347 research outputs found

    A CMOS Time to Digital Converter IC with 2 Level Analog CAM

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    A time to charge converter IC with an analog memory unit (TCCAMU) has been designed and fabricated in HP\u27s CMOS 1.2-”m n-well process. The TCCAMU is an event driven system designed for front end data acquisition in high energy physics experiments. The chip includes a time to charge converter, analog Level 1 and Level 2 associative memories for input pipelining and data filtering, and an A/D converter. The intervals measured and digitized range from 8-24 ns. Testing of the fabricated chip resulted in an LSB width of 107 ps, a typical differential nonlinearity of \u3c 35 ps, and a typical integral nonlinearity of \u3c 200 ps. The average power dissipation is 8.28 mW per channel. By counting the reference clock, a time resolution of 107 ps over ~ 1 s range could be realized

    Industrial Process Design for the Production of Aniline by Direct Amination

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    The objective is to design a plant from raw material to product for the production of aniline by direct amination of benzene. The process design is started on a conceptual level and ended on a basic engineering level as well as a techno-economical evaluation. The amination of benzene by hydroxylamine was used as basis. For the production of hydroxylamine four routes are proposed. The most promising route is the chemical reduction of nitric oxide with hydrogen. The process evaluation shows that 27 % of the atomic nitrogen is lost. The atomic carbon efficiency is close to unity. Furthermore, a significant amount of steam can be produced. From an economical perspective, there is still room for improvement because the return of investment is quite low and the payback period is quite high

    Families in comparison: An individual-level comparison of life-course and family reconstructions between population and vital event registers

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    It remains unknown how different types of sources affect the reconstruction of life courses and families in large-scale databases increasingly common in demographic research. Here, we compare family and life-course reconstructions for 495 individuals simultaneously present in two well-known Dutch data sets: LINKS, based on the Zeeland province’s full-population vital event registration data (passive registration), and the Historical Sample of the Netherlands (HSN), based on a national sample of birth certificates, with follow-up of individuals in population registers (active registration). We compare indicators of fertility, marriage, mortality, and occupational status, and conclude that reconstructions in the HSN and LINKS reflect each other well: LINKS provides more complete information on siblings and parents, whereas the HSN provides more complete life-course information. We conclude that life-course and family reconstructions based on linked passive registration of individuals constitute a reliable alternative to reconstructions based on active registration, if case selection is carefully considered

    Female Sex and IL28B, a Synergism for Spontaneous Viral Clearance in Hepatitis C Virus (HCV) Seroconverters from a Community-Based Cohort

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    BACKGROUND & AIMS: Since acute hepatitis C virus (HCV) infection is often asymptomatic, it is difficult to examine the rate and determinants of spontaneous clearance. Consequently, these studies are subject to bias, which can potentially lead to biased rates of viral clearance and risk estimates. We evaluated determinants of spontaneous HCV clearance among HCV seroconverters identified in a unique community-based cohort. METHODS: Subjects were 106 drug users with documented dates of HCV seroconversion from the Amsterdam Cohort Study. Logistic regression was used to examine sociodemographic, behavioral, clinical, viral and host determinants, measured around acute infection, of HCV clearance. RESULTS: The spontaneous viral clearance rate was 33.0% (95% confidence interval (CI) 24.2-42.8). In univariate analyses female sex and fever were significantly associated with spontaneous clearance. The favorable genotypes for rs12979860 (CC) and rs8099917 (TT) were associated with spontaneous clearance, although borderline significant. In multivariate analysis, females with the favorable genotype for rs12979860 (CC) had an increased odds to spontaneously clear HCV infection (adjusted OR 6.62, 95% 2.69-26.13), whereas females with the unfavorable genotype were as likely as men with the favorable and unfavorable genotype to clear HCV. Chronic Hepatitis B infection and absence of HIV coinfection around HCV seroconversion also favor HCV clearance. CONCLUSIONS: This study shows that co-infection with HIV and HBV and genetic variation in the IL28B region play an important role in spontaneous clearance of HCV. Our findings suggest a possible synergistic interaction between female sex and IL28B in spontaneous clearance of HCV

