The role of childhood social position in adult type 2 diabetes: Evidence from the English Longitudinal Study of Ageing

Copyright @ 2014 Pikhartova et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background: Socioeconomic circumstances in childhood and early adulthood may influence the later onset of chronic disease, although such research is limited for type 2 diabetes and its risk factors at the different stages of life. The main aim of the present study is to examine the role of childhood social position and later inflammatory markers and health behaviours in developing type 2 diabetes at older ages using a pathway analytic approach. Methods. Data on childhood and adult life circumstances of 2,994 men and 4,021 women from English Longitudinal Study of Ageing (ELSA) were used to evaluate their association with diabetes at age 50 years and more. The cases of diabetes were based on having increased blood levels of glycated haemoglobin and/or self-reported medication for diabetes and/or being diagnosed with type 2 diabetes. Father's job when ELSA participants were aged 14 years was used as the measure of childhood social position. Current social characteristics, health behaviours and inflammatory biomarkers were used as potential mediators in the statistical analysis to assess direct and indirect effects of childhood circumstances on diabetes in later life. Results: 12.6 per cent of participants were classified as having diabetes. A disadvantaged social position in childhood, as measured by father's manual occupation, was associated at conventional levels of statistical significance with an increased risk of type 2 diabetes in adulthood, both directly and indirectly through inflammation, adulthood social position and a risk score constructed from adult health behaviours including tobacco smoking and limited physical activity. The direct effect of childhood social position was reduced by mediation analysis (standardised coefficient decreased from 0.089 to 0.043) but remained statistically significant (p = 0.035). All three indirect pathways made a statistically significantly contribution to the overall effect of childhood social position on adulthood type 2 diabetes. Conclusions: Childhood social position influences adult diabetes directly and indirectly through inflammatory markers, adulthood social position and adult health behaviours. © 2014Pikhartova et al.; licensee BioMed Central Ltd.Economic and Social Research Council-funded International Centre for Life Course Studies in Society and Health (RES-596-28-0001)

Zinc intake, status and indices of cognitive function in adults and children: a systematic review and meta-analysis

In developing countries, deficiencies of micronutrients are thought to have a major impact on child development; however, a consensus on the specific relationship between dietary zinc intake and cognitive function remains elusive. The aim of this systematic review was to examine the relationship between zinc intake, status and indices of cognitive function in children and adults. A systematic literature search was conducted using EMBASE, MEDLINE and Cochrane Library databases from inception to March 2014. Included studies were those that supplied zinc as supplements or measured dietary zinc intake. A meta-analysis of the extracted data was performed where sufficient data were available. Of all of the potentially relevant papers, 18 studies met the inclusion criteria, 12 of which were randomised controlled trials (RCTs; 11 in children and 1 in adults) and 6 were observational studies (2 in children and 4 in adults). Nine of the 18 studies reported a positive association between zinc intake or status with one or more measure of cognitive function. Meta-analysis of data from the adult’s studies was not possible because of limited number of studies. A meta-analysis of data from the six RCTs conducted in children revealed that there was no significant overall effect of zinc intake on any indices of cognitive function: intelligence, standard mean difference of <0.001 (95% confidence interval (CI) –0.12, 0.13) P=0.95; executive function, standard mean difference of 0.08 (95% CI, –0.06, 022) P=0.26; and motor skills standard mean difference of 0.11 (95% CI –0.17, 0.39) P=0.43. Heterogeneity in the study designs was a major limitation, hence only a small number (n=6) of studies could be included in the meta-analyses. Meta-analysis failed to show a significant effect of zinc supplementation on cognitive functioning in children though, taken as a whole, there were some small indicators of improvement on aspects of executive function and motor development following supplementation but high-quality RCTs are necessary to investigate this further

