Bayesian modeling of differential gene expression.

We present a Bayesian hierarchical model for detecting differentially expressing genes that includes simultaneous estimation of array effects, and show how to use the output for choosing lists of genes for further investigation. We give empirical evidence that expression-level dependent array effects are needed, and explore different nonlinear functions as part of our model-based approach to normalization. The model includes gene-specific variances but imposes some necessary shrinkage through a hierarchical structure. Model criticism via posterior predictive checks is discussed. Modeling the array effects (normalization) simultaneously with differential expression gives fewer false positive results. To choose a list of genes, we propose to combine various criteria (for instance, fold change and overall expression) into a single indicator variable for each gene. The posterior distribution of these variables is used to pick the list of genes, thereby taking into account uncertainty in parameter estimates. In an application to mouse knockout data, Gene Ontology annotations over- and underrepresented among the genes on the chosen list are consistent with biological expectations

Bayesian modeling of differential gene expression.

We present a Bayesian hierarchical model for detecting differentially expressing genes that includes simultaneous estimation of array effects, and show how to use the output for choosing lists of genes for further investigation. We give empirical evidence that expression-level dependent array effects are needed, and explore different nonlinear functions as part of our model-based approach to normalization. The model includes gene-specific variances but imposes some necessary shrinkage through a hierarchical structure. Model criticism via posterior predictive checks is discussed. Modeling the array effects (normalization) simultaneously with differential expression gives fewer false positive results. To choose a list of genes, we propose to combine various criteria (for instance, fold change and overall expression) into a single indicator variable for each gene. The posterior distribution of these variables is used to pick the list of genes, thereby taking into account uncertainty in parameter estimates. In an application to mouse knockout data, Gene Ontology annotations over- and underrepresented among the genes on the chosen list are consistent with biological expectations

Effectiveness of aerobic exercise for adults living with HIV: systematic review and meta-analysis using the Cochrane Collaboration protocol

Background: People with HIV are living longer with the health-related consequences of HIV, multi-morbidity, and aging. Exercise is a key strategy that may improve or sustain health for people living with HIV. Our aim was to examine the safety and effectiveness of aerobic exercise interventions on immunological, virological, cardiorespiratory, strength, weight, body composition, and psychological outcomes in adults living with HIV. Methods: We conducted a systematic review using the Cochrane Collaboration protocol. We searched databases up to April 2013. We included randomized controlled trials comparing aerobic exercise with no exercise or another intervention performed at least three times per week for at least four weeks among adults living with HIV. Two reviewers independently determined study eligibility. Data were extracted from studies that met inclusion criteria using standardized forms. We assessed risk of bias using the Cochrane Collaboration’s tool for assessing risk of bias. Outcomes were analyzed as continuous and meta-analyses conducted using random effects models with Review Manager (RevMan) computer software. Results: Twenty-four studies met inclusion criteria (n = 936 participants at study completion); the majority of participants were men (73 %) and the majority were taking antiretroviral therapy (19/24 included studies). The exercise intervention included aerobic exercise alone (11 studies) or a combination of aerobic and resistive exercise (13 studies) ranging from 5 to 52 weeks. Fifty-eight meta-analyses were performed. Main results indicated statistically significant improvements in selected outcomes of cardiorespiratory status (maximum oxygen consumption, exercise time), strength (chest press, knee flexion), body composition (lean body mass, percent body fat, leg muscle area), depression symptoms, and quality of life (SF-36 questionnaire) among exercisers compared with non-exercisers. No significant differences in change in CD4 count and viral load were found. Conclusions: Performing aerobic exercise or a combination of aerobic and resistive exercise at least three times per week for at least five weeks is safe and can lead to improvements in cardiorespiratory fitness, strength, body composition and quality of life for adults with HIV. Aerobic exercise is safe and beneficial for adults living with HIV who are medically stable

