285 research outputs found

    Flavor Changing Neutral Current Effects and CP Violation in the Minimal 3-3-1 Model

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    We investigate in detail the flavor structure of the minimal 331 model and its implications for several flavor changing neutral current (FCNC) processes. In this model, where the weak SU(2)_L gauge group of the Standard Model is extended to a SU(3)_L, the by far dominant new contributions come from an additional neutral Z' gauge boson, that can transmit FCNCs at tree-level. At the same time, electroweak precision observables receive new contributions only at the loop level and do not constrain the model very strongly. In our analysis, we take into account new CP violating effects that have been neglected in earlier analyses, and account for a general flavor structure without reference to a certain parameterization of the new mixing matrix. We begin by studying the bounds obtained from quantities such as Delta M_K, epsilon_K, Delta M_{d/s} as well as sin 2 beta|_{J/psi K_S}, and go on to explore the implications for several clean rare decay channels, namely the decays K+->pi+ nu nu, K_L -> pi0 nu nu, B_{d/s} -> mu+ mu- and K_L -> pi0 l+l-. We find sizeable effects in all these decays, but the most interesting quantity turns out to be the B_s - bar B_s mixing phase beta_s, as measured in the mixing induced CP asymmetry of B_s -> J/psi phi, which can be large. In general, we find effects in purely hadronic channels to be larger than in (semi-)leptonic ones, due to a suppression of the Z'-lepton couplings.Comment: 29 pages, 11 figures, Some Comments and References added, version to appear in Phys Rev

    2-Undecanone : a new attractant for anthropophilic mosquitoes

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    Stechmücken der Art Stegomyia aegypti (ehemals Aedes aegypti, REINERT et al. 2004) sind die wichtigsten Überträger von Gelbfieber- und Dengueviren. Diverse Arten der Gattung Anopheles verbreiten die Erreger der Malaria. Bei Versuchen, Malaria, Gelbfieber und Dengue einzudämmen, wurden in den letzten Jahrzehnten wiederholt Kampagnen gegen Stechmücken geführt. Dabei wurden Insektizide vielfach flächendeckend ausgebracht. Dies führte kurzfristig zu geringeren Mückendichten, allerdings entwickelten sich auch vielerorts gegen diese Gifte resistente Mückenpopulationen. Anstelle des flächendeckenden Gifteinsatzes wird heute versucht, die Insektizide örtlich und zeitlich effektiv einzusetzen, um so die Gefahr weiterer Resistenzbildung zu minimieren und sowohl die Kosten als auch die Belastung für Umwelt und Bevölkerung möglichst gering zu halten. Um Insektizide zur richtigen Zeit gezielt ausbringen zu können, ist ein Monitoring der Mücken erforderlich. Mückenfallen, die durch optische Effekte und Duftstoffe gezielt anthropophile Stechmückenarten anlocken, sind für ein derartiges Bestandsmonitoring besonders geeignet. Auf der Suche nach attraktiven Duftstoffen, welche die Effektivität solcher Fallen erhöhen, wurde unter anderem auch 2-Undecanon getestet. In Verhaltensversuchen mit den anthropophilen Mückenarten Stegomyia aegypti und Anopheles stephensi konnte die Attraktivität dieser Substanz sowohl als Einzelreiz als auch in Kombination mit anderen Attraktanzien gezeigt und quantifiziert werden.The attractiveness of 2-undecanone to host-seeking female Stegomyia aegpyti (former Aedes aegypti) and female Anopheles stephensi (Diptera: Culicidae) mosquitoes was tested in a Y-tube bioassay under laboratory conditions. -Undecanone alone in a concentration of 40 ppm was significantly more attractive to S. aegypti mosquitoes than pure air. In combination with other kairomones such as caproic acid, lactic acid and ammonia doses of 2-undecanone from 4 ppm up to 130 ppm augmented significantly the attractiveness of these kairomones. The synergism of 2-undecanone with other attractants is comparable to that one described for lactic acid. The combination of 2-undecanone with lactic acid, however, was more attractive than the two compounds as single stimuli. Interestingly 2-undecanone is neither known as an human skin compound nor as a volatile in human breath. First field experiments near Regensburg in Germany with BG-Sentinel® mosquito traps could not confirm the attractive effect of 2-undecanone (ROSE et al. 2006) for Culex species. A possible explanation could be that the tested dose of 2-undecanone was not in the optimum range or that the studied species do not respond to this compound

