540 research outputs found

    Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

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    The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

    Mobile HIV Screening in Cape Town, South Africa: Clinical Impact, Cost and Cost-Effectiveness

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    Background: Mobile HIV screening may facilitate early HIV diagnosis. Our objective was to examine the cost-effectiveness of adding a mobile screening unit to current medical facility-based HIV testing in Cape Town, South Africa. Methods and Findings: We used the Cost Effectiveness of Preventing AIDS Complications International (CEPAC-I) computer simulation model to evaluate two HIV screening strategies in Cape Town: 1) medical facility-based testing (the current standard of care) and 2) addition of a mobile HIV-testing unit intervention in the same community. Baseline input parameters were derived from a Cape Town-based mobile unit that tested 18,870 individuals over 2 years: prevalence of previously undiagnosed HIV (6.6%), mean CD4 count at diagnosis (males 423/µL, females 516/µL), CD4 count-dependent linkage to care rates (males 31%–58%, females 49%–58%), mobile unit intervention cost (includes acquisition, operation and HIV test costs, 29.30pernegativeresultand29.30 per negative result and 31.30 per positive result). We conducted extensive sensitivity analyses to evaluate input uncertainty. Model outcomes included site of HIV diagnosis, life expectancy, medical costs, and the incremental cost-effectiveness ratio (ICER) of the intervention compared to medical facility-based testing. We considered the intervention to be “very cost-effective” when the ICER was less than South Africa's annual per capita Gross Domestic Product (GDP) (8,200in2012).Weprojectedthat,withmedicalfacilitybasedtesting,thediscounted(undiscounted)HIVinfectedpopulationlifeexpectancywas132.2(197.7)months;thisincreasedto140.7(211.7)monthswiththeadditionofthemobileunit.TheICERforthemobileunitwas8,200 in 2012). We projected that, with medical facility-based testing, the discounted (undiscounted) HIV-infected population life expectancy was 132.2 (197.7) months; this increased to 140.7 (211.7) months with the addition of the mobile unit. The ICER for the mobile unit was 2,400/year of life saved (YLS). Results were most sensitive to the previously undiagnosed HIV prevalence, linkage to care rates, and frequency of HIV testing at medical facilities. Conclusion: The addition of mobile HIV screening to current testing programs can improve survival and be very cost-effective in South Africa and other resource-limited settings, and should be a priority

    Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer

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    Background Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. Main body The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability. Cancer cells have acquired the ability to overcome their fate of senescence via telomere length maintenance mechanisms, mainly by telomerase activation. hTERT expression is up-regulated in tumors via multiple genetic and epigenetic mechanisms including hTERT amplifications, hTERT structural variants, hTERT promoter mutations and epigenetic modifications through hTERT promoter methylation. Genetic (hTERT promoter mutations) and epigenetic (hTERT promoter methylation and miRNAs) events were shown to have clinical implications in cancers that depend on hTERT activation. Knowing that telomeres are crucial for cellular self-renewal, the mechanisms responsible for telomere maintenance have a crucial role in cancer diseases and might be important oncological biomarkers. Thus, rather than quantifying TERT expression and its correlation with telomerase activation, the discovery and the assessment of the mechanisms responsible for TERT upregulation offers important information that may be used for diagnosis, prognosis, and treatment monitoring in oncology. Furthermore, a better understanding of these mechanisms may promote their translation into effective targeted cancer therapies. Conclusion Herein, we reviewed the underlying mechanisms of hTERT regulation, their role in oncogenesis, and the potential clinical applications in telomerase-dependent cancers.info:eu-repo/semantics/publishedVersio

    Presumed Symbolic Use of Diurnal Raptors by Neanderthals

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    In Africa and western Eurasia, occurrences of burials and utilized ocher fragments during the late Middle and early Late Pleistocene are often considered evidence for the emergence of symbolically-mediated behavior. Perhaps less controversial for the study of human cognitive evolution are finds of marine shell beads and complex designs on organic and mineral artifacts in early modern human (EMH) assemblages conservatively dated to ≈100–60 kilo-years (ka) ago. Here we show that, in France, Neanderthals used skeletal parts of large diurnal raptors presumably for symbolic purposes at Combe-Grenal in a layer dated to marine isotope stage (MIS) 5b (≈90 ka) and at Les Fieux in stratigraphic units dated to the early/middle phase of MIS 3 (60–40 ka). The presence of similar objects in other Middle Paleolithic contexts in France and Italy suggest that raptors were used as means of symbolic expression by Neanderthals in these regions

