Stressed and overworked? A cross-sectional study of the working situation of urban and rural general practitioners in Austria in the framework of the QUALICOPC project

Aim To assess the workload of general practitioners (GPs) in Austria, with a focus on identifying the differences between GPs working in urban and rural areas. Methods Within the framework of the Quality and Costs of Primary Care in Europe (QUALICOPC) study, data were collected from a stratified sample of GPs using a standardized questionnaire between November 2011 and May 2012. Data analysis included descriptive statistics and regression analysis. Results The analysis included data from 173 GPs. GPs in rural areas reported an average of 49.3 working hours per week, plus 23.7 on-call duties per 3 months and 26.2 outof- office care services per week. Compared to GPs working in urban areas, even in the fully adjusted regression model, rural GPs had significantly more working hours (B 7.00; P = 0.002) and on-call duties (B 18.91; P < 0.001). 65.8% of all GPs perceived their level of stress as high and 84.6% felt they were required to do unnecessary administrative work. Conclusion Our findings show a high workload among Austrian GPs, particularly those working in rural areas. Since physicians show a diminishing interest to work as GPs, there is an imperative to improve this situation

Electron Standing Wave Formation in Atomic Wires

Using the Landauer formulation of transport theory and tight binding models of the electronic structure, we study electron transport through atomic wires that form 1D constrictions between pairs of metallic nano-contacts. Our results are interpreted in terms of electron standing waves formed in the atomic wires due to interference of electron waves reflected at the ends of the atomic constrictions. We explore the influence of the chemistry of the atomic wire-metal contact interfaces on these standing waves and the associated transport resonances by considering two types of atomic wires: gold wires attached to gold contacts and carbon wires attached to gold contacts. We find that the conductance of the gold wires is roughly $1 G_0 = 2 e^2/h$ for the wire lengths studied, in agreement with experiments. By contrast, for the carbon wires the conductance is found to oscillate strongly as the number of atoms in the wire varies, the odd numbered chains being more conductive than the even numbered ones, in agreement with previous theoretical work that was based on a different model of the carbon wire and metal contacts.Comment: 14 pages, includes 6 figure

Amantadine variant - aryl conjugates that inhibit multiple M2 mutant - amantadine resistant influenza a viruses

Influenza A viruses can cause a serious future threat due to frequent mutations. Amantadine and rimantadine inhibit influenza A M2 wild-type (WT) viruses by binding and blocking M2 WT channel-mediated proton current. The resistant to the drugs amantadine and rimantadine influenza A viruses bearing the S31 N mutant in the M2 proton channel can be inhibited by amantadine - aryl conjugates, in which amantadine and an aryl group are linked through a methylene, which block M2 S31 N channel-mediated proton current. However, the M2 amantadine/rimantadine resistant viruses bearing one of the four mutations L26F, V27A, A30T, G34E in residues that line the M2 protein pore pose an additional concern for public health. Here, we designed 33 compounds based on the structure of three previously published and potent amantadine-aryl conjugates against M2 S31 N virus, by replacing amantadine with 16 amantadine variants. The compounds were tested against M2 WT and the five M2 amantadine-resistant viruses aiming at identifying inhibitors against multiple M2 mutant - amantadine resistant viruses. We identified 16 compounds that inhibited in vitro two influenza A viruses with M2 WT or L26F channels. Additionally, compounds 21 or 32 or 33, which are conjugates of the rimantadine variant with CMe2 (instead of CHMe in rimantadine) or the diamantylamine or the 4-(1-adamantyl)benzenamine with the 2-hydroxy-4-methoxyphenyl aryl group, were in vitro inhibitors against three influenza A viruses with M2 WT or L26F or S31 N, while compound 21 inhibited also in vitro the M2 G34E virus and 32 inhibited also in vitro the M2 A30T virus. For these compounds we performed a preliminary drug metabolism and pharmacokinetics study. Also, using electrophysiology, we showed that compound 21 was an efficient blocker of the M2 WT and M2 L26F channels, compound 32 blocked efficiently the M2 WT channel and compound 33 blocked the M2 WT, L26F and V27A channels. The drug metabolism and pharmacokinetics studies showed these compounds need further optimization

The formation, properties and impact of secondary organic aerosol: current and emerging issues

Secondary organic aerosol (SOA) accounts for a significant fraction of ambient tropospheric aerosol and a detailed knowledge of the formation, properties and transformation of SOA is therefore required to evaluate its impact on atmospheric processes, climate and human health. The chemical and physical processes associated with SOA formation are complex and varied, and, despite considerable progress in recent years, a quantitative and predictive understanding of SOA formation does not exist and therefore represents a major research challenge in atmospheric science. This review begins with an update on the current state of knowledge on the global SOA budget and is followed by an overview of the atmospheric degradation mechanisms for SOA precursors, gas-particle partitioning theory and the analytical techniques used to determine the chemical composition of SOA. A survey of recent laboratory, field and modeling studies is also presented. The following topical and emerging issues are highlighted and discussed in detail: molecular characterization of biogenic SOA constituents, condensed phase reactions and oligomerization, the interaction of atmospheric organic components with sulfuric acid, the chemical and photochemical processing of organics in the atmospheric aqueous phase, aerosol formation from real plant emissions, interaction of atmospheric organic components with water, thermodynamics and mixtures in atmospheric models. Finally, the major challenges ahead in laboratory, field and modeling studies of SOA are discussed and recommendations for future research directions are proposed

