Deviation Increase In Concentration Research Articles

Vascular endothelium as a target for perfluroalkyl substances (PFAs)

IntroductionPerfluoroalkyl substances (PFAs) are ubiquitous, anthropogenic organic compounds that have been linked with cardiovascular disease and cardiovascular risk factors. Older, long-chain PFAs have been phased out due to adverse cardiometabolic health effect and replaced by newer short-chain PFAs. However, emerging research suggests that short-chain PFAs may also have adverse cardiovascular effects. Non-invasive measures of vascular function can detect preclinical cardiovascular disease and serve as a useful surrogate for early CVD risk. We hypothesized that serum concentrations of PFAs would be associated with noninvasive measures of vascular function, carotid-femoral pulse wave velocity (PWV) and brachial artery reactivity testing (BART), in adults with non-occupational exposure to PFAs. MethodsWe measured serum concentrations of 14 PFAs with hybrid solid-phase extraction and ultrahigh-performance liquid chromatography–tandem mass spectrometry in 94 adult outpatients with no known cardiovascular disease. We collected clinical and demographic data; and measured vascular function, PWV and BART, using standard protocols. We assessed associations of individual PFAs with log-transformed BART and PWV using linear regression. We used weighted quantile sum regression to assess effects of correlated PFA mixtures on BART and PWV. ResultsTen PFAs were measured above the limit of detection in >50% of participants. Each standard deviation increase in concentration of perfluoroheptanoic acid (PFHpA) was associated with 15% decrease in BART (95% CI: −28.5, −0.17). The weighted index of a mixture of PFAs with correlated concentrations was inversely associated with BART: each tertile increase in the weighted PFA mixture was associated with 25% lower BART, with 73% of the effect driven by PFHpA. In contrast, no PFAs or mixtures were associated with PWV. ConclusionsSerum concentration of PFHpA, a new, short-chain PFA, was associated with impaired vascular function among outpatients without CVD. Our findings support a potential adverse cardiovascular effect of newer, short-chain PFAs.

The association of lymphotoxin-beta receptor with the subsequent diagnosis of incident gastrointestinal cancer: results from the Dallas Heart Study.

Lymphotoxin-beta receptor (LTβR) is an immunological protein associated with inflammation, and from preclinical studies is implicated in tumorigenesis. The epidemiological relationships with cancer are unknown, hence this study investigated their associations. From a multiethnic population-based cohort, 3,032 participants without a prevalent cancer (a diagnosis prior to or within one year of enrollment) at baseline underwent measurement of plasma LTβR. These participants were followed for incident cancer using the Texas Cancer Registry (TCR). Over a median follow-up of 12.1 years, 178 participants developed incident cancer, of which 30 participants developed incident gastrointestinal (GI) cancer. Median plasma LTβR (1.10 vs. 1.00 ng/mL, P<0.02) levels were higher in individuals with overall incident cancer compared to those without cancer. After adjustments for age, sex, and race/ethnicity, these relationships were no longer significant. When analyses were stratified by cancer type, LTβR was positively associated with GI cancer after adjustments: HR, 95% CI per 1-standard deviation increase in concentration 2.64 (1.23-5.68), P=0.013. LTβR stratified by quartiles was significantly associated temporally with the risk of incident GI cancer, log-rank: P=0.011. The median interval to incident GI cancer diagnosis was 5.9 years. Increased plasma levels of LTβR are associated with the development of GI cancer. The antecedent findings years prior to a subsequent diagnosis of incident GI cancer suggest a role for LTβR in the pathogenesis of GI cancer. Further studies are needed to determine if LTβR can serve as an immune biomarker for GI cancer, in particular hepatocellular and colorectal cancers.

Pre-diagnostic metabolite concentrations and prostate cancer risk in 1077 cases and 1077 matched controls in the European Prospective Investigation into Cancer and Nutrition

