Determination of Pericardial Adipose Tissue Increases the Prognostic Accuracy of Coronary Artery Calcification for Future Cardiovascular Events

Objectives: Pericardial adipose tissue (PAT) is associated with coronary artery plaque accumulation and the incidence of coronary heart disease. We evaluated the possible incremental prognostic value of PAT for future cardiovascular events. Methods: 145 patients (94 males, age 60 10 years) with stable coronary artery disease underwent coronary artery calcification (CAC) scanning in a multislice CT scanner, and the volume of pericardial fat was measured. Mean observation time was 5.4 years. Results: 34 patients experienced a severe cardiac event. They had a significantly higher CAC score (1,708 +/- 2,269 vs. 538 +/- 1,150, p 400, 3.5 (1.9-5.4; p = 0.007) for scores > 800 and 5.9 (3.7-7.8; p = 0.005) for scores > 1,600. When additionally a PAT volume > 200 cm(3) was determined, there was a significant increase in the event rate and relative risk. We calculated a relative risk of 2.9 (1.9-4.2; p = 0.01) for scores > 400, 4.0 (2.1-5.0; p = 0.006) for scores > 800 and 7.1 (4.1-10.2; p = 0.005) for scores > 1,600. Conclusions:The additional determination of PAT increases the predictive power of CAC for future cardiovascular events. PAT might therefore be used as a further parameter for risk stratification. Copyright (C) 2012 S. Karger AG, Base

Wall roughness induces asymptotic ultimate turbulence

Turbulence is omnipresent in Nature and technology, governing the transport of heat, mass, and momentum on multiple scales. For real-world applications of wall-bounded turbulence, the underlying surfaces are virtually always rough; yet characterizing and understanding the effects of wall roughness for turbulence remains a challenge, especially for rotating and thermally driven turbulence. By combining extensive experiments and numerical simulations, here, taking as example the paradigmatic Taylor-Couette system (the closed flow between two independently rotating coaxial cylinders), we show how wall roughness greatly enhances the overall transport properties and the corresponding scaling exponents. If only one of the walls is rough, we reveal that the bulk velocity is slaved to the rough side, due to the much stronger coupling to that wall by the detaching flow structures. If both walls are rough, the viscosity dependence is thoroughly eliminated in the boundary layers and we thus achieve asymptotic ultimate turbulence, i.e. the upper limit of transport, whose existence had been predicted by Robert Kraichnan in 1962 (Phys. Fluids {\bf 5}, 1374 (1962)) and in which the scalings laws can be extrapolated to arbitrarily large Reynolds numbers

A Phase II study of pulse dose imatinib mesylate and weekly paclitaxel in patients aged 70 and over with advanced non-small cell lung cancer

Background: In non-small cell lung cancer (NSCLC), interstitial hypertension is a barrier to chemotherapy delivery, and is mediated by platelet derived growth factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve intra-tumoral delivery of paclitaxel, increasing response rate (RR).Methods: This single-stage, open-label phase II study evaluated pulse dose imatinib and weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were aged ≥ 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. Primary endpoint was RR. Secondary endpoints included median progression free and overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline Charlson Comorbidity Index (CCI) and Vulnerable Elder Survey-13 (VES-13) were correlated with outcomes.Results: Thirty-four patients with median age 75 enrolled. Eleven of 29 (38%) were frail by VES-13 score. Overall RR was 11/34 (32%; 95% CI 17%-51%), meeting the primary endpoint. Median PFS and OS were 3.6 and 7.3 months, respectively. High tumoral PDGF-B expression predicted inferior PFS. Frail patients by VES-13 had significantly worse median PFS (3.2 vs. 4.5 months; p=0.02) and OS (4.8 vs. 12 months; p=0.02) than non-frail.Conclusions: The combination of imatinib and paclitaxel had encouraging activity as measured by the primary endpoint of RR. However, PFS and OS were typical for elderly patients treated with single agent chemotherapy and the regimen is not recommended for further study. Adjunct imatinib did not overcome the established association of tumoral PDGF-B expression with inferior PFS. VES-13 was a powerful predictor of poor survival outcomes. Frailty should be further studied as a predictor of non-benefit from chemotherapy.Trial Registration: ClinicalTrials.gov NCT01011075. © 2012 Bauman et al.; licensee BioMed Central Ltd

Meditation Awareness Training (MAT) for Work-related Wellbeing and Job Performance: A Randomised Controlled Trial

Due to its potential to concurrently improve work-related wellbeing (WRW) and job performance, occupational stakeholders are becoming increasingly interested in the applications of meditation. The present study conducted the first randomized controlled trial to assess the effects of meditation on outcomes relating to both WRW and job performance. Office-based middle-hierarchy managers (n = 152) received an eight-week meditation intervention (Meditation Awareness Training; MAT) or an active control intervention. MAT participants demonstrated significant and sustainable improvements (with strong effect sizes) over control-group participants in levels of work-related stress, job satisfaction, psychological distress, and employer-rated job performance. There are a number of novel implications: (i) meditation can effectuate a perceptual shift in how employees experience their work and psychological environment and may thus constitute a cost-effective WRW intervention, (ii) meditation-based (i.e., present-moment-focussed) working styles may be more effective than goal-based (i.e., future-orientated) working styles, and (iii) meditation may reduce the separation made by employees between their own interests and those of the organizations they work for