Higher sociability leads to lower reproductive success in female kangaroos

In social mammals, social integration is generally assumed to improve females' reproductive success. Most species demonstrating this relationship exhibit complex forms of social bonds and interactions. However, female eastern grey kangaroos (Macropus giganteus) exhibit differentiated social relationships, yet do not appear to cooperate directly. It is unclear what the fitness consequences of such sociability could be in species that do not exhibit obvious forms of cooperation. Using 4 years of life history, spatial and social data from a wild population of approximately 200 individually recognizable female eastern grey kangaroos, we tested whether higher levels of sociability are associated with greater reproductive success. Contrary to expectations, we found that the size of a female's social network, her numbers of preferential associations with other females and her group sizes all negatively influenced her reproductive success. These factors influenced the survival of dependent young that had left the pouch rather than those that were still in the pouch. We also show that primiparous females (first-time breeders) were less likely to have surviving young. Our findings suggest that social bonds are not always beneficial for reproductive success in group-living species, and that female kangaroos may experience trade-offs between successfully rearing young and maintaining affiliative relationships

Higher sociability leads to lower reproductive success in female kangaroos: Sociability and fitness in kangaroos

In social mammals, social integration is generally assumed to improve females’ reproductive success. Most species demonstrating this relationship exhibit complex forms of social bonds and interactions. However, female eastern grey kangaroos (Macropus giganteus) exhibit differentiated social relationships, yet do not appear to cooperate directly. It is unclear what the fitness consequences of such sociability could be in species that do not exhibit obvious forms of cooperation. Using 4 years of life history, spatial and social data from a wild population of approximately 200 individually recognizable female eastern grey kangaroos, we tested whether higher levels of sociability are associated with greater reproductive success. Contrary to expectations, we found that the size of a female’s social network, her numbers of preferential associations with other females and her group sizes all negatively influenced her reproductive success. These factors influenced the survival of dependent young that had left the pouch rather than those that were still in the pouch. We also show that primiparous females (first-time breeders) were less likely to have surviving young. Our findings suggest that social bonds are not always beneficial for reproductive success in group-living species, and that female kangaroos may experience trade-offs between successfully rearing young and maintaining affiliative relationships

mRNA concentrations of MIF in subcutaneous abdominal adipose cells are associated with adipocyte size and insulin action

Objective To determine whether the mRNA concentrations of inflammation response genes in isolated adipocytes and in cultured preadipocytes are related to adipocyte size and in vivo insulin action in obese individuals. Design Cross-sectional inpatient study. Subjects Obese Pima Indians with normal glucose tolerance. Measurements Adipocyte diameter (by microscope technique; n=29), expression of candidate genes (by quantitative real-time PCR) in freshly isolated adipocytes (monocyte chemoattractant protein [MCP] 1 and MCP2, macrophage inflammatory protein [MIP] 1α, MIP1β and MIP2, macrophage migration inhibitory factor [MIF], tumor necrosis factor alpha, interleukin [IL] 6 and IL8; n=22) and cultured preadipocytes (MCP1, MIP1α, MIF, IL6 and matrix metalloproteinase 2; n=33) from subcutaneous abdominal adipose tissue (by aspiration biopsy, n=34), body fat by dual-energy X-ray absorptiometry, glucose tolerance by 75-gram oral glucose tolerance test, and insulin action by euglycemic-hyperinsulinemic clamp (insulin infusion rate 40 mU/m2.min)(all n=34). Results MIF was the only gene whose expression in both freshly isolated adipocytes and cultured preadipocytes was positively associated with adipocytes diameter and negatively associated with peripheral and hepatic insulin action (all P<0.05). In multivariate analysis, the association between adipocyte MIF mRNA concentrations and adipocytes diameter was independent of percent body fat (P=0.03), whereas adipocyte MIF mRNA concentrations but not adipocytes diameter independently predicted peripheral insulin action. The mRNA expression concentrations of MIF gene in adipocytes were not associated with plasma concentrations of MIF, but were negatively associated with plasma adiponectin concentrations (P=0.004). In multivariate analysis, adipocyte MIF RNA concentrations (P=0.03) but not plasma adiponectin concentrations (P=0.4) remained a significant predictor of insulin action. Conclusions Increased expression of MIF gene in adipose cells may be an important link between obesity characterized by enlarged adipocytes and insulin resistance in normal glucose tolerant people

