Haptoglobin Phenotype, Preeclampsia Risk and the Efficacy of Vitamin C and E Supplementation to Prevent Preeclampsia in a Racially Diverse Population

Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia

On the scaling of activity in tropical forest mammals

Activity range – the amount of time spent active per day – is a fundamental aspect contributing to the optimization process by which animals achieve energetic balance. Based on their size and the nature of their diet, theoretical expectations are that larger carnivores need more time active to fulfil their energetic needs than do smaller ones and also more time active than similar‐sized non‐carnivores. Despite the relationship between daily activity, individual range and energy acquisition, large‐scale relationships between activity range and body mass among wild mammals have never been properly addressed. This study aimed to understand the scaling of activity range with body mass, while controlling for phylogeny and diet. We built simple empirical predictions for the scaling of activity range with body mass for mammals of different trophic guilds and used a phylogenetically controlled mixed model to test these predictions using activity records of 249 mammal populations (128 species) in 19 tropical forests (in 15 countries) obtained using camera traps. Our scaling model predicted a steeper scaling of activity range in carnivores (0.21) with higher levels of activity (higher intercept), and near‐zero scaling in herbivores (0.04). Empirical data showed that activity ranges scaled positively with body mass for carnivores (0.061), which also had higher intercept value, but not for herbivores, omnivores and insectivores, in general, corresponding with the predictions. Despite the many factors that shape animal activity at local scales, we found a general pattern showing that large carnivores need more time active in a day to meet their energetic demands. Introduction Activity range – the amount of time, in hours, spent active per day – is a fundamental outcome of the complex physiological and behavioral optimization process by which animals ensure that energy input keeps pace with energy output. In addition to basal metabolism, animals face costs of foraging, acquiring mates and shelter, building reserves for lean times and escaping predators (Carbone et al. 2007, Halle and Stenseth 2012). Environmental and ecological factors that vary through the day (e.g. luminosity, temperature, predation risk and competition avoidance) constrain activity to certain times, depending on morpho‐physiological limitations (Castillo‐Ruiz et al. 2012, Hut et al. 2012). In addition, animals need time to rest in order to recover their cognitive or physical condition (Siegel 2005). Thus, they must optimize their activity range to meet their resource requirements, while dealing with natural daily cycles and saving time for sleep/rest (Downes 2001, Siegel 2005, Cozzi et al. 2012). The resource requirements of mammals are related to basal metabolic rate, which scales positively with body mass (Kleiber 1932, Isaac and Carbone 2010), while predation risk decreases with body mass (Sinclair et al. 2003, Hopcraft et al. 2009). Because high predation risk constrains activity while high resource needs increases activity range (Cozzi et al. 2012, Suselbeek et al. 2014), the question arises whether and how activity range also scales with body mass. Day range (total distance travelled in a day) and home range (area in which animals perform their daily activities) scales positively with body mass and are key metrics to understand the resource requirements of an animal (McNab 1963, Kelt and Van Vuren 2001, Carbone et al. 2005, Tamburello et al. 2015). As activity range is related to space‐use metrics (i.e. home range and day range), it is hence, also related to the acquisition of energy. Given that, one might expect activity range to increase with body mass. However, we have a poor understanding of how this relationship actually looks. Previous work developed predictions of body mass scaling with day range (Garland 1983, Carbone et al. 2005) and travel speed (Carbone et al. 2007, Rowcliffe et al. 2016). From a simple physical viewpoint, activity range should equal the day range divided by average travel speed. It should thus be possible to infer the scaling of activity range with body mass from these relationships. Some of the variation in space use across species that is not explained by body mass is associated with different evolutionary histories and ecological traits (McNab 1963, Kelt and Van Vuren 2001, Price and Hopkins 2015, Tamburello et al. 2015). Diet is the most conspicuous of these, because primary and secondary productivity present different overall yields and accessibility for consumers (Jetz et al. 2004), which in turn influence individual movements (Carbone et al. 2005) and potentially activity range, when exploiting resources at different trophic levels. The nature of the diet aggravates the higher energetic demands of larger carnivores. Predators have considerable energetic constraints related to hunting and handling their prey (Gorman et al. 1998, Carbone et al. 1999) as animal prey can be rare, widely dispersed, unpredictable in time and space and not storable (Jetz et al. 2004, Carbone et al. 2007). Therefore, carnivores have the lowest energy supply rates (supply rate of usable resources available inside the home range), independent of body mass, when compared to other diet categories (Jetz et al. 2004) besides exploring larger areas and traveling greater daily distances (McNab 1963, Kelt and Van Vuren 2001, Carbone et al. 2005, Tamburello et al. 2015). Therefore, larger animals occupy larger areas than small ones, and carnivores occupy larger areas than do similar‐sized non‐carnivores (Jetz et al. 2004, Tamburello et al. 2015). To date, few studies have considered interspecific variation in activity range with body mass and other species traits. For example, van Schaik and Griffiths (1996) and Gómez et al. (2005) anecdotally suggested that larger mammal species are cathemeral (i.e. active day and night), which implies that they can be active during a larger proportion of the 24‐h cycle. Rowcliffe et al. (2014) found that activity range is positively correlated with body mass in tropical forest mammals in Panama. Ramesh et al. (2015) found a negative relationship between body mass and activity concentration (i.e. how concentrated in few hours is the activity of an animal during the day) in Indian mammals, also equating to a positive association between activity range and body mass. However, no study has explored variation in activity range across a diverse range of species, while controlling for phylogeny and diet. This has been, at least in part, due to a lack of consistent data available on a wide range of species. Recent work using camera traps (Oliveira‐Santos et al. 2013, Rowcliffe et al. 2014), however, has demonstrated that accurate estimates of activity range can be obtained from photographic records from camera traps. Given the large and rapidly increasing volume of camera‐trapping data available globally (Burton et al. 2015), these approaches, consistently applied across a wide range of studies, can provide an important basis for the large‐scale study of activity. Here, we provided simple empirical predictions for the scaling of activity range with body mass for mammals of different trophic guilds. To test these predictions, we estimated the activity range for 249 populations of 128 terrestrial mammal species across 19 tropical forests, and used a phylogenetically controlled mixed model to determine how activity range scales with body mass by diet. As larger animals occupy larger areas than small ones, and carnivores occupy larger areas than do similar‐sized non‐carnivores (Jetz et al. 2004), we hypothesize that carnivores will present a higher scaling of activity range with body mass and also higher activity ranges for a given mass (higher intercept) when compared to herbivores, omnivores and insectivores

