Seladelpar treatment reduces interleukin-31 and pruritus in patients with primary biliary cholangitis

BACKGROUND AND AIMS: Pruritus is a debilitating symptom for many people living with primary biliary cholangitis (PBC). In studies with seladelpar, a selective PPAR-delta agonist, PBC patients experienced significant improvement in pruritus and reduction of serum bile acids. Interleukin-31 (IL-31) is a cytokine known to mediate pruritus and blocking IL-31 signaling provides relief in pruritic skin diseases. This study examined the connection between seladelpar's anti-pruritic effects, IL-31 and bile acid levels in PBC patients. APPROACH AND RESULTS: IL-31 levels were quantified in serum samples from the ENHANCE study of PBC patients receiving daily oral doses of placebo (n=55), seladelpar 5 mg (n=53) or 10 mg (n=53) for 3 months and for healthy volunteers (n=55). IL-31 levels were compared with pruritus using a numerical rating scale (NRS, 0-10) and with bile acid levels. Baseline IL-31 levels closely correlated with pruritus NRS (r=0.54, p<0.0001), and total (r=0.54, p<0.0001) and conjugated bile acids (up to 0.64, p<0.0001). Decreases in IL-31 were observed with seladelpar 5 mg (-30%, p=0.0003) and 10 mg (-52%, p<0.0001) versus placebo (+31%). Patients with clinically meaningful improvement in pruritus (NRS≥2 decrease) demonstrated greater dose-dependent reductions in IL-31 compared to those without pruritus improvement (NRS<2 decrease). Strong correlations were observed for the changes between levels of IL-31 and total bile acids (r=0.63, p<0.0001) in the seladelpar 10 mg group. CONCLUSIONS: Seladelpar decreased serum IL-31 and bile acids in PBC patients. The reductions of IL-31 and bile acids correlated closely with each other and pruritus improvement suggesting a mechanism to explain seladelpar's anti-pruritic effects

Whole genome sequencing and phylogenetic analysis of \u3ci\u3eBluetongue virus\u3c/i\u3e serotype 2 strains isolated in the Americas including a novel strain from the western United States

Bluetongue is a potentially fatal arboviral disease of domestic and wild ruminants that is characterized by widespread edema and tissue necrosis. Bluetongue virus (BTV) serotypes 10, 11, 13, and 17 occur throughout much of the United States, whereas serotype 2 (BTV-2) was previously only detected in the southeastern United States. Since 1998, 10 other BTV serotypes have also been isolated from ruminants in the southeastern United States. In 2010, BTV-2 was identified in California for the first time, and preliminary sequence analysis indicated that the virus isolate was closely related to BTV strains circulating in the southeastern United States. In the current study, the whole genome sequence of the California strain of BTV-2 was compared with those of other BTV-2 strains in the Americas. The results of the analysis suggest co-circulation of genetically distinct viruses in the southeastern United States, and further suggest that the 2010 western isolate is closely related to southeastern strains of BTV. Although it remains uncertain as to how this novel virus was translocated to California, the findings of the current study underscore the need for ongoing surveillance of this economically important livestock disease

Planet Hunters: Assessing the Kepler Inventory of Short Period Planets

We present the results from a search of data from the first 33.5 days of the Kepler science mission (Quarter 1) for exoplanet transits by the Planet Hunters citizen science project. Planet Hunters enlists members of the general public to visually identify transits in the publicly released Kepler light curves via the World Wide Web. Over 24,000 volunteers reviewed the Kepler Quarter 1 data set. We examine the abundance of \geq 2 R\oplus planets on short period (< 15 days) orbits based on Planet Hunters detections. We present these results along with an analysis of the detection efficiency of human classifiers to identify planetary transits including a comparison to the Kepler inventory of planet candidates. Although performance drops rapidly for smaller radii, \geq 4 R\oplus Planet Hunters \geq 85% efficient at identifying transit signals for planets with periods less than 15 days for the Kepler sample of target stars. Our high efficiency rate for simulated transits along with recovery of the majority of Kepler \geq 4 R\oplus planets suggest suggests the Kepler inventory of \geq 4 R\oplus short period planets is nearly complete.Comment: 41 pages,13 figures, 8 tables, accepted to Ap

Rapid climate-driven circulation changes threaten conservation of endangered north atlantic right whales

As climate trends accelerate, ecosystems will be pushed rapidly into new states, reducing the potential efficacy of conservation strategies based on historical patterns. In the Gulf of Maine, climate-driven changes have restructured the ecosystem rapidly over the past decade. Changes in the Atlantic meridional overturning circulation have altered deepwater dynamics, driving warming rates twice as high as the fastest surface rates. This has had implications for the copepod Calanus finmarchicus, a critical food supply for the endangered North Atlantic right whale (Eubalaena glacialis). The oceanographic changes have driven a deviation in the seasonal foraging patterns of E. glacialis upon which conservation strategies depend, making the whales more vulnerable to ship strikes and gear entanglements. The effects of rapid climate-driven changes on a species at risk undermine current management approaches.publishedVersio

