A coupled level set and volume of fluid method with a re-initialisation step suitable for unstructured meshes

This paper presents a coupling method of the level set and volume of fluid methods based on a simple local-gradient based re-initialisation approach that evaluates the distance function depending on the computational cell location. If a cell belongs to the interface, the signed distance is updated based on a search in the neighbouring cells and an interpolation procedure is applied depending on the local curvature or the sign of the level set function following [41]. The search algorithm does not distinguish between the upwind and downwind directions and hence it is able to be used for cells with an arbitrary number of faces increasing the robustness of the method. The coupling with the volume of fluid method is achieved by mapping the volume fraction field which is advected from the isoface evolution at a subgrid level. Consequently, the coupling with the level set approach is utilised without solving the level set equation. This coupled method provides better accuracy than the volume of fluid method alone and is capable of capturing sharp interfaces in all the classical numerical tests that are presented here

Prevalence of the metabolic syndrome in Luxembourg according to the Joint Interim Statement definition estimated from the ORISCAV-LUX study

ABSTRACT: BACKGROUND: The prevalence of the metabolic syndrome (MS) has been determined in many countries worldwide but never in Luxembourg. This research aimed to 1) establish the gender- and age-specific prevalence of MS and its components in the general adult population of Luxembourg, according to the most recent Joint Interim Statement (JIS) definition, by using both the high and low cut-off points to define abdominal obesity, and 2) compare and assess the degree of agreement with the Revised National Cholesterol Education Programme-Adult Treatment Panel III (R-ATPIII) and the International Diabetes Federation (IDF) definitions. METHODS: A representative stratified random sample of 1349 European subjects, aged 18-69 years, participated to ORISCAV-LUX survey. Logistic regression and odds ratios (OR) were used to study MS prevalence with respect to gender and age. The Framingham risk score (FRS) to predict the 10-year coronary heart disease (CHD) risk was calculated to compare the proportion of MS cases below or above 20%, according to both high and low waist circumference (WC) thresholds. Cohen's kappa coefficient (kappa) was utilized to measure the degree of agreement between MS definitions. RESULTS: The prevalence of the MS defined by the JIS was 28.0% and 24.7% when using the low (94/80) and the high (102/88) WC cut-off points, respectively. The prevalence was significantly higher in men than in women (OR = 2.6 and 2.3 for the low and high WC thresholds), as were all components of the MS except abdominal obesity measured by both thresholds. It also increased with age (OR values in age categories ranging from 2.7 to 28 when compared to the younger subjects for low WC and from 3.3 to 31 for the high WC cut-offs). The 10-year predicted risk of CHD by FRS did not depend on the threshold used. Globally, excellent agreement was observed between the three definitions of MS (kappa= 0.89), in particular between JIS and IDF (kappa = 0.93). Agreement was significantly higher in women than in men, and differed between age groups. CONCLUSION: Regardless of the definition used, the adult population of Luxembourg reveals a high MS prevalence. Our findings contribute to build evidence regarding the definitive construct of the MS, to help selecting the waist circumference thresholds for Europid populations, and to support the need to revise the guidelines for abdominal obesity levels

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

The Development of a Content Analysis Model for Assessing Students’ Cognitive Learning in Asynchronous Online Discussions

The purpose of this study was to develop and validate a content analysis model for assessing students\u27 cognitive learning in asynchronous online discussions. It adopted a fully mixed methods design, in which qualitative and quantitative methods were employed sequentially for data analysis and interpretation. Specifically, the design was a sequential exploratory (QUAL→ quan) design with priority given to qualitative data and methods. Qualitative data were 800 online postings collected in two online courses. Quantitative data were 803 online postings from the same two courses but from different discussion topics and different weeks. During the qualitative process, a grounded theory approach was adopted to construct a content analysis model based on qualitative data. During the quantitative process, chi-square tests and confirmative factor analysis (CFA) which used online postings as cases or observations and was the first of its kind were performed to test if the new model fit the quantitative data

Proximal correlates of metabolic phenotypes during ‘at-risk' and ‘case' stages of the metabolic disease continuum

