1,141 research outputs found
Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes
BACKGROUND:Cardiovascular disease (CVD) and its most common
manifestations - including coronary heart disease (CHD), stroke, heart failure (HF), and
atrial fibrillation (AF) - are major causes of morbidity and mortality. In many
industrialized countries, cardiovascular disease (CVD) claims more lives each year than any
other disease. Heart disease and stroke are the first and third leading causes of death in
the United States. Prior investigations have reported several single gene variants
associated with CHD, stroke, HF, and AF. We report a community-based genome-wide association
study of major CVD outcomes.METHODS:In 1345 Framingham Heart Study participants from the
largest 310 pedigrees (54% women, mean age 33 years at entry), we analyzed associations of
70,987 qualifying SNPs (Affymetrix 100K GeneChip) to four major CVD outcomes: major
atherosclerotic CVD (n = 142; myocardial infarction, stroke, CHD death), major CHD (n = 118;
myocardial infarction, CHD death), AF (n = 151), and HF (n = 73). Participants free of the
condition at entry were included in proportional hazards models. We analyzed model-based
deviance residuals using generalized estimating equations to test associations between SNP
genotypes and traits in additive genetic models restricted to autosomal SNPs with minor
allele frequency [greater than or equal to]0.10, genotype call rate [greater than or equal
to]0.80, and Hardy-Weinberg equilibrium p-value [greater than or equal to] 0.001.RESULTS:Six
associations yielded p <10-5. The lowest p-values for each CVD trait were as follows:
major CVD, rs499818, p = 6.6 x 10-6; major CHD, rs2549513, p = 9.7 x 10-6; AF, rs958546, p =
4.8 x 10-6; HF: rs740363, p = 8.8 x 10-6. Of note, we found associations of a 13 Kb region
on chromosome 9p21 with major CVD (p 1.7 - 1.9 x 10-5) and major CHD (p 2.5 - 3.5 x 10-4)
that confirm associations with CHD in two recently reported genome-wide association studies.
Also, rs10501920 in CNTN5 was associated with AF (p = 9.4 x 10-6) and HF (p = 1.2 x 10-4).
Complete results for these phenotypes can be found at the dbgap website
http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.CONCLUSION:No
association attained genome-wide significance, but several intriguing findings emerged.
Notably, we replicated associations of chromosome 9p21 with major CVD. Additional studies
are needed to validate these results. Finding genetic variants associated with CVD may point
to novel disease pathways and identify potential targeted preventive therapies
Assessment of cardiovascular risk factors prior to NHS Health Checks in an urban setting: cross-sectional study
OBJECTIVES: To assess the completeness of cardiovascular disease (CVD) risk factor recording and levels of risk factors in patients eligible for the NHS Health Check. DESIGN: Cross-sectional study. SETTING: Twenty-eight general practices located in Hammersmith and Fulham, London, UK. PARTICIPANTS: 42,306 patients aged 40 to 74 years without existing cardiovascular disease or diabetes. MAIN OUTCOME MEASURES: MEASUREMENT AND LEVEL OF CVD RISK FACTORS: blood pressure, cholesterol, body mass index (BMI), blood glucose and smoking status. RESULTS: There was a high recording of smoking status (86.1%) and blood pressure (82.5%); whilst BMI, cholesterol and glucose recording was lower. There was large variation in BMI, cholesterol, glucose recording between practices (29.7-91.5% for BMI). Women had significantly better risk factor recording than men (AOR = 1.70 [1.61-1.80] for blood pressure). All risk factors were better recorded in the least deprived patient group (AOR = 0.79 [0.73-0.85] for blood pressure) and patients with diagnosed hypertension (AOR = 7.24 [6.67-7.86] for cholesterol). Risk factor recording varied considerably between practices but was more strongly associated with patient than practice level characteristics. Age-adjusted levels of cholesterol and BMI were not significantly different between men and women. More men had raised blood glucose, blood pressure and BMI than women (29.7% [29.1-30.4] compared to 19.8% [19.3-20.3] for blood pressure). CONCLUSIONS: Before the NHS Health Check, CVD risk factor recording varied considerably by practice and patient characteristics. We identified significant elevated levels of raised CVD risk factors in the population eligible for a Health Check, which will require considerable work to manage
Survivability Is More Fundamental Than Evolvability
For a lineage to survive over long time periods, it must sometimes change. This has given rise to the term evolvability, meaning the tendency to produce adaptive variation. One lineage may be superior to another in terms of its current standing variation, or it may tend to produce more adaptive variation. However, evolutionary outcomes depend on more than standing variation and produced adaptive variation: deleterious variation also matters. Evolvability, as most commonly interpreted, is not predictive of evolutionary outcomes. Here, we define a predictive measure of the evolutionary success of a lineage that we call the k-survivability, defined as the probability that the lineage avoids extinction for k generations. We estimate the k-survivability using multiple experimental replicates. Because we measure evolutionary outcomes, the initial standing variation, the full spectrum of generated variation, and the heritability of that variation are all incorporated. Survivability also accounts for the decreased joint likelihood of extinction of sub-lineages when they 1) disperse in space, or 2) diversify in lifestyle. We illustrate measurement of survivability with in silico models, and suggest that it may also be measured in vivo using multiple longitudinal replicates. The k-survivability is a metric that enables the quantitative study of, for example, the evolution of 1) mutation rates, 2) dispersal mechanisms, 3) the genotype-phenotype map, and 4) sexual reproduction, in temporally and spatially fluctuating environments. Although these disparate phenomena evolve by well-understood microevolutionary rules, they are also subject to the macroevolutionary constraint of long-term survivability
Evaluation of the performance of existing non-laboratory based cardiovascular risk assessment algorithms
