Contextual influences on social enterprise management in rural and urban communities

The idea that difference exists between rural and urban enterprise activity is not new, the obvious comparators are measures such as social architecture, resource availability and accessibility. However, when the concept and practice of management in social enterprise is compared in these two contexts then there is opportunity to further our understanding of the contextual challenges encountered by social enterprise. In this paper six cases studies are compared and analysed: three cases are urban social enterprises and three classified as remote rural social enterprises. The urban cases are social enterprises located around Glasgow in the west of Scotland and are compared with three remote rural location studies, one on the Scottish mainland peninsula, the other in northern Scotland and the final case on a Scottish western island. We conclude that the main differences between remote rural and urban management of social enterprise are heavily nuanced by in-migration levels in both rural and urban locations, leadership and community needs and therefore deserving of context relevant policy

Asperity level frictional interactions of cylinder bore materials and lubricant composition

Parasitic frictional losses in internal combustion engines of race vehicles adversely affect their performance. A significant proportion of these losses occur within the piston-cylinder system. This paper presents a study of the compatibility of cylinder bore surface materials with typical lubricant base constituent stock (Poly Alpha Olefin (PAO) and Polyolester (POE)) as well as a fully formulated lubricant. Nanoscale boundary friction is measured using lateral force microscopy. The effect of material properties, nanoscale roughness and lubricant species upon underlying mechanisms of generated friction is presented. Advanced cylinder materials and coatings and lubricant molecular species used for high performance engines are investigated, an integrated approach not hitherto reported in literature

Effects of Acute Tryptophan Depletion on Human Taste Perception

Taste perception has been reported to vary with changes in affective state. Distortions of taste perception, including blunted recognition thresholds, intensity, and hedonic ratings have been identified in those suffering from depressive disorders. Serotonin is a key neurotransmitter implicated in the etiology of anxiety and depression; systemic and peripheral manipulations of serotonin signaling have previously been shown to modulate taste detection. However, the specific effects of central serotonin function on taste processing have not been widely investigated. Here, in a double-blind placebo-controlled study, acute tryptophan depletion was used to investigate the effect of reduced central serotonin function on taste perception. Twenty-five female participants aged 18–28 attended the laboratory on two occasions at least 1 week apart. On one visit, they received a tryptophan depleting drink and on the other, a control drink was administered. Approximately, 6 h after drink consumption, they completed a taste perception task which measured detection thresholds and supra-threshold perceptions of the intensity and pleasantness of four basic tastes (sweet, sour, bitter, and salt). While acutely reducing central levels of serotonin had no effect on the detection thresholds of sweet, bitter, or sour tastes, it significantly enhanced detection of salt. For supra-threshold stimuli, acutely reduced serotonin levels significantly enhanced the perceived intensity of both bitter and sour tastes and blunted pleasantness ratings of bitter quinine. These findings show manipulation of central serotonin levels can modulate taste perception and are consistent with previous reports that depletion of central serotonin levels enhances neural and behavioral responsiveness to aversive signals

Safety evaluation of substituted thiophenes used as flavoring ingredients.

This publication is the second in a series by the Expert Panel of the Flavor and Extract Manufacturers Association summarizing the conclusions of its third systematic re-evaluation of the safety of flavorings previously considered to be generally recognized as safe (GRAS) under conditions of intended use. Re-evaluation of GRAS status for flavorings is based on updated considerations of exposure, structural analogy, metabolism, pharmacokinetics and toxicology and includes a comprehensive review of the scientific information on the flavorings and structurally related substances. Of the 12 substituted thiophenes reviewed here, 11 were reaffirmed as GRAS based on their rapid absorption, metabolism and excretion in humans and animals; the low estimated dietary exposure from flavor use; the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels; and the lack of significant genotoxic and mutagenic potential. For one of the substituted thiophenes, 3-acetyl-2,5-dimethylthiophene, it was concluded that more detailed exposure information, comparative metabolism studies and comprehensive toxicity data, including an in-depth evaluation of the mechanism of action for any adverse effects observed, are required for continuation of its FEMA GRAS™ status. In the absence of these data, the compound was removed from the FEMA GRAS list

Application of the LymphGen classification tool to 928 clinically and genetically-characterised cases of diffuse large B cell lymphoma (DLBCL).

We recently published results of targeted sequencing applied to 928 unselected cases of DLBCL registered in the Haematological Malignancy Research Network (HMRN) registry (1). Clustering allowed us to resolve five genomic subtypes. These subtypes shared considerable overlap with those proposed in two independent genomic studies(2, 3), suggesting the potential to use genetics to stratify patients by both risk and biology. In the original studies, clustering techniques were applied to sample cohorts to reveal molecular substructure, but left open the challenge of how to classify an individual patient. This was addressed by the LymphGen classification tool (4). LymphGen assigns an individual case to one of six molecular subtypes. The tool accommodates data from exome or targeted sequencing, either with or without copy number variant (CNV) data. Separate gene expression data allows classification of a seventh, MYC-driven subtype defined by a double hit (DHL) or molecular high-grade (MHG) gene expression signature(5-7).HR was funded by a studentship from the Medical Research Council. DH was supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/M008584/1). The Hodson laboratory receives core funding from Wellcome and MRC to the Wellcome-MRC Cambridge Stem Cell Institute and core funding from the CRUK Cambridge Cancer Centre. HMRN is supported by BCUK 15037 and CRUK 18362

