139 research outputs found

    A machine learning toolkit for CRISM image analysis

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    Hyperspectral images collected by remote sensing have played a significant role in the discovery of aqueous alteration minerals, which in turn have important implications for our understanding of the changing habitability on Mars. Traditional spectral analyzes based on summary parameters have been helpful in converting hyperspectral cubes into readily visualizable three channel maps highlighting high-level mineral composition of the Martian terrain. These maps have been used as a starting point in the search for specific mineral phases in images. Although the amount of labor needed to verify the presence of a mineral phase in an image is quite limited for phases that emerge with high abundance, manual processing becomes laborious when the task involves determining the spatial extent of detected phases or identifying small outcrops of secondary phases that appear in only a few pixels within an image. Thanks to extensive use of remote sensing data and rover expeditions, significant domain knowledge has accumulated over the years about mineral composition of several regions of interest on Mars, which allow us to collect reliable labeled data required to train machine learning algorithms. In this study we demonstrate the utility of machine learning in two essential tasks for hyperspectral data analysis: nonlinear noise removal and mineral classification. We develop a simple yet effective hierarchical Bayesian model for estimating distributions of spectral patterns and extensively validate this model for mineral classification on several test images. Our results demonstrate that machine learning can be highly effective in exposing tiny outcrops of specific phases in orbital data that are not uncovered by traditional spectral analysis. We package implemented scripts, documentation illustrating use cases, and pixel-scale training data collected from dozens of well-characterized images into a new toolkit. We hope that this new toolkit will provide advanced and effective processing tools and improve community’s ability to map compositional units in remote sensing data quickly, accurately, and at scale

    Jury Systems Around the World

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    Lay citizens participate as decision makers in the legal systems of many countries. This review describes the different approaches that countries employ to integrate lay decision makers, contrasting in particular the use of juries composed of all citizens with mixed decision-making bodies of lay and law-trained judges. The review discusses research on the benefits and drawbacks of lay legal decision making as well as international support for the use of ordinary citizens as legal decision makers, with an eye to explaining a recent increase in new jury systems around the world. The review calls for more comparative work on diverse approaches to lay participation, examining how different methods of including lay participation promote or detract from fact finding, legal consciousness, civic engagement, and citizen power

    The development and initial evaluation of the Diarrhoea Management Diary (DMD) in patients with metastatic breast cancer

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    Purpose Chemotherapy-induced diarrhoea (CID) is a common, but often underreported problem in patients with breast cancer that has a profound effect on quality of life. It is best measured from a patient’s perspective, but tools are limited. The aim of this study was to develop and evaluate the Diarrhoea Management Diary (DMD), a self-report measure to assess CID, use of self-management strategies and treatment adherence. Methods The DMD was constructed using an iterative process of instrument development: concept elicitation (literature review), item generation and reduction (cognitive debriefing), and pilot testing in the target population. After translation into eight languages, the DMD was used in an international randomised trial for women receiving lapatinib and capecitabine for metastatic breast cancer with or without prophylactic octreotide. Patterns of missing data and sensitivity to change were examined. Results The understandability and completeness of the 8-item DMD was confirmed in cognitive interviews and pilot testing. Practicability of the DMD was evaluated in 62 women with metastatic breast cancer (median age 57). Up to 68% reported CID at any given time-point, and 19% had diarrhoea at each time-point. Patients also described efficacy of different strategies for diarrhoea management. Missing data were associated with study discontinuation. DMD missing item response was 0.9%. Sensitivity to change was good at most assessment points. Conclusions Although further psychometric testing is recommended, initial evaluation of the DMD showed good content validity and practicability in international research with cancer patients

    International collaborative study to assess cardiovascular risk and evaluate long-term health in cats with preclinical hypertrophic cardiomyopathy and apparently healthy cats:The REVEAL Study

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    Background: Hypertrophic cardiomyopathy is the most prevalent heart disorder in cats and principal cause of cardiovascular morbidity and mortality. Yet, the impact of preclinical disease is unresolved. Hypothesis/Objectives: Observational study to characterize cardiovascular morbidity and survival in cats with preclinical nonobstructive (HCM) and obstructive (HOCM) hypertrophic cardiomyopathy and in apparently healthy cats (AH). Animals: One thousand seven hundred and thirty client-owned cats (430 preclinical HCM; 578 preclinical HOCM; 722 AH). Methods: Retrospective multicenter, longitudinal, cohort study. Cats from 21 countries were followed through medical record review and owner or referring veterinarian interviews. Data were analyzed to compare long-term outcomes, incidence, and risk for congestive heart failure (CHF), arterial thromboembolism (ATE), and cardiovascular death. Results: During the study period, CHF, ATE, or both occurred in 30.5% and cardiovascular death in 27.9% of 1008 HCM/HOCM cats. Risk assessed at 1, 5, and 10 years after study entry was 7.0%/3.5%, 19.9%/9.7%, and 23.9%/11.3% for CHF/ATE, and 6.7%, 22.8%, and 28.3% for cardiovascular death, respectively. There were no statistically significant differences between HOCM compared with HCM for cardiovascular morbidity or mortality, time from diagnosis to development of morbidity, or cardiovascular survival. Cats that developed cardiovascular morbidity had short survival (mean \ub1 standard deviation, 1.3 \ub1 1.7 years). Overall, prolonged longevity was recorded in a minority of preclinical HCM/HOCM cats with 10% reaching 9-15 years. Conclusions and Clinical Importance: Preclinical HCM/HOCM is a global health problem of cats that carries substantial risk for CHF, ATE, and cardiovascular death. This finding underscores the need to identify therapies and monitoring strategies that decrease morbidity and mortality

    Life and living in advanced age: a cohort study in New Zealand - Te Puāwaitanga o Nga Tapuwae Kia Ora Tonu, LiLACS NZ: Study protocol

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    The number of people of advanced age (85 years and older) is increasing and health systems may be challenged by increasing health-related needs. Recent overseas evidence suggests relatively high levels of wellbeing in this group, however little is known about people of advanced age, particularly the indigenous Māori, in Aotearoa, New Zealand. This paper outlines the methods of the study Life and Living in Advanced Age: A Cohort Study in New Zealand. The study aimed to establish predictors of successful advanced ageing and understand the relative importance of health, frailty, cultural, social & economic factors to successful ageing for Māori and non-Māori in New Zealand

    Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

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    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

    The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

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    Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

    Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States

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    Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks

    Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

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