Association of subclinical atherosclerosis with echocardiographic indices of cardiac remodeling: The Framingham Study

BACKGROUND: It is well established that coronary artery disease progresses along with myocardial disease. However, data on the association between coronary artery calcium (CAC) and echocardiographic variables are lacking. METHODS AND RESULTS: Among 2,650 Framingham Study participants (mean age 51 yrs, 48% women; 40% with CAC \u3e 0), we related CT-based CAC score to left ventricular (LV) mass index (LVMi), LV ejection fraction (LVEF), E/e\u27, global longitudinal strain (GLS), left atrial emptying fraction (LAEF), and aortic root diameter (AoR), using multivariable-adjusted generalized linear models. CAC score (independent variable) was used as log-transformed continuous [ln(CAC+1)] and as a categorical (0, 1-100, and \u3e /=101) variable. Adjusting for standard risk factors, higher CAC score was associated with higher LVMi and AoR (betaLVMI per 1-SD increase 0.012, betaAoR 0.008; P \u3c 0.05, for both). Participants with 1 \u3c /=CAC \u3c /=100 and those with CAC \u3e /=101 had higher AoR (betaAoR 0.013 and 0.020, respectively, P = 0.01) than those with CAC = 0. CAC score was not significantly associated with LVEF, E/e\u27, GLS or LAEF. Age modified the association of CAC score with AoR; higher CAC scores were associated with larger AoR more strongly in older ( \u3e 58 years; betaAoR0.0042;P \u3c 0.007) than in younger ( \u3c /=58 years) participants (betaAoR0.0027;P \u3c 0.03). CONCLUSIONS: We observed that subclinical atherosclerosis was associated with ventricular and aortic remodeling. The prognostic significance of these associations warrants evaluation in additional mechanistic studies

Scale invariance of a diodelike tunnel junction

We measure the current vs voltage (I-V) characteristics of a diodelike tunnel junction consisting of a sharp metallic tip placed at a variable distance d from a planar collector and emitting electrons via electric-field assisted emission. All curves collapse onto one single graph when I is plotted as a function of the single scaling variable Vd^{-\lambda}, d being varied from a few mm to a few nm, i.e., by about six orders of magnitude. We provide an argument that finds the exponent {\lambda} within the singular behavior inherent to the electrostatics of a sharp tip. A simulation of the tunneling barrier for a realistic tip reproduces both the scaling behavior and the small but significant deviations from scaling observed experimentally.Comment: 6 pages, 6 figures. Accepted for publication in Physical Review

Association of Novel Biomarkers of Cardiovascular Stress With Left Ventricular Hypertrophy and Dysfunction: Implications for Screening

Background: Currently available screening tools for left ventricular (LV) hypertrophy (LVH) and systolic dysfunction (LVSD) are either expensive (echocardiography) or perform suboptimally (B‐type natriuretic peptide [BNP]). It is unknown whether newer biomarkers are associated with LVH and LVSD and can serve as screening tools. Methods and Results: We studied 2460 Framingham Study participants (mean age 58 years, 57% women) with measurements of biomarkers mirroring cardiac biomechanical stress (soluble ST‐2 [ST2], growth differentiation factor‐15 [GDF‐15] and high‐sensitivity troponin I [hsTnI]) and BNP. We defined LVH as LV mass/height2 ≥the sex‐specific 80th percentile and LVSD as mild/greater impairment of LV ejection fraction (LVEF) or a fractional shortening <0.29. Adjusting for standard risk factors in logistic models, BNP, GDF‐15, and hsTnI were associated with the composite echocardiographic outcome (LVH or LVSD), odds ratios (OR) per SD increment in log‐biomarker 1.29, 1.14, and 1.18 (95% CI: 1.15 to 1.44, 1.004 to 1.28, and 1.06 to 1.31), respectively. The C‐statistic for the composite outcome increased from 0.765 with risk factors to 0.770 adding BNP, to 0.774 adding novel biomarkers. The continuous Net Reclassification Improvement was 0.212 (95% CI: 0.119 to 0.305, P<0.0001) after adding the novel biomarkers to risk factors plus BNP. BNP was associated with LVH and LVSD in multivariable models, whereas GDF‐15 was associated with LVSD (OR 1.41, 95% CI: 1.16 to 1.70), and hsTnI with LVH (OR 1.22, 95% CI: 1.09 to 1.36). ST2 was not significantly associated with any outcome. Conclusions: Our community‐based investigation suggests that cardiac stress biomarkers are associated with LVH and LVSD but may have limited clinical utility as screening tools