How does study quality affect the results of a diagnostic meta-analysis?

Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited

Cancer Appetite and Symptom Questionnaire (CASQ) for Brazilian Patients: Cross-Cultural Adaptation and Validation Study

Background Appetite and symptoms, conditions generally reported by the patients with cancer, are somewhat challenging for professionals to measure directly in clinical routine (latent conditions). Therefore, specific instruments are required for this purpose. This study aimed to perform a cultural adaptation of the Cancer Appetite and Symptom Questionnaire (CASQ), into Portuguese and evaluate its psychometric properties on a sample of Brazilian cancer patients. Methods This is a validation study with Brazilian cancer patients. The face, content, and construct (factorial and convergent) validities of the Cancer Appetite and Symptom Questionnaire, the study tool, were estimated. Further, a confirmatory factor analysis (CFA) was conducted. The ratio of chi-square and degrees of freedom (χ2 /df), comparative fit index (CFI), goodness of fit index (GFI) and root mean square error of approximation (RMSEA) were used for fit model assessment. In addition, the reliability of the instrument was estimated using the composite reliability (CR) and Cronbach’s alpha coefficient (α), and the invariance of the model in independent samples was estimated by a multigroup analysis (Δχ2). Results Participants included 1,140 cancer patients with a mean age of 53.95 (SD = 13.25) years; 61.3% were women. After the CFA of the original CASQ structure, 2 items with inadequate factor weights were removed. Four correlations between errors were included to provide adequate fit to the sample (χ2 /df = 8.532, CFI = .94, GFI = .95, and RMSEA = .08). Themodel exhibited a low convergent validity (AVE = .32). The reliability was adequate (CR = .82 α = .82). The refined model showed strong invariance in two independent samples (Δχ2 : λ: p = .855; i: p = .824; Res: p = .390). A weak stability was obtained between patients undergoing chemotherapy and radiotherapy (Δχ2 : λ: p = .155; i: p < .001; Res: p < .001), and between patients undergoing chemotherapy combined with radiotherapy and palliative care (Δχ2 : λ: p = .058; i: p < .001; Res: p < .001). Conclusion The Portuguese version of the CASQ had good face and construct validity and reliability. However, the CASQ still presented invariance in independent samples of Brazilian patients with cancer. However, the tool has low convergent validity and weak invariance in samples with different treatment

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Co-creating FabLab La Campana: Empowering a Marginalised Community in the North of Mexico

