300 research outputs found

    Comparison of quantum mechanical and classical trajectory calculations of cross sections for ion-atom impact ionization of negative - and positive -ions for heavy ion fusion applications

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    Stripping cross sections in nitrogen have been calculated using the classical trajectory approximation and the Born approximation of quantum mechanics for the outer shell electrons of 3.2GeV I^{-} and Cs+^{+} ions. A large difference in cross section, up to a factor of six, calculated in quantum mechanics and classical mechanics, has been obtained. Because at such high velocities the Born approximation is well validated, the classical trajectory approach fails to correctly predict the stripping cross sections at high energies for electron orbitals with low ionization potential.Comment: submitted to Phys. Rev.

    Comportamento inicial de progênies de cafeeiros com resistência à ferrugem selecionadas de ensaios em vários campos experimentais do Procafé.

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    O programa de melhoramento genético de cafeeiros, a cargo do Mapa-Fundação Procafé, vem sendo executado em campos experimentais de diferentes regiões cafeeiras, visando associar resistência à ferrugem e boa produtividade das plantas. Nos ensaios, após 3-4 safras, são selecionadas as melhores plantas, para inclusão das progênies em competição conjunta. No presente trabalho foram reunidas, em ensaio em execução na FEX Varginha, 78 seleções, correspondentes a plantas selecionadas de ensaios em Mal Floriano-ES, em Coromandel-FSA, no CEPEC em Martins Soares e também em Varginha. O ensaio foi delineado em blocos ao acaso, com 2 repetições e parcelas de 8 plantas. O plantio foi realizado em janeiro de 2009 no espaçamento de 3,5 x 1 m. Os tratos culturais foram os usuais, com 2 aplicações de fungicidas triazóis mais cúpricos, para controle da ferrugem e cercosporiose, em todo o ensaio

    Paradoxical antidepressant effects of alcohol are related to acid sphingomyelinase and its control of sphingolipid homeostasis

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    Alcohol is a widely consumed drug that can lead to addiction and severe brain damage. However, alcohol is also used as self-medication for psychiatric problems, such as depression, frequently resulting in depression-alcoholism comorbidity. Here, we identify the first molecular mechanism for alcohol use with the goal to self-medicate and ameliorate the behavioral symptoms of a genetically induced innate depression. An induced over-expression of acid sphingomyelinase (ASM), as was observed in depressed patients, enhanced the consumption of alcohol in a mouse model of depression. ASM hyperactivity facilitates the establishment of the conditioned behavioral effects of alcohol, and thus drug memories. Opposite effects on drinking and alcohol reward learning were observed in animals with reduced ASM function. Importantly, free-choice alcohol drinking—but not forced alcohol exposure—reduces depression-like behavior selectively in depressed animals through the normalization of brain ASM activity. No such effects were observed in normal mice. ASM hyperactivity caused sphingolipid and subsequent monoamine transmitter hypo-activity in the brain. Free-choice alcohol drinking restores nucleus accumbens sphingolipid- and monoamine homeostasis selectively in depressed mice. A gene expression analysis suggested strong control of ASM on the expression of genes related to the regulation of pH, ion transmembrane transport, behavioral fear response, neuroprotection and neuropeptide signaling pathways. These findings suggest that the paradoxical antidepressant effects of alcohol in depressed organisms are mediated by ASM and its control of sphingolipid homeostasis. Both emerge as a new treatment target specifically for depression-induced alcoholism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-016-1658-6) contains supplementary material, which is available to authorized users

    The Wage Premium of Globalization: Evidence from European Mergers and Acquisitions

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    We provide evidence on the impact of globalization on labor market outcomes analyzing pay differences between foreign-acquired and domestically-owned firms. For this purpose, we use firm level data from 16 European countries over the time period 1999-2006. Applying propensity score matching techniques we estimate positive wage premia of cross-boarder merger and acquisitions (M&As), suggesting that foreign acquired firms exhibit higher short-run (post-acquisition) wages than their domestic counterparts. The observed wage disparities are most pronounced for low paying firms (with average wages below the median). Finally, we find systematic wage premia in Western European countries, but not so in Eastern Europe

    The Novel Immunosuppressive Protein Kinase C Inhibitor Sotrastaurin Has No Pro-Viral Effects on the Replication Cycle of Hepatitis B or C Virus

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    The pan-protein kinase C (PKC) inhibitor sotrastaurin (AEB071) is a novel immunosuppressant currently in phase II trials for immunosuppression after solid organ transplantation. Besides T-cell activation, PKC affects numerous cellular processes that are potentially important for the replication of hepatitis B virus (HBV) and hepatitis C virus (HCV), major blood-borne pathogens prevalent in solid organ transplant recipients. This study uses state of the art virological assays to assess the direct, non-immune mediated effects of sotrastaurin on HBV and HCV. Most importantly, sotrastaurin had no pro-viral effect on either HBV or HCV. In the presence of high concentrations of sotrastaurin, well above those used clinically and close to levels where cytotoxic effects become detectable, there was a reduction of HCV and HBV replication. This reduction is very likely due to cytotoxic and/or anti-proliferative effects rather than direct anti-viral activity of the drug. Replication cycle stages other than genome replication such as viral cell entry and spread of HCV infection directly between adjacent cells was clearly unaffected by sotrastaurin. These data support the evaluation of sotrastaurin in HBV and/or HCV infected transplant recipients