Circulating ceramide ratios and risk of vascular brain aging and dementia

BACKGROUND: We determined the association between ratios of plasma ceramide species of differing fatty-acyl chain lengths and incident dementia and Alzheimer\u27s disease (AD) dementia in a large, community-based sample. METHODS: We measured plasma ceramide levels in 1892 [54% women, mean age 70.1 (SD 6.9) yr.] dementia-free Framingham Offspring Study cohort participants between 2005 and 2008. We related ratios of very long-chain (C24:0, C22:0) to long-chain (C16:0) ceramides to subsequent risk of incident dementia and AD dementia. Structural MRI brain measures were included as secondary outcomes. RESULTS: During a median 6.5 year follow-up, 81 participants developed dementia, of whom 60 were diagnosed with AD dementia. In multivariable Cox-proportional hazards analyses, each standard deviation (SD) increment in the ratio of ceramides C24:0/C16:0 was associated with a 27% reduction in the risk of dementia (HR 0.73, 95% CI 0.56-0.96) and AD dementia (HR 0.73, 95% CI 0.53-1.00). The ratio of ceramides C22:0/C16:0 was also inversely associated with incident dementia (HR per SD 0.75, 95% CI 0.57-0.98), and approached statistical significance for AD (HR 0.73, 95% CI 0.53-1.01, P = 0.056). Higher ratios of ceramides C24:0/C16:0 and C22:0/C16:0 were also cross-sectionally associated with lower white matter hyperintensity burden on MRI (-0.05 ± 0.02, P = 0.02; -0.06 ± 0.02, P = 0.003; respectively per SD increase), but not with other MRI brain measures. CONCLUSIONS: Higher plasma ratios of very long-chain to long-chain ceramides are associated with a reduced risk of incident dementia and AD dementia in our community-based sample. Circulating ceramide ratios may serve as potential biomarkers for predicting dementia risk in cognitively healthy adults

Development and Validation of Risk Prediction Models for Cardiovascular Events in Black Adults: The Jackson Heart Study Cohort

Cardiovascular risk assessment is a fundamental component of prevention of cardiovascular disease (CVD). However, commonly used prediction models have been formulated in primarily or exclusively white populations. Whether risk assessment in black adults is dissimilar to that in white adults is uncertain

Potential value of PTEN in predicting cetuximab response in colorectal cancer: An exploratory study

<p>Abstract</p> <p>Background</p> <p>The epidermal growth factor receptor (EGFR) is over-expressed in 70–75% of colorectal adenocarcinomas (CRC). The anti-EGFR monoclonal antibody cetuximab has been approved for the treatment of metastatic CRC, however tumor response to cetuximab has not been found to be associated with EGFR over-expression by immunohistochemistry (IHC). The aim of this study was to explore EGFR and the downstream effector phosphatase and tensin homologue deleted on chromosome 10 (PTEN) as potential predictors of response to cetuximab.</p> <p>Methods</p> <p>CRC patients treated with cetuximab by the Hellenic Cooperative Oncology group, whose formalin-fixed paraffin-embedded tumor tissue was available, were included. Tissue was tested for EGFR and PTEN by IHC and fluorescence in situ hybridization (FISH).</p> <p>Results</p> <p>Eighty-eight patients were identified and 72 were included based on the availability of tissue blocks with adequate material for analysis on them. All patients, except one, received cetuximab in combination with chemotherapy. Median follow-up was 53 months from diagnosis and 17 months from cetuximab initiation. At the time of the analysis 53% of the patients had died. Best response was complete response in one and partial response in 23 patients. In 16 patients disease stabilized. Lack of PTEN gene amplification was associated with more responses to cetuximab and longer time to progression (p = 0.042).</p> <p>Conclusion</p> <p>PTEN could be one of the molecular determinants of cetuximab response. Due to the heterogeneity of the population and the retrospective nature of the study, our results are hypothesis generating and should be approached with caution. Further prospective studies are needed to validate this finding.</p