    Early Onset Ataxia with Comorbid Dystonia:Clinical, Anatomical and Biological Pathway Analysis Expose Shared Pathophysiology

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    In degenerative adult onset ataxia (AOA), dystonic comorbidity is attributed to one disease continuum. However, in early adult onset ataxia (EOA), the prevalence and pathogenesis of dystonic comorbidity (EOAD(+)), are still unclear. In 80 EOA-patients, we determined the EOAD(+)-prevalence in association with MRI-abnormalities. Subsequently, we explored underlying biological pathways by genetic network and functional enrichment analysis. We checked pathway-outcomes in specific EOAD(+)-genotypes by comparing results with non-specifically (in-silico-determined) shared genes in up-to-date EOA, AOA and dystonia gene panels (that could concurrently cause ataxia and dystonia). In the majority (65%) of EOA-patients, mild EOAD(+)-features concurred with extra-cerebellar MRI abnormalities (at pons and/or basal-ganglia and/or thalamus (p = 0.001)). Genetic network and functional enrichment analysis in EOAD(+)-genotypes indicated an association with organelle- and cellular-component organization (important for energy production and signal transduction). In non-specifically, in-silico-determined shared EOA, AOA and dystonia genes, pathways were enriched for Krebs-cycle and fatty acid/lipid-metabolic processes. In frequently occurring EOAD(+)-phenotypes, clinical, anatomical and biological pathway analyses reveal shared pathophysiology between ataxia and dystonia, associated with cellular energy metabolism and network signal transduction. Insight in the underlying pathophysiology of heterogeneous EOAD(+)-phenotype-genotype relationships supports the rationale for testing with complete, up-to-date movement disorder gene lists, instead of single EOA gene-panels.</p

    Chondrodysplasia, enchondromas and a chest deformity causing severe pulmonary morbidity in a boy with a PTHLH duplication:A case report

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    Parathyroid hormone-like hormone (PTHLH) plays an important role in bone formation. Several skeletal dysplasias have been described that are associated with disruption of PTHLH functioning. Here we report on a new patient with a 898 Kb duplication on chromosome 12p11.22 including the PTHLH gene. The boy has multiple skeletal abnormalities including chondrodysplasia, lesions radiographically resembling enchondromas and posterior rib deformities leading to a severe chest deformity. Severe pulmonary symptoms were thought to be caused by limited mobility and secondary sputum evacuation problems due to the chest deformity. Imaging studies during follow-up revealed progression of the number of skeletal lesions over time. This case extends the phenotypic spectrum associated with copy number variation of PTHLH

    Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

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    Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted

    Cost-effectiveness of clopidogrel vs. ticagrelor in patients of 70 years or older with non-ST-elevation acute coronary syndrome

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    OBJECTIVE: The POPular AGE trial showed that clopidogrel significantly reduced bleeding risk compared with ticagrelor without any signs of an increase in thrombotic events. The aim of this analysis was to estimate the long-term cost-effectiveness of clopidogrel compared with ticagrelor in these patients aged 70 years or older with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS AND RESULTS: A 1-year decision tree based on the POPular AGE trial in combination with a lifelong Markov model was developed to compare clopidogrel with ticagrelor in terms of clinical outcomes, costs, and quality-adjusted life years (QALYs) in elderly patients (above 70 year) with NSTE-ACS. Cost-effectiveness was assessed from a Dutch healthcare system perspective. Events rates and utility data observed in the POPular AGE trial were combined with lifetime projections to evaluate costs and effects for a fictional cohort of 1000 patients. Treatment with clopidogrel instead of ticagrelor led to a cost saving of €1484 575 (€1485 per patient) and a decrease of 10.96 QALYs (0.011 QALY per patient) in the fictional cohort. In an alternative base case with equal distribution over health states in the first year, treatment with clopidogrel led to an increase in QALYs. In all scenario analyses, treatment with clopidogrel was cost-saving. CONCLUSION: Clopidogrel is a cost-saving alternative to ticagrelor in elderly patients after NSTE-ACS, though regarding overall cost-effectiveness clopidogrel was not superior to ticagrelor, as it resulted in a small negative effect on QALYs. However, based on the results of the alternative base case and clinical outcomes of the POPular AGE trial, clopidogrel could be a reasonable alternative to ticagrelor for elderly NSTE-ACS patients with a higher bleeding risk