FabLabs are a celebrated approach to formal and informal learning through making with digital fabrication tools. This paper discusses the co-creation of a FabLab with a marginalised community in Monterrey, Mexico. One of the main challenges in establishing these Makerspaces is in sustaining the activities and community engagement on an ongoing basis. In responding to this challenge, this process focused on the empowerment of community members to make the changes they desire, either for themselves or their community. Beyond skills for making and playful engagement in STEAM learning, makerspaces also facilitate the building of networks and partnerships, and the development of social competencies and soft skills, that are often overlooked in the process of empowerment and social mobility. Primary insights from the co-creation process of the La Campana FabLab are reported here. A Mexican higher education institution with a strong social responsibility agenda facilitated the process, securing funds and connecting project partners, locally and globally. Framing the cocreation of the FabLab with the partners was and is an ongoing process. Key factors included the donation of a safe space and tools for the community to host and run the FabLab. Establishing the role of the FabLab in the community from the participants’ point-of-view and committing to regular ongoing educational dialogue was important in forming an equitable partnership between institutions and community. Beyond the physical space, equipment and educational activities, a community architecture intervention demonstrated the large-scale impact digital fabrication could have in creating spaces shaped by and for the community

Study of DJ meson decays to D+π−, D0π+ and D∗+π− final states in pp collisions

A study of D+π−, D0π+ and D∗+π− final states is performed using pp collision data, corresponding to an integrated luminosity of 1.0 fb−1, collected at a centre-of-mass energy of 7 TeV with the LHCb detector. The D1(2420)0 resonance is observed in the D∗+π− final state and the D∗2(2460) resonance is observed in the D+π−, D0π+ and D∗+π− final states. For both resonances, their properties and spin-parity assignments are obtained. In addition, two natural parity and two unnatural parity resonances are observed in the mass region between 2500 and 2800 MeV. Further structures in the region around 3000 MeV are observed in all the D∗+π−, D+π− and D0π+ final states

Drosophila Duplication Hotspots Are Associated with Late-Replicating Regions of the Genome

Duplications play a significant role in both extremes of the phenotypic spectrum of newly arising mutations: they can have severe deleterious effects (e.g. duplications underlie a variety of diseases) but can also be highly advantageous. The phenotypic potential of newly arisen duplications has stimulated wide interest in both the mutational and selective processes shaping these variants in the genome. Here we take advantage of the Drosophila simulans–Drosophila melanogaster genetic system to further our understanding of both processes. Regarding mutational processes, the study of two closely related species allows investigation of the potential existence of shared duplication hotspots, and the similarities and differences between the two genomes can be used to dissect its underlying causes. Regarding selection, the difference in the effective population size between the two species can be leveraged to ask questions about the strength of selection acting on different classes of duplications. In this study, we conducted a survey of duplication polymorphisms in 14 different lines of D. simulans using tiling microarrays and combined it with an analogous survey for the D. melanogaster genome. By integrating the two datasets, we identified duplication hotspots conserved between the two species. However, unlike the duplication hotspots identified in mammalian genomes, Drosophila duplication hotspots are not associated with sequences of high sequence identity capable of mediating non-allelic homologous recombination. Instead, Drosophila duplication hotspots are associated with late-replicating regions of the genome, suggesting a link between DNA replication and duplication rates. We also found evidence supporting a higher effectiveness of selection on duplications in D. simulans than in D. melanogaster. This is also true for duplications segregating at high frequency, where we find evidence in D. simulans that a sizeable fraction of these mutations is being driven to fixation by positive selection

A pooling-based genome-wide analysis identifies new potential candidate genes for atopy in the European Community Respiratory Health Survey (ECRHS)

<p>Abstract</p> <p>Background</p> <p>Asthma and atopy are complex phenotypes with shared genetic component. In this study we attempt to identify genes related to these traits performing a two-stage DNA pooling genome-wide analysis in order to reduce costs. First, we assessed all markers in a subset of subjects using DNA pooling, and in a second stage we evaluated the most promising markers at an individual level.</p> <p>Methods</p> <p>For the genome-wide analysis, we constructed DNA pools from 75 subjects with atopy and asthma, 75 subjects with atopy and without asthma and 75 control subjects without atopy or asthma. In a second stage, the most promising regions surrounding significant markers after correction for false discovery rate were replicated with individual genotyping of samples included in the pools and an additional set of 429 atopic subjects and 222 controls from the same study centres.</p> <p>Results</p> <p><it>Homo sapiens </it>protein kinase-like protein SgK493 (<it>SGK493</it>) was found to be associated with atopy. To lesser extent mitogen-activated protein kinase 5 (<it>MAP3K5</it>), collagen type XVIII alpha 1 (<it>COL18A1</it>) and collagen type XXIX alpha 1 (<it>COL29A1</it>) were also found to be associated with atopy. Functional evidences points out a role for <it>MAP3K5</it>, <it>COL18A1 </it>and <it>COL29A1 </it>but the function of <it>SGK493 </it>is unknown.</p> <p>Conclusion</p> <p>In this analysis we have identified new candidate regions related to atopy and suggest <it>SGK493 </it>as an atopy locus, although these results need further replication.</p