Ab initio simulations of liquid NaSn alloys: Zintl anions and network formation

Using the Car-Parrinello technique, ab initio molecular dynamics simulations are performed for liquid NaSn alloys in five different compositions (20, 40, 50, 57 and 80 % sodium). The obtained structure factors agree well with the data from neutron scattering experiments. The measured prepeak in the structure factor is reproduced qualitatively for most compositions. The calculated and measured positions of all peaks show the same trend as function of the composition.\\ The dynamic simulations also yield information about the formation and stability of Sn$_4$ clusters (Zintl anions) in the liquid. In our simulations of compositions with 50 and 57 % sodium we observe the formation of networks of tin atoms. Thus, isolated tin clusters are not stable in such liquids. For the composition with 20 % tin only isolated atoms or dimers of tin appear, ``octet compounds'' of one Sn atom surrounded by 4 Na atoms are not observed.Comment: 12 pages, Latex, 3 Figures on reques

The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model

To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women, enrolled in EORTC trials 10801, 10854, or 10902 treated for early-stage breast cancer. Data were analysed in a multivariate, multistate model by using multivariate Cox regression models, including a state-dependent covariate. The presence of a LRR in itself is a significant prognostic risk factor (HR: 3.64; 95%-CI: 2.02-6.5) for the occurrence of DM. Main prognostic risk factors for a DM are young age at diagnosis (</=40: HR: 1.79; 95%-CI: 1.28-2.51), larger tumour size (HR: 1.58; 95%-CI: 1.35-1.84) and node positivity (HR: 2.00; 95%-CI: 1.74-2.30). Adjuvant chemotherapy is protective for a DM (HR: 0.66; 95%-CI: 0.55-0.80). After the occurrence of a LRR the latter protective effect has disappeared (P = 0.009). The presence of LRR in itself is a significant risk factor for DM. For patients who are at risk of developing LRR, effective local control should be the main target of therapy

The feasibility of an allergy management support system (AMSS) for IgE-mediated allergy in primary care

Background: The allergy management support system (AMSS) was developed to assist general practitioners (GPs) to handle the increasing burden of allergic diseases and facilitates the diagnosis and management of allergy. The aim of this cluster-randomized controlled pilot study was to test the feasibility of this AMSS for primary care. Methods: GPs received diagnostic and management recommendations generated by the AMSS in addition to sIgE-test results (intervention) or GPs received sIgE-test results only (control). The AMSS recommendations are based on the previously developed patient-completed AMSS questionnaire and sIgE-test results. The AMSS was considered feasible when > 70% of the AMSS recommendations were sent to the GP within ten working days of sIgE-testing. GPs completed a questionnaire on their diagnosis and management before (T1) and after (T2) receiving sIgE test results. Agreement and disagreement concerning diagnosis, medication and referrals between GPs and AMSS was investigated at T1 and T2. A total agreement score between GPs and AMSS was calculated. GPs in the intervention group completed a questionnaire to evaluate the utility of the AMSS. Semi-structured interviews were used to explore the motivation of GPs who did not include patients in this pilot study. Results: Twenty-seven GPs included 101 patients. Forty-two patients (72%) completed the AMSS questionnaire in the intervention group. The majority of the AMSS recommendations (93%) were returned to the GP within 10 working days after sIgE-test results were known [mean (SD) 4.7 (4.0) working days]. GPs in the intervention group reported largely following the AMSS recommendations in 71% of cases. The total agreement scores concerning diagnosis were significantly higher (p < 0.001) in the intervention group than the control group [mean (SD); 0.9 (1.8) vs - 0.8 (1.0)]. The agreement concerning medication or referral between GPs and AMSS did not differ between the intervention and the control group. GPs in the intervention group were reasonably positive about the AMSS. Not enrolling patients was not caused by anticipated ineffectiveness of the AMSS. Conclusion: The AMSS can be considered to be feasible for primary care. GPs tend to follow the AMSS recommendations. The AMSS may contribute to the empowerment of GPs to better manage allergy patients in primary care.Trial registration ISRCTN ISRCTN36780877. Registered 23 November 2017 (retrospectively registered)

Improved ventricular function during inhalation of PGI(2) aerosol partly relies on enhanced myocardial contractility

Inhaled prostacyclin (PGI(2)) aerosol induces selective pulmonary vasodilation. Further, it improves right ventricular ( RV) function, which may largely rely on pulmonary vasodilation, but also on enhanced myocardial contractility. We investigated the effects of the inhaled PGI(2) analogs epoprostenol (EPO) and iloprost (ILO) on RV function and myocardial contractility in 9 anesthetized pigs receiving aerosolized EPO (25 and 50 ng center dot kg(-1) center dot min(-1)) and, consecutively, ILO (60 ng center dot kg(-1) center dot min(-1)) for 20 min each. We measured pulmonary artery pressure ( PAP), RV ejection fraction (RVEF) and RV end-diastolic-volume (RV-EDV), and left ventricular end-systolic pressure-volume-relation (end-systolic elastance, E-es). EPO and ILO reduced PAP, increased RVEF and reduced RVEDV. E-es was enhanced during all doses tested, which reached statistical significance during EPO25ng and ILO, but not during EPO50ng. PGI(2) aerosol enhances myocardial contractility in healthy pigs, contributing to improve RV function. Copyright (C) 2005 S. Karger AG, Basel

