78 research outputs found

    PhosFox: a bioinformatics tool for peptide-level processing of LC-MS/MS-based phosphoproteomic data

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    Background: It is possible to identify thousands of phosphopeptides and -proteins in a single experiment with mass spectrometry-based phosphoproteomics. However, a current bottleneck is the downstream data analysis which is often laborious and requires a number of manual steps.Results: Toward automating the analysis steps, we have developed and implemented a software, PhosFox, which enables peptide-level processing of phosphoproteomic data generated by multiple protein identification search algorithms, including Mascot, Sequest, and Paragon, as well as cross-comparison of their identification results. The software supports both qualitative and quantitative phosphoproteomics studies, as well as multiple between-group comparisons. Importantly, PhosFox detects uniquely phosphorylated peptides and proteins in one sample compared to another. It also distinguishes differences in phosphorylation sites between phosphorylated proteins in different samples. Using two case study examples, a qualitative phosphoproteome dataset from human keratinocytes and a quantitative phosphoproteome dataset from rat kidney inner medulla, we demonstrate here how PhosFox facilitates an efficient and in-depth phosphoproteome data analysis. PhosFox was implemented in the Perl programming language and it can be run on most common operating systems. Due to its flexible interface and open source distribution, the users can easily incorporate the program into their MS data analysis workflows and extend the program with new features. PhosFox source code, implementation and user instructions are freely available from https://bitbucket.org/phintsan/phosfox.Conclusions: PhosFox facilitates efficient and more in-depth comparisons between phosphoproteins in case-control settings. The open source implementation is easily extendable to accommodate additional features for widespread application use cases

    Variable Compression in ProbLog

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    In order to compute the probability of a query, ProbLog represents the proofs of the query as disjunctions of conjunctions, for which a Reduced Ordered Binary Decision Diagram (ROBDD) is computed. The paper identifies patterns of Boolean variables that occur in Boolean formulae, namely AND-clusters and OR-clusters. Our method compresses the variables in these clusters and thus reduces the size of ROBDDs without affecting the probability. We give a polynomial algorithm that detects AND-clusters in disjunctive normal form (DNF) Boolean formulae, or OR-clusters in conjunctive normal form (CNF) Boolean formulae. We do an experimental evaluation of the effects of AND-cluster compression for a real application of ProbLog. With our prototype implementation we have a significant improvement in performance (up to 87%) for the generation of ROBDDs. Moreover, compressing AND-clusters of Boolean variables in the DNFs makes it feasible to deal with ProbLog queries that give rise to larger DNFs.acceptance rate: 38%status: publishe

    The biometric antecedents to happiness

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    It has been suggested that biological markers are associated with human happiness. We contribute to the empirical literature by examining the independent association between various aspects of biometric wellbeing measured in childhood and happiness in adulthood. Using Young Finns Study data (n = 1905) and nationally representative linked data we examine whether eight biomarkers measured in childhood (1980) are associated with happiness in adulthood (2001). Using linked data we account for a very rich set of confounders including age, sex, body size, family background, nutritional intake, physical activity, income, education and labour market experiences. We find that there is a negative relationship between triglycerides and subjective well-being but it is both gender-and age-specific and the relationship does not prevail using the later measurements (1983/1986) on triglycerides. In summary, we conclude that none of the eight biomarkers measured in childhood predict happiness robustly in adulthood

    Healthy learning mind - Effectiveness of a mindfulness program on mental health compared to a relaxation program and teaching as usual in schools: A cluster-randomised controlled trial

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    A short 9-week MBI in school-setting provides slight benefits over a relaxation program and teaching as usual. Future research should investigate whether embedding regular mindfulness-based practice in curriculums could intensify the effects.\nMindfulness-Based Interventions (MBIs) have shown promising effects on mental health among children and adolescents, but high-quality studies examining the topic are lacking. The present study assessed the effects of MBI on mental health in school-setting in an extensive randomised controlled trial.\nFinnish school children and adolescents (N = 3519), aged 12-15 years (6th to 8th graders), from 56 schools were randomized into a 9 week MBI group, and control groups with a relaxation program or teaching as usual. The primary outcomes were resilience, socio-emotional functioning, and depressive symptoms at baseline, at completion of the programs at 9 weeks (T9), and at follow-up at 26 weeks (T26).\nOverall, mindfulness did not show more beneficial effects on the primary outcomes compared to the controls except for resilience for which a positive intervention effect was found at T9 in all participants (β=1.18, SE 0.57, p = 0.04) as compared to the relaxation group. In addition, in gender and grade related analyses, MBI lowered depressive symptoms in girls at T26 (β=-0.49, SE 0.21, p = 0.02) and improved socio-emotional functioning at T9 (β=-1.37, SE 0.69, p = 0.049) and at T26 (β=-1.71, SE 0.73, p = 0.02) among 7th graders as compared to relaxation.\nThe inactive control group was smaller than the intervention and active control groups, reducing statistical power.\nCONCLUSIONS\nBACKGROUND\nMETHODS\nRESULTS\nLIMITATION