Communitarian perspectives on social enterprise

Concepts of social enterprise have been debated repeatedly, and continue to cause confusion. In this paper, a meta-theoretical framework is developed through discussion of individualist and communitarian philosophy. Philosophers from both traditions build social theories that emphasise either consensus (a unitarist outlook) or diversity (a pluralist outlook). The various discourses in corporate governance reflect these assumptions and create four distinct approaches that impact on the relationship between capital and labour. In rejecting the traditional discourse of private enterprise, social enterprises have adopted other approaches to tackle social exclusion, each derived from different underlying beliefs about the purpose of enterprise and the nature of governance. The theoretical framework offers a way to understand the diversity found within the sector, including the newly constituted Community Interest Company (CIC).</p

An Attribute-Based Approach to Classifying Community-Based Tourism Networks

This conceptual paper proposes the adoption of a collaborative network approach as a prospective means of improving success in implementing community-based tourism (CBT) initiatives. Drawing upon relevant literature, the researchers identify the key attributes that characterise a network-based approach. By proposing alternatives for each attribute, the research provides CBT practitioners with options for making informed decisions about how to build collaboration connecting individual CBT initiatives in multiple locations. The researchers discuss the implications of different approaches for power relations between stakeholders. The proposed framework provides a means of classifying existing CBT networks and analyses the types of network and the circumstances which lead to better outcomes for community development. Further empirical research is required to test the validity of the key network attributes and to develop a comprehensive classification system of CBT networks.School of Hotel and Tourism Managemen

Effect of fortification of fresh cow milk with coconut milk on the proximate composition and yield of warankashi, a traditional cheese

Cheese is a concentrated dairy product produced by acid or rennet coagulation or curdling of milk, stirring and heating the curd, draining off the whey, collecting and pressing the curd. The effect of partial substitution of fresh cow milk with coconut milk on the yield and proximate composition of cheese was examined. Extracted coconut milk was mixed with fresh raw cow milk at varying proportions of 5%: 95%, 10%: 90%, 15%: 85%, 20%: 80%, 25%:75%, 70%: 30% and the control (0%:100%) to produce cheese. The control and the partially substituted cheeses were stored in a refrigerator and examined for sensory quality, percentage yield, total titrable acidity, and proximate analysis. The yield of cheese showed significant (p< 0.05) decrease from 26.71% (control sample) to 13.55% as the level of coconut milk increased. The total titrable acidity of cheese was found to be between the ranges of 0.20% - 0.29% which displayed a significant increase from 0.20% - 0.29%. The protein content of the cow-coconut cheese blends showed a significant difference (p<0.05) and an increase of 14.05%-15.33% (at 5%-30% substitution of coconut milk), with the control sample having 13.75%. There was also an increase in fat content from 9.20% - 9.64% (5% - 30% substitution of coconut milk, with the control sample having 8.94%. There was a decrease in the carbohydrate content of the cheese blends which ranged between 8.23% -2.82%, with the control sample having 9.60%. There was a significant decrease (p<0.05) in the ash content of the cow-coconut cheese blends, with the control sample having 1.02%. Significant difference (p<0.05) was observed in the colour, aroma, taste, texture, and overall acceptability as influenced by varying proportions of added coconut milk. The blend with 5% coconut milk and 95% cow milk was most acceptable by panellists. The work showed the potential of coconut as an alternative source of milk in cheese making with improved nutritional value and consumer acceptability

Covert observation in practice: lessons from the evaluation of the prohibition of smoking in public places in Scotland

Background: A ban on smoking in wholly or substantially enclosed public places has been in place in Scotland since 26th March 2006. The impact of this legislation is currently being evaluated in seven studies, three of which involve direct observation of smoking in bars and other enclosed public places. While the ethical issues around covert observation have been widely discussed there is little practical guidance on the conduct of such research. A workshop was therefore convened to identify practical lessons learned so far from the Scottish evaluation. Methods: We convened a workshop involving researchers from the three studies which used direct observation. In addition, one of the fieldwork managers collected written feedback on the fieldwork, identifying problems that arose in the field and some solutions. Results: There were four main themes identified: (i) the difficulty of achieving and maintaining concealment; (ii) the experience of being an observer; (iii) the risk of bias in the observations and (iv) issues around training and recruitment. These are discussed. Conclusion: Collecting covert observational data poses unique practical challenges, in particular in relation to the health and safety of the researcher. The findings and solutions presented in this paper will be of value to researchers designing similar studies

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types