Burnout Syndrome and alcohol consumption in prison employees

Objective: The aims of this study were to estimate the association between an at-risk drinking pattern and sociodemographic variables, and to compare the mean scores of the factors associated with the Burnout Syndrome, according to the alcohol consumption pattern in staff members from two Brazilian prisons. Methods: A cross-sectional study was developed with 339 participants (response rate = 63.8%). The instruments used were a sociodemographic questionnaire, the Alcohol Use Disorders Identification Test (AUDIT), and the Maslach Burnout Inventory – General Survey (MBI-GS). Results: The participants’ average age was 40.2 (SD = 8.8) years, and 81.0% were male. Among 78.5% of participants (95%CI 74.1 – 82.8) reported consuming alcoholic beverages. The prevalence of at-risk drinking behavior in the sample was 22.4% (95%CI 18.0 – 26.9), and of the Burnout Syndrome was 14.6% (95%CI 10.8 – 18.4). We observed a significant association between at-risk drinking behavior with gender, higher risk for men (OR = 7.32, p < 0.001), smoking, increased risk for smokers (OR = 2.77, p < 0.001), and religious practice, showing lower risks for religion practitioners (OR = 0.364, p < 0.001). We noticed significantly higher mean scores (p < 0.001) of emotional exhaustion and cynicism, and lower scores of professional achievement among individuals who reported consuming alcoholic beverages. Conclusion: Men who smoke were more likely to develop an at-risk drinking pattern, while religion is presented as a protective factor. Individuals who consume alcohol were more affected by the different factors of the Burnout Syndrome

Priorities for Mediterranean marine turtle conservation and management in the face of climate change

As climate-related impacts threaten marine biodiversity globally, it is important to adjust conservation efforts to mitigate the effects of climate change. Translating scientific knowledge into practical management, however, is often complicated due to resource, economic and policy constraints, generating a knowledge-action gap. To develop potential solutions for marine turtle conservation, we explored the perceptions of key actors across 18 countries in the Mediterranean. These actors evaluated their perceived relative importance of 19 adaptation and mitigation measures that could safeguard marine turtles from climate change. Of importance, despite differences in expertise, experience and focal country, the perceptions of researchers and management practitioners largely converged with respect to prioritizing adaptation and mitigation measures. Climate change was considered to have the greatest impacts on offspring sex ratios and suitable nesting sites. The most viable adaptation/mitigation measures were considered to be reducing other pressures that act in parallel to climate change. Ecological effectiveness represented a key determinant for implementing proposed measures, followed by practical applicability, financial cost, and societal cost. This convergence in opinions across actors likely reflects long-standing initiatives in the Mediterranean region towards supporting knowledge exchange in marine turtle conservation. Our results provide important guidance on how to prioritize measures that incorporate climate change in decision-making processes related to the current and future management and protection of marine turtles at the ocean-basin scale, and could be used to guide decisions in other regions globally. Importantly, this study demonstrates a successful example of how interactive processes can be used to fill the knowledge-action gap between research and management.This work was conducted under FutureMares EU project that received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 869300. The Mediterranean Marine Turtle Working Group was established in 2017 and is continuously supported by MedPAN and the National Marine Park of Zakynthos. The work of AC was supported by the Hellenic Foundation for Research and Innovation (H.F.R.I.) under the “First Call for H.F.R.I. Research Projects to support Faculty members and Researchers and the procurement of high-cost research equipment grant” (Project Number: 2340).Peer reviewe