    Polizisten haben kein Recht: Ein dogmatischer Zwischenruf

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    Rescuers at Risk: Posttraumatic Stress Symptoms Among Police Officers, Fire Fighters, Ambulance Personnel, and Emergency and Psychiatric Nurses.

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    Emergency personnel and rescue workers may be at a risk of posttraumatic stress symptoms (PTSS) due to exposure to trauma and work-related stressors. Though rescuers of different professions are often engaged in the same type of emergency, they have different tasks and responsibilities and receive different training in coping with traumatic events and stress; hence, we speculated that the salience of identified risk factors for PTSS vary across their respective professions. The present cross-sectional survey aimed to identify influencing variables on PTSS, well-being, and suicidal ideation that can act differently across professions of rescue workers and emergency personnel. In this anonymous online study, data from 1,002 rescue workers and emergency personnel in Switzerland, were collected: 499 police officers, 239 firefighters, 97 ambulance personnel, and 85 emergency and 82 psychiatric nurses. PTSS, coping strategies, well-being, suicidal ideation, previously experienced and work-related trauma, and self-efficacy were measured and analyzed using multiple regression and structural equation modeling (SEM). The prevalence of suspected posttraumatic stress disorder varied across the professions, ranged from 8% (firefighters) to 22% (psychiatric nurses), and was associated with psychological strain and suicidal ideation. The SEM showed that dysfunctional coping strategies, self-efficacy, previously experienced and work-related trauma, years on job, and female sex explained up to 78% of PTSS and that PTSS itself explained up to 68% of the psychological strain experienced in the different professions. Independent of the profession, dysfunctional coping such as alcohol use, avoidance, and distraction, as well as work-related trauma were the most robust predictors of PTSS. However, while self-efficacy was a risk factor for police officers, firefighters and ambulance personnel, it was a protective factor for emergency and psychiatric nurses. Furthermore, female sex was only a risk factor for ambulance personnel and emergency nurses. In agreement with prior research, emergency personnel and rescuers exhibited enhanced prevalence of PTSS and suspected PTSD, leading to significant psychological strain and suicidal ideation. However, risk factors varied across the professions. Thus, the development of profession-specific trainings to improve self-efficacy and coping with work-related stressors to reduce PTSS, and enhance quality of life, is needed for individuals in such high-risk professions. Clinical Trial Registration: ClinicalTrials.gov Nr. NCT03842553

    Physiologically Based Pharmacokinetic Models for Prediction of Complex CYP2C8 and OATP1B1 (SLCO1B1) Drug-Drug-Gene Interactions : A Modeling Network of Gemfibrozil, Repaglinide, Pioglitazone, Rifampicin, Clarithromycin and Itraconazole

