Network analysis of synovial RNA sequencing identifies gene-gene interactions predictive of response in rheumatoid arthritis

Abstract Background To determine whether gene-gene interaction network analysis of RNA sequencing (RNA-Seq) of synovial biopsies in early rheumatoid arthritis (RA) can inform our understanding of RA pathogenesis and yield improved treatment response prediction models. Methods We utilized four well curated pathway repositories obtaining 10,537 experimentally evaluated gene-gene interactions. We extracted specific gene-gene interaction networks in synovial RNA-Seq to characterize histologically defined pathotypes in early RA and leverage these synovial specific gene-gene networks to predict response to methotrexate-based disease-modifying anti-rheumatic drug (DMARD) therapy in the Pathobiology of Early Arthritis Cohort (PEAC). Differential interactions identified within each network were statistically evaluated through robust linear regression models. Ability to predict response to DMARD treatment was evaluated by receiver operating characteristic (ROC) curve analysis. Results Analysis comparing different histological pathotypes showed a coherent molecular signature matching the histological changes and highlighting novel pathotype-specific gene interactions and mechanisms. Analysis of responders vs non-responders revealed higher expression of apoptosis regulating gene-gene interactions in patients with good response to conventional synthetic DMARD. Detailed analysis of interactions between pairs of network-linked genes identified the SOCS2/STAT2 ratio as predictive of treatment success, improving ROC area under curve (AUC) from 0.62 to 0.78. We identified a key role for angiogenesis, observing significant statistical interactions between NOS3 (eNOS) and both CAMK1 and eNOS activator AKT3 when comparing responders and non-responders. The ratio of CAMKD2/NOS3 enhanced a prediction model of response improving ROC AUC from 0.63 to 0.73. Conclusions We demonstrate a novel, powerful method which harnesses gene interaction networks for leveraging biologically relevant gene-gene interactions leading to improved models for predicting treatment response

Hunger among Inuit children in Canada

Background and objectives. Inuit populations may be at increased risk for experiencing poor nutrition or hunger due to limited access and availability to food. The prevalence and correlates of parental perceptions of hunger among a nationally representative sample of Inuit children in Canada have not yet been reported. Design. Data are from the 2006 Aboriginal Children's Survey (ACS). Sociodemographic information, dietary behaviours and hunger status were parent-reported via a household interview for Inuit children aged 2–5 years (n=1,234). Prevalence of hunger was calculated among Inuit children by sociodemographic factors and by dietary behaviours. In addition, a multivariate logistic regression model was conducted to determine factors associated with parental perception of ever experiencing hunger. Results. The prevalence of Inuit children in Canada aged 2–5 years ever experiencing hunger was 24.4%. Children who were reported to have experienced hunger consumed milk and milk products (p<0.001); fish, eggs and meat (p<0.05); fruits (p<0.001); and vegetables (p<0.001) significantly less often than never-hungry children. Fast food and processed foods, soft drinks and juice, and salty snacks, sweets and desserts were consumed as often as never-hungry children (all p>0.05). The majority (81%) of Inuit parents/guardians of ever-hungry children sought help from family or friends. Factors associated with an increased likelihood of experiencing hunger include sociodemographic characteristics (such as income and household size), living in an Inuit region and living in a community with cultural activities. Conclusion. About 1 in 4 Inuit children were reported by their parents to have experienced hunger, and hunger was associated with region, sociodemographic and community factors. Future research could further examine the impact of ever experiencing hunger on the health status of Inuit children and their families in Canada