    Detection of a Single Identical Cytomegalovirus (CMV) Strain in Recently Seroconverted Young Women

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    Infection with multiple CMV strains is common in immunocompromised hosts, but its occurrence in normal hosts has not been well-studied.We analyzed CMV strains longitudinally in women who acquired CMV while enrolled in a CMV glycoprotein B (gB) vaccine trial. Sequencing of four variable genes was performed in samples collected from seroconversion and up to 34 months thereafter.199 cultured isolates from 53 women and 65 original fluids from a subset of 19 women were sequenced. 51 women were infected with one strain each without evidence for genetic drift; only two women shed multiple strains. Genetic variability among strains increased with the number of sequenced genetic loci. Nevertheless, 13 of 53 women proved to be infected with an identical CMV strain based on sequencing at all four variable genes. CMV vaccine did not alter the degree of genetic diversity amongst strains.Primary CMV infection in healthy women nearly always involves shedding of one strain that remains stable over time. Immunization with CMVgB-1 vaccine strain is not selective against specific strains. Although 75% of women harbored their unique strain, or a strain shared with only one other woman, 25% shared a single common strain, suggesting that this predominant strain with a particular combination of genetic loci is advantageous in this large urban area

    The cost of illness attributable to diabetic foot and cost-effectiveness of secondary prevention in Peru

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    BACKGROUND: Diabetes mellitus is a public health challenge worldwide, and roughly 25 % of patients with diabetes in developing countries will develop at least one foot ulcer during their lifetime. The gravest outcome of an ulcerated foot is amputation, leading to premature death and larger economic costs. METHODS: This study aimed to estimate the economic costs of diabetic foot in high-risk patients in Peru in 2012 and to model the cost-effectiveness of a year-long preventive strategy for foot ulceration including: sub-optimal care (baseline), standard care as recommended by the International Diabetes Federation, and standard care plus daily self-monitoring of foot temperature. A decision tree model using a population prevalence-based approach was used to calculate the costs and the incremental cost-effectiveness ratio (ICER). Outcome measures were deaths and major amputations, uncertainty was tested with a one-way sensitivity analysis. RESULTS: The direct costs for prevention and management with sub-optimal care for high-risk diabetics is around US74.5milliondollarsinasingleyear,whichdecreasestoUS74.5 million dollars in a single year, which decreases to US71.8 million for standard care and increases to US96.8millionforstandardcareplustemperaturemonitoring.Theimplementationofastandardcarestrategywouldavert791deathsandiscostsavingincomparisontosuboptimalcare.ForstandardcareplustemperaturemonitoringcomparedtosuboptimalcaretheICERrisestoUS96.8 million for standard care plus temperature monitoring. The implementation of a standard care strategy would avert 791 deaths and is cost-saving in comparison to sub-optimal care. For standard care plus temperature monitoring compared to sub-optimal care the ICER rises to US16,124 per death averted and averts 1,385 deaths. CONCLUSION: Diabetic foot complications are highly costly and largely preventable in Peru. The implementation of a standard care strategy would lead to net savings and avert deaths over a one-year period. More intensive prevention strategies such as incorporating temperature monitoring may also be cost-effective. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12913-015-1141-4) contains supplementary material, which is available to authorized users

    Treatment patterns of patients with migraine eligible for anti-CGRP pathway monoclonal antibodies

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    IntroductionMigraine is a debilitating neurological disorder, with a wide range of symptoms and disease burden, underscoring the heterogeneity of patients’ disease characteristics and treatment needs. To characterize the profile of migraine patients in the US who may be eligible for preventive treatment with an anti-CGRP pathway mAb and to better understand treatment patterns and real-world use of acute and preventive medications for migraine, we conducted a retrospective cohort study of adult patients.MethodsThese patients were identified as having migraine using diagnosis codes or migraine-specific medication use (first = index) in the IQVIA PharMetrics® Plus database. Patients were required to have ≥ 12 months of continuous enrollment in medical and pharmacy benefits prior to index (baseline) and after index (follow-up). Patients were stratified into chronic migraine (CM) and non-chronic migraine (non-CM) by diagnosis codes. Based on acute migraine-specific medication dispensing data in the follow-up period, non-CM patients were divided into 3 cohorts: highest, middle, and lowest tertile of total units of dispensed acute migraine-specific medication (gepants, ditans, ergot derivatives, and triptans). Migraine medication use was captured in the baseline and follow-up periods.ResultsA total of 22,584 CM and 216,807 non-CM patients (72,269 patients in each tertile) were identified and included in the study. Over the follow-up, CM patients had a mean of 70 units of acute migraine-specific medications dispensed, while the highest, middle, and lowest tertile of non-CM patients had a mean of 92, 29, and 10 units, respectively. Anti-calcitonin gene-related peptide pathway mAbs were dispensed for 28.9% of CM patients, and for 6.9%, 4.1%, and 2.9% of non-CM patients in the highest, middle, and lowest tertiles, respectively.ConclusionA lower proportion of non-CM patients had use of anti-calcitonin gene-related peptide pathway mAbs compared to CM patients, confirming the unmet need with appropriate preventive medication. There appears to be a persistent gap in management of patients without a diagnosis of CM who are dispensed high quantities of acute migraine-specific medications
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