A Measurement of Rb using a Double Tagging Method
The fraction of Z to bbbar events in hadronic Z decays has been measured by
the OPAL experiment using the data collected at LEP between 1992 and 1995. The
Z to bbbar decays were tagged using displaced secondary vertices, and high
momentum electrons and muons. Systematic uncertainties were reduced by
measuring the b-tagging efficiency using a double tagging technique. Efficiency
correlations between opposite hemispheres of an event are small, and are well
understood through comparisons between real and simulated data samples. A value
of Rb = 0.2178 +- 0.0011 +- 0.0013 was obtained, where the first error is
statistical and the second systematic. The uncertainty on Rc, the fraction of Z
to ccbar events in hadronic Z decays, is not included in the errors. The
dependence on Rc is Delta(Rb)/Rb = -0.056*Delta(Rc)/Rc where Delta(Rc) is the
deviation of Rc from the value 0.172 predicted by the Standard Model. The
result for Rb agrees with the value of 0.2155 +- 0.0003 predicted by the
Standard Model.Comment: 42 pages, LaTeX, 14 eps figures included, submitted to European
Physical Journal
Detection and Functional Characterization of a 215 Amino Acid N-Terminal Extension in the Xanthomonas Type III Effector XopD
During evolution, pathogens have developed a variety of strategies to suppress plant-triggered immunity and promote successful infection. In Gram-negative phytopathogenic bacteria, the so-called type III protein secretion system works as a molecular syringe to inject type III effectors (T3Es) into plant cells. The XopD T3E from the strain 85-10 of Xanthomonas campestris pathovar vesicatoria (Xcv) delays the onset of symptom development and alters basal defence responses to promote pathogen growth in infected tomato leaves. XopD was previously described as a modular protein that contains (i) an N-terminal DNA-binding domain (DBD), (ii) two tandemly repeated EAR (ERF-associated amphiphillic repression) motifs involved in transcriptional repression, and (iii) a C-terminal cysteine protease domain, involved in release of SUMO (small ubiquitin-like modifier) from SUMO-modified proteins. Here, we show that the XopD protein that is produced and secreted by Xcv presents an additional N-terminal extension of 215 amino acids. Closer analysis of this newly identified N-terminal domain shows a low complexity region rich in lysine, alanine and glutamic acid residues (KAE-rich) with high propensity to form coiled-coil structures that confers to XopD the ability to form dimers when expressed in E. coli. The full length XopD protein identified in this study (XopD1-760) displays stronger repression of the XopD plant target promoter PR1, as compared to the XopD version annotated in the public databases (XopD216-760). Furthermore, the N-terminal extension of XopD, which is absent in XopD216-760, is essential for XopD type III-dependent secretion and, therefore, for complementation of an Xcv mutant strain deleted from XopD in its ability to delay symptom development in tomato susceptible cultivars. The identification of the complete sequence of XopD opens new perspectives for future studies on the XopD protein and its virulence-associated functions in planta
Measurement of the B+ and B-0 lifetimes and search for CP(T) violation using reconstructed secondary vertices
The lifetimes of the B+ and B-0 mesons, and their ratio, have been measured in the OPAL experiment using 2.4 million hadronic Z(0) decays recorded at LEP. Z(0) --> b (b) over bar decays were tagged using displaced secondary vertices and high momentum electrons and muons. The lifetimes were then measured using well-reconstructed charged and neutral secondary vertices selected in this tagged data sample. The results aretau(B+) = 1.643 +/- 0.037 +/- 0.025 pstau(Bo) = 1.523 +/- 0.057 +/- 0.053 pstau(B+)/tau(Bo) = 1.079 +/- 0.064 +/- 0.041,where in each case the first error is statistical and the second systematic.A larger data sample of 3.1 million hadronic Z(o) decays has been used to search for CP and CPT violating effects by comparison of inclusive b and (b) over bar hadron decays, No evidence fur such effects is seen. The CP violation parameter Re(epsilon(B)) is measured to be Re(epsilon(B)) = 0.001 +/- 0.014 +/- 0.003and the fractional difference between b and (b) over bar hadron lifetimes is measured to(Delta tau/tau)(b) = tau(b hadron) - tau((b) over bar hadron)/tau(average) = -0.001 +/- 0.012 +/- 0.008
Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy
Background
A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets.
Methods
Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis.
Results
A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001).
Conclusion
We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty
Classical risk factors of cardiovascular disease among Chinese male steel workers: a prospective cohort study for 20 years
<p>Abstract</p> <p>Background</p> <p>Cardiovascular disease (CVD) constitutes a major public health problem in China and worldwide. We aimed to examine classical risk factors and their magnitudes for CVD in a Chinese cohort with over 20 years follow-up.</p> <p>Methods</p> <p>A cohort of 5092 male steelworkers recruited from 1974 to 1980 in Beijing of China was followed up for an average of 20.84 years. Cox proportional-hazards regression model were used to evaluate the risk of developing a first CVD event in the study participants who were free of CVD at the baseline.</p> <p>Results</p> <p>The multivariable-adjusted hazard ratio (HR) associated with every 20 mmHg rise in systolic blood pressure (SBP) was 1.63 in this Chinese male population, which was higher than in Caucasians. Compared to non-smokers, men who smoked not less than one-pack-a-day had a HR of 2.43 (95% confidence interval [CI], 1.75-3.38). The HR (95% CI) for every 20 mg/dl increase in total serum cholesterol (TC) and for every point rise in body mass index (BMI) was 1.13 (1.04-1.23) and 1.06 (1.02-1.09), respectively.</p> <p>Conclusions</p> <p>Our study documents that hypertension, smoking, overweight and hypercholesterolemia are major conventional risk factors of CVD in Chinese male adults. Continued strengthening programs for prevention and intervention on these risk factors are needed to reduce the incidence of CVD in China.</p
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