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    Background Drug–drug interactions (DDIs) and drug–gene interactions (DGIs) pose a serious health risk that can be avoided by dose adaptation. These interactions are investigated in strictly controlled setups, quantifying the efect of one perpetrator drug or polymorphism at a time, but in real life patients frequently take more than two medications and are very heterogenous regarding their genetic background. Objectives The frst objective of this study was to provide whole-body physiologically based pharmacokinetic (PBPK) models of important cytochrome P450 (CYP) 2C8 perpetrator and victim drugs, built and evaluated for DDI and DGI studies. The second objective was to apply these models to describe complex interactions with more than two interacting partners. Methods PBPK models of the CYP2C8 and organic-anion-transporting polypeptide (OATP) 1B1 perpetrator drug gemfbrozil (parent–metabolite model) and the CYP2C8 victim drugs repaglinide (also an OATP1B1 substrate) and pioglitazone were developed using a total of 103 clinical studies. For evaluation, these models were applied to predict 34 diferent DDI studies, establishing a CYP2C8 and OATP1B1 PBPK DDI modeling network. Results The newly developed models show a good performance, accurately describing plasma concentration–time profles, area under the plasma concentration–time curve (AUC) and maximum plasma concentration (Cmax) values, DDI studies as well as DGI studies. All 34 of the modeled DDI AUC ratios (AUC during DDI/AUC control) and DDI Cmax ratios (Cmax during DDI/Cmax control) are within twofold of the observed values. Conclusions Whole-body PBPK models of gemfbrozil, repaglinide, and pioglitazone have been built and qualifed for DDI and DGI prediction. PBPK modeling is applicable to investigate complex interactions between multiple drugs and genetic polymorphisms

    Soil Contamination with Trace Metals: Quantification, Speciation, and Source Identification

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    Developing new analytical techniques to measure heavy stable isotope ratios or to quantify the different species of trace metals present in the environment is essential to understand, ultimately prevent, and limit trace metal pollution in the environment

    Submarine mass wasting and associated tsunami risk offshore western Thailand, Andaman Sea, Indian Ocean

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    2-D seismic data from the top and the western slope of Mergui Ridge in water depths between 300 and 2200 m off the Thai west coast have been investigated in order to identify mass transport deposits (MTDs) and evaluate the tsunamigenic potential of submarine landslides in this outer shelf area. Based on our newly collected data, 17 mass transport deposits have been identified. Minimum volumes of individual MTDs range between 0.3 km3 and 14 km3. Landslide deposits have been identified in three different settings: (i) stacked MTDs within disturbed and faulted basin sediments at the transition of the East Andaman Basin to the Mergui Ridge; (ii) MTDs within a pile of drift sediments at the basin-ridge transition; and (iii) MTDs near the edge of/on top of Mergui Ridge in relatively shallow water depths ( 1000 m) and/or comprise small volumes suggesting a small tsunami potential. Moreover, the recurrence rates of failure events seem to be low. Some MTDs with tsunami potential, however, have been identified on top of Mergui Ridge. Mass-wasting events that may occur in the future at similar locations may trigger tsunamis if they comprise sufficient volumes. Landslide tsunamis, emerging from slope failures in the working area and affecting western Thailand coastal areas therefore cannot be excluded, though the probability is very small compared to the probability of earthquake-triggered tsunamis, arising from the Sunda Trench

    Physiologically-Based Pharmacokinetic Models for CYP1A2 Drug-Drug Interaction Prediction: A Modeling Network of Fluvoxamine, Theophylline, Caffeine, Rifampicin, and Midazolam

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    This study provides whole-body physiologically-based pharmacokinetic models of the strong index cytochrome P450 (CYP)1A2 inhibitor and moderate CYP3A4 inhibitor fluvoxamine and of the sensitive CYP1A2 substrate theophylline. Both models were built and thoroughly evaluated for their application in drug-drug interaction (DDI) prediction in a network of perpetrator and victim drugs, combining them with previously developed models of caffeine (sensitive index CYP1A2 substrate), rifampicin (moderate CYP1A2 inducer), and midazolam (sensitive index CYP3A4 substrate). Simulation of all reported clinical DDI studies for combinations of these five drugs shows that the presented models reliably predict the observed drug concentrations, resulting in seven of eight of the predicted DDI area under the plasma curve (AUC) ratios (AUC during DDI/AUC control) and seven of seven of the predicted DDI peak plasma concentration (Cmax ) ratios (Cmax during DDI/Cmax control) within twofold of the observed values. Therefore, the models are considered qualified for DDI prediction. All models are comprehensively documented and publicly available, as tools to support the drug development and clinical research community
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