100 research outputs found

    Synorogenic evolution of large-scale drainage patterns: Isotope paleohydrology of sequential Laramide basins

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    In the past decade, we and others have compiled an extensive dataset of O, C and Sr isotope stratigraphies from sedimentary basins throughout the Paleogene North American Cordillera. In this study, we present new results from the Piceance Creek Basin of northwest Colorado, which record the evolving hydrology of the Eocene Green River Lake system. We then place the new data in the context of the broader Cordilleran dataset and summarize implications for understanding the synorogenic evolution of large-scale drainage patterns. The combined data reflect (1) a period of throughgoing foreland rivers heading in the Sevier fold-and-thrust belt and flowing east, (2) ponding of freshwater lakes in the foredeep as Laramide uplifts blocked drainage, (3) hydrologic closure that led to both intensive evaporation in the terminal sink of the Piceance Creek Basin and integration of catchments over length-scales \u3e1000 km, (4) infilling of basin accommodation by southward migrating magmatism in distal catchments, leading to the freshening and demise of intraforeland lakes that also stepped south over time

    Vestiges of the proto-Caribbean seaway: origin of the San Souci Volcanic Group, Trinidad

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    Outcrops of volcanic–hypabyssal rocks in Trinidad document the opening of the proto-Caribbean seaway during Jurassic–Cretaceous break-up of the Americas. The San Souci Group on the northern coast of Trinidad comprises the San Souci Volcanic Formation (SSVF) and passive margin sediments of the ~ 130–125 Ma Toco Formation. The Group was trapped at the leading edge of the Pacific-derived Caribbean Plate during the Cretaceous–Palaeogene, colliding with the para-autochthonous margin of Trinidad during the Oligocene–Miocene. In-situ U–Pb ion probe dating of micro-zircons from a mafic volcanic breccia reveal the SSVF crystallised at 135.0 ± 7.3 Ma. The age of the SSVF is within error of the age of the Toco Formation. Assuming a conformable contact, geodynamic models indicate a likely origin for the SSVF on the passive margin close to the northern tip of South America. Immobile element and Nd–Hf radiogenic isotope signatures of the mafic rocks indicate the SSVF was formed by ≪10% partial melting of a heterogeneous spinel peridotite source with no subduction or continental lithospheric mantle component. Felsic breccias within the SSVF are more enriched in incompatible elements, with isotope signatures that are less radiogenic than the mafic rocks of the SSVF. The felsic rocks may be derived from re-melting of mafic crust. Although geochemical comparisons are drawn here with proto-Caribbean igneous outcrops in Venezuela and elsewhere in the Caribbean more work is needed to elucidate the development of the proto-Caribbean seaway and its rifted margins. In particular, ion probe dating of micro-zircons may yield valuable insights into magmatism and metamorphism in the Caribbean, and in altered basaltic terranes more generally

    Emotions in context: examining pervasive affective sensing systems, applications, and analyses

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    Pervasive sensing has opened up new opportunities for measuring our feelings and understanding our behavior by monitoring our affective states while mobile. This review paper surveys pervasive affect sensing by examining and considering three major elements of affective pervasive systems, namely; “sensing”, “analysis”, and “application”. Sensing investigates the different sensing modalities that are used in existing real-time affective applications, Analysis explores different approaches to emotion recognition and visualization based on different types of collected data, and Application investigates different leading areas of affective applications. For each of the three aspects, the paper includes an extensive survey of the literature and finally outlines some of challenges and future research opportunities of affective sensing in the context of pervasive computing

    Rosetta-Alice Observations of Exospheric Hydrogen and Oxygen on Mars

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    The European Space Agency's Rosetta spacecraft, en route to a 2014 encounter with comet 67P/Churyumov-Gerasimenko, made a gravity assist swing-by of Mars on 25 February 2007, closest approach being at 01:54UT. The Alice instrument on board Rosetta, a lightweight far-ultraviolet imaging spectrograph optimized for in situ cometary spectroscopy in the 750-2000 A spectral band, was used to study the daytime Mars upper atmosphere including emissions from exospheric hydrogen and oxygen. Offset pointing, obtained five hours before closest approach, enabled us to detect and map the HI Lyman-alpha and Lyman-beta emissions from exospheric hydrogen out beyond 30,000 km from the planet's center. These data are fit with a Chamberlain exospheric model from which we derive the hydrogen density at the 200 km exobase and the H escape flux. The results are comparable to those found from the the Ultraviolet Spectrometer experiment on the Mariner 6 and 7 fly-bys of Mars in 1969. Atomic oxygen emission at 1304 A is detected at altitudes of 400 to 1000 km above the limb during limb scans shortly after closest approach. However, the derived oxygen scale height is not consistent with recent models of oxygen escape based on the production of suprathermal oxygen atoms by the dissociative recombination of O2+.Comment: 17 pages, 8 figures, accepted for publication in Icaru

    The implementation of medical revalidation: an assessment using normalisation process theory

