to the mission and outcomes, the evaluation of the training process and the continuous renewal (respectively areas 1, 7 and 9 of the WFME framework).</p> <p>Conclusions</p> <p>The majority of the reviews provided information about the training process, the assessment of trainees and the trainees. Indicators used for quality assessment purposes of post graduate training should be based on this evidence but further research is needed for some areas in particular to assess the quality of the training process.</p

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrPSc negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed

A New Method for the Characterization of Strain-Specific Conformational Stability of Protease-Sensitive and Protease-Resistant PrPSc

Although proteinacious in nature, prions exist as strains with specific self-perpetuating biological properties. Prion strains are thought to be associated with different conformers of PrPSc, a disease-associated isoform of the host-encoded cellular protein (PrPC). Molecular strain typing approaches have been developed which rely on the characterization of protease-resistant PrPSc. However, PrPSc is composed not only of protease-resistant but also of protease-sensitive isoforms. The aim of this work was to develop a protocol for the molecular characterization of both, protease-resistant and protease-sensitive PrPSc aggregates. We first set up experimental conditions which allowed the most advantageous separation of PrPC and PrPSc by means of differential centrifugation. The conformational solubility and stability assay (CSSA) was then developed by measuring PrPSc solubility as a function of increased exposure to GdnHCl. Brain homogenates from voles infected with human and sheep prion isolates were analysed by CSSA and showed strain-specific conformational stabilities, with mean [GdnHCl]1/2 values ranging from 1.6 M for MM2 sCJD to 2.1 for scrapie and to 2.8 M for MM1/MV1 sCJD and E200K gCJD. Interestingly, the rank order of [GdnHCl]1/2 values observed in the human and sheep isolates used as inocula closely matched those found following transmission in voles, being MM1 sCJD the most resistant (3.3 M), followed by sheep scrapie (2.2 M) and by MM2 sCJD (1.6 M). In order to test the ability of CSSA to characterise protease-sensitive PrPSc, we analysed sheep isolates of Nor98 and compared them to classical scrapie isolates. In Nor98, insoluble PrPSc aggregates were mainly protease-sensitive and showed a conformational stability much lower than in classical scrapie. Our results show that CSSA is able to reveal strain-specified PrPSc conformational stabilities of protease-resistant and protease-sensitive PrPSc and that it is a valuable tool for strain typing in natural hosts, such as humans and sheep