Medium-chain triglyceride supplementation may increase working memory in older adults: A pilot study

Poster presentatio

Polymer-Layered Silicate Nanocomposites for Cryotank Applications

Previous composite cryotank designs have relied on the use of conventional composite materials to reduce microcracking and permeability. However, revolutionary advances in nanotechnology derived materials may enable the production of ultra-lightweight cryotanks with significantly enhanced durability and damage tolerance, as well as reduced propellant permeability. Layered silicate nanocomposites are especially attractive in cryogenic storage tanks based on results that have been reported for epoxy nanocomposite systems. These materials often exhibit an order of magnitude reduction in gas permeability when compared to the base resin. In addition, polymer-silicate nanocomposites have been shown to yield improved dimensional stability, strength, and toughness. The enhancement in material performance of these systems occurs without property trade-offs which are often observed in conventionally filled polymer composites. Research efforts at NASA Glenn Research Center have led to the development of epoxy-clay nanocomposites with 70% lower hydrogen permeability than the base epoxy resin. Filament wound carbon fiber reinforced tanks made with this nanocomposite had a five-fold lower helium leak rate than the corresponding tanks made without clay. The pronounced reduction observed with the tank may be due to flow induced alignment of the clay layers during processing. Additionally, the nanocomposites showed CTE reductions of up to 30%, as well as a 100% increase in toughness

Roadwork:Expertise at work building roads in the Maldives

This article engages critically with concepts of ‘skill’, ‘expertise’, and ‘capacity’ as they operate as markers of distinction and domination and shape migratory labour relations among road construction workers from across South Asia in the Maldives archipelago. The article examines roadwork at three levels: the professional biographies leading to ‘flexible specialization’ rather than technical expertise amongst Maldivian managers; the technical expertise and social incorporation of ‘skilled’ Sri Lankan supervisors; and the key material expertise of ‘non-skilled’ Bangladeshi labourers in precarious employment. Whilst discussions of South Asian labour migration have been dominated by caste and class, this article argues that it is important to consider how the cultural production and understanding of concepts such as ‘expertise’, ‘capacity’, and ‘exposure’ at worksites can (also) become distinguishing factors in (hierarchical) migratory labour relations

A type 2 diabetes subtype responsive to ACCORD intensive glycemia treatment

OBJECTIVE Current type 2 diabetes (T2D) management contraindicates intensive glycemia treatment in patients with high cardiovascular disease (CVD) risk and is partially motivated by evidence of harms in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Heterogeneity in response to intensive glycemia treatment has been observed, suggesting potential benefit for some individuals. RESEARCH DESIGN AND METHODS ACCORD was a randomized controlled trial that investigated whether intensively treating glycemia in individuals with T2D would reduce CVD outcomes. Using a novel approach to cluster HbA1c trajectories, we identified groups in the intensive glycemia arm with modified CVD risk. Genome-wide analysis and polygenic score (PS) were developed to predict group membership. Mendelian randomization was performed to infer causality. RESULTS We identified four clinical groupings in the intensive glycemia arm, and clinical group 4 (C4) displayed fewer CVD (hazard ratio [HR] 0.34; P 5 2.01 × 10-3) and microvascular outcomes (HR 0.86; P 5 0.015) than those receiving standard treatment. A singlenucleotide polymorphism, rs220721, in MAS1 reached suggestive significance in C4 (P 5 4.343 10-7). PS predicted C4 with high accuracy (area under the receiver operating characteristic curve 0.98), and this predicted C4 displayed reduced CVD risk with intensive versus standard glycemia treatment (HR 0.53; P 5 4.02 × 10-6), but not reduced risk of microvascular outcomes (P < 0.05). Mendelian randomization indicated causality between PS, on-trial HbA1c, and reduction in CVD outcomes (P < 0.05). CONCLUSIONS We found evidence of a T2D clinical group in ACCORD that benefited from intensive glycemia treatment, and membership in this group could be predicted using genetic variants. This study generates new hypotheses with implications for precision medicine in T2D and represents an important development in this landmark clinical trial warranting further investigation

Genetic variants in CPA6 and PRPF31 are associated with variation in response to metformin in individuals with type 2 diabetes

Metformin is the first-line treatment for type 2 diabetes (T2D). Although widely prescribed, the glucose-lowering mechanism for metformin is incompletely understood. Here, we used a genome-wide association approach in a diverse group of individuals with T2D from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial to identify common and rare variants associated with HbA 1c response to metformin treatment and followed up these findings in four replication cohorts. Common variants in PRPF31 and CPA6 were associated with worse and better metformin response, respectively (P &lt; 5 3 10 26 ), and meta-analysis in independent cohorts displayed similar associations with metformin response (P = 1.2 3 10 2 8 and P = 0.005, respectively). Previous studies have shown that PRPF31(+/2) knockout mice have increased total body fat (P = 1.78 3 10 26 ) and increased fasted circulating glucose (P = 5.73 3 10 26 ). Furthermore, rare variants in STAT3 associated with worse metformin response (q &lt;0.1). STAT3 is a ubiquitously expressed pleiotropic transcriptional activator that participates in the regulation of metabolism and feeding behavior. Here, we provide novel evidence for associations of common and rare variants in PRPF31, CPA6, and STAT3 with metformin response that may provide insight into mechanisms important for metformin efficacy in T2D

Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes

Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin-treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed-up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10 -6 ). Rare variant and gene expression changes were assessed using a false discovery rate approach. AKR7A3 and HSD17B13 were associated with lipid changes in white subjects (q < 0.2). Mice fed fenofibrate displayed reductions in Hsd17b13 gene expression (q < 0.1). Associations of variants in SMAD3, IPO11, and HSD17B13, with gene expression changes in mice indicate that transforming growth factor-beta (TGF-β) and NRF2 signaling pathways may influence fenofibrate effects on dyslipidemia in patients with T2D

Urban coral reefs: Degradation and resilience of hard coral assemblages in coastal cities of East and Southeast Asia

© 2018 The Author(s) Given predicted increases in urbanization in tropical and subtropical regions, understanding the processes shaping urban coral reefs may be essential for anticipating future conservation challenges. We used a case study approach to identify unifying patterns of urban coral reefs and clarify the effects of urbanization on hard coral assemblages. Data were compiled from 11 cities throughout East and Southeast Asia, with particular focus on Singapore, Jakarta, Hong Kong, and Naha (Okinawa). Our review highlights several key characteristics of urban coral reefs, including “reef compression” (a decline in bathymetric range with increasing turbidity and decreasing water clarity over time and relative to shore), dominance by domed coral growth forms and low reef complexity, variable city-specific inshore-offshore gradients, early declines in coral cover with recent fluctuating periods of acute impacts and rapid recovery, and colonization of urban infrastructure by hard corals. We present hypotheses for urban reef community dynamics and discuss potential of ecological engineering for corals in urban areas

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

Cellular mechanisms in basic and clinical gastroenterology and hepatolog