Spatial extent and historical context of North Sea oxygen depletion in August 2010

Prompted by recent observations of seasonal low dissolved oxygen from two moorings in the North Sea, a hydrographic survey in August 2010 mapped the spatial extent of summer oxygen depletion. Typical near-bed dissolved oxygen saturations in the stratified regions of the North Sea were 75–80 % while the well-mixed regions of the southern North Sea reached 90 %. Two regions of strong thermal stratification, the area between the Dooley and Central North Sea Currents and the area known as the Oyster Grounds, had oxygen saturations as low as 65 and 70 % (200 and 180 µmol dm-3) respectively. Low dissolved oxygen was apparent in regions characterised by low advection, high stratification, elevated organic matter production from the spring bloom and a deep chlorophyll maximum. Historical data over the last century from the International Council for the Exploration of the Sea oceanographic database highlight an increase in seasonal oxygen depletion and a warming over the past 20 years. The 2010 survey is consistent with, and reinforces, the signal of recent depleted oxygen at key locations seen in the (albeit sparse) historical data

Regulation of early steps of GPVI signal transduction by phosphatases: a systems biology approach

We present a data-driven mathematical model of a key initiating step in platelet activation, a central process in the prevention of bleeding following Injury. In vascular disease, this process is activated inappropriately and causes thrombosis, heart attacks and stroke. The collagen receptor GPVI is the primary trigger for platelet activation at sites of injury. Understanding the complex molecular mechanisms initiated by this receptor is important for development of more effective antithrombotic medicines. In this work we developed a series of nonlinear ordinary differential equation models that are direct representations of biological hypotheses surrounding the initial steps in GPVI-stimulated signal transduction. At each stage model simulations were compared to our own quantitative, high-temporal experimental data that guides further experimental design, data collection and model refinement. Much is known about the linear forward reactions within platelet signalling pathways but knowledge of the roles of putative reverse reactions are poorly understood. An initial model, that includes a simple constitutively active phosphatase, was unable to explain experimental data. Model revisions, incorporating a complex pathway of interactions (and specifically the phosphatase TULA-2), provided a good description of the experimental data both based on observations of phosphorylation in samples from one donor and in those of a wider population. Our model was used to investigate the levels of proteins involved in regulating the pathway and the effect of low GPVI levels that have been associated with disease. Results indicate a clear separation in healthy and GPVI deficient states in respect of the signalling cascade dynamics associated with Syk tyrosine phosphorylation and activation. Our approach reveals the central importance of this negative feedback pathway that results in the temporal regulation of a specific class of protein tyrosine phosphatases in controlling the rate, and therefore extent, of GPVI-stimulated platelet activation