Mapping the genetic architecture of gene expression in human liver

Genetic variants that are associated with common human diseases do not lead directly to disease, but instead act on intermediate, molecular phenotypes that in turn induce changes in higher-order disease traits. Therefore, identifying the molecular phenotypes that vary in response to changes in DNA and that also associate with changes in disease traits has the potential to provide the functional information required to not only identify and validate the susceptibility genes that are directly affected by changes in DNA, but also to understand the molecular networks in which such genes operate and how changes in these networks lead to changes in disease traits. Toward that end, we profiled more than 39,000 transcripts and we genotyped 782,476 unique single nucleotide polymorphisms (SNPs) in more than 400 human liver samples to characterize the genetic architecture of gene expression in the human liver, a metabolically active tissue that is important in a number of common human diseases, including obesity, diabetes, and atherosclerosis. This genome-wide association study of gene expression resulted in the detection of more than 6,000 associations between SNP genotypes and liver gene expression traits, where many of the corresponding genes identified have already been implicated in a number of human diseases. The utility of these data for elucidating the causes of common human diseases is demonstrated by integrating them with genotypic and expression data from other human and mouse populations. This provides much-needed functional support for the candidate susceptibility genes being identified at a growing number of genetic loci that have been identified as key drivers of disease from genome-wide association studies of disease. By using an integrative genomics approach, we highlight how the gene RPS26 and not ERBB3 is supported by our data as the most likely susceptibility gene for a novel type 1 diabetes locus recently identified in a large-scale, genome-wide association study. We also identify SORT1 and CELSR2 as candidate susceptibility genes for a locus recently associated with coronary artery disease and plasma low-density lipoprotein cholesterol levels in the process. © 2008 Schadt et al

Analysis of factors influencing the ultrasonic fetal weight estimation

Objective: The aim of our study was the evaluation of sonographic fetal weight estimation taking into consideration 9 of the most important factors of influence on the precision of the estimation. Methods: We analyzed 820 singleton pregnancies from 22 to 42 weeks of gestational age. We evaluated 9 different factors that potentially influence the precision of sonographic weight estimation ( time interval between estimation and delivery, experts vs. less experienced investigator, fetal gender, gestational age, fetal weight, maternal BMI, amniotic fluid index, presentation of the fetus, location of the placenta). Finally, we compared the results of the fetal weight estimation of the fetuses with poor scanning conditions to those presenting good scanning conditions. Results: Of the 9 evaluated factors that may influence accuracy of fetal weight estimation, only a short interval between sonographic weight estimation and delivery (0-7 vs. 8-14 days) had a statistically significant impact. Conclusion: Of all known factors of influence, only a time interval of more than 7 days between estimation and delivery had a negative impact on the estimation

The median and the mode as robust meta‐analysis estimators in the presence of small‐study effects and outliers

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.  Meta‐analyses based on systematic literature reviews are commonly used to obtain a quantitative summary of the available evidence on a given topic. However, the reliability of any meta‐analysis is constrained by that of its constituent studies. One major limitation is the possibility of small study effects, when estimates from smaller and larger studies differ systematically. Small study effects may result from reporting biases (ie, publication bias), from inadequacies of the included studies that are related to study size, or from reasons unrelated to bias. We propose two estimators based on the median and mode to increase the reliability of findings in a meta‐analysis by mitigating the influence of small study effects. By re‐examining data from published meta‐analyses and by conducting a simulation study, we show that these estimators offer robustness to a range of plausible bias mechanisms, without making explicit modelling assumptions. They are also robust to outlying studies without explicitly removing such studies from the analysis. When meta‐analyses are suspected to be at risk of bias because of small study effects, we recommend reporting the mean, median and modal pooled estimates.Medical Research Council (MRC)Brazilian National Council for Scientific and Technological Development (CNPq

Degrees of belief, expected and actual

A framework of degrees of belief, or credences, is often advocated to model our uncertainty about how things are or will turn out. It has also been employed in relation to the kind of uncertainty or indefiniteness that arises due to vagueness, such as when we consider “a is F” in a case where a is borderline F. How should we understand degrees of belief when we take into account both these phenomena? Can the right kind of theory of the semantics of vagueness help us answer this? Nicholas J.J. Smith defends a unified account, according to which “degree of belief is expected truth-value”; this builds on his Degree Theory of vagueness that offers an account of the semantics and logic of vagueness in terms of degrees of truth. I argue that his account fails. Degree theories of vagueness do not help us understand degrees of belief and, I argue, we shouldn’t expect a theory of vagueness to yield a detailed uniform story about this. The route from the semantics to psychological states needn’t be straightforward or uniform even before we attempt to combine vagueness with probabilistic uncertainty