Chromatographic Separation Apparatus

An apparatus for the monitoring of a column chromatography separation process includes a segmented column with a seal positioned at the joint defined by the segments of the column. A connector is provided for connecting the segments of the column together. The apparatus further includes a sensor for monitoring an analyte in an eluant within a separation zone of the column. The sensor includes a mesh grid made of optical fibers or metal wires which is placed so as to extend through the separation zone of the column. The metal wires or optical fibers extend through the seal of the joint in the segmented column and connect to signal processing and data analysis equipment for purposes of monitoring the movements and concentration of an analyte in an eluant at various locations within the column. Certain segments of the optical fibers or metal wires which make up the mesh grid are coated so as to be desensitized and other segments are uncoated for sensing the analyte. This provides an effective apparatus to monitor in detail the cross-section of a column chromatography process in-situ

Racial and Geographic Variation in Effects of Maternal Education and Neighborhood-Level Measures of Socioeconomic Status on Gestational Age at Birth: Findings From the ECHO Cohorts

Preterm birth occurs at excessively high and disparate rates in the United States. In 2016, the National Institutes of Health (NIH) launched the Environmental influences on Child Health Outcomes (ECHO) program to investigate the influence of early life exposures on child health. Extant data from the ECHO cohorts provides the opportunity to examine racial and geographic variation in effects of individual- and neighborhood-level markers of socioeconomic status (SES) on gestational age at birth. The objective of this study was to examine the association between individual-level (maternal education) and neighborhood-level markers of SES and gestational age at birth, stratifying by maternal race/ethnicity, and whether any such associations are modified by US geographic region. Twenty-six ECHO cohorts representing 25,526 mother-infant pairs contributed to this disseminated meta-analysis that investigated the effect of maternal prenatal level of education (high school diploma, GED, or less; some college, associate\u27s degree, vocational or technical training [reference category]; bachelor\u27s degree, graduate school, or professional degree) and neighborhood-level markers of SES (census tract [CT] urbanicity, percentage of black population in CT, percentage of population below the federal poverty level in CT) on gestational age at birth (categorized as preterm, early term, full term [the reference category], late, and post term) according to maternal race/ethnicity and US region. Multinomial logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). Cohort-specific results were meta-analyzed using a random effects model. For women overall, a bachelor\u27s degree or above, compared with some college, was associated with a significantly decreased odds of preterm birth (aOR 0.72; 95% CI: 0.61-0.86), whereas a high school education or less was associated with an increased odds of early term birth (aOR 1.10, 95% CI: 1.00-1.21). When stratifying by maternal race/ethnicity, there were no significant associations between maternal education and gestational age at birth among women of racial/ethnic groups other than non-Hispanic white. Among non-Hispanic white women, a bachelor\u27s degree or above was likewise associated with a significantly decreased odds of preterm birth (aOR 0.74 (95% CI: 0.58, 0.94) as well as a decreased odds of early term birth (aOR 0.84 (95% CI: 0.74, 0.95). The association between maternal education and gestational age at birth varied according to US region, with higher levels of maternal education associated with a significantly decreased odds of preterm birth in the Midwest and South but not in the Northeast and West. Non-Hispanic white women residing in rural compared to urban CTs had an increased odds of preterm birth; the ability to detect associations between neighborhood-level measures of SES and gestational age for other race/ethnic groups was limited due to small sample sizes within select strata. Interventions that promote higher educational attainment among women of reproductive age could contribute to a reduction in preterm birth, particularly in the US South and Midwest. Further individual-level analyses engaging a diverse set of cohorts are needed to disentangle the complex interrelationships among maternal education, neighborhood-level factors, exposures across the life course, and gestational age at birth outcomes by maternal race/ethnicity and US geography

Addressing barriers in comprehensiveness, accessibility, reusability, interoperability and reproducibility of computational models in systems biology