    Highly variable upper and abyssal overturning cells in the South Atlantic

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    The Meridional Overturning Circulation (MOC) is a primary mechanism driving oceanic heat redistribution on Earth, thereby affecting Earth’s climate and weather. However, the full-depth structure and variability of the MOC are still poorly understood, particularly in the South Atlantic. This study presents unique multiyear records of the oceanic volume transport of both the upper (~3100 meters) overturning cells based on daily moored measurements in the South Atlantic at 34.5°S. The vertical structure of the time-mean flows is consistent with the limited historical observations. Both the upper and abyssal cells exhibit a high degree of variability relative to the temporal means at time scales, ranging from a few days to a few weeks. Observed variations in the abyssal flow appear to be largely independent of the flow in the overlying upper cell. No meaningful trends are detected in either cell.Fil: KersalĂ©, Marion. National Ocean And Atmospheric Administration; Estados Unidos. University of Miami; Estados UnidosFil: Meinen, Christopher S.. National Ocean And Atmospheric Administration; Estados UnidosFil: Perez, Renellys C.. National Ocean And Atmospheric Administration; Estados UnidosFil: Le HĂ©naff, Matthieu. National Ocean And Atmospheric Administration; Estados Unidos. University of Miami; Estados UnidosFil: Valla, Daniel. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas; Argentina. Ministerio de Defensa. Armada Argentina. Servicio de HidrografĂ­a Naval. Departamento OceanografĂ­a; ArgentinaFil: Lamont, Tarron. University of Cape Town; SudĂĄfricaFil: Sato, Olga T.. Universidade de Sao Paulo; BrasilFil: Dong, Shenfu. National Ocean And Atmospheric Administration; Estados UnidosFil: Terre, T.. University of Brest; Francia. Centre National de la Recherche Scientifique; FranciaFil: van Caspel, M.. Universidade de Sao Paulo; BrasilFil: Chidichimo, MarĂ­a Paz. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas; Argentina. Ministerio de Defensa. Armada Argentina. Servicio de HidrografĂ­a Naval. Departamento OceanografĂ­a; ArgentinaFil: van den Berg, Marcel Alexander. Department of Environmental Affairs; SudĂĄfricaFil: Speich, Sabrina. University Of Cape Town; SudĂĄfricaFil: Piola, Alberto Ricardo. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas; Argentina. Ecole Normale Superieure. Laboratoire de Meteorologie Dynamique; Francia. Ministerio de Defensa. Armada Argentina. Servicio de HidrografĂ­a Naval. Departamento OceanografĂ­a; Argentina. Instituto Franco-Argentino sobre Estudios del Clima y sus Impactos; Argentina. Universidad de Buenos Aires; ArgentinaFil: Campos, Edmo. Universidade de Sao Paulo; Brasil. American University Of Sharjah.; Emiratos Árabes UnidosFil: Ansorge, Isabelle. University of Cape Town; SudĂĄfricaFil: Volkov, Denis L.. University of Miami; Estados Unidos. National Ocean And Atmospheric Administration; Estados UnidosFil: Lumpkin, Rick. National Ocean And Atmospheric Administration; Estados UnidosFil: Garzoli, S. L.. University of Miami; Estados Unidos. National Ocean And Atmospheric Administration; Estados Unido