Education in Time: Cohort Differences in Educational Attainment in African-American Twins

OBJECTIVES:Educational opportunities for African-Americans expanded throughout the 20(th) century. Twin pairs are an informative population in which to examine changes in educational attainment because each twin has the same parents and childhood socioeconomic status. We hypothesized that correlation in educational attainment of older twin pairs would be higher compared to younger twin pairs reflecting changes in educational access over time and potentially reflecting a "ceiling effect" associated with Jim Crow laws and discrimination. METHODOLOGY AND PRINCIPAL FINDINGS:We used data from 211 same-sex twin pairs (98 identical, 113 fraternal) in the Carolina African-American Twin Study of Aging who were identified through birth records. Participants completed an in-person interview. The twins were predominantly female (61%), with a mean age of 50 years (SD = 0.5). We found that older age groups had a stronger intra-twin correlation of attained educational level. Further analysis across strata revealed a trend across zygosity, with identical twins demonstrating more similar educational attainment levels than did their fraternal twin counterparts, suggesting a genetic influence. DISCUSSION:These findings suggest that as educational opportunities broadened in the 20th century, African-Americans gained access to educational opportunities that better matched their individual abilities

A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis

BACKGROUND: Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. METHODS: We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast the skin and lung microenvironments and to assess the functional role of the inflammatory and fibrotic genes in each organ. Lastly, we tested the expression of macrophage activation state-associated gene sets for enrichment in skin and lung using a Wilcoxon rank sum test. RESULTS: We identified a common pathogenic gene expression signature-an immune-fibrotic axis-indicative of pro-fibrotic macrophages (MØs) in multiple tissues (skin, lung, esophagus, and peripheral blood mononuclear cells) affected by SSc. While the co-expression of these genes is common to all tissues, the functional consequences of this upregulation differ by organ. We used this disease-associated signature to query tissue-specific functional genomic networks to identify common and tissue-specific pathologies of SSc and related conditions. In contrast to skin, in the lung-specific functional network we identify a distinct lung-resident MØ signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct MØ alternative activation transcriptional programs in SSc-associated PF lung and in the skin of patients with an "inflammatory" SSc gene expression signature. CONCLUSIONS: Our results suggest that the innate immune system is central to SSc disease processes but that subtle distinctions exist between tissues. Our approach provides a framework for examining molecular signatures of disease in fibrosis and autoimmune diseases and for leveraging publicly available data to understand common and tissue-specific disease processes in complex human diseases

Origami: Single-cell 3D shape dynamics oriented along the apico-basal axis of folding epithelia from fluorescence microscopy data

A common feature of morphogenesis is the formation of three-dimensional structures from the folding of two-dimensional epithelial sheets, aided by cell shape changes at the cellular-level. Changes in cell shape must be studied in the context of cell-polarised biomechanical processes within the epithelial sheet. In epithelia with highly curved surfaces, finding single-cell alignment along a biological axis can be difficult to automate in silico. We present ‘Origami’, a MATLAB-based image analysis pipeline to compute direction-variant cell shape features along the epithelial apico-basal axis. Our automated method accurately computed direction vectors denoting the apico-basal axis in regions with opposing curvature in synthetic epithelia and fluorescence images of zebrafish embryos. As proof of concept, we identified different cell shape signatures in the developing zebrafish inner ear, where the epithelium deforms in opposite orientations to form different structures. Origami is designed to be user-friendly and is generally applicable to fluorescence images of curved epithelia

Routine Antenatal Anti-D Prophylaxis in Women Who Are Rh(D) Negative: Meta-Analyses Adjusted for Differences in Study Design and Quality

