Measuring hsCRP—An Important Part of a Comprehensive Risk Profile or a Clinically Redundant Practice?

James McCormack and Michael Allan discuss issues and questions surrounding hsCRP measurements in patients

Insulin Resistance and Body Fat Distribution in South Asian Men Compared to Caucasian Men

South Asians are susceptible to insulin resistance even without obesity. We examined the characteristics of body fat content, distribution and function in South Asian men and their relationships to insulin resistance compared to Caucasians.Twenty-nine South Asian and 18 Caucasian non-diabetic men (age 27+/-3 and 27+/-3 years, respectively) underwent euglycemic-hyperinsulinemic clamp for insulin sensitivity, underwater weighing for total body fat, MRI of entire abdomen for intraperitoneal (IP) and subcutaneous abdominal (SA) fat and biopsy of SA fat for adipocyte size.Compared to Caucasians, in spite of similar BMI, South Asians had higher total body fat (22+/-6 and 15+/-4% of body weight; p-value<0.0001), higher SA fat (3.5+/-1.9 and 2.2+/-1.3 kg, respectively; p-value = 0.004), but no differences in IP fat (1.0+/-0.5 and 1.0+/-0.7 kg, respectively; p-value = 0.4). SA adipocyte cell size was significantly higher in South Asians (3491+/-1393 and 1648+/-864 microm2; p-value = 0.0001) and was inversely correlated with both glucose disposal rate (r-value = -0.57; p-value = 0.0008) and plasma adiponectin concentrations (r-value = -0.71; p-value<0.0001). Adipocyte size differences persisted even when SA was matched between South Asians and Caucasians.Insulin resistance in young South Asian men can be observed even without increase in IP fat mass and is related to large SA adipocytes size. Hence ethnic excess in insulin resistance in South Asians appears to be related more to excess truncal fat and dysfunctional adipose tissue than to excess visceral fat

Sex difference in the association of metabolic syndrome with high sensitivity C-reactive protein in a Taiwanese population

<p>Abstract</p> <p>Background</p> <p>Although sex differences have been reported for associations between components of metabolic syndrome and inflammation, the question of whether there is an effect modification by sex in the association between inflammation and metabolic syndrome has not been investigated in detail. Therefore, the aim of this study was to compare associations of high sensitivity C-creative protein (hs-CRP) with metabolic syndrome and its components between men and women.</p> <p>Methods</p> <p>A total of 1,305 subjects aged 40 years and over were recruited in 2004 in a metropolitan city in Taiwan. The biochemical indices, such as hs-CRP, fasting glucose levels, lipid profiles, urinary albumin, urinary creatinine and anthropometric indices, were measured. Metabolic syndrome was defined using the American Heart Association and the National Heart, lung and Blood Institute (AHA/NHLBI) definition. The relationship between metabolic syndrome and hs-CRP was examined using multivariate logistic regression analysis.</p> <p>Results</p> <p>After adjustment for age and lifestyle factors including smoking, and alcohol intake, elevated concentrations of hs-CRP showed a stronger association with metabolic syndrome in women (odds ratio comparing tertile extremes 4.80 [95% CI: 3.31-6.97]) than in men (2.30 [1.65-3.21]). The p value for the sex interaction was 0.002. All components were more strongly associated with metabolic syndrome in women than in men, and all sex interactions were significant except for hypertension.</p> <p>Conclusions</p> <p>Our data suggest that inflammatory processes may be of particular importance in the pathogenesis of metabolic syndrome in women.</p

Diagnostic criteria and tumor screening for individuals with isolated hemihyperplasia

Isolated hemihyperplasia, formerly termed isolated hemihypertrophy, is a congenital overgrowth disorder associated with an increased risk for embryonal tumors, mainly Wilms tumor and hepatoblastoma. This practice guideline will set forth the diagnostic criteria and tumor screening recommendations for children with isolated hemihyperplasia, based on the best information available. There is clinical overlap between isolated hemihyperplasia with Beckwith-Wiedemann syndrome. The majority of Beckwith-Wiedemann syndrome patients have a molecular abnormality involving the imprinted cluster of genes at 11p15.5. In contrast, the preponderance of isolated hemihyperplasia patients studied have no identified etiology. Tumors have developed in isolated hemihyperplasia patients with and without molecular abnormalities. For this reason, molecular diagnostics are not helpful in identifying the subset of isolated hemihyperplasia patients with tumor risk and all isolated hemihyperplasia patients should undergo tumor screening