Imaging modalities for characterising focal pancreatic lesions

Background: Increasing numbers of incidental pancreatic lesions are being detected each year. Accurate characterisation of pancreatic lesions into benign, precancerous, and cancer masses is crucial in deciding whether to use treatment or surveillance. Distinguishing benign lesions from precancerous and cancerous lesions can prevent patients from undergoing unnecessary major surgery. Despite the importance of accurately classifying pancreatic lesions, there is no clear algorithm for management of focal pancreatic lesions. Objectives: To determine and compare the diagnostic accuracy of various imaging modalities in detecting cancerous and precancerous lesions in people with focal pancreatic lesions. Search methods: We searched the CENTRAL, MEDLINE, Embase, and Science Citation Index until 19 July 2016. We searched the references of included studies to identify further studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. Selection criteria: We planned to include studies reporting cross-sectional information on the index test (CT (computed tomography), MRI (magnetic resonance imaging), PET (positron emission tomography), EUS (endoscopic ultrasound), EUS elastography, and EUS-guided biopsy or FNA (fine-needle aspiration)) and reference standard (confirmation of the nature of the lesion was obtained by histopathological examination of the entire lesion by surgical excision, or histopathological examination for confirmation of precancer or cancer by biopsy and clinical follow-up of at least six months in people with negative index tests) in people with pancreatic lesions irrespective of language or publication status or whether the data were collected prospectively or retrospectively. Data collection and analysis: Two review authors independently searched the references to identify relevant studies and extracted the data. We planned to use the bivariate analysis to calculate the summary sensitivity and specificity with their 95% confidence intervals and the hierarchical summary receiver operating characteristic (HSROC) to compare the tests and assess heterogeneity, but used simpler models (such as univariate random-effects model and univariate fixed-effect model) for combining studies when appropriate because of the sparse data. We were unable to compare the diagnostic performance of the tests using formal statistical methods because of sparse data. Main results: We included 54 studies involving a total of 3,196 participants evaluating the diagnostic accuracy of various index tests. In these 54 studies, eight different target conditions were identified with different final diagnoses constituting benign, precancerous, and cancerous lesions. None of the studies was of high methodological quality. None of the comparisons in which single studies were included was of sufficiently high methodological quality to warrant highlighting of the results. For differentiation of cancerous lesions from benign or precancerous lesions, we identified only one study per index test. The second analysis, of studies differentiating cancerous versus benign lesions, provided three tests in which meta-analysis could be performed. The sensitivities and specificities for diagnosing cancer were: EUS-FNA: sensitivity 0.79 (95% confidence interval (CI) 0.07 to 1.00), specificity 1.00 (95% CI 0.91 to 1.00); EUS: sensitivity 0.95 (95% CI 0.84 to 0.99), specificity 0.53 (95% CI 0.31 to 0.74); PET: sensitivity 0.92 (95% CI 0.80 to 0.97), specificity 0.65 (95% CI 0.39 to 0.84). The third analysis, of studies differentiating precancerous or cancerous lesions from benign lesions, only provided one test (EUS-FNA) in which meta-analysis was performed. EUS-FNA had moderate sensitivity for diagnosing precancerous or cancerous lesions (sensitivity 0.73 (95% CI 0.01 to 1.00) and high specificity 0.94 (95% CI 0.15 to 1.00), the extremely wide confidence intervals reflecting the heterogeneity between the studies). The fourth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (dysplasia) provided three tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing invasive carcinoma were: CT: sensitivity 0.72 (95% CI 0.50 to 0.87), specificity 0.92 (95% CI 0.81 to 0.97); EUS: sensitivity 0.78 (95% CI 0.44 to 0.94), specificity 0.91 (95% CI 0.61 to 0.98); EUS-FNA: sensitivity 0.66 (95% CI 0.03 to 0.99), specificity 0.92 (95% CI 0.73 to 0.98). The fifth analysis, of studies differentiating cancerous (high-grade dysplasia or invasive carcinoma) versus precancerous (low- or intermediate-grade dysplasia) provided six tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing cancer (high-grade dysplasia or invasive carcinoma) were: CT: sensitivity 0.87 (95% CI 0.00 to 1.00), specificity 0.96 (95% CI 0.00 to 1.00); EUS: sensitivity 0.86 (95% CI 0.74 to 0.92), specificity 0.91 (95% CI 0.83 to 0.96); EUS-FNA: sensitivity 0.47 (95% CI 0.24 to 0.70), specificity 0.91 (95% CI 0.32 to 1.00); EUS-FNA carcinoembryonic antigen 200 ng/mL: sensitivity 0.58 (95% CI 0.28 to 0.83), specificity 0.51 (95% CI 0.19 to 0.81); MRI: sensitivity 0.69 (95% CI 0.44 to 0.86), specificity 0.93 (95% CI 0.43 to 1.00); PET: sensitivity 0.90 (95% CI 0.79 to 0.96), specificity 0.94 (95% CI 0.81 to 0.99). The sixth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (low-grade dysplasia) provided no tests in which meta-analysis was performed. The seventh analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) provided two tests in which meta-analysis was performed. The sensitivity and specificity for diagnosing cancer were: CT: sensitivity 0.83 (95% CI 0.68 to 0.92), specificity 0.83 (95% CI 0.64 to 0.93) and MRI: sensitivity 0.80 (95% CI 0.58 to 0.92), specificity 0.81 (95% CI 0.53 to 0.95), respectively. The eighth analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) or benign lesions provided no test in which meta-analysis was performed. There were no major alterations in the subgroup analysis of cystic pancreatic focal lesions (42 studies; 2086 participants). None of the included studies evaluated EUS elastography or sequential testing. Authors' conclusions: We were unable to arrive at any firm conclusions because of the differences in the way that study authors classified focal pancreatic lesions into cancerous, precancerous, and benign lesions; the inclusion of few studies with wide confidence intervals for each comparison; poor methodological quality in the studies; and heterogeneity in the estimates within comparisons