The role of plasma concentrations and drug characteristics of beta-blockers in fall risk of older persons

Beta-blocker usage is inconsistently associated with increased fall risk in the literature. However, due to age-related changes and interindividual heterogeneity in pharmacokinetics and dynamics, it is difficult to predict which older adults are more at risk for falls. Therefore, we wanted to explore whether elevated plasma concentrations of selective and nonselective beta-blockers are associated with an increased risk of falls in older beta-blocker users. To answer our research question, we analyzed samples of selective (metoprolol, n = 316) and nonselective beta-blockers (sotalol, timolol, propranolol, and carvedilol, n = 179) users from the B-PROOF cohort. The associations between the beta-blocker concentration and time to first fall were assessed using Cox proportional hazard models. Change of concentration over time in relation to fall risk was assessed with logistic regression models. Models were adjusted for potential confounders. Our results showed that above the median concentration of metoprolol was associated with an increased fall risk (HR 1.55 [1.11–2.16], p =.01). No association was found for nonselective beta-blocker concentrations. Also, changes in concentration over time were not associated with increased fall risk. To conclude, metoprolol plasma concentrations were associated with an increased risk of falls in metoprolol users while no associations were found for nonselective beta-blockers users. This might be caused by a decreased β1-selectivity in high plasma concentrations. In the future, beta-blocker concentrations could potentially help clinicians estimate fall risk in older beta-blockers users and personalize treatment.</p

Constraints on Gamma-ray Emission from the Galactic Plane at 300 TeV

We describe a new search for diffuse ultrahigh energy gamma-ray emission associated with molecular clouds in the galactic disk. The Chicago Air Shower Array (CASA), operating in coincidence with the Michigan muon array (MIA), has recorded over 2.2 x 10^{9} air showers from April 4, 1990 to October 7, 1995. We search for gamma rays based upon the muon content of air showers arriving from the direction of the galactic plane. We find no significant evidence for diffuse gamma-ray emission, and we set an upper limit on the ratio of gamma rays to normal hadronic cosmic rays at less than 2.4 x 10^{-5} at 310 TeV (90% confidence limit) from the galactic plane region: (50 degrees < l < 200 degrees); -5 degrees < b < 5 degrees). This limit places a strong constraint on models for emission from molecular clouds in the galaxy. We rule out significant spectral hardening in the outer galaxy, and conclude that emission from the plane at these energies is likely to be dominated by the decay of neutral pions resulting from cosmic rays interactions with passive target gas molecules.Comment: Astrophysical Journal, submitted, 11 pages, AASTeX Latex, 3 Postscript figure

Vibrational Excitations in Weakly Coupled Single-Molecule Junctions: A Computational Analysis

In bulk systems, molecules are routinely identified by their vibrational spectrum using Raman or infrared spectroscopy. In recent years, vibrational excitation lines have been observed in low-temperature conductance measurements on single molecule junctions and they can provide a similar means of identification. We present a method to efficiently calculate these excitation lines in weakly coupled, gateable single-molecule junctions, using a combination of ab initio density functional theory and rate equations. Our method takes transitions from excited to excited vibrational state into account by evaluating the Franck-Condon factors for an arbitrary number of vibrational quanta, and is therefore able to predict qualitatively different behaviour from calculations limited to transitions from ground state to excited vibrational state. We find that the vibrational spectrum is sensitive to the molecular contact geometry and the charge state, and that it is generally necessary to take more than one vibrational quantum into account. Quantitative comparison to previously reported measurements on pi-conjugated molecules reveals that our method is able to characterize the vibrational excitations and can be used to identify single molecules in a junction. The method is computationally feasible on commodity hardware.Comment: 9 pages, 7 figure

Synchronisation of egg hatching of brown hairstreak (Thecla betulae) and budburst of blackthorn (Prunus spinosa) in a warmer future

Synchronisation of the phenology of insect herbivores and their larval food plant is essential for the herbivores’ fitness. The monophagous brown hairstreak (Thecla betulae) lays its eggs during summer, hibernates as an egg, and hatches in April or May in the Netherlands. Its main larval food plant blackthorn (Prunus spinosa) flowers in early spring, just before the leaves appear. As soon as the Blackthorn opens its buds, and this varies with spring temperatures, food becomes available for the brown hairstreak. However, the suitability of the leaves as food for the young caterpillars is expected to decrease rapidly. Therefore, the timing of egg hatch is an important factor for larval growth. This study evaluates food availability for brown hairstreak at different temperatures. Egg hatch and budburst were monitored from 2004 to 2008 at different sites in the Netherlands. Results showed ample food availability at all monitored temperatures and sites but the degree of synchrony varied strongly with spring temperatures. To further study the effect of temperature on synchronisation, an experiment using normal temperatures of a reference year (T) and temperatures of T + 5°C was carried out in climate chambers. At T + 5°C, both budburst and egg hatch took place about 20 days earlier and thus, on average, elevated temperature did not affect synchrony. However, the total period of budburst was 11 days longer, whereas the period of egg hatching was 3 days shorter. The implications for larval growth by the brown hairstreak under a warmer climate are considered.