402 research outputs found

    An extraterrestrial trigger for the Early Cretaceous massive volcanism? Evidence from the paleo-Tethys Ocean

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    The Early Cretaceous Greater Ontong Java Event in the Pacific Ocean may have covered ca. 1% of the Earth's surface with volcanism. It has puzzled scientists trying to explain its origin by several mechanisms possible on Earth, leading others to propose an extraterrestrial trigger to explain this event. A large oceanic extraterrestrial impact causing such voluminous volcanism may have traces of its distal ejecta in sedimentary rocks around the basin, including the paleo-Tethys Ocean which was then contiguous with the Pacific Ocean. The contemporaneous marine sequence at central Italy, containing the sedimentary expression of a global oceanic anoxic event (OAE1a), may have recorded such ocurrence as indicated by two stratigraphic intervals with 187Os/188Os indicative of meteoritic influence. Here we show, for the first time, that platinum group element abundances and inter-element ratios in this paleo-Tethyan marine sequence provide no evidence for an extraterrestrial trigger for the Early Cretaceous massive volcanism

    Errores de medicaciĂłn en pediatrĂ­a

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    Concerns regarding patient safety affect healthcare, and medication errors are the most frequent category of medical errors and linked with severe consequences. This study discusses epidemiologic characteristics of medication errors in pediatric patients and points out prevention strategies. Approximately 8% of the studies on the subject of medication errors identified in different national and international databases are distinctively related to the pediatric population. Children are vulnerable to medication errors due to intrinsic factors, such as proper anatomic and physiological characteristics; and due to extrinsic factors, with emphasis on the lack of public health politics and changes in the pharmaceutical industry to attend children's needs. The available evidences indicate, as imperative, the implementation of strategies to prevent medication errors, contributing to promote patient safety.La seguridad del paciente es un problema de salud pĂșblica y los errores con medicamentos son los mĂĄs frecuentes y mĂĄs graves. Este artĂ­culo describe caracterĂ­sticas epidemiolĂłgicas de errores de medicaciĂłn en ĂĄreas de atenciĂłn pediĂĄtrica y algunas estrategias de prevenciĂłn. Aproximadamente 8% de las investigaciones sobre errores de medicaciĂłn identificadas en las bases de datos nacionales e internacionales se refieren especĂ­ficamente a niños. Los niños tienen mayor vulnerabilidad a la ocurrencia de errores debidos a factores intrĂ­nsecos, con destaque para caracterĂ­sticas anatĂłmicas y fisiolĂłgicas, e extrĂ­nsecos, en particular con respecto a falta de polĂ­ticas sanitarias y de la industria farmacĂ©utica orientada a la atenciĂłn de tales caracterĂ­sticas. Evidencias muestran la necesidad de aplicar estrategias para prevenir errores de medicaciĂłn, promoviendo la seguridad del paciente.A segurança do paciente constitui problema de saĂșde pĂșblica, e erros com medicamentos sĂŁo os mais freqĂŒentes e graves. O artigo apresenta caracterĂ­sticas epidemiolĂłgicas dos erros de medicação em diferentes ĂĄreas de atendimento pediĂĄtrico, e aponta estratĂ©gias de prevenção. Aproximadamente 8% das pesquisas sobre erros de medicação identificadas em bases de dados nacionais e internacionais referem-se Ă  população pediĂĄtrica. Crianças apresentam maior vulnerabilidade Ă  ocorrĂȘncia de erros devido a fatores intrĂ­nsecos, destacando-se caracterĂ­sticas anatĂŽmicas e fisiolĂłgicas; e extrĂ­nsecos, relativos Ă  falta de polĂ­ticas de saĂșde e da indĂșstria farmacĂȘutica voltadas ao atendimento de tais especificidades. As evidĂȘncias apontam para a necessidade de implementação de estratĂ©gias de prevenção de erros de medicação, contribuindo para promover a segurança do paciente.Universidade Federal de SĂŁo Paulo (UNIFESP) Departamento de EnfermagemUNIFESP, Depto. de EnfermagemSciEL

    Increased RPA1 gene dosage affects genomic stability potentially contributing to 17p13.3 duplication syndrome

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    A novel microduplication syndrome involving various-sized contiguous duplications in 17p13.3 has recently been described, suggesting that increased copy number of genes in 17p13.3, particularly PAFAH1B1, is associated with clinical features including facial dysmorphism, developmental delay, and autism spectrum disorder. We have previously shown that patient-derived cell lines from individuals with haploinsufficiency of RPA1, a gene within 17p13.3, exhibit an impaired ATR-dependent DNA damage response (DDR). Here, we show that cell lines from patients with duplications specifically incorporating RPA1 exhibit a different although characteristic spectrum of DDR defects including abnormal S phase distribution, attenuated DNA double strand break (DSB)-induced RAD51 chromatin retention, elevated genomic instability, and increased sensitivity to DNA damaging agents. Using controlled conditional over-expression of RPA1 in a human model cell system, we also see attenuated DSB-induced RAD51 chromatin retention. Furthermore, we find that transient over-expression of RPA1 can impact on homologous recombination (HR) pathways following DSB formation, favouring engagement in aberrant forms of recombination and repair. Our data identifies unanticipated defects in the DDR associated with duplications in 17p13.3 in humans involving modest RPA1 over-expression

    Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis

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    Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease of the joints that has been associated with variation in the peripheral blood methylome. In this study, we aim to identify epigenetic variation that is associated with the response to tumor necrosis factor inhibitor (TNFi) therapy.Peripheral blood genome-wide DNA methylation profiles were analyzed in a discovery cohort of 62 RA patients at baseline and at week 12 of TNFi therapy. DNA methylation of individual CpG sites and enrichment of biological pathways were evaluated for their association with drug response. Using a novel cell deconvolution approach, altered DNA methylation associated with TNFi response was also tested in the six main immune cell types in blood. Validation of the results was performed in an independent longitudinal cohort of 60 RA patients.Treatment with TNFi was associated with significant longitudinal peripheral blood methylation changes in biological pathways related to RA (FDR<0.05). 139 biological functions were modified by therapy, with methylation levels changing systematically towards a signature similar to that of healthy controls. Differences in the methylation profile of T cell activation and differentiation, GTPase-mediated signaling, and actin filament organization pathways were associated with the clinical response to therapy. Cell type deconvolution analysis identified CpG sites in CD4+T, NK, neutrophils and monocytes that were significantly associated with the response to TNFi.Our results show that treatment with TNFi restores homeostatic blood methylation in RA. The clinical response to TNFi is associated to methylation variation in specific biological pathways, and it involves cells from both the innate and adaptive immune systems.The Instituto de Salud Carlos III.Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved

    Striking increase in incidence of prostate cancer in men aged < 60 years without improvement in prognosis

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    Increased awareness and improved diagnostic techniques have led to earlier diagnosis of prostate cancer and increased detection of subclinical cases, resulting in improved prognosis. We postulated that the considerable increase in incidence under age 60 is not attributable only to increased detection. To test this hypothesis, we studied incidence, mortality and relative survival among middle-aged patients diagnosed in south-east Netherlands and East Anglia (UK) between 1971 and 1994. Prostate-specific antigen (PSA) testing did not occur before 1990. Between 1971 and 1989, the age-standardized incidence at ages40–59 increased from 8.8 to 12.5 per 105 in The Netherlands and from 7.0 to 11.6 per 105 in East Anglia.Five-year relative survival did not improve in East Anglia and even declined in south-east Netherlands from 65% [95% confidence interval (CI) 47–83) in 1975–79 to 48% (CI 34–62) in 1985–89. Mortality due to prostate cancer among men aged 45–64 years increased by 50% in south-east Netherlands and by 61% in East Anglia between 1971 and 1989, but decreased slightly in the 1990s. Because other factors adversely influencing the prognosis are unlikely, our results indicate an increase in the incidence of fatal prostate cancer among younger men in the era preceding PSA testing. © 1999 Cancer Research Campaig

    Was There Shortening of the Interval Between Diagnosis and Treatment of Colorectal Cancer in Southern Netherlands Between 2005 and 2008?

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    Background: The Dutch Cancer Society proposed that the interval between diagnosis and start of treatment should be less than 15 working days. The purpose of this study was to determine whether the interval from diagnosis to treatment for patients with colorectal cancer (CRC) shortened between 2005 and 2008 in hospitals in southern Netherlands. Methods: Patients with CRC diagnosed in six hospitals in southern Netherlands during January to December in 2005 (n = 445) and January to July in 2008 (n = 353) were included. The time between diagnosis and start of treatment was assessed, and the proportion of patients treated within the recommended time (70 years and those with stage I disease. Substantial variation was seen among hospitals. Conclusions: Time to treatment for patients with CRC in southern Netherlands did not shorten between 2005 and 2008. The time to treatment should be reduced to meet the advice of the Dutch Cancer Society

    Small-cell lung cancer in England: trends in survival and chemotherapy using the National Lung Cancer Audit

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    Background: The purpose of this study was to identify trends in survival and chemotherapy use for individuals with smallcell lung cancer (SCLC) in England using the National Lung Cancer Audit (NLCA). Methods: We used data from the NLCA database to identify people with histologically proven SCLC from 2004–2011. We calculated the median survival by stage and assessed whether patient characteristics changed over time. We also assessed whether the proportion of patients with records of chemotherapy and/or radiotherapy changed over time. Results: 18,513 patients were diagnosed with SCLC in our cohort. The median survival was 6 months for all patients, 1 year for those with limited stage and 4 months for extensive stage. 69% received chemotherapy and this proportion changed very slightly over time (test for trends p = 0.055). Age and performance status of patients remained stable over the study period, but the proportion of patients staged increased (p-value,0.001), mainly because of improved data completeness. There has been an increase in the proportion of patients that had a record of receiving both chemotherapy and radiotherapy each year (from 19% to 40% in limited and from 9% to 21% in extensive stage from 2004 to 2011). Patients who received chemotherapy with radiotherapy had better survival compared with any other treatment (HR 0.24, 95% CI 0.23–0.25). Conclusion: Since 2004, when the NLCA was established, the proportion of patients with SCLC having chemotherapy has remained static. We have found an upward trend in the proportion of patients receiving both chemotherapy and radiotherapy which corresponded to a better survival in this group, but as it only applied for a small proportion of patients, it was not enough to change the overall survival

    Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

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    This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}andcorrespondtoanintegratedluminosityof and correspond to an integrated luminosity of 4.6\;{\rm f}{{{\rm b}}^{-1}}.ThemeasurementisperformedbyreconstructingtheboostedWorZbosonsinsinglejets.ThereconstructedjetmassisusedtoidentifytheWandZbosons,andajetsubstructuremethodbasedonenergyclusterinformationinthejetcentre−of−massframeisusedtosuppressthelargemulti−jetbackground.Thecross−sectionforeventswithahadronicallydecayingWorZboson,withtransversemomentum. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum {{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}andpseudorapidity and pseudorapidity |\eta |\lt 1.9,ismeasuredtobe, is measured to be {{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques
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