Folic acid prescription in pregnancy.

We resolved to prescribe folic acid supplements for all women who attended this practice during the first twelve weeks of pregnancy. Six months after this decision a prescription was recorded in only 13% of cases: this compared with 18% during the two months immediately following the decision. It was resolved to improve this performance and observations six months later revealed a prescription recorded in 63% of cases. Subsequently a new form for recording an antenatal consultation was devised and six months after its implementation, 100% recording of folate prescription for appropriate cases was observed. It was concluded that these simple audit exercises prompted changes in practice which helped to improve standards of patient care

Motherhood in the teens and twenties: some surprises.

We report a study of the association of health and social support variables with motherhood in teenagers and older mothers. Both teenage and older mothers reported poorer physical and mental health and fewer and less frequent social contacts than their nulliparous peers. Contrary to expectation, however, older mothers reported less extensive and less adequate social support networks than did teenagers

Harold A. Kahn (1920–2009): A Remembrance of a Life Devoted to Public Health

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licens

Two-stage approach for identifying single-nucleotide polymorphisms associated with rheumatoid arthritis using random forests and Bayesian networks

We used the simulated data set from Genetic Analysis Workshop 15 Problem 3 to assess a two-stage approach for identifying single-nucleotide polymorphisms (SNPs) associated with rheumatoid arthritis (RA). In the first stage, we used random forests (RF) to screen large amounts of genetic data using the variable importance measure, which takes into account SNP interaction effects as well as main effects without requiring model specification. We used the simulated 9187 SNPs mimicking a 10 K SNP chip, along with covariates DR (the simulated DRB1 gentoype), smoking, and sex as input to the RF analyses with a training set consisting of 750 unrelated RA cases and 750 controls. We used an iterative RF screening procedure to identify a smaller set of variables for further analysis. In the second stage, we used the software program CaMML for producing Bayesian networks, and developed complex etiologic models for RA risk using the variables identified by our RF screening procedure. We evaluated the performance of this method using independent test data sets for up to 100 replicates

Integromic analysis of genetic variation and gene expression identifies networks for cardiovascular disease phenotypes

Cataloged from PDF version of article.Background-Cardiovascular disease (CVD) reflects a highly coordinated complex of traits. Although genome-wide association studies have reported numerous single nucleotide polymorphisms (SNPs) to be associated with CVD, the role of most of these variants in disease processes remains unknown. Methods and Results-We built a CVD network using 1512 SNPs associated with 21 CVD traits in genome-wide association studies (at P <= 5x10(-8)) and cross-linked different traits by virtue of their shared SNP associations. We then explored whole blood gene expression in relation to these SNPs in 5257 participants in the Framingham Heart Study. At a false discovery rate <0.05, we identified 370 cis-expression quantitative trait loci (eQTLs; SNPs associated with altered expression of nearby genes) and 44 trans-eQTLs (SNPs associated with altered expression of remote genes). The eQTL network revealed 13 CVD-related modules. Searching for association of eQTL genes with CVD risk factors (lipids, blood pressure, fasting blood glucose, and body mass index) in the same individuals, we found examples in which the expression of eQTL genes was significantly associated with these CVD phenotypes. In addition, mediation tests suggested that a subset of SNPs previously associated with CVD phenotypes in genome-wide association studies may exert their function by altering expression of eQTL genes (eg, LDLR and PCSK7), which in turn may promote interindividual variation in phenotypes. Conclusions-Using a network approach to analyze CVD traits, we identified complex networks of SNP-phenotype and SNP-transcript connections. Integrating the CVD network with phenotypic data, we identified biological pathways that may provide insights into potential drug targets for treatment or prevention of CVD.(Circulation. 2015;131:536-549. DOI: 10.1161/CIRCULATIONAHA.114.010696.

An Intact Kidney Slice Model to Investigate Vasa Recta Properties and Function in situ

Background: Medullary blood flow is via vasa recta capillaries, which possess contractile pericytes. In vitro studies using isolated descending vasa recta show that pericytes can constrict/dilate descending vasa recta when vasoactive substances are present. We describe a live kidney slice model in which pericyte-mediated vasa recta constriction/dilation can be visualized in situ. Methods: Confocal microscopy was used to image calcein, propidium iodide and Hoechst labelling in ‘live’ kidney slices, to determine tubular and vascular cell viability and morphology. DIC video-imaging of live kidney slices was employed to investigate pericyte-mediated real-time changes in vasa recta diameter. Results: Pericytes were identified on vasa recta and their morphology and density were characterized in the medulla. Pericyte-mediated changes in vasa recta diameter (10–30%) were evoked in response to bath application of vasoactive agents (norepinephrine, endothelin-1, angiotensin-II and prostaglandin E2) or by manipulating endogenous vasoactive signalling pathways (using tyramine, L-NAME, a cyclo-oxygenase (COX-1) inhibitor indomethacin, and ATP release). Conclusions: The live kidney slice model is a valid complementary technique for investigating vasa recta function in situ and the role of pericytes as regulators of vasa recta diameter. This technique may also be useful in exploring the role of tubulovascular crosstalk in regulation of medullary blood flow

Genotype-by-Sex Interaction in the Regulation of High-Density Lipoprotein: TheFramingham Heart Study

