Changes in the expression of the type 2 diabetes-associated gene VPS13C in the β cell are associated with glucose intolerance in humans and mice

Single nucleotide polymorphisms (SNPs) close to the VPS13C, C2CD4A and C2CD4B genes on chromosome 15q are associated with impaired fasting glucose and increased risk of type 2 diabetes. eQTL analysis revealed an association between possession of risk (C) alleles at a previously implicated causal SNP, rs7163757, and lowered VPS13C and C2CD4A levels in islets from female (n = 40, P < 0.041) but not from male subjects. Explored using promoter-reporter assays in β-cells and other cell lines, the risk variant at rs7163757 lowered enhancer activity. Mice deleted for Vps13c selectively in the β-cell were generated by crossing animals bearing a floxed allele at exon 1 to mice expressing Cre recombinase under Ins1 promoter control (Ins1Cre). Whereas Vps13cfl/fl:Ins1Cre (βVps13cKO) mice displayed normal weight gain compared with control littermates, deletion of Vps13c had little effect on glucose tolerance. Pancreatic histology revealed no significant change in β-cell mass in KO mice vs. controls, and glucose-stimulated insulin secretion from isolated islets was not altered in vitro between control and βVps13cKO mice. However, a tendency was observed in female null mice for lower insulin levels and β-cell function (HOMA-B) in vivo. Furthermore, glucose-stimulated increases in intracellular free Ca2+ were significantly increased in islets from female KO mice, suggesting impaired Ca2+ sensitivity of the secretory machinery. The present data thus provide evidence for a limited role for changes in VPS13C expression in conferring altered disease risk at this locus, particularly in females, and suggest that C2CD4A may also be involved

Variability in spatial distribution of mineral phases in the Lower Bowland Shale, UK, from the mm- to μm-scale: quantitative characterization and modelling

The microstructure of a highly laminated Lower Bowland Shale sample is characterized at the micron-to millimeter scale, to investigate how such characterization can be utilized for microstructure-based modelling of the shale's geomechanical behavior. A mosaic of scanning electron microscope (SEM) back-scattered electron (BSE) images was studied. Mineral and organic content and their anisotropy vary between laminae, with a high variability in fracturing and multi-micrometer aggregates of feldspars, carbonates, quartz and organics. The different microstructural interface types and heterogeneities were located and quantified, demonstrating the microstructural complexity of the Bowland Shale, and defining possible pathways for fracture propagation. A combination of counting-box, dispersion, covariance and 2D mapping approaches were used to determine that the total surface of each lamina is 3 to 11 times larger than the scale of heterogeneities relative to mineral proportion and size. The dispersion approach seems to be the preferential technique for determining the representative elementary area (REA) of phase area fraction for these highly heterogeneous large samples, supported by 2D quantitative mapping of the same parameter. Representative microstructural models were developed using Voronoï tessellation using these characteristic scales. These models encapsulate the microstructural features required to simulate fluid flow through these porous Bowland Shales at the mesoscale

Clinical Effectiveness of the Queen Square Intensive Comprehensive Aphasia Service for Patients With Poststroke Aphasia

BACKGROUND AND PURPOSE: Poststroke aphasia has a major impact on peoples' quality of life. Speech and language therapy interventions work, especially in high doses, but these doses are rarely achieved outside of research studies. Intensive Comprehensive Aphasia Programs (ICAPs) are an option to deliver high doses of therapy to people with aphasia over a short period of time. METHODS: Forty-six people with aphasia in the chronic stage poststroke completed the ICAP over a 3-week period, attending for 15 days and averaging 6 hours of therapy per day. Outcome measures included the Comprehensive Aphasia Test, an impairment-based test of the 4 main domains of language (speaking, writing, auditory comprehension, and reading) which was measured at 3 time points (baseline, immediately posttreatment at 3 weeks and follow-up at 12-week post-ICAP); and, the Communicative Effectiveness Index, a carer-reported measure of functional communication skills collected at baseline and 12 weeks. RESULTS: A 2-way repeated measures multivariate ANOVA was conducted. We found a significant domain-by-time interaction, F=12.7, P<0.0005, indicating that the ICAP improved people with aphasia's language scores across all 4 domains, with the largest gains in speaking (Cohen's d=1.3). All gains were maintained or significantly improved further at 12-week post-ICAP. Importantly, patients' functional communication, as indexed by changes on the Communicative Effectiveness Index, also significantly improved at 12-week post-ICAP, t=5.4, P<0.0005, also with a large effect size (Cohen's d=0.9). CONCLUSIONS: People with aphasia who participated in the Queen Square ICAP made large and clinically meaningful gains on both impairment-based and functional measures of language. Gains were sustained and in some cases improved further over the subsequent 12 weeks

The effect of birth-weight with genetic susceptibility on depressive symptoms in childhood and adolescence