BackgroundLittle is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death from prostate cancer.MethodsIn a case-control study nested in the European Prospective Investigation into Cancer and Nutrition, pre-diagnostic plasma concentrations of 122 metabolites (including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids) were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit) and compared between 1077 prostate cancer cases and 1077 matched controls. Risk of prostate cancer associated with metabolite concentrations was estimated by multi-variable conditional logistic regression, and multiple testing was accounted for by using a false discovery rate controlling procedure.ResultsSeven metabolite concentrations, i.e. acylcarnitine C18:1, amino acids citrulline and trans-4-hydroxyproline, glycerophospholipids PC aa C28:1, PC ae C30:0 and PC ae C30:2, and sphingolipid SM (OH) C14:1, were associated with prostate cancer (p < 0.05), but none of the associations were statistically significant after controlling for multiple testing. Citrulline was associated with a decreased risk of prostate cancer (odds ratio (OR1SD) = 0.73; 95% confidence interval (CI) 0.62–0.86; ptrend = 0.0002) in the first 5 years of follow-up after taking multiple testing into account, but not after longer follow-up; results for other metabolites did not vary by time to diagnosis. After controlling for multiple testing, 12 glycerophospholipids were inversely associated with advanced stage disease, with risk reduction up to 46% per standard deviation increase in concentration (OR1SD = 0.54; 95% CI 0.40–0.72; ptrend = 0.00004 for PC aa C40:3). Death from prostate cancer was associated with higher concentrations of acylcarnitine C3, amino acids methionine and trans-4-hydroxyproline, biogenic amine ADMA, hexose and sphingolipid SM (OH) C14:1 and lower concentration of glycerophospholipid PC aa C42:4.ConclusionsSeveral metabolites, i.e. C18:1, citrulline, trans-4-hydroxyproline, three glycerophospholipids and SM (OH) C14:1, might be related to prostate cancer. Analyses by time to diagnosis indicated that citrulline may be a marker of subclinical prostate cancer, while other metabolites might be related to aetiology. Several glycerophospholipids were inversely related to advanced stage disease. More prospective data are needed to confirm these associations.

New evidence that omega-3 fatty acids have a role in primary prevention of coronary heart disease

A recently published study (1) provides new evidence that omega-3 fatty acids have a role in the primary prevention of coronary heart disease (CHD). This new publication included pooled data from 19 cohort studies conducted in 16 countries and including over 45,000 individuals with a median follow-up time of 10 years. Importantly, omega-3 fatty acid concentrations in blood or tissue compartments at study entry were used as the measure of exposure. It was found that each of the four omega-3 fatty acids reported α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) was associated with reduced risk of fatal CHD, with about a 10% reduction in relative risk (RR) for each one standard deviation increase in concentration of the omega-3 fatty acid. These findings make a very valuable contribution to the ongoing discussion about the role of omega-3 fatty acids in cardiovascular disease (CVD) and provide further evidence to support recommendations for the population to consume these fatty acids as part of a healthy diet.

Media markets, special interests, and voters

This paper examines the role of mass media in countering special interest group influence. I use the concentration of campaign contributions from Political Action Committees to proxy for special interests' capture of US Senate candidates from 1980 to 2002, and compare the reaction of voters to increases in concentration in two different types of media markets: in-state media markets and out-of-state media markets. Unlike in-state media markets, out-of-state markets focus on neighboring states' politics and elections. Thus, if citizens punish political capture, increases in concentration of special interest contributions to a particular candidate should reduce his vote share in in-state counties relative to the out-of-state counties, where the candidate receives less coverage. I find that a one-standard deviation increase in concentration of special interest contributions to incumbents reduces their vote share by about 0.5 to 1.5percentage points in in-state counties relative to the out-of-state counties. Robustness checks suggest that these results are not driven by omitted Senator characteristics or by differences between in-state and out-of-state counties along dimensions other than the media environment.

Media Markets, Special Interests, and Voters

This paper examines the role of mass media in countering special interest group influence. I use the concentration of campaign contributions from Political Action Committees to proxy special interests’ capture US Senate candidates from 1980 to 2002, and compare the reaction of voters to increases in concentration in two different types of media markets – in-state media markets and out-of-state media markets. Unlike in-state media markets, out-of-state markets focus on neighboring states’ politics and elections. Thus, if citizens punish political capture, increases in concentration of special interest contributions to a particular candidate should reduce his vote share in in-state counties relative to the out-of-state counties, where the candidate receives less coverage. I find that a one standard deviation increase in concentration of special interest contributions to incumbents reduces their vote share by about 0.5 to 1.5 percentage points in in-state counties relative to the out-of-state counties. Results are similar in specifications that rely solely on variation in concentration across time within the same county, and when the sample is limited to in-state counties that are contiguous to out-of-state counties and have similar demographic structures. A placebo test where in-state counties bordering out-of-state ones are compared to other in-state counties shows no effect, confirming the identification hypothesis that the results are not driven by geographic characteristics or distance from the media center of the state.