Low levels of high-density lipoprotein (HDL) are widely documented as a risk factor for cardiovascular disease (CVD). Furthermore, there is marked sexual dimorphism in both HDL levels and the prevalence of CVD. However, the extent to which genetic factors contribute to such dimorphism has been largely unexplored. We examined the evidence for genotypeby- sex effects on HDL in a longitudinal sample of 1,562 participants from 330 families in the Framingham Heart Study at three times points corresponding approximately to 1971-1974, 1980-1983, and 1988-1991. Using a variance component method, we conducted a genome scan of HDL at each time point in males and females, separately and combined, and tested for genotype-by-sex interaction at a quantitative trait locus (QTL) at each time point. Consistent findings were noted only for females on chromosome 2 near marker D2S1328, with adjusted LOD scores of 2.6, 2.2, and 2.1 across the three time points, respectively. In males suggestive linkage was detected on chromosome 16 near marker D16S3396 at the second time point and on chromosome 18 near marker D18S851 at the third time point (adjusted LOD = 2.2 and 2.4, respectively). Although the heritability of HDL is similar in males and females, sex appears to exert a substantial effect on the QTL-specific variance of HDL. When genotype-by-sex interactions exist and are not modeled, the power to detect linkage is reduced; thus our results may explain in part the paucity of significant linkage findings for HDL

Integromic analysis of genetic variation and gene expression identifies networks for cardiovascular disease phenotypes

BACKGROUND - : Cardiovascular disease (CVD) reflects a highly coordinated complex of traits. Although genome-wide association studies have reported numerous single nucleotide polymorphisms (SNPs) to be associated with CVD, the role of most of these variants in disease processes remains unknown. METHODS AND RESULTS - : We built a CVD network using 1512 SNPs associated with 21 CVD traits in genome-wide association studies (at P≤5×10) and cross-linked different traits by virtue of their shared SNP associations. We then explored whole blood gene expression in relation to these SNPs in 5257 participants in the Framingham Heart Study. At a false discovery rate <0.05, we identified 370 cis-expression quantitative trait loci (eQTLs; SNPs associated with altered expression of nearby genes) and 44 trans-eQTLs (SNPs associated with altered expression of remote genes). The eQTL network revealed 13 CVD-related modules. Searching for association of eQTL genes with CVD risk factors (lipids, blood pressure, fasting blood glucose, and body mass index) in the same individuals, we found examples in which the expression of eQTL genes was significantly associated with these CVD phenotypes. In addition, mediation tests suggested that a subset of SNPs previously associated with CVD phenotypes in genome-wide association studies may exert their function by altering expression of eQTL genes (eg, LDLR and PCSK7), which in turn may promote interindividual variation in phenotypes. CONCLUSIONS - : Using a network approach to analyze CVD traits, we identified complex networks of SNP-phenotype and SNP-transcript connections. Integrating the CVD network with phenotypic data, we identified biological pathways that may provide insights into potential drug targets for treatment or prevention of CVD

The SPHERE Study. Secondary prevention of heart disease in general practice: protocol of a randomised controlled trial of tailored practice and patient care plans with parallel qualitative, economic and policy analyses. [ISRCTN24081411]

BACKGROUND: The aim of the SPHERE study is to design, implement and evaluate tailored practice and personal care plans to improve the process of care and objective clinical outcomes for patients with established coronary heart disease (CHD) in general practice across two different health systems on the island of Ireland. CHD is a common cause of death and a significant cause of morbidity in Ireland. Secondary prevention has been recommended as a key strategy for reducing levels of CHD mortality and general practice has been highlighted as an ideal setting for secondary prevention initiatives. Current indications suggest that there is considerable room for improvement in the provision of secondary prevention for patients with established heart disease on the island of Ireland. The review literature recommends structured programmes with continued support and follow-up of patients; the provision of training, tailored to practice needs of access to evidence of effectiveness of secondary prevention; structured recall programmes that also take account of individual practice needs; and patient-centred consultations accompanied by attention to disease management guidelines. METHODS: SPHERE is a cluster randomised controlled trial, with practice-level randomisation to intervention and control groups, recruiting 960 patients from 48 practices in three study centres (Belfast, Dublin and Galway). Primary outcomes are blood pressure, total cholesterol, physical and mental health status (SF-12) and hospital re-admissions. The intervention takes place over two years and data is collected at baseline, one-year and two-year follow-up. Data is obtained from medical charts, consultations with practitioners, and patient postal questionnaires. The SPHERE intervention involves the implementation of a structured systematic programme of care for patients with CHD attending general practice. It is a multi-faceted intervention that has been developed to respond to barriers and solutions to optimal secondary prevention identified in preliminary qualitative research with practitioners and patients. General practitioners and practice nurses attend training sessions in facilitating behaviour change and medication prescribing guidelines for secondary prevention of CHD. Patients are invited to attend regular four-monthly consultations over two years, during which targets and goals for secondary prevention are set and reviewed. The analysis will be strengthened by economic, policy and qualitative components

Hallux Valgus and Lesser Toe Deformities are Highly Heritable in Adult Men and Women: the Framingham Foot Study

To estimate heritability of three common disorders affecting the forefoot: hallux valgus, lesser toe deformities and plantar forefoot soft tissue atrophy in adult Caucasian men and women