    Healthy Learning Mind - Effectiveness of a mindfulness program on mental health compared to a relaxation program and teaching as usual in schools: a cluster-randomised controlled trial

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    Background Mindfulness-Based Interventions (MBIs) have shown promising effects on mental health among children and adolescents, but high-quality studies examining the topic are lacking. The present study assessed the effects of MBI on mental health in school-setting in an extensive randomised controlled trial. Methods Finnish school children and adolescents (N=3519), aged 12-15 years (6th to 8th graders), from 56 schools were randomized into a 9 week MBI group, and control groups with a relaxation program or teaching as usual. The primary outcomes were resilience, socio-emotional functioning, and depressive symptoms at baseline, at completion of the programs at 9 weeks (T9), and at follow-up at 26 weeks (T26). Results Overall, mindfulness did not show more beneficial effects on the primary outcomes compared to the controls except for resilience for which a positive intervention effect was found at T9 in all participants (β=1.18, SE 0.57, p=0.04) as compared to the relaxation group. In addition, in gender and grade related analyses, MBI lowered depressive symptoms in girls at T26 (β=-0.49, SE 0.21, p=0.02) and improved socio-emotional functioning at T9(β=-1.37, SE 0.69, p=0.049) and at T26 (β=-1.71, SE 0.73, p=0.02) among 7th graders as compared to relaxation. Limitations The inactive control group was smaller than the intervention and active control groups, reducing statistical power. Conclusions A short 9-week MBI in school-setting provides slight benefits over a relaxation program and teaching as usual. Future research should investigate whether embedding regular mindfulness-based practice in curriculums could intensify the effects.Peer reviewe

    Family- and population-based designs identify different rare causal variants

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    Both family- and population-based samples are used to identify genetic variants associated with phenotypes. Each strategy has demonstrated advantages, but their ability to identify rare variants and genes containing rare variants is unclear. To compare these two study designs in the identification of rare causal variants, we applied various methods to the population- and family-based data simulated by the Genetic Analysis Workshop 17 with knowledge of the simulated model. Our results suggest that different variants can be identified by different study designs. Family-based and population-based study designs can be complementary in the identification of rare causal variants and should be considered in future studies

    Positive Psychosocial Factors in Childhood Predicting Lower Risk for Adult Type 2 Diabetes : The Cardiovascular Risk in Young Finns Study, 1980-2012

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    Introduction: Type 2 diabetes is a public health concern, but psychosocial factors that may protect against the disease are unknown. This study examines whether a positive psychosocial environment in childhood is associated with lower risk for Type 2 diabetes in adulthood or healthier glucose trajectories over the life course, and whether BMI mediates the associations. Methods: A cohort of 3,596 Finnish children was followed into adulthood over 32 years. An overall positive psychosocial score, consisting of six subdomains, was measured at study baseline (1980). Relative risk ratios and multilevel growth curve modeling were used to examine associations of the psychosocial score with Type 2 diabetes (2012) and glucose trajectories (1986-2012). The mediating effect by BMI was examined using mediation analysis. The analyses were conducted between June 2015 and January 2016. Results: There was a 21% decrease in the rate of Type 2 diabetes (relative risk ratio, 0.79; 95% CI = 0.66, 0.94) for each 1-SD increase in the positive psychosocial score after adjustment for childhood cardiovascular risk factors and dietary behaviors. Adult BMI mediated 52% and weight gain mediated 25% of the association. The growth curve model showed healthier glucose trajectories (age X psychosocial score interaction, b = -0.01; p = 0.010) for participants with higher versus lower positive psychosocial score in childhood. Conclusions: Positive psychosocial environment in childhood seems to have beneficial influences on the risk for Type 2 diabetes over the life span. RCTs will be required to see if interventions directed at early-life circumstances are warranted. (C) 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.Peer reviewe

    New Developments in Understanding Cardiovascular Disease and the Implications for Social Work

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    Cardiovascular disease is now viewed as an inflammatory disease. An index of chronic inflammation (viz., C-Reactive Protein) is as good a predictor of heart attacks as are fats in blood. The data suggest that stressful events are so closely associated with chronic inflammatory states, that the body’s stress response can be viewed as an inflammatory state. This paper summarizes and explains the link between stress and cardiovascular disease. Negative health outcomes, particularly for cardiovascular diseases, are higher among those of lower socio-economic status. Differential stress among socio-economic tiers is considered as an explanation for the disparities. The literature linking cardiovascular risk factors to the stressors of workplace unfairness and lack of control over working conditions is reviewed. The role of the stressor of racism in explaining the higher rates of cardiovascular mortality in African Americans is discussed. Finally, for societies with wider gaps in income between the rich and the poor, increased stress is explored as a possible explanation for the diminished health outcomes found across all socio-economic tiers. The implications for social work direct practice and macro-practice are considered
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