Low birth-weight has been associated with depression and related outcomes in adults, and with problem behaviours in children. This study aimed to examine the association between low birth-weight for gestation and depressive symptoms in children and adolescents and to examine whether the relationship is moderated by genetic risk for depression. An epidemiological, genetically sensitive design was used including 2,046 twins aged 8–17 years (1,023 families). Data were obtained by parental report and analysed using regression analysis. A small but significant association between birth-weight for gestation and early depressive symptoms was observed. The unit increase in depressive symptoms per unit decrease in birth-weight for gestation was greater for individuals at genetic or familial risk for depression. For low birth-weight children, genetic risk for depression moderated the influence of birth-weight for gestation in predicting early depressive symptoms. Birth-weight for gestation is moderated by genetic and familial risk for depression in influencing early depression symptoms. These observations have clinical implications in that the impact of being small for gestational age on depressive symptoms is greater in children at familial/genetic risk although the association between birth weight and depression does not imply causality

Hominin occupation of the Chinese Loess Plateau since about 2.1 million years ago

Considerable attention has been paid to dating the earliest appearance of hominins outside Africa. The earliest skeletal and artefactual evidence for the genus Homo in Asia currently comes from Dmanisi, Georgia, and is dated to approximately 1.77-1.85 million years ago (Ma)(1). Two incisors that may belong to Homo erectus come from Yuanmou, south China, and are dated to 1.7 Ma(2); the next-oldest evidence is an H. erectus cranium from Lantian (Gongwangling)-which has recently been dated to 1.63 Ma(3) and the earliest hominin fossils from the Sangiran dome in Java, which are dated to about 1.5-1.6 Ma(4). Artefacts from Majuangou III5 and Shangshazui(6) in the Nihewan basin, north China, have also been dated to 1.6-1.7 Ma. Here we report an Early Pleistocene and largely continuous artefact sequence from Shangchen, which is a newly discovered Palaeolithic locality of the southern Chinese Loess Plateau, near Gongwangling in Lantian county. The site contains 17 artefact layers that extend from palaeosol S15-dated to approximately 1.26 Ma-to loess L28, which we date to about 2.12 Ma. This discovery implies that hominins left Africa earlier than indicated by the evidence from Dmanisi

Place branding of seaports in the Middle East

This paper analyses seaports’ brand personalities as a means of understanding similarities and differences of these important locations and their relationship with their host place image. Drawing upon Aaker’s (J Mark Res 34:347–356, 1997) brand personality construct, the study presents lexical analysis from the websites of nine seaports in the Middle East. Each seaport’s website is content analysed, and the brand personality is measured using Aaker’s (1997) framework and Opoku’s (Licentiate Thesis, Lulea University of Technology, ISSN, 1402-1757, 2005) dictionary of synonyms. Findings show that seaports have developed a level of isomorphism upon particular dimensions of brand image; however, the findings also show the most distinctive seaports were linking their seaport to their place brand. In particular, the findings show only the Port of Jebel Ali has a clear and distinctive brand personality and to a lesser extent the Ports of Sohar, Shahid Rajee and Khor Fakkan. The research has important management implications of branding for public diplomacy and demonstrates seaport brand positioning in relation to place branding, used to inform public communication and marketing

Causal inference based on counterfactuals

BACKGROUND: The counterfactual or potential outcome model has become increasingly standard for causal inference in epidemiological and medical studies. DISCUSSION: This paper provides an overview on the counterfactual and related approaches. A variety of conceptual as well as practical issues when estimating causal effects are reviewed. These include causal interactions, imperfect experiments, adjustment for confounding, time-varying exposures, competing risks and the probability of causation. It is argued that the counterfactual model of causal effects captures the main aspects of causality in health sciences and relates to many statistical procedures. SUMMARY: Counterfactuals are the basis of causal inference in medicine and epidemiology. Nevertheless, the estimation of counterfactual differences pose several difficulties, primarily in observational studies. These problems, however, reflect fundamental barriers only when learning from observations, and this does not invalidate the counterfactual concept

Measuring Resilience in Adult Women Using the 10-Items Connor-Davidson Resilience Scale (CD-RISC). Role of Trauma Exposure and Anxiety Disorders

International audiencePURPOSE: Resilience is the ability of individuals to adapt positively in the face of trauma. Little is known, however, about lifetime factors affecting resilience. METHODS: We assessed the effects of psychiatric disorder and lifetime trauma history on the resilience self-evaluation using the Connor-Davidson Resilience Scale (CD-RISC-10) in a high-risk-women sample. Two hundred and thirty eight community-dwelling women, including 122 participants in a study of breast cancer survivors and 116 participants without previous history of cancer completed the CD-RISC-10. Lifetime psychiatric symptoms were assessed retrospectively using two standardized psychiatric examinations (Mini International Neuropsychiatric Interview and Watson's Post-Traumatic Stress Disorder Inventory). RESULTS: Multivariate logistic regression adjusted for age, education, trauma history, cancer, current psychiatric diagnoses, and psychoactive treatment indicated a negative association between current psychiatric disorder and high resilience compared to low resilience level (OR = 0.44, 95% CI [0.21-0.93]). This was related to anxiety and not mood disorder. A positive and independent association with a trauma history was also observed (OR = 3.18, 95% CI [1.44-7.01]). CONCLUSION: Self-evaluation of resilience is influenced by both current anxiety disorder and trauma history. The independent positive association between resilience and trauma exposure may indicate a "vaccination" effect. This finding need to be taken into account in future studies evaluating resilience in general or clinical populations