Operator theory and function theory in Drury-Arveson space and its quotients

The Drury-Arveson space $H^2_d$, also known as symmetric Fock space or the $d$-shift space, is a Hilbert function space that has a natural $d$-tuple of operators acting on it, which gives it the structure of a Hilbert module. This survey aims to introduce the Drury-Arveson space, to give a panoramic view of the main operator theoretic and function theoretic aspects of this space, and to describe the universal role that it plays in multivariable operator theory and in Pick interpolation theory.Comment: Final version (to appear in Handbook of Operator Theory); 42 page

K70Q Adds High-Level Tenofovir Resistance to “Q151M Complex” HIV Reverse Transcriptase through the Enhanced Discrimination Mechanism

HIV-1 carrying the “Q151M complex” reverse transcriptase (RT) mutations (A62V/V75I/F77L/F116Y/Q151M, or Q151Mc) is resistant to many FDA-approved nucleoside RT inhibitors (NRTIs), but has been considered susceptible to tenofovir disoproxil fumarate (TFV-DF or TDF). We have isolated from a TFV-DF-treated HIV patient a Q151Mc-containing clinical isolate with high phenotypic resistance to TFV-DF. Analysis of the genotypic and phenotypic testing over the course of this patient's therapy lead us to hypothesize that TFV-DF resistance emerged upon appearance of the previously unreported K70Q mutation in the Q151Mc background. Virological analysis showed that HIV with only K70Q was not significantly resistant to TFV-DF. However, addition of K70Q to the Q151Mc background significantly enhanced resistance to several approved NRTIs, and also resulted in high-level (10-fold) resistance to TFV-DF. Biochemical experiments established that the increased resistance to tenofovir is not the result of enhanced excision, as K70Q/Q151Mc RT exhibited diminished, rather than enhanced ATP-based primer unblocking activity. Pre-steady state kinetic analysis of the recombinant enzymes demonstrated that addition of the K70Q mutation selectively decreases the binding of tenofovir-diphosphate (TFV-DP), resulting in reduced incorporation of TFV into the nascent DNA chain. Molecular dynamics simulations suggest that changes in the hydrogen bonding pattern in the polymerase active site of K70Q/Q151Mc RT may contribute to the observed changes in binding and incorporation of TFV-DP. The novel pattern of TFV-resistance may help adjust therapeutic strategies for NRTI-experienced patients with multi-drug resistant (MDR) mutations

Neck circumference is associated with adipose tissue content in thigh skeletal muscle in overweight and obese premenopausal women

Neck circumference (NC) has been proposed as a simple and practical tool, independently associated with cardiometabolic risk factors. However, the association of NC with inter-muscular adipose tissue (IMAT) is still to be determined. We aimed to examine the association of NC with thigh IMAT, and visceral adipose tissue (VAT) measured with computed tomography (CT) in overweight/obese women. 142 premenopausal overweight and obese Caucasian women participated in this crosssectional study. NC was measured with an inextensible metallic tape above the thyroid cartilage according to International Society for Advancement of Kinanthropometry protocol. Thigh IMAT and VAT volumes were measured with a single cross-sectional CT. Regarding the covariates, fat mass (FM) was assessed with dual-energy x-ray absorptiometry and physical activity was objectively measured with accelerometry. NC was positively associated with thigh IMAT and VAT volumes (standardized β coefcient: β=0.45, P-value= ≤0.001, β=0.60, P=≤0.001; respectively), which persisted after adjusting for age, height, overall FM or moderate-to-vigorous physical activity. Our fndings show that NC is associated with thigh IMAT volume in overweight and obese premenopausal Caucasian women, regardless of the amount of lower-body fatness. These results suggest underscoring the relevance of NC as a marker of adipose tissue content in thigh skeletal muscle.Portuguese Foundation for Science and Technology Sapiens 358007/99Oeiras City CouncilBecel PortugalRoche Pharmaceuticals PortugalCompal PortugalUniversity of Granada Plan Propio de Investigacion 2016 -Excellence actions: Unit of Excellence on Exercise and Health (UCEES)Junta de AndaluciaEuropean Union (EU) SOMM17/6107/UGRFundacion Carolina C.201657496

Decolonisation of MRSA, S. aureus and E. coli by Cold-Atmospheric Plasma Using a Porcine Skin Model In Vitro

In the last twenty years new antibacterial agents approved by the U.S. FDA decreased whereas in parallel the resistance situation of multi-resistant bacteria increased. Thus, community and nosocomial acquired infections of resistant bacteria led to a decrease in the efficacy of standard therapy, prolonging treatment time and increasing healthcare costs. Therefore, the aim of this work was to demonstrate the applicability of cold atmospheric plasma for decolonisation of Gram-positive (Methicillin-resistant Staphylococcus aureus (MRSA), Methicillin-sensitive Staphylococcus aureus) and Gram-negative bacteria (E. coli) using an ex vivo pig skin model. Freshly excised skin samples were taken from six month old female pigs (breed: Pietrain). After application of pure bacteria on the surface of the explants these were treated with cold atmospheric plasma for up to 15 min. Two different plasma devices were evaluated. A decolonisation efficacy of 3 log10 steps was achieved already after 6 min of plasma treatment. Longer plasma treatment times achieved a killing rate of 5 log10 steps independently from the applied bacteria strains. Histological evaluations of untreated and treated skin areas upon cold atmospheric plasma treatment within 24 h showed no morphological changes as well as no significant degree of necrosis or apoptosis determined by the TUNEL-assay indicating that the porcine skin is still vital. This study demonstrates for the first time that cold atmospheric plasma is able to very efficiently kill bacteria applied to an intact skin surface using an ex vivo porcine skin model. The results emphasize the potential of cold atmospheric plasma as a new possible treatment option for decolonisation of human skin from bacteria in patients in the future without harming the surrounding tissue