Extent: 11p.OBJECTIVE: To examine the social and behavioural correlates of metabolic phenotypes during ‘at-risk’ and ‘case’ stages of the metabolic disease continuum. DESIGN: Cross-sectional study of a random population sample. PARTICIPANTS: A total of 718 community-dwelling adults (57% female), aged 18--92 years from a regional South Australian city. MEASUREMENTS: Total body fat and lean mass and abdominal fat mass were assessed by dual energy x-ray absorptiometry. Fasting venous blood was collected in the morning for assessment of glycated haemoglobin, plasma glucose, serum triglycerides, cholesterol lipoproteins and insulin. Seated blood pressure (BP) was measured. Physical activity and smoking, alcohol and diet (96-item food frequency), sleep duration and frequency of sleep disordered breathing (SDB) symptoms, and family history of cardiometabolic disease, education, lifetime occupation and household income were assessed by questionnaire. Current medications were determined by clinical inventory. RESULTS: 36.5% were pharmacologically managed for a metabolic risk factor or had known diabetes (‘cases’), otherwise were classified as the ‘at-risk’ population. In both ‘at-risk’ and ‘cases’, four major metabolic phenotypes were identified using principal components analysis that explained over 77% of the metabolic variance between people: fat mass/insulinemia (FMI); BP; lipidaemia/lean mass (LLM) and glycaemia (GLY). The BP phenotype was uncorrelated with other phenotypes in ‘cases’, whereas all phenotypes were inter-correlated in the ‘at-risk’. Over and above other socioeconomic and behavioural factors, medications were the dominant correlates of all phenotypes in ‘cases’ and SDB symptom frequency was most strongly associated with FMI, LLM and GLY phenotypes in the ‘at-risk’. CONCLUSION: Previous research has shown FMI, LLM and GLY phenotypes to be most strongly predictive of diabetes development. Reducing SDB symptom frequency and optimising the duration of sleep may be important concomitant interventions to standard diabetes risk reduction interventions. Prospective studies are required to examine this hypothesis.MT Haren, G Misan, JF Grant, JD Buckley, PRC Howe, AW Taylor, J Newbury and RA McDermot

Proximal correlates of metabolic phenotypes during ‘at-risk' and ‘case' stages of the metabolic disease continuum

Extent: 11p.OBJECTIVE: To examine the social and behavioural correlates of metabolic phenotypes during ‘at-risk’ and ‘case’ stages of the metabolic disease continuum. DESIGN: Cross-sectional study of a random population sample. PARTICIPANTS: A total of 718 community-dwelling adults (57% female), aged 18--92 years from a regional South Australian city. MEASUREMENTS: Total body fat and lean mass and abdominal fat mass were assessed by dual energy x-ray absorptiometry. Fasting venous blood was collected in the morning for assessment of glycated haemoglobin, plasma glucose, serum triglycerides, cholesterol lipoproteins and insulin. Seated blood pressure (BP) was measured. Physical activity and smoking, alcohol and diet (96-item food frequency), sleep duration and frequency of sleep disordered breathing (SDB) symptoms, and family history of cardiometabolic disease, education, lifetime occupation and household income were assessed by questionnaire. Current medications were determined by clinical inventory. RESULTS: 36.5% were pharmacologically managed for a metabolic risk factor or had known diabetes (‘cases’), otherwise were classified as the ‘at-risk’ population. In both ‘at-risk’ and ‘cases’, four major metabolic phenotypes were identified using principal components analysis that explained over 77% of the metabolic variance between people: fat mass/insulinemia (FMI); BP; lipidaemia/lean mass (LLM) and glycaemia (GLY). The BP phenotype was uncorrelated with other phenotypes in ‘cases’, whereas all phenotypes were inter-correlated in the ‘at-risk’. Over and above other socioeconomic and behavioural factors, medications were the dominant correlates of all phenotypes in ‘cases’ and SDB symptom frequency was most strongly associated with FMI, LLM and GLY phenotypes in the ‘at-risk’. CONCLUSION: Previous research has shown FMI, LLM and GLY phenotypes to be most strongly predictive of diabetes development. Reducing SDB symptom frequency and optimising the duration of sleep may be important concomitant interventions to standard diabetes risk reduction interventions. Prospective studies are required to examine this hypothesis.MT Haren, G Misan, JF Grant, JD Buckley, PRC Howe, AW Taylor, J Newbury and RA McDermot

Clofazimine Inhibits Human Kv1.3 Potassium Channel by Perturbing Calcium Oscillation in T Lymphocytes

