Mobile Air Quality Studies (MAQS) - an international project

Due to an increasing awareness of the potential hazardousness of air pollutants, new laws, rules and guidelines have recently been implemented globally. In this respect, numerous studies have addressed traffic-related exposure to particulate matter using stationary technology so far. By contrast, only few studies used the advanced technology of mobile exposure analysis. The Mobile Air Quality Study (MAQS) addresses the issue of air pollutant exposure by combining advanced high-granularity spatial-temporal analysis with vehicle-mounted, person-mounted and roadside sensors. The MAQS-platform will be used by international collaborators in order 1) to assess air pollutant exposure in relation to road structure, 2) to assess air pollutant exposure in relation to traffic density, 3) to assess air pollutant exposure in relation to weather conditions, 4) to compare exposure within vehicles between front and back seat (children) positions, and 5) to evaluate "traffic zone"- exposure in relation to non-"traffic zone"-exposure. Primarily, the MAQS-platform will focus on particulate matter. With the establishment of advanced mobile analysis tools, it is planed to extend the analysis to other pollutants including including NO2, SO2, nanoparticles, and ozone

Enhanced Growth and Osteogenic Differentiation of Human Osteoblast-Like Cells on Boron-Doped Nanocrystalline Diamond Thin Films

Intrinsic nanocrystalline diamond (NCD) films have been proven to be promising substrates for the adhesion, growth and osteogenic differentiation of bone-derived cells. To understand the role of various degrees of doping (semiconducting to metallic-like), the NCD films were deposited on silicon substrates by a microwave plasma-enhanced CVD process and their boron doping was achieved by adding trimethylboron to the CH4:H2 gas mixture, the B∶C ratio was 133, 1000 and 6700 ppm. The room temperature electrical resistivity of the films decreased from >10 MΩ (undoped films) to 55 kΩ, 0.6 kΩ, and 0.3 kΩ (doped films with 133, 1000 and 6700 ppm of B, respectively). The increase in the number of human osteoblast-like MG 63 cells in 7-day-old cultures on NCD films was most apparent on the NCD films doped with 133 and 1000 ppm of B (153,000±14,000 and 152,000±10,000 cells/cm2, respectively, compared to 113,000±10,000 cells/cm2 on undoped NCD films). As measured by ELISA per mg of total protein, the cells on NCD with 133 and 1000 ppm of B also contained the highest concentrations of collagen I and alkaline phosphatase, respectively. On the NCD films with 6700 ppm of B, the cells contained the highest concentration of focal adhesion protein vinculin, and the highest amount of collagen I was adsorbed. The concentration of osteocalcin also increased with increasing level of B doping. The cell viability on all tested NCD films was almost 100%. Measurements of the concentration of ICAM-1, i.e. an immunoglobuline adhesion molecule binding inflammatory cells, suggested that the cells on the NCD films did not undergo significant immune activation. Thus, the potential of NCD films for bone tissue regeneration can be further enhanced and tailored by B doping and that B doping up to metallic-like levels is not detrimental for cells

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Stentless vs. stented bioprosthesis for aortic valve replacement: A case matched comparison of long-term follow-up and subgroup analysis of patients with native valve endocarditis.

Current retrospective evidence suggests similar clinical and superior hemodynamic outcomes of the Sorin Freedom Solo stentless aortic valve (SFS) (LivaNova PLC, London, UK) compared to the Carpentier Edwards Perimount stented aortic valve (CEP) (Edwards Lifesciences Inc., Irvine, California, USA). To date, no reports exist describing case-matched long-term outcomes and analysis for treatment of native valve endocarditis (NVE).From 2004 through 2014, 77 consecutive patients (study group, 59.7% male, 68.9 ± 12.5 years, logEuroSCORE II 7.6 ± 12.3%) received surgical aortic valve replacement (SAVR) with the SFS. A control group of patients after SAVR with the CEP was retrieved from our database and matched to the study group regarding 15 parameters including preoperative endocarditis. Acute perioperative outcomes and follow-up data (mean follow-up time 48.7±29.8 months, 95% complete) were retrospectively analyzed.No differences in early mortality occurred during 30-day follow up (3/77; 3.9% vs. 4/77; 5.2%; p = 0.699). Echocardiographic findings revealed lower postprocedural transvalvular pressure gradients (max. 17.0 ± 8.2 vs. 24.5 ± 9.2 mmHg, p< 0.001/ mean pressure of 8.4 ± 4.1 vs. 13.1 ± 5.9 mmHg, p< 0.001) in the SFS group. Structural valve degeneration (SVD) (5.2% vs. 0%; p = 0.04) and valve explantation due to SVD or prosthetic valve endocarditis (PVE) (9.1% vs. 1.3%; p = 0.04) was more frequent in the SFS group. All-cause mortality during follow-up was 20.8% vs. 14.3% (p = 0.397). When patients were divided into subgroups of NVE and respective utilized bioprosthesis, the SFS presented impaired outcomes regarding mortality in NVE cases (p = 0.031).The hemodynamic superiority of the SFS was confirmed in this comparison. However, clinical outcomes in terms of SVD and PVE rates, as well as survival after NVE, were inferior in this study. Therefore, we are reluctant to recommend utilization of the SFS for treatment of NVE

Stentless vs. stented bioprosthesis for aortic valve replacement: A case matched comparison of long-term follow-up and subgroup analysis of patients with native valve endocarditis - Fig 1

<p><b>Kaplan-Meier survival curve for survival comparison of Sorin Freedom Solo and Carpentier Edwards Perimount bioprosthetic heart valves (A) and survival probability for patients with or without re-do surgery after index procedure [no = without re-do surgery; yes = with re-do surgery] (B)</b>.</p

Baseline demographics and matching results.

<p>Baseline demographics and matching results.</p

Clinical 30-day outcome and echocardiographic results at discharge.

<p>Clinical 30-day outcome and echocardiographic results at discharge.</p

Forest-plot of multivariate COX-analysis with inclusion of four parameters; NVE native valve endocarditis.

<p>Forest-plot of multivariate COX-analysis with inclusion of four parameters; NVE native valve endocarditis.</p