Background: To estimate the effectiveness of routine antenatal anti-D prophylaxis for preventing sensitisation in pregnant Rhesus negative women, and to explore whether this depends on the treatment regimen adopted. Methods: Ten studies identified in a previous systematic literature search were included. Potential sources of bias were systematically identified using bias checklists, and their impact and uncertainty were quantified using expert opinion. Study results were adjusted for biases and combined, first in a random-effects meta-analysis and then in a random-effects metaregression analysis. Results: In a conventional meta-analysis, the pooled odds ratio for sensitisation was estimated as 0.25 (95 % CI 0.18, 0.36), comparing routine antenatal anti-D prophylaxis to control, with some heterogeneity (I 2 = 19%). However, this naïve analysis ignores substantial differences in study quality and design. After adjusting for these, the pooled odds ratio for sensitisation was estimated as 0.31 (95 % CI 0.17, 0.56), with no evidence of heterogeneity (I 2 = 0%). A meta-regression analysis wa

Adapting a Markov Monte Carlo simulation model for forecasting the number of Coronary Artery Revascularisation Procedures in an era of rapidly changing technology and policy

<p>Abstract</p> <p>Background</p> <p>Treatments for coronary heart disease (CHD) have evolved rapidly over the last 15 years with considerable change in the number and effectiveness of both medical and surgical treatments. This period has seen the rapid development and uptake of statin drugs and coronary artery revascularization procedures (CARPs) that include Coronary Artery Bypass Graft procedures (CABGs) and Percutaneous Coronary Interventions (PCIs). It is difficult in an era of such rapid change to accurately forecast requirements for treatment services such as CARPs. In a previous paper we have described and outlined the use of a Markov Monte Carlo simulation model for analyzing and predicting the requirements for CARPs for the population of Western Australia (Mannan et al, 2007). In this paper, we expand on the use of this model for forecasting CARPs in Western Australia with a focus on the lack of adequate performance of the (standard) model for forecasting CARPs in a period during the mid 1990s when there were considerable changes to CARP technology and implementation policy and an exploration and demonstration of how the standard model may be adapted to achieve better performance.</p> <p>Methods</p> <p>Selected key CARP event model probabilities are modified based on information relating to changes in the effectiveness of CARPs from clinical trial evidence and an awareness of trends in policy and practice of CARPs. These modified model probabilities and the ones obtained by standard methods are used as inputs in our Markov simulation model.</p> <p>Results</p> <p>The projected numbers of CARPs in the population of Western Australia over 1995–99 only improve marginally when modifications to model probabilities are made to incorporate an increase in effectiveness of PCI procedures. However, the projected numbers improve substantially when, in addition, further modifications are incorporated that relate to the increased probability of a PCI procedure and the reduced probability of a CABG procedure stemming from changed CARP preference following the introduction of PCI operations involving stents.</p> <p>Conclusion</p> <p>There is often knowledge and sometimes quantitative evidence of the expected impacts of changes in surgical practice and procedure effectiveness and these may be used to improve forecasts of future requirements for CARPs in a population.</p

Diffusion of an e-learning programme among Danish General Practitioners: A nation-wide prospective survey

<p>Abstract</p> <p>Background</p> <p>We were unable to identify studies that have considered the diffusion of an e-learning programme among a large population of general practitioners. The aim of this study was to investigate the uptake of an e-learning programme introduced to General Practitioners as part of a nation-wide disseminated dementia guideline.</p> <p>Methods</p> <p>A prospective study among all 3632 Danish GPs. The GPs were followed from the launching of the e-learning programme in November 2006 and 6 months forward. Main outcome measures: Use of the e-learning programme. A logistic regression model (GEE) was used to identify predictors for use of the e-learning programme.</p> <p>Results</p> <p>In the study period, a total of 192 different GPs (5.3%) were identified as users, and 17% (32) had at least one re-logon. Among responders at first login most have learnt about the e-learning programme from written material (41%) or from the internet (44%). A total of 94% of the users described their ability of conducting a diagnostic evaluation as good or excellent. Most of the respondents used the e-learning programme due to general interest (90%). Predictors for using the e-learning programme were Males (OR = 1.4, 95% CI 1.1; 2.0) and members of Danish College of General Practice (OR = 2.2, 95% CI 1.5; 3.1), whereas age, experience and working place did not seem to be influential.</p> <p>Conclusion</p> <p>Only few Danish GPs used the e-learning programme in the first 6 months after the launching. Those using it were more often males and members of Danish College of General Practice. Based on this study we conclude, that an active implementation is needed, also when considering electronic formats of CME like e-learning.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: NCT00392483.</p