Combining Experiments and Simulations Using the Maximum Entropy Principle

A key component of computational biology is to compare the results of computer modelling with experimental measurements. Despite substantial progress in the models and algorithms used in many areas of computational biology, such comparisons sometimes reveal that the computations are not in quantitative agreement with experimental data. The principle of maximum entropy is a general procedure for constructing probability distributions in the light of new data, making it a natural tool in cases when an initial model provides results that are at odds with experiments. The number of maximum entropy applications in our field has grown steadily in recent years, in areas as diverse as sequence analysis, structural modelling, and neurobiology. In this Perspectives article, we give a broad introduction to the method, in an attempt to encourage its further adoption. The general procedure is explained in the context of a simple example, after which we proceed with a real-world application in the field of molecular simulations, where the maximum entropy procedure has recently provided new insight. Given the limited accuracy of force fields, macromolecular simulations sometimes produce results that are at not in complete and quantitative accordance with experiments. A common solution to this problem is to explicitly ensure agreement between the two by perturbing the potential energy function towards the experimental data. So far, a general consensus for how such perturbations should be implemented has been lacking. Three very recent papers have explored this problem using the maximum entropy approach, providing both new theoretical and practical insights to the problem. We highlight each of these contributions in turn and conclude with a discussion on remaining challenges

Cytomegalovirus Infections among African-Americans

<p>Abstract</p> <p>Background</p> <p>Since African-Americans have twice the prevalence of cytomegalovirus (CMV) infections as age-matched Caucasians we sought to determine the ages and possible sources of infection of African-American children.</p> <p>Methods</p> <p>Subjects were 157 African-American healthy children and adolescents and their 113 household adults in Richmond VA. Families completed a questionnaire, provided saliva for antibody testing, and adolescents were interviewed regarding sexual activity.</p> <p>Results</p> <p>Regardless of age CMV seropositivity was not associated with gender, breast feeding, health insurance, sexual activity, or household income, education, or size. In the final regression model, prior CMV infection in adults was over two-fold higher than in children (chi-square = 18.8, p < 0.0001). At one year of age the CMV seropositivity rate was 11% (95%CI = 4% – 24%) and increased 1.8% each year until age 13 years. Between ages 13 and 20 years the CMV seropositivity rate remained between 22% and 33%. For adults, the CMV seropositivity rate was 84% in 21 year olds (95%CI = 69%–.92%). There was no association between CMV infections of the children and their mothers but CMV infections among siblings were associated.</p> <p>Conclusion</p> <p>We observed that African-American children had CMV seroprevalence rates by age 20 years at less than one-half of that of their adult mothers and caregivers. Sibling-to-sibling transmission was a likely source of CMV infections for the children. The next generation of African-American women may be highly susceptible to a primary CMV infection during pregnancy and may benefit from a CMV vaccine.</p