    Telomerase activity in melanoma and non-melanoma skin cancer

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    Telomeres are specialized structures consisting of repeat arrays of TTAGGGn located at the ends of chromosomes. They are essential for chromosome stability and, in the majority of normal somatic cells, telomeres shorten with each cell division. Most immortalized cell lines and tumours reactivate telomerase to stabilize the shortening chromosomes. Telomerase activation is regarded as a central step in carcinogenesis and, here, we demonstrate telomerase activation in premalignant skin lesions and also in all forms of skin cancer. Telomerase activation in normal skin was a rare event, and among 16 samples of normal skin (one with a history of chronic sun exposure) 12.5% (2 out of 16) exhibited telomerase activity. One out of 16 (6.25%) benign proliferative lesions, including viral and seborrhoeic wart samples, had telomerase activity. In premalignant actinic keratoses and Bowen's disease, 42% (11 out of 26) of samples exhibited telomerase activity. In the basal cell carcinoma and cutaneous malignant melanoma (CMM) lesions, telomerase was activated in 77% (10 out of 13) and 69% (22 out of 32) respectively. However, only 25% (3 out of 12) of squamous cell carcinomas (SCC) had telomerase activity. With the exception of one SCC sample, telomerase activity in a positive control cell line derived from a fibrosarcoma (HT1080) was not inhibited when mixed with the telomerase-negative SCC or CMM extracts, indicating that, overall, Taq polymerase and telomerase inhibitors were not responsible for the negative results. Mean telomere hybridizing restriction fragment (TRF) analysis was performed in a number of telomerase-positive and -negative samples and, although a broad range of TRF sizes ranging from 3.6 to 17 kb was observed, a relationship between telomerase status and TRF size was not found

    Pulmonary hemodynamic responses to in utero ventilation in very immature fetal sheep

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    <p>Abstract</p> <p>Background</p> <p>The onset of ventilation at birth decreases pulmonary vascular resistance (PVR) resulting in a large increase in pulmonary blood flow (PBF). As the large cross sectional area of the pulmonary vascular bed develops late in gestation, we have investigated whether the ventilation-induced increase in PBF is reduced in immature lungs.</p> <p>Methods</p> <p>Surgery was performed in fetal sheep at 105 d GA (n = 7; term ~147 d) to insert an endotracheal tube, which was connected to a neonatal ventilation circuit, and a transonic flow probe was placed around the left pulmonary artery. At 110 d GA, fetuses (n = 7) were ventilated <it>in utero </it>(IUV) for 12 hrs while continuous measurements of PBF were made, fetuses were allowed to develop <it>in utero </it>for a further 7 days following ventilation.</p> <p>Results</p> <p>PBF changes were highly variable between animals, increasing from 12.2 ± 6.6 mL/min to a maximum of 78.1 ± 23.1 mL/min in four fetuses after 10 minutes of ventilation. In the remaining three fetuses, little change in PBF was measured in response to IUV. The increases in PBF measured in responding fetuses were not sustained throughout the ventilation period and by 2 hrs of IUV had returned to pre-IUV control values.</p> <p>Discussion and conclusion</p> <p>Ventilation of very immature fetal sheep <it>in utero </it>increased PBF in 57% of fetuses but this increase was not sustained for more than 2 hrs, despite continuing ventilation. Immature lungs can increase PBF during ventilation, however, the present studies show these changes are transient and highly variable.</p

    Bionomics of Culex quinquefasciatus within urban areas of Rio de Janeiro, Southeastern Brazil

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    OBJECTIVE: To evaluate density, parity rates, daily survival and longevity of natural populations of Culex quinquefasciatus in three neighborhoods with distinct socio-economic and infrastructure profiles. METHODS: Mosquito collections of the Culex quinquefasciatus species were performed weekly during two four month periods, from August to November 2008 (spring) and March to June 2009 (fall), in a favela (slum), a suburban area and a middle class area of Rio de Janeiro, Southeastern Brazil. Collections were performed with backpack aspirators, in 20 randomly selected houses in each area per week, during 15-20 minutes per house. Ovaries were removed from captured females and classified as initial, intermediary or final stage. Furthermore, females were dissected for determination of parity based on the condition of the tracheal system. Mosquito survival rate and longevity were estimated on a per month basis for each neighborhood. RESULTS: We collected a total of 2,062 Culex quinquefasciatus, but monthly vector density was not correlated with temperature and rainfall. We dissected the ovaries of 625 Culex quinquefasciatus, and overall, there was a higher proportion of nulliparous females during the dryer months, while gravid females were more frequent in rainy months. In the middle class neighborhood, the parity rate reached up to 93.75% with survivorship of 0.979. Lower parity and survival rates were obtained in the suburban area (as low as 36.4% parity and 0.711 daily survival). Up to 84.7% of Culex quinquefasciatus females could survive the eight day period needed to complete West Nile Virus incubation. CONCLUSIONS: The survival rate of Culex quinquefasciatus varied significantly between the neighborhoods. This suggests that vectorial capacity and disease transmission risk may vary greatly between different urban areas, which is potentially useful information for vector control programs

    Who Tests, Who Doesn't, and Why? Uptake of Mobile HIV Counseling and Testing in the Kilimanjaro Region of Tanzania

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    BACKGROUND: Optimally, expanded HIV testing programs should reduce barriers to testing while attracting new and high-risk testers. We assessed barriers to testing and HIV risk among clients participating in mobile voluntary counseling and testing (MVCT) campaigns in four rural villages in the Kilimanjaro Region of Tanzania. METHODS: Between December 2007 and April 2008, 878 MVCT participants and 506 randomly selected community residents who did not access MVCT were surveyed. Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics, HIV exposure risk, testing histories, HIV related stigma, and attitudes toward testing between MVCT participants and community residents who did not access MVCT. Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics, HIV exposure risk, testing histories, HIV related stigma, and attitudes toward testing, between the two groups. RESULTS: MVCT clients reported greater HIV exposure risk (OR 1.20 [1.04 to 1.38] for males; OR 1.11 [1.03 to 1.19] for females). Female MVCT clients were more likely to report low household expenditures (OR 1.47 [1.04 to 2.05]), male clients reported higher rates of unstable income sources (OR 1.99 [1.22 to 3.24]). First-time testers were more likely than non-testers to cite distance to testing sites as a reason for not having previously tested (OR 2.17 [1.05 to 4.48] for males; OR 5.95 [2.85 to 12.45] for females). HIV-related stigma, fears of testing or test disclosure, and not being able to leave work were strongly associated with non-participation in MVCT (ORs from 0.11 to 0.84). CONCLUSIONS: MVCT attracted clients with increased exposure risk and fewer economic resources; HIV related stigma and testing-related fears remained barriers to testing. MVCT did not disproportionately attract either first-time or frequent repeat testers. Educational campaigns to reduce stigma and fears of testing could improve the effectiveness of MVCT in attracting new and high-risk populations

    The Importance of Socio-Economic Versus Environmental Risk Factors for Reported Dengue Cases in Java, Indonesia

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    Background: Dengue is a major mosquito-borne viral disease and an important public health problem. Identifying which factors are important determinants in the risk of dengue infection is critical in supporting and guiding preventive measures. In South-East Asia, half of all reported fatal infections are recorded in Indonesia, yet little is known about the epidemiology of dengue in this country. Methodology/Principal findings: Hospital-reported dengue cases in Banyumas regency, Central Java were examined to build Bayesian spatial and spatio-temporal models assessing the influence of climatic, demographic and socio-economic factors on the risk of dengue infection. A socio-economic factor linking employment type and economic status was the most influential on the risk of dengue infection in the Regency. Other factors such as access to healthcare facilities and night-time temperature were also found to be associated with higher risk of reported dengue infection but had limited explanatory power. Conclusions/Significance: Our data suggest that dengue infections are triggered by indoor transmission events linked to socio-economic factors (employment type, economic status). Preventive measures in this area should therefore target also specific environments such as schools and work areas to attempt and reduce dengue burden in this community. Although our analysis did not account for factors such as variations in immunity which need further investigation, this study can advise preventive measures in areas with similar patterns of reported dengue cases and environmen
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