A frequentist framework of inductive reasoning

Reacting against the limitation of statistics to decision procedures, R. A. Fisher proposed for inductive reasoning the use of the fiducial distribution, a parameter-space distribution of epistemological probability transferred directly from limiting relative frequencies rather than computed according to the Bayes update rule. The proposal is developed as follows using the confidence measure of a scalar parameter of interest. (With the restriction to one-dimensional parameter space, a confidence measure is essentially a fiducial probability distribution free of complications involving ancillary statistics.) A betting game establishes a sense in which confidence measures are the only reliable inferential probability distributions. The equality between the probabilities encoded in a confidence measure and the coverage rates of the corresponding confidence intervals ensures that the measure's rule for assigning confidence levels to hypotheses is uniquely minimax in the game. Although a confidence measure can be computed without any prior distribution, previous knowledge can be incorporated into confidence-based reasoning. To adjust a p-value or confidence interval for prior information, the confidence measure from the observed data can be combined with one or more independent confidence measures representing previous agent opinion. (The former confidence measure may correspond to a posterior distribution with frequentist matching of coverage probabilities.) The representation of subjective knowledge in terms of confidence measures rather than prior probability distributions preserves approximate frequentist validity.Comment: major revisio

Prevalence of the metabolic syndrome in patients with carotid disease according to NHLBI/AHA and IDF criteria: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) has been related to type 2 diabetes and cardiovascular diseases. Different criteria for diagnosis of MetS have been recommended, but there is no agreement about which criteria are best to use. The aim of the present study was to investigate agreement between the National Heart, Lung, and Blood Institute, American Heart Association (NHLBI/AHA) and the International Diabetes Federation (IDF) definitions of MetS in patients with symptomatic carotid disease and to compare the frequency of cardiovascular risk factor in patients with MetS diagnosed by these two sets of criteria.</p> <p>Methods</p> <p>The study was a cross-sectional one involving 644 consecutive patients with verified carotid disease who referred to the Vascular Surgery Clinic Dedinje in Belgrade during the period April 2006 - November 2007. Anthropometric parameters blood pressure, fasting plasma glucose and lipoproteins were measured using standard procedures.</p> <p>Results</p> <p>MetS was present in 67.9% of participants, according to IDF criteria, and in 64.9% of participants, according to the NHLBI/AHA criteria. A total of 119 patients were categorized differently by the two definitions. Out of all participants 10.7% had MetS by IDF criteria only and 7.8% of patients had MetS by NHLBI/AHA criteria only. The overall agreement of IDF and NHLBI/AHA criteria was 81.5% (Kappa 0.59, <it>p </it>< 0.001). In comparison with patients who met only IDF criteria, patients who met only NHLBI/AHA criteria had significantly more frequently cardiovascular risk factors with the exception of obesity which was significantly more frequent in patients with MetS diagnosed by IDF criteria.</p> <p>Conclusion</p> <p>The MetS prevalence in patients with symptomatic carotid disease was high regardless of criteria used for its diagnosis. Since some patients with known cardiovascular risk factors were lost by the use of IDF criteria it seems that NHLBI/AHA definition is more suitable for diagnosis of MetS. Large follow-up studies are needed to test prognostic value of these definitions.</p

Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study

Statins are commonly used for reducing cardiovascular disease risk but therapeutic benefit and reductions in levels of low-density lipoprotein cholesterol (LDL-C) vary among individuals. Other effects, including reductions in C-reactive protein (CRP), also contribute to treatment response. Metabolomics provides powerful tools to map pathways implicated in variation in response to statin treatment. This could lead to mechanistic hypotheses that provide insight into the underlying basis for individual variation in drug response. Using a targeted lipidomics platform, we defined lipid changes in blood samples from the upper and lower tails of the LDL-C response distribution in the Cholesterol and Pharmacogenetics study. Metabolic changes in responders are more comprehensive than those seen in non-responders. Baseline cholesterol ester and phospholipid metabolites correlated with LDL-C response to treatment. CRP response to therapy correlated with baseline plasmalogens, lipids involved in inflammation. There was no overlap of lipids whose changes correlated with LDL-C or CRP responses to simvastatin suggesting that distinct metabolic pathways govern statin effects on these two biomarkers. Metabolic signatures could provide insights about variability in response and mechanisms of action of statins

Quantum-over-classical Advantage in Solving Multiplayer Games

We study the applicability of quantum algorithms in computational game theory and generalize some results related to Subtraction games, which are sometimes referred to as one-heap Nim games. In quantum game theory, a subset of Subtraction games became the first explicitly defined class of zero-sum combinatorial games with provable separation between quantum and classical complexity of solving them. For a narrower subset of Subtraction games, an exact quantum sublinear algorithm is known that surpasses all deterministic algorithms for finding solutions with probability $1$. Typically, both Nim and Subtraction games are defined for only two players. We extend some known results to games for three or more players, while maintaining the same classical and quantum complexities: $\Theta\left(n^2\right)$ and $\tilde{O}\left(n^{1.5}\right)$ respectively