Sex differences in the immune system become evident in the perinatal period in the four core genotypes mouse

We have used the four core genotypes (FCG) mouse model, which allows a distinction between effects of gonadal secretions and chromosomal complement, to determine when sex differences in the immune system first appear and what influences their development. Using splenic T cell number as a measure that could be applied to neonates with as yet immature immune responses, we found no differences among the four genotypes at postnatal day 1, but by day 7, clear sex differences were observed. These sex differences were unexpectedly independent of chromosomal complement and similar in degree to gonadectomized FCG adults: both neonatal and gonadectomized adult females (XX and XY) showed 2-fold the number of CD4+ and 7-fold the number of CD8+ T cells versus their male (XX and XY) counterparts. Appearance of this long-lived sex difference between days 1 and 7 suggested a role for the male-specific perinatal surge of testicular testosterone. Interference with the testosterone surge significantly de-masculinized the male CD4+, but not CD8+ splenic profile. Treatment of neonates demonstrated elevated testosterone limited mature cell egress from the thymus, whereas estradiol reduced splenic T cell seeding in females. Neonatal male splenic epithelium/stroma expressed aromatase mRNA, suggesting capacity for splenic conversion of perinatal testosterone into estradiol in males, which, similar to administration of estradiol in females, would result in reduced splenic T cell seeding. These sex steroid effects affected both CD4+ and CD8+ cells and yet interference with the testosterone surge only significantly de-masculinized the splenic content of CD4+ cells. For CD8+ cells, male cells in the thymus were also found to express one third the density of sphingosine-1-phosphate thymic egress receptors per cell compared to female, a male characteristic most likely an indirect result of Sry expression. Interestingly, the data also support a previously unrecognized role for non-gonadal estradiol in the promotion of intra-thymic cell proliferation in neonates of both sexes. Microarray analysis suggested the thymic epithelium/stroma as the source of this hormone. We conclude that some immune sex differences appear long before puberty and more than one mechanism contributes to differential numbers and distribution of T cells

Predictors of well child care adherence over time in a cohort of urban Medicaid-eligible infants

<p>Abstract</p> <p>Background</p> <p>Changes in well child care (WCC) adherence over time have not previously been examined. Our objective is to describe adherence rates to WCC over time in a low-income urban population of infants 0-24 months of age, and to identify predictors of WCC adherence in this population.</p> <p>Methods</p> <p>This is a secondary analysis of a cohort of Medicaid-eligible children followed from birth to 2 years between 2005 and 2008 with structured telephone surveys to assess maternal well-being, social support, and household and demographic information. For the 260 children attending 4 urban pediatric practices, WCC adherence was assessed based on visit data abstracted from electronic medical records. A random-intercept mixed effects logit model clustered on subject was used.</p> <p>Results</p> <p>92% of the mothers were African-American, 27% had not finished high school, 87% were single, and 43% earned < $500/month; mean age was 23. WCC adherence decreased from 88% at 6 months to 47% (12 mo), 44% (18 mo), and 67% (24 mo). The difference across time periods was statistically significant (p < 0.001). Married (OR 1.71, p = 0.02) and primiparous (OR 1.89, p < 0.001) mothers had significantly greater odds of adherence, along with women who reported having been adherent to prenatal care visits (OR 1.49, p = 0.03) and those with the lowest household income (OR 1.40, p = 0.03).</p> <p>Conclusions</p> <p>Maternal education efforts should emphasize the importance of establishing WCC, especially for mothers of more than one child. Further studies using larger, more broadly defined populations are needed to confirm our findings that efforts to increase WCC adherence should be intensified after 6 months of age, particularly for children at higher risk.</p

Annotation analysis for testing drug safety signals using unstructured clinical notes

BackgroundThe electronic surveillance for adverse drug events is largely based upon the analysis of coded data from reporting systems. Yet, the vast majority of electronic health data lies embedded within the free text of clinical notes and is not gathered into centralized repositories. With the increasing access to large volumes of electronic medical data-in particular the clinical notes-it may be possible to computationally encode and to test drug safety signals in an active manner.ResultsWe describe the application of simple annotation tools on clinical text and the mining of the resulting annotations to compute the risk of getting a myocardial infarction for patients with rheumatoid arthritis that take Vioxx. Our analysis clearly reveals elevated risks for myocardial infarction in rheumatoid arthritis patients taking Vioxx (odds ratio 2.06) before 2005.ConclusionsOur results show that it is possible to apply annotation analysis methods for testing hypotheses about drug safety using electronic medical records

