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

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

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

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

The evolution o constitutive and induced defences to infectious disease

In response to infectious disease, hosts typically mount both constitutive and induced defences. Constitutive defence prevents infection in the first place, while induced defence typically shortens the infectious period. The two routes to defence, therefore, have very different implications not only to individuals but also to the epidemiology of the disease. Moreover, the costs of constitutive defences are likely to be paid even in the absence of disease, while induced defences are likely to incur the most substantial costs when they are used in response to infection. We examine theoretically the evolutionary implications of these fundamental differences. A key result is that high virulence in the parasite typically selects for higher induced defences even if they result in immunopathology leading to very high disease mortality. Disease impacts on fecundity are critical to the relative investment in constitutive and induced defence with important differences found when parasites castrate their hosts. The trade-off between constitutive and induced defence has been cited as a cause of the diversity in defence, but we show that the trade-off alone is unlikely to lead to diversity. Our models provide a framework to examine relative investment in different defence components both experimentally and in the field

Randomised, double-blind, multicentre, mixed-methods, dose-escalation feasibility trial of mirtazapine for better treatment of severe breathlessness in advanced lung disease (BETTER-B feasibility)

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ. New treatments are required for severe breathlessness in advanced disease. We conducted a randomised feasibility trial of mirtazapine over 28 days in adults with a modified medical research council breathlessness scale score ≥3. Sixty-four patients were randomised (409 screened), achieving our primary feasibility endpoint of recruitment. Most patients had COPD or interstitial lung disease; 52 (81%) completed the trial. There were no differences between placebo and mirtazapine in tolerability or safety, and blinding was maintained. Worst breathlessness ratings at day 28 (primary clinical activity endpoint) were, 7.1 (SD 2.3, placebo) and 6.3 (SD 1.8, mirtazapine). A phase III trial of mirtazapine is indicated. Trial registration: ISRCTN 32236160; European Clinical Trials Database (EudraCT no: 2015-004064-11)

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)

CT scanning for diagnosing blunt ureteral and ureteropelvic junction injuries

<p>Abstract</p> <p>Background</p> <p>Blunt ureteral and ureteropelvic (UPJ) injuries are extremely rare and very difficult to diagnose. Many of these injuries are missed by the initial trauma evaluation.</p> <p>Methods</p> <p>Trauma registry data was used to identify all blunt trauma patients with ureteral or UPJ injuries, from 1 April 2001 to 30 November 2006. Demographics, injury information and outcomes were determined. Chart review was then performed to record initial clinical and all CT findings.</p> <p>Results</p> <p>Eight patients had ureteral or UPJ injuries. Subtle findings such as perinephric stranding and hematomas, and low density retroperitoneal fluid were evident on all initial scans, and prompted delayed excretory scans in 7/8 cases. As a result, ureteral and UPJ injuries were diagnosed immediately for these seven patients. These findings were initially missed in the eighth patient because significant associated visceral findings mandated emergency laparotomy. All ureteral and UPJ injuries have completely healed except for the case with the delay in diagnosis.</p> <p>Conclusion</p> <p>Most blunt ureteral and UPJ injuries can be identified if delayed excretory CT scans are performed based on initial CT findings of perinephric stranding and hematomas, or the finding of low density retroperitoneal fluid.</p

Knowledge transfer & exchange through social networks: building foundations for a community of practice within tobacco control

BACKGROUND: Health services and population health innovations advance when knowledge transfer and exchange (KTE) occurs among researchers, practitioners, policy-makers and consumers using high-quality evidence. However, few KTE models have been evaluated in practice. Communities of practice (CoP) – voluntary, self-organizing, and focused groups of individuals and organizations – may provide one option. This paper outlines an approach to lay the foundation for a CoP within the area of Web-assisted tobacco interventions (WATI). The objectives of the study were to provide a data-driven foundation to inform decisions about organizing a CoP within the geographically diverse, multi-disciplinary WATI group using evaluation and social network methodologies. METHODS: A single-group design was employed using a survey of expectations, knowledge, and interpersonal WATI-related relationships administered prior to a meeting of the WATI group followed by a 3-week post-meeting Web survey to assess short-term impact on learning and networking outcomes. RESULTS: Twenty-three of 27 WATI attendees (85%) from diverse disciplinary and practice backgrounds completed the baseline survey, with 21 (91%) of those participants completing the three-week follow-up. Participants had modest expectations of the meeting at baseline. A social network map produced from the data illustrated a centralized, yet sparse network comprising of interdisciplinary teams with little trans-sectoral collaboration. Three-week follow-up survey results showed that participants had made new network connections and had actively engaged in KTE activities with WATI members outside their original network. CONCLUSION: Data illustrating both the shape and size of the WATI network as well as member's interests and commitment to KTE, when shared and used to frame action steps, can positively influence the motivation to collaborate and create communities of practice. Guiding KTE planning through blending data and theory can create more informed transdisciplinary and trans-sectoral collaboration environments

Differential Roles of the PKC Novel Isoforms, PKCδ and PKCε, in Mouse and Human Platelets

Background Increasing evidence suggests that individual isoforms of protein kinase C (PKC) play distinct roles in regulating platelet activation. Methodology/Principal Findings In this study, we focus on the role of two novel PKC isoforms, PKCδ and PKCε, in both mouse and human platelets. PKCδ is robustly expressed in human platelets and undergoes transient tyrosine phosphorylation upon stimulation by thrombin or the collagen receptor, GPVI, which becomes sustained in the presence of the pan-PKC inhibitor, Ro 31-8220. In mouse platelets, however, PKCδ undergoes sustained tyrosine phosphorylation upon activation. In contrast the related isoform, PKCε, is expressed at high levels in mouse but not human platelets. There is a marked inhibition in aggregation and dense granule secretion to low concentrations of GPVI agonists in mouse platelets lacking PKCε in contrast to a minor inhibition in response to G protein-coupled receptor agonists. This reduction is mediated by inhibition of tyrosine phosphorylation of the FcRγ-chain and downstream proteins, an effect also observed in wild-type mouse platelets in the presence of a PKC inhibitor. Conclusions These results demonstrate a reciprocal relationship in levels of the novel PKC isoforms δ and ε in human and mouse platelets and a selective role for PKCε in signalling through GPVI