Lipopolysaccharide O1 Antigen Contributes to the Virulence in Klebsiella pneumoniae Causing Pyogenic Liver Abscess

Klebsiella pneumoniae is the common cause of a global emerging infectious disease, community-acquired pyogenic liver abscess (PLA). Capsular polysaccharide (CPS) and lipopolysaccharide (LPS) are critical for this microorganism's ability to spread through the blood and to cause sepsis. While CPS type K1 is an important virulence factor in K. pneumoniae causing PLA, the role of LPS in PLA is not clear. Here, we characterize the role of LPS O antigen in the pathogenesis of K. pneumoniae causing PLA. NTUH-K2044 is a LPS O1 clinical strain; the presence of the O antigen was shown via the presence of 1,3-galactan in the LPS, and of sequences that align with the wb gene cluster, known to produce O-antigen. Serologic analysis of K. pneumoniae clinical isolates demonstrated that the O1 serotype was more prevalent in PLA strains than that in non-tissue-invasive strains (38/42 vs. 9/32, P<0.0001). O1 serotype isolates had a higher frequency of serum resistance, and mutation of the O1 antigen changed serum resistance in K. pneumoniae. A PLA-causing strain of CPS capsular type K2 and LPS serotype O1 (i.e., O1:K2 PLA strain) deleted for the O1 synthesizing genes was profoundly attenuated in virulence, as demonstrated in separate mouse models of septicemia and liver abscess. Immunization of mice with the K2044 magA-mutant (K1− O1) against LPS O1 provided protection against infection with an O1:K2 PLA strain, but not against infection with an O1:K1 PLA strain. Our findings indicate that the O1 antigen of PLA-associated K. pneumoniae contributes to virulence by conveying resistance to serum killing, promoting bacterial dissemination to and colonization of internal organs after the onset of bacteremia, and could be a useful vaccine candidate against infection by an O1:K2 PLA strain

Gene expression throughout a vertebrate's embryogenesis

Abstract Background Describing the patterns of gene expression during embryonic development has broadened our understanding of the processes and patterns that define morphogenesis. Yet gene expression patterns have not been described throughout vertebrate embryogenesis. This study presents statistical analyses of gene expression during all 40 developmental stages in the teleost Fundulus heteroclitus using four biological replicates per stage. Results Patterns of gene expression for 7,000 genes appear to be important as they recapitulate developmental timing. Among the 45% of genes with significant expression differences between pairs of temporally adjacent stages, significant differences in gene expression vary from as few as five to more than 660. Five adjacent stages have disproportionately more significant changes in gene expression (&gt; 200 genes) relative to other stages: four to eight and eight to sixteen cell stages, onset of circulation, pre and post-hatch, and during complete yolk absorption. The fewest differences among adjacent stages occur during gastrulation. Yet, at stage 16, (pre-mid-gastrulation) the largest number of genes has peak expression. This stage has an over representation of genes in oxidative respiration and protein expression (ribosomes, translational genes and proteases). Unexpectedly, among all ribosomal genes, both strong positive and negative correlations occur. Similar correlated patterns of expression occur among all significant genes. Conclusions These data provide statistical support for the temporal dynamics of developmental gene expression during all stages of vertebrate development

Expression of key ion transporters in the gill and esophageal- gastrointestinal tract of euryhaline mozambique tilapia oreochromis mossambicus acclimated to fresh water, seawater and hypersaline water

10.1371/journal.pone.0087591PLoS ONE91-POLN