Computing the everyday: social media as data platforms

We conceive social media platforms as sociotechnical entities that variously shape user platform involvement and participation. Such shaping develops along three fundamental data operations that we subsume under the terms of encoding, aggregation, and computation. Encoding entails the engineering of user platform participation along narrow and standardized activity types (e.g., tagging, liking, sharing, following). This heavily scripted platform participation serves as the basis for the procurement of discrete and calculable data tokens that are possible to aggregate and, subsequently, compute in a variety of ways. We expose these operations by investigating a social media platform for shopping. We contribute to the current debate on social media and digital platforms by describing social media as posttransactional spaces that are predominantly concerned with charting and profiling the online predispositions, habits, and opinions of their user base. Such an orientation sets social media platforms apart from other forms of mediating online interaction. In social media, we claim, platform participation is driven toward an endless online conversation that delivers the data footprint through which a computed sociality is made the source of value creation and monetization

Bridging topological and functional information in protein interaction networks by short loops profiling

Protein-protein interaction networks (PPINs) have been employed to identify potential novel interconnections between proteins as well as crucial cellular functions. In this study we identify fundamental principles of PPIN topologies by analysing network motifs of short loops, which are small cyclic interactions of between 3 and 6 proteins. We compared 30 PPINs with corresponding randomised null models and examined the occurrence of common biological functions in loops extracted from a cross-validated high-confidence dataset of 622 human protein complexes. We demonstrate that loops are an intrinsic feature of PPINs and that specific cell functions are predominantly performed by loops of different lengths. Topologically, we find that loops are strongly related to the accuracy of PPINs and define a core of interactions with high resilience. The identification of this core and the analysis of loop composition are promising tools to assess PPIN quality and to uncover possible biases from experimental detection methods. More than 96% of loops share at least one biological function, with enrichment of cellular functions related to mRNA metabolic processing and the cell cycle. Our analyses suggest that these motifs can be used in the design of targeted experiments for functional phenotype detection.This research was supported by the Biotechnology and Biological Sciences Research Council (BB/H018409/1 to AP, ACCC and FF, and BB/J016284/1 to NSBT) and by the Leukaemia & Lymphoma Research (to NSBT and FF). SSC is funded by a Leukaemia & Lymphoma Research Gordon Piller PhD Studentship

Subclinical Thyroid Disorders and Cognitive Performance Among Adolescents in the United States

Background: Thyroid hormone plays a crucial role in the growth and function of the central nervous system. The purpose of the study was to examine the relationships between the status of subclinical thyroid conditions and cognition among adolescents in the United States. Methods: Study sample included 1,327 adolescents 13 to 16 years old who participated in the Third National Health and Nutrition Examination Survey (NHANES III). Serum thyroxine (T4) and thyroid stimulating hormone (TSH) were measured and subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroid groups were defined. Cognitive performance was assessed using the subscales of the Wide Range Achievement Test-Revised (WRAT-R) and the Wechsler Intelligence Scale for Children-Revised (WISC-R). The age-corrected scaled scores for arithmetic, reading, block design, and digit span were derived from the cognitive assessments. Results: Subclinical hypothyroidism was found in 1.7% and subclinical hyperthyroidism was found in 2.3% of the adolescents. Cognitive assessment scores on average tended to be lower in adolescents with subclinical hyperthyroidism and higher in those with subclinical hypothyroidism than the score for the euthyroid group. Adolescents with subclinical hypothyroidism had significantly better scores in block design and reading than the euthyroid subjects even after adjustment for a number of variables including sex, age, and family income level. Conclusion: Subclinical hypothyroidism was associated with better performance in some areas of cognitive functions while subclinical hyperthyroidism could be a potential risk factor

Reframing gender and feminist knowledge construction in marketing and consumer research: missing feminisms and the case of men and masculinities

Gender has been theorised and studied in many ways and across different disciplines. Although a number of these theorisations have been recognised and adopted in marketing and consumer research, the significance of feminism in knowledge construction has largely remained what we would call ‘unfinished’. Based on a critical reframing of gender research in marketing and consumer research, in dialogue with feminist theory, this article offers theoretical and practical suggestions for how to reinvigorate these research efforts. The analysis highlights dominant theorisations of gender, relating to gender as variable, difference and role; as fundamental difference and structuring; and as cultural and identity constructions. This reframing emphasises various neglected or ‘missing feminisms’, including queer theory; critical race, intersectional and transnational feminisms; material-discursive feminism; and critical studies on men and masculinities. A more detailed discussion of the latter, as a relatively new, growing and politically contentious area, is further developed to highlight more specifically which feminist and gender theories are mainly in use in marketing and consumer research and which are little or not used. In the light of this, it is argued that marketing and related disciplines have thus far largely neglected several key contemporary gender and feminist theorisations, particularly those that centre on gender power relations. The potential impact of these theoretical frames on transdisciplinary studies in marketing and consumer research and research agenda(s) is discussed