The Kv1.3 potassium channel plays an essential role in effector memory T cells and has been implicated in several important autoimmune diseases including multiple sclerosis, psoriasis and type 1 diabetes. A number of potent small molecule inhibitors of Kv1.3 channel have been reported, some of which were found to be effective in various animal models of autoimmune diseases. We report herein the identification of clofazimine, a known anti-mycobacterial drug, as a novel inhibitor of human Kv1.3. Clofazimine was initially identified as an inhibitor of intracellular T cell receptor-mediated signaling leading to the transcriptional activation of human interleukin-2 gene in T cells from a screen of the Johns Hopkins Drug Library. A systematic mechanistic deconvolution revealed that clofazimine selectively blocked the Kv1.3 channel activity, perturbing the oscillation frequency of the calcium-release activated calcium channel, which in turn led to the inhibition of the calcineurin-NFAT signaling pathway. These effects of clofazimine provide the first line of experimental evidence in support of a causal relationship between Kv1.3 and calcium oscillation in human T cells. Furthermore, clofazimine was found to be effective in blocking human T cell-mediated skin graft rejection in an animal model in vivo. Together, these results suggest that clofazimine is a promising immunomodulatory drug candidate for treating a variety of autoimmune disorders

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Early changes in biochemical markers of bone turnover and their relationship with bone mineral density changes after 24 months of treatment with teriparatide

Summary We report the changes in biochemical markers of bone formation during the first 6 months of teriparatide therapy in postmenopausal women with osteoporosis according to previous antiresorptive treatment. Prior therapy does not adversely affect the response to teriparatide treatment. Similar bone markers levels are reached after 6 months of treatment. Introduction The response of biochemical markers of bone turnover with teriparatide therapy in subjects who have previously received osteoporosis drugs is not fully elucidated. We examined biochemical markers of bone formation in women with osteoporosis treated with teriparatide and determined: (1) whether the response is associated with prior osteoporosis therapy, (2) which marker shows the best performance for detecting a response to therapy, and (3) the correlations between early changes in bone markers and subsequent bone mineral density (BMD) changes after 24 months of teriparatide. Methods We conducted a prospective, open-label, 24-month study at 95 centers in 10 countries in 758 postmenopausal women with established osteoporosis (n = 181 treatment-naïve) who had at least one post-baseline bone marker determination. Teriparatide (20 μg/day) was administered for up to 24 months. We measured procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (b-ALP), and total alkaline phosphatase (t-ALP) at baseline, 1 and 6 months, and change in BMD at the lumbar spine, total hip and femoral neck from baseline to 24 months. Results Significant increases in formation markers occurred after 1 month of teriparatide regardless of prior osteoporosis therapy. The absolute increase at 1 month was lower in previously treated versus treatment-naïve patients, but after 6 months all groups reached similar levels. PINP showed the best signal-to-noise ratio. Baseline PINP correlated positively and significantly with BMD response at 24 months. Conclusions This study suggests that the long-term responsiveness of bone formation markers to teriparatide is not affected in subjects previously treated with antiresorptive drugs

Demand-side financing for maternal and newborn health: what do we know about factors that affect implementation of cash transfers and voucher programmes?

BackgroundDemand-side financing (DSF) interventions, including cash transfers and vouchers, have been introduced to promote maternal and newborn health in a range of low- and middle-income countries. These interventions vary in design but have typically been used to increase health service utilisation by offsetting some financial costs for users, or increasing household income and incentivising 'healthy behaviours'. This article documents experiences and implementation factors associated with use of DSF in maternal and newborn health.MethodsA secondary analysis (using an adapted Supporting the Use of Research Evidence framework - SURE) was performed on studies that had previously been identified in a systematic review of evidence on DSF interventions in maternal and newborn health.ResultsThe article draws on findings from 49 quantitative and 49 qualitative studies. The studies give insights on difficulties with exclusion of migrants, young and multiparous women, with demands for informal fees at facilities, and with challenges maintaining quality of care under increasing demand. Schemes experienced difficulties if communities faced long distances to reach participating facilities and poor access to transport, and where there was inadequate health infrastructure and human resources, shortages of medicines and problems with corruption. Studies that documented improved care-seeking indicated the importance of adequate programme scope (in terms of programme eligibility, size and timing of payments and voucher entitlements) to address the issue of concern, concurrent investments in supply-side capacity to sustain and/or improve quality of care, and awareness generation using community-based workers, leaders and women's groups. ConclusionsEvaluations spanning more than 15 years of implementation of DSF programmes reveal a complex picture of experiences that reflect the importance of financial and other social, geographical and health systems factors as barriers to accessing care. Careful design of DSF programmes as part of broader maternal and newborn health initiatives would need to take into account these barriers, the behaviours of staff and the quality of care in health facilities. Research is still needed on the policy context for DSF schemes in order to understand how they become sustainable and where they fit, or do not fit, with plans to achieve equitable universal health coverage