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    Abstract Background Medical revalidation is the process by which all licensed doctors are legally required to demonstrate that they are up to date and fit to practise in order to maintain their licence. Revalidation was introduced in the United Kingdom (UK) in 2012, constituting significant change in the regulation of doctors. The governing body, the General Medical Council (GMC), envisages that revalidation will improve patient care and safety. This potential however is, in part, dependent upon how successfully revalidation is embedded into routine practice. The aim of this study was to use Normalisation Process Theory (NPT) to explore issues contributing to or impeding the implementation of revalidation in practice. Methods We conducted seventy-one interviews with sixty UK policymakers and senior leaders at different points during the development and implementation of revalidation: in 2011 (n = 31), 2013 (n = 26) and 2015 (n = 14). We selected interviewees using purposeful sampling. NPT was used as a framework to enable systematic analysis across the interview sets. Results Initial lack of consensus over revalidation’s purpose, and scepticism about its value, decreased over time as participants recognised the benefits it brought to their practice (coherence category of NPT). Though acceptance increased across time, revalidation was not seen as a legitimate part of their role by all doctors. Key individuals, notably the Responsible Officer (RO), were vital for the successful implementation of revalidation in organisations (cognitive participation category). The ease with which revalidation could be integrated into working practices varied greatly depending on the type of role a doctor held and the organisation they work for and the provision of resources was a significant variable in this (collective action category). Formal evaluation of revalidation in organisations was lacking but informal evaluation was taking place. Revalidation had not yet reached the stage where feedback was being used for improvement (reflexive monitoring category). Conclusions Requiring all organisations to use the same revalidation model made revalidation easy to integrate into existing work for some but problematic for others. In order for revalidation to be fully embedded and successful, impeding factors, such as a lack of resources, need to be addressed

    The satisfactory growth and development at 2 years of age of the INTERGROWTH-21st Fetal Growth Standards cohort support its appropriateness for constructing international standards.

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    BACKGROUND: The World Health Organization recommends that human growth should be monitored with the use of international standards. However, in obstetric practice, we continue to monitor fetal growth using numerous local charts or equations that are based on different populations for each body structure. Consistent with World Health Organization recommendations, the INTERGROWTH-21st Project has produced the first set of international standards to date pregnancies; to monitor fetal growth, estimated fetal weight, Doppler measures, and brain structures; to measure uterine growth, maternal nutrition, newborn infant size, and body composition; and to assess the postnatal growth of preterm babies. All these standards are based on the same healthy pregnancy cohort. Recognizing the importance of demonstrating that, postnatally, this cohort still adhered to the World Health Organization prescriptive approach, we followed their growth and development to the key milestone of 2 years of age. OBJECTIVE: The purpose of this study was to determine whether the babies in the INTERGROWTH-21st Project maintained optimal growth and development in childhood. STUDY DESIGN: In the Infant Follow-up Study of the INTERGROWTH-21st Project, we evaluated postnatal growth, nutrition, morbidity, and motor development up to 2 years of age in the children who contributed data to the construction of the international fetal growth, newborn infant size and body composition at birth, and preterm postnatal growth standards. Clinical care, feeding practices, anthropometric measures, and assessment of morbidity were standardized across study sites and documented at 1 and 2 years of age. Weight, length, and head circumference age- and sex-specific z-scores and percentiles and motor development milestones were estimated with the use of the World Health Organization Child Growth Standards and World Health Organization milestone distributions, respectively. For the preterm infants, corrected age was used. Variance components analysis was used to estimate the percentage variability among individuals within a study site compared with that among study sites. RESULTS: There were 3711 eligible singleton live births; 3042 children (82%) were evaluated at 2 years of age. There were no substantive differences between the included group and the lost-to-follow up group. Infant mortality rate was 3 per 1000; neonatal mortality rate was 1.6 per 1000. At the 2-year visit, the children included in the INTERGROWTH-21st Fetal Growth Standards were at the 49th percentile for length, 50th percentile for head circumference, and 58th percentile for weight of the World Health Organization Child Growth Standards. Similar results were seen for the preterm subgroup that was included in the INTERGROWTH-21st Preterm Postnatal Growth Standards. The cohort overlapped between the 3rd and 97th percentiles of the World Health Organization motor development milestones. We estimated that the variance among study sites explains only 5.5% of the total variability in the length of the children between birth and 2 years of age, although the variance among individuals within a study site explains 42.9% (ie, 8 times the amount explained by the variation among sites). An increase of 8.9 cm in adult height over mean parental height is estimated to occur in the cohort from low-middle income countries, provided that children continue to have adequate health, environmental, and nutritional conditions. CONCLUSION: The cohort enrolled in the INTERGROWTH-21st standards remained healthy with adequate growth and motor development up to 2 years of age, which supports its appropriateness for the construction of international fetal and preterm postnatal growth standards

    Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

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    BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known

    Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

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    OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

    Genetic mechanisms of critical illness in COVID-19.

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    Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
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