Self-reported drunkenness among adolescents in four sub-Saharan African countries: associations with adverse childhood experiences

<p>Abstract</p> <p>Background</p> <p>Consumption of alcohol is associated with acute and chronic adverse health outcomes. There is a paucity of studies that explore the determinants of alcohol use among adolescents in sub-Saharan Africa and, in particular, that examine the effects of adverse childhood experiences on alcohol use.</p> <p>Methods</p> <p>The paper draws on nationally-representative data from 9,819 adolescents aged 12-19 years from Burkina Faso, Ghana, Malawi, and Uganda. Logistic regression models were employed to identify correlates of self-reported past-year drunkenness. Exposure to four adverse childhood experiences comprised the primary independent variables: living in a food-insecure household, living with a problem drinker, having been physically abused, and having been coerced into having sex. We controlled for age, religiosity, current schooling status, the household head's sex, living arrangements, place of residence, marital status, and country of survey. All analyses were conducted separately for males and females.</p> <p>Results</p> <p>At the bivariate level, all independent variables (except for coerced sex among males) were associated with the outcome variable. Overall, 9% of adolescents reported that they had been drunk in the 12 months preceding the survey. In general, respondents who had experienced an adverse event during childhood were more likely to report drunkenness. In the multivariate analysis, only two adverse childhood events emerged as significant predictors of self-reported past-year drunkenness among males: living in a household with a problem drinker before age 10, and being physically abused before age 10. For females, exposure to family-alcoholism, experience of physical abuse, and coerced sex increased the likelihood of reporting drunkenness in the last 12 months. The association between adverse events and reported drunkenness was more pronounced for females. For both males and females there was a graded relationship between the number of adverse events experienced and the proportion reporting drunkenness.</p> <p>Conclusions</p> <p>We find an association between experience of adverse childhood events and drunkenness among adolescents in four sub-Saharan African countries. The complex impacts of adverse childhood experiences on young people's development and behavior may have an important bearing on the effectiveness of interventions geared at reducing alcohol dependence among the youth.</p

Household food security is associated with infant feeding practices in rural Bangladesh.

Although household food security (HHFS) has been shown to affect diet, nutrition, and health of adults and also learning in children, no study has examined associations with infant feeding practices (IFP). We studied 1343 infants born between May 2002 and December 2003 in the Maternal and Infant Nutrition Intervention in Matlab study to investigate the effect of HHFS on IFP in rural Bangladesh. We measured HHFS using a previously developed 11-item scale. Cumulative and current infant feeding scales were created from monthly infant feeding data for the age groups of 1-3, 1-6, 1-9, and 1-12 mo based on comparison to infant feeding recommendations. We used lagged, dynamic, and difference longitudinal regression models adjusting for various infant and maternal variables to examine the association between HHFS and changes in IFP, and Cox proportional hazards models to examine the influence of HHFS on the duration of breast-feeding and the time of introduction of complementary foods. Better HHFS status was associated with poor IFP during 3-6 mo but was associated with better IFP during 6-9 and 9-12 mo of age. Although better HHFS was not associated with the time of introduction of complementary foods, it was associated with the type of complementary foods given to the infants. Intervention programs to support proper IFP should target mothers in food-secure households when their babies are 3-6 mo old and also mothers in food-insecure households during the 2nd half of infancy. Our results provide strong evidence that HHFS influences IFP in rural Bangladesh