Interrelations Between Arterial Stiffness, Target Organ Damage, and Cardiovascular Disease Outcomes

Background-Excess transmission of pressure pulsatility caused by increased arterial stiffness may incur microcirculatory damage in end organs (target organ damage [TOD]) and, in turn, elevate risk for cardiovascular disease (CVD) events.Methods and Results-We related arterial stiffness measures (carotid-femoral pulse wave velocity, mean arterial pressure, central pulse pressure) to the prevalence and incidence of TOD (defined as albuminuria and/or echocardiographic left ventricular hypertrophy) in up to 6203 Framingham Study participants (mean age 50 +/- 15 years, 54% women). We then related presence of TOD to incident CVD in multivariable Cox regression models without and with adjustment for arterial stiffness measures. Cross-sectionally, greater arterial stiffness was associated with a higher prevalence of TOD (adjusted odds ratios ranging from 1.23 to 1.54 per SD increment in arterial stiffness measure, P<0.01). Prospectively, increased carotid-femoral pulse wave velocity was associated with incident albuminuria (odds ratio per SD 1.28, 95% CI, 1.02-1.61; P<0.05), whereas higher mean arterial pressure and central pulse pressure were associated with incident left ventricular hypertrophy (odds ratio per SD 1.37 and 1.45, respectively; P<0.01). On follow-up, 297 of 5803 participants experienced a first CVD event. Presence of TOD was associated with a 33% greater hazard of incident CVD (95% CI, 0-77%; P<0.05), which was attenuated upon adjustment for baseline arterial stiffness measures by 5-21%.Conclusions-Elevated arterial stiffness is associated with presence of TOD and may partially mediate the relations of TOD with incident CVD. Our observations in a large community-based sample suggest that mitigating arterial stiffness may lower the burden of TOD and, in turn, clinical CVD

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

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories

Graph Homomorphisms and Qualitative Software System Analysis

Abstract:- In this paper we present a mathematical model based on graph homomorphisms permitting the analysis and the behavioral envisioning of software based systems. We first try to explain why a qualitative approach is needed and which are the limitations and problems of quantitative analysis techniques. Follow some results of a qualitative abstraction tool and some simple application examples on telecommunication protocol software. We then introduce the concept of a system qualitative graph and the role of graph homomorphisms for modeling a software as a continuous phase transition map operating on an abstract data space. In our presentation this model has been successfully applied to software based systems but it can be generalized to any hybrid system. We finish with the presentation of the underlying mathematical framework and some properties of graph homomorphism invariants. Key-Words:- software engineering, qualitative reasoning, software testing, dynamic system analysis, graph homomorphisms, software phase spaces

Unequal optical emissions between the east and the west part of the solar corona

We extent the results of previous studies where the east part of the solar corona had been found brighter than the west in most of the cases. In the present article, conclusions which have been derived by data obtained by the Kislovodsk observatory, support very well the aspects which have been stated by previous studies based on the Pic-du-Midi data. It is very hopeful that two data sets obtained by two observatories located far each other and operating in quite different time spans have driven towards the same results. Perhaps this fact gives the right to think seriously on the possibility the east part of the solar corona to be brighter than the west, in most of the cases. © 1995, All rights reserved

Implications for preferred longitudes in the coronal optical intensities

From the analysis of the optical intensities of the solar corona in various spectral emissions obtained by the Pic-du-Midi and Kislovodsk observatories has been derived that systematic North-South and East-West asymmetries appear in all the data sets. The combination of these two asymmetries makes the Northeast/Southeast solar quarters to appear brighter than the rest in most of the cases of all the data sets. It is very possible the excess of the Northeast/Southeast solar quarter to coincide with the preferred longitudes effect which has been mentioned by several authors in the past. © 1995, All rights reserved