230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Costa, K. M., Hayes, C. T., Anderson, R. F., Pavia, F. J., Bausch, A., Deng, F., Dutay, J., Geibert, W., Heinze, C., Henderson, G., Hillaire-Marcel, C., Hoffmann, S., Jaccard, S. L., Jacobel, A. W., Kienast, S. S., Kipp, L., Lerner, P., Lippold, J., Lund, D., Marcantonio, F., McGee, D., McManus, J. F., Mekik, F., Middleton, J. L., Missiaen, L., Not, C., Pichat, S., Robinson, L. F., Rowland, G. H., Roy-Barman, M., Alessandro, Torfstein, A., Winckler, G., & Zhou, Y. 230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean. Paleoceanography and Paleoclimatology, 35(2), (2020): e2019PA003820, doi:10.1029/2019PA003820.230Th normalization is a valuable paleoceanographic tool for reconstructing high‐resolution sediment fluxes during the late Pleistocene (last ~500,000 years). As its application has expanded to ever more diverse marine environments, the nuances of 230Th systematics, with regard to particle type, particle size, lateral advective/diffusive redistribution, and other processes, have emerged. We synthesized over 1000 sedimentary records of 230Th from across the global ocean at two time slices, the late Holocene (0–5,000 years ago, or 0–5 ka) and the Last Glacial Maximum (18.5–23.5 ka), and investigated the spatial structure of 230Th‐normalized mass fluxes. On a global scale, sedimentary mass fluxes were significantly higher during the Last Glacial Maximum (1.79–2.17 g/cm2kyr, 95% confidence) relative to the Holocene (1.48–1.68 g/cm2kyr, 95% confidence). We then examined the potential confounding influences of boundary scavenging, nepheloid layers, hydrothermal scavenging, size‐dependent sediment fractionation, and carbonate dissolution on the efficacy of 230Th as a constant flux proxy. Anomalous 230Th behavior is sometimes observed proximal to hydrothermal ridges and in continental margins where high particle fluxes and steep continental slopes can lead to the combined effects of boundary scavenging and nepheloid interference. Notwithstanding these limitations, we found that 230Th normalization is a robust tool for determining sediment mass accumulation rates in the majority of pelagic marine settings (>1,000 m water depth).We thank Zanna Chase and one anonymous reviewer for valuable feedback. K. M. C. was supported by a Postdoctoral Scholarship at WHOI. L. M. acknowledges funding from the Australian Research Council grant DP180100048. The contribution of C. T. H., J. F. M., and R. F. A. were supported in part by the U.S. National Science Foundation (US‐NSF). G. H. R. was supported by the Natural Environment Research Council (grant NE/L002434/1). S. L. J. acknowledges support from the Swiss National Science Foundation (grants PP002P2_144811 and PP00P2_172915). This study was supported by the Past Global Changes (PAGES) project, which in turn received support from the Swiss Academy of Sciences and the US‐NSF. This work grew out of a 2018 workshop in Aix‐Marseille, France, funded by PAGES, GEOTRACES, SCOR, US‐NSF, Aix‐Marseille Université, and John Cantle Scientific. All data are publicly available as supporting information to this document and on the National Center for Environmental Information (NCEI) at https://www.ncdc.noaa.gov/paleo/study/28791

State Orthogonalization by Building a Hilbert Space: A New Approach to Electronic Quantum Transport in Molecular Wires

Quantum descriptions of many complex systems are formulated most naturally in bases of states that are not mutually orthogonal. We introduce a general and powerful yet simple approach that facilitates solving such models exactly by embedding the non-orthogonal states in a new Hilbert space in which they are by definition mutually orthogonal. This novel approach is applied to electronic transport in molecular quantum wires and is used to predict conductance antiresonances of a new type that arise solely out of the non-orthogonality of the local orbitals on different sites of the wire.Comment: 4 pages 1 figur

Negative Effect of Smoking on the Performance of the QuantiFERON TB Gold in Tube Test.

False negative and indeterminate Interferon Gamma Release Assay (IGRA) results are a well documented problem. Cigarette smoking is known to increase the risk of tuberculosis (TB) and to impair Interferon-gamma (IFN-γ) responses to antigenic challenge, but the impact of smoking on IGRA performance is not known. The aim of this study was to evaluate the effect of smoking on IGRA performance in TB patients in a low and high TB prevalence setting respectively. Patients with confirmed TB from Denmark (DK, n = 34; 20 smokers) and Tanzania (TZ, n = 172; 23 smokers) were tested with the QuantiFERON-TB Gold In tube (QFT). Median IFN-γ level in smokers and non smokers were compared and smoking was analysed as a risk factor for false negative and indeterminate QFT results. Smokers from both DK and TZ had lower IFN-γ antigen responses (median 0.9 vs. 4.2 IU/ml, p = 0.04 and 0.4 vs. 1.6, p < 0.01), less positive (50 vs. 86%, p = 0.03 and 48 vs. 75%, p < 0.01) and more false negative (45 vs. 0%, p < 0.01 and 26 vs. 11%, p = 0.04) QFT results. In Tanzanian patients, logistic regression analysis adjusted for sex, age, HIV and alcohol consumption showed an association of smoking with false negative (OR 17.1, CI: 3.0-99.1, p < 0.01) and indeterminate QFT results (OR 5.1, CI: 1.2-21.3, p = 0.02). Cigarette smoking was associated with false negative and indeterminate IGRA results in both a high and a low TB endemic setting independent of HIV status

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P &lt; 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification