204 research outputs found

    Degenerating families of rank two bundles

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    We construct families of rank two bundles εton P4, in characteristic two, where for t ≠ 0 , εt is a sum of line bundles, and ε0 is non-split. We construct families of rank two bundles εt on P3, in characteristic p, where for t ≠ 0, εt is a sum of line bundles, and ε0 is non-split

    Monads on projective spaces

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    Let Ε be a vector bundle on P n. There is a strong relationship between Ε and its intermediate cohomology modules. In the case where Ε has low rank, we exploit this relationship to provide various splitting criteria for Ε. In particular, we give a splitting criterion for Ε in terms of the vanishing of certain intermediate cohomology modules. We also show that the Horrocks-Mumford bundle is the only non-split rank two bundle on P4 with a Buchsbaum second cohomology module

    Health seeking behavior acceptability of available health facilities and knowledge about tuberculosis in a tribal area

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    A study was undertaken among the tribals living in Buttayagudem Mandal consisting of 53 villages in West Godavari district of Andhra Pradesh to study their health seeking behaviour, acceptability of available health facilities and knowledge about tuberculosis. Information was also obtained on their practices to get relief from illness and type of health facilities used. In all, 429 households belonging to 34 villages were selected at random and the heads of these households or the next responsible persons were interviewed. A total of 189 (44%) had heard of tuberculosis and of these, 72 (38%) attributed it to tubercle bacilli. A majority of the tribals were in favour of modern medicine and accepted the available health facilities

    Prevalence and Assessment of Clinical Management of Sexually Transmitted Infections among Female Sex Workers in Two Cities of India

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    Objective. Control of sexually transmitted infections (STIs) among female sex workers (FSWs) is an important strategy to reduce HIV transmission. A study was conducted to determine the prevalence and assess the current clinical management of STIs in India. Methods. FSWs attending three clinics for regular checkups or symptoms were screened for study eligibility. A behavioral questionnaire was administered, clinical examination performed, and laboratory samples collected. Results. 417 study participants reported a mean number of 4.9 (SD 3.5) commercial clients in the last week. 14.6% reported anal sex in the last three months. Consistent condom use with commercial and regular partners was 70.1% and 17.5%, respectively. The prevalence of gonorrhea was 14.1%, chlamydia 16.1%, and trichomoniasis 31.1% with a third of all infections being asymptomatic. Syphilis seropositivity was 10.1%. Conclusions. At study sites, presumptive treatment for gonorrhea, chlamydia, and syphilis screening should continue. Presumptive treatment for trichomoniasis should be considered. Consistent condom use and partner treatment need to be reemphasized

    Photoconductance Quantization in a Single-Photon Detector

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    We have made a single-photon detector that relies on photoconductive gain in a narrow electron channel in an AlGaAs/GaAs 2-dimensional electron gas. Given that the electron channel is 1-dimensional, the photo-induced conductance has plateaus at multiples of the quantum conductance 2e2^{2}/h. Super-imposed on these broad conductance plateaus are many sharp, small, conductance steps associated with single-photon absorption events that produce individual photo-carriers. This type of photoconductive detector could measure a single photon, while safely storing and protecting the spin degree of freedom of its photo-carrier. This function is valuable for a quantum repeater that would allow very long distance teleportation of quantum information.Comment: 4 pages, 4 figure

    TNF-α promoter polymorphism: a factor contributing to the different immunological and clinical phenotypes in Japanese encephalitis

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    <p>Abstract</p> <p>Background</p> <p>More than three billion populations are living under the threat of Japanese encephalitis in South East Asian (SEA) countries including India. The pathogenesis of this disease is not clearly understood and is probably attributed to genomic variations in viral strains as well as the host genetic makeup. The present study is to determine the role of polymorphism of TNF-alpha promoter regions at positions -238G/A, -308G/A, -857C/T and -863C/A in the severity of Japanese encephalitis patients.</p> <p>Methods</p> <p>Total of 142 patients including 66 encephalitis case (IgM/RT-PCR positive), 16 fever cases (IgM positive) without encephalitis and 60 apparently healthy individuals (IgG positive) were included in the study. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) using site specific restriction enzymes were implemented for polymorphism study of TNF alpha promoter.</p> <p>Results</p> <p>Following the analysis of the digestion patterns of four polymorphic sites of the TNF- alpha promoter region, a significant association was observed between the allele -308A and -863C with the patients of Japanese encephalitis.</p> <p>Conclusions</p> <p>TNF- alpha 308 G/A has been shown to be associated with elevated TNF- alpha transcriptional activity. On the other hand, polymorphism at position -863C/A in the promoter region has been reported to be associated with reduced TNF- alpha promoter activity and lower plasma TNF levels. As per the literature search, this is the first study to identify the role of TNF- alpha promoter in JE infection. Our results show that subjects with - 308A and -863C alleles are more vulnerable to the severe form of JE infection.</p

    A systematic review of population health interventions and Scheduled Tribes in India

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    <p>Abstract</p> <p>Background</p> <p>Despite India's recent economic growth, health and human development indicators of Scheduled Tribes (ST) or <it>Adivasi </it>(India's indigenous populations) lag behind national averages. The aim of this review was to identify the public health interventions or components of these interventions that are effective in reducing morbidity or mortality rates and reducing risks of ill health among ST populations in India, in order to inform policy and to identify important research gaps.</p> <p>Methods</p> <p>We systematically searched and assessed peer-reviewed literature on evaluations or intervention studies of a population health intervention undertaken with an ST population or in a tribal area, with a population health outcome(s), and involving primary data collection.</p> <p>Results</p> <p>The evidence compiled in this review revealed three issues that promote effective public health interventions with STs: (1) to develop and implement interventions that are low-cost, give rapid results and can be easily administered, (2): a multi-pronged approach, and (3): involve ST populations in the intervention.</p> <p>Conclusion</p> <p>While there is a growing body of knowledge on the health needs of STs, there is a paucity of data on how we can address these needs. We provide suggestions on how to undertake future population health intervention research with ST populations and offer priority research avenues that will help to address our knowledge gap in this area.</p

    EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy

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    Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0–49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed myelination and, less frequently, thalamic signal intensity changes evolving over time. Typical muscle biopsy features included fibre size variability, central/internal nuclei, abnormal glycogen storage, presence of autophagic vacuoles and secondary mitochondrial abnormalities. Nerve biopsy performed in one case revealed subtotal absence of myelinated axons. Post-mortem examinations in three patients confirmed neurodevelopmental and neurodegenerative features and multisystem involvement. Finally, downregulation of epg5 (CG14299) in Drosophila resulted in autophagic abnormalities and progressive neurodegeneration. We conclude that EPG5-related Vici syndrome defines a novel group of neurodevelopmental disorders that should be considered in patients with suggestive features in whom mitochondrial, glycogen, or lysosomal storage disorders have been excluded. Neurological progression over time indicates an intriguing link between neurodevelopment and neurodegeneration, also supported by neurodegenerative features in epg5-deficient Drosophila, and recent implication of other autophagy regulators in late-onset neurodegenerative disease

    Prediction of overall survival for patients with metastatic castration-resistant prostate cancer : development of a prognostic model through a crowdsourced challenge with open clinical trial data

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    Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0.791; Bayes factor >5) and surpassed the reference model (iAUC 0.743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3.32, 95% CI 2.39-4.62, p Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer.Peer reviewe
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