63 research outputs found

    A Model of Secular Stagnation.

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    Japan's two-decade-long malaise and the Grea

    A rainfall model for drought risk analysis in south-east UK

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    Drought risk assessment ideally requires long-term rainfall records especially where inter-annual droughts are of potential concern, and spatially consistent estimates of rainfall to support regional and inter-regional scale assessments. This paper addresses these challenges by developing a spatially consistent stochastic model of monthly rainfall for south-east UK. Conditioned on 50 gauged sites, the model infills the historic record from 1855-2011 in both space and time, and extends the record by synthesising droughts which are consistent with the observed rainfall statistics. The long record length allows more insight into the variability of rainfall and potentially a stronger basis for risk assessment than is generally possible. It is shown that, although localised biases exist in both space and time, the model results are generally consistent with the observed record including for a range of inter-annual droughts and spatial statistics. Simulations show that some of the most severe inter-annual droughts on the record may recur, despite a trend towards generally wetter winters

    Design and development of the ‘POD Adventures’ smartphone game: a blended problem-solving intervention for adolescent mental health in India

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    Introduction: Digital technology platforms offer unparalleled opportunities to reach vulnerable adolescents at scale and overcome many barriers that exist around conventional service provision. This paper describes the design and development of POD Adventures, a blended problem-solving game-based intervention for adolescents with or at risk of anxiety, depression and conduct difficulties in India. This intervention was developed as part of the PRemIum for ADolEscents (PRIDE) research programme, which aims to establish a suite of transdiagnostic psychological interventions organised around a stepped care system in Indian secondary schools. Methods and materials: Intervention development followed a person-centered approach consisting of four iterative activities: (i) review of recent context-specific evidence on mental health needs and preferences for the target population of school-going Indian adolescents, including a multiple stakeholder analysis of school counselling priorities and pilot studies of a brief problem-solving intervention; (ii) new focus group discussions with N=46 student participants and N=8 service providers; (iii) co-design workshops with N=22 student participants and N=8 service providers; and (iv) user-testing with N=50 student participants. Participants were aged 12-17 years and recruited from local schools in New Delhi and Goa, including a subgroup with self-identified mental health needs (N=6). Results: Formative data from existing primary sources, new focus groups and co-design workshops supported a blended format for delivering a brief problem-solving intervention, with counsellors supporting use of a game-based app on ‘offline’ smartphones. User-testing with prototypes identified a need for simplification of language, use of concrete examples of concepts and practice elements to enhance engagement. There were also indications that participants most valued relatability and interactivity within real-world stories with judicious support from an in-app guide. The final prototype comprised a set of interactive and gamified vignettes and a structured set of problem-solving questions to consolidate and generalise learning while encouraging real-world application. Discussion: Findings shaped the design of POD Adventures and its delivery as an open-access blended intervention for secondary school students with a felt need for psychological support, consistent with an early intervention paradigm. A randomised controlled trial is planned to evaluate processes and impacts of POD Adventures when delivered for help-seeking students in low-resource school settings

    Establishing a core outcome set for peritoneal dialysis : report of the SONG-PD (standardized outcomes in nephrology-peritoneal dialysis) consensus workshop

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    Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD

    Choice of dialysis modality among patients initiating dialysis : results of the Peridialysis study

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    © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.Background: In patients with end-stage kidney disease (ESKD), home dialysis offers socio-economic and health benefits compared with in-centre dialysis but is generally underutilized. We hypothesized that the pre-dialysis course and institutional factors affect the choice of dialysis modality after dialysis initiation (DI). Methods: The Peridialysis study is a multinational, multicentre prospective observational study assessing the causes and timing of DI and consequences of suboptimal DI. Clinical and biochemical data, details of the pre-dialytic course, reasons for DI and causes of the choice of dialysis modality were registered. Results: Among 1587 included patients, 516 (32.5%) were judged unsuitable for home dialysis due to contraindications [384 ( 24.2%)] or no assessment [106 (6.7%); mainly due to late referral and/or suboptimal DI] or death [26 (1.6%)]. Older age, comorbidity, late referral, suboptimal DI, acute illness and rapid loss of renal function associated with unsuitability. Of the remaining 1071 patients, 700 (65.4%) chose peritoneal dialysis (61.7%) or home haemodialysis (HD; 3.6%), while 371 (34.6%) chose in-centre HD. Somatic differences between patients choosing home dialysis and in-centre dialysis were minor; factors linked to the choice of in-centre dialysis were late referral, suboptimal DI, acute illness and absence of a 'home dialysis first' institutional policy. Conclusions: Given a personal choice with shared decision making, 65.4% of ESKD patients choose home dialysis. Our data indicate that the incidence of home dialysis potentially could be further increased to reduce the incidence of late referral and unplanned DI and, in acutely ill patients, by implementing an educational programme after improvement of their clinical condition.publishersversionPeer reviewe

    Discovery of Novel Hypermethylated Genes in Prostate Cancer Using Genomic CpG Island Microarrays

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    BACKGROUND: Promoter and 5' end methylation regulation of tumour suppressor genes is a common feature of many cancers. Such occurrences often lead to the silencing of these key genes and thus they may contribute to the development of cancer, including prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: In order to identify methylation changes in prostate cancer, we performed a genome-wide analysis of DNA methylation using Agilent human CpG island arrays. Using computational and gene-specific validation approaches we have identified a large number of potential epigenetic biomarkers of prostate cancer. Further validation of candidate genes on a separate cohort of low and high grade prostate cancers by quantitative MethyLight analysis has allowed us to confirm DNA hypermethylation of HOXD3 and BMP7, two genes that may play a role in the development of high grade tumours. We also show that promoter hypermethylation is responsible for downregulated expression of these genes in the DU-145 PCa cell line. CONCLUSIONS/SIGNIFICANCE: This study identifies novel epigenetic biomarkers of prostate cancer and prostate cancer progression, and provides a global assessment of DNA methylation in prostate cancer

    The association of functional status with mortality and dialysis modality change : results from the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS)

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    BACKGROUND: Little is known about the prevalence of functional impairment in peritoneal dialysis (PD) patients, its variation by country, and its association with mortality or transfer to hemodialysis. METHODS: A prospective cohort study was conducted in PD patients from 7 countries in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) (2014 - 2017). Functional status (FS) was assessed by combining self-reports of 8 instrumental and 5 basic activities of daily living, using the Lawton-Brody and the Katz questionnaires. Summary FS scores, ranging from 