Computational models are often employed in systems biology to study the dynamic behaviours of complex systems. With the rise in the number of computational models, finding ways to improve the reusability of these models and their ability to reproduce virtual experiments becomes critical. Correct and effective model annotation in community-supported and standardised formats is necessary for this improvement. Here,we present recent efforts toward a common framework for annotated, accessible, reproducible and interoperable computational models in biology, and discuss key challenges of the field. Scientists from different systems biology fields have long been developing community-driven guidelines and best practices for annotation, interoperability and reusability of computational models in biology. However, the parallel work, grounded on shared needs and similar aims, of separate communities creates a need for exchange and alignment of the different efforts to harmonise best practices. Hence, members of the Consortium for Logical Models and Tools (CoLoMoTo, http://colomoto.org) and the Computational Modelling of Biological Systems community of the International Society for Computational Biology (SysMod, https:// sysmod.info/) organised aworkshop to discusscommunitydriven guidelines and efforts for the curation and annotation of computational models during [BC]2 2021. The workshop grew from a previous edition organised during [BC]2 2019 focused on logical modelling [1]. The second edition brought together scientists with various research backgrounds and from different working groups such as BioModels [2], a central repository of mathematical models of biological/biomedical processes; the Computational Modelling in Biology Network initiative (COMBINE) [3]; CoLoMoTo, [4]; SysMod, [5]; the Systems Biology Graphical Notation (SBGN) project [6]; the systems biology markup language (SBML) [7] and simulation experiment description markup language (SED-ML) [8], to exchange and expand on several key topics of common interest (Figure 1). While the modelling approaches across these communities differ, several critical points are shared, such as (i) the importance of annotations for reproducibility, (ii) the use of community standards for exchange and annotation encoding, (iii) the need to implement standards in tools and platforms to boost reusability and interoperability, (iv) the importance of transparency of modelling frameworks in publications and (v) the use of shared repositories to enhance model accessibility (Figure 2). We use the term annotation to describe ‘a computeraccessible metadata item that captures, entirely or in part, the meaning of a model, model component or data element’. We borrow this definition from [9] which is in accordance with its use in [1]. We discuss the identified needs in the following sections

Disparities in pre-eclampsia and eclampsia among immigrant women giving birth in six industrialised countries

OBJECTIVE: To assess disparities in pre-eclampsia and eclampsia among immigrant women from various world regions giving birth in six industrialised countries. DESIGN: Cross-country comparative study of linked population-based databases. SETTING: Provincial or regional obstetric delivery data from Australia, Canada, Spain and the USA and national data from Denmark and Sweden. POPULATION: All immigrant and non-immigrant women delivering in the six industrialised countries within the most recent 10-year period available to each participating centre (1995–2010). METHODS: Data was collected using standardised definitions of the outcomes and maternal regions of birth. Pooled data were analysed with multilevel models. Within-country analyses used stratified logistic regression to obtain odds ratios (OR) with 95% confidence intervals (95% CI). MAIN OUTCOME MEASURES: Pre-eclampsia, eclampsia and pre-eclampsia with prolonged hospitalisation (cases per 1000 deliveries). RESULTS: There were 9 028 802 deliveries (3 031 399 to immigrant women). Compared with immigrants from Western Europe, immigrants from Sub-Saharan Africa and Latin America & the Caribbean were at higher risk of pre-eclampsia (OR: 1.72; 95% CI: 1.63, 1.80 and 1.63; 95% CI: 1.57, 1.69) and eclampsia (OR: 2.12; 95% CI: 1.61, 2.79 and 1.55; 95% CI: 1.26, 1. 91), respectively, after adjustment for parity, maternal age and destination country. Compared with native-born women, European and East Asian immigrants were at lower risk in most industrialised countries. Spain exhibited the largest disparities and Australia the smallest. CONCLUSION: Immigrant women from Sub-Saharan Africa and Latin America & the Caribbean require increased surveillance due to a consistently high risk of pre-eclampsia and eclampsia