A novel physics informed deep learning method for simulation-based modelling

In this paper, we present a brief review of the state of the art physics informed deep learning methodology and examine its applicability, limits, advantages, and disadvantages via several applications. The main advantage of this method is that it can predict the solution of the partial differential equations by using only boundary and initial conditions without the need for any training data or pre-process phase. Using physics informed neural network algorithms, it is possible to solve partial differential equations in many different problems encountered in engineering studies with a low cost and time instead of traditional numerical methodologies. A direct comparison between the initial results of the current model, analytical solutions, and computational fluid dynamics methods shows very good agreement. The proposed methodology provides a crucial basis for solution of more advance partial differential equation systems and offers a new analysis and mathematical modelling tool for aerospace application

Recycling Attitudes and Behavior among a Clinic-Based Sample of Low-Income Hispanic Women in Southeast Texas

We examined attitudes and behavior surrounding voluntary recycling in a population of low-income Hispanic women. Participants (N = 1,512) 18–55 years of age completed a self-report survey and responded to questions regarding household recycling behavior, recycling knowledge, recycling beliefs, potential barriers to recycling (transportation mode, time), acculturation, demographic characteristics (age, income, employment, marital status, education, number of children, birth country), and social desirability. Forty-six percent of participants (n = 810) indicated that they or someone else in their household recycled. In a logistic regression model controlling for social desirability, recycling behavior was related to increased age (P<0.05), lower acculturation (P<0.01), knowing what to recycle (P<0.01), knowing that recycling saves landfill space (P<0.05), and disagreeing that recycling takes too much time (P<0.001). A Sobel test revealed that acculturation mediated the relationship between recycling knowledge and recycling behavior (P<0.05). We offer new information on recycling behavior among Hispanic women and highlight the need for educational outreach and intervention strategies to increase recycling behavior within this understudied population

Causal Network Accounts Of Ill-being: Depression & Digital Well-being

Depression is a common and devastating instance of ill-being which deserves an account. Moreover, the ill-being of depression is impacted by digital technology: some uses of digital technology increase such ill-being while other uses of digital technology increase well-being. So a good account of ill-being would explicate the antecedents of depressive symptoms and their relief, digitally and otherwise. This paper borrows a causal network account of well-being and applies it to ill-being, particularly depression. Causal networks are found to provide a principled, coherent, intuitively plausible, and empirically adequate account of cases of depression in every-day and digital contexts. Causal network accounts of ill-being also offer philosophical, scientific, and practical utility. Insofar as other accounts of ill-being cannot offer these advantages, we should prefer causal network accounts of ill-being

Impact of chronic stress protocols in learning and memory in rodents: systematic review and meta-analysis

The idea that maladaptive stress impairs cognitive function has been a cornerstone of decades in basic and clinical research. However, disparate findings have reinforced the need to aggregate results from multiple sources in order to confirm the validity of such statement. In this work, a systematic review and meta-analyses were performed to aggregate results from rodent studies investigating the impact of chronic stress on learning and memory. Results obtained from the included studies revealed a significant effect of stress on global cognitive performance. In addition, stressed rodents presented worse consolidation of learned memories, although no significantly differences between groups at the acquisition phase were found. Despite the methodological heterogeneity across studies, these effects were independent of the type of stress, animals' strains or age. However, our findings suggest that stress yields a more detrimental effect on spatial navigation tests' performance. Surprisingly, the vast majority of the selected studies in this field did not report appropriate statistics and were excluded from the quantitative analysis. We have therefore purposed a set of guidelines termed PROBE (Preferred Reporting Orientations for Behavioral Experiments) to promote an adequate reporting of behavioral experiments.This work was funded by the European Commission (FP7) "SwitchBox" (Contract HEALTH-F2-2010-259772) project and co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER), and by Fundacao Calouste Gulbenkian (Portugal) (Contract grant number: P-139977; project "Better mental health during ageing based on temporal prediction of individual brain ageing trajectories (TEMPO)"). PSM is supported by an FCT fellowship grant, from the PhD-iHES program, with the reference PDE/BDE/113601/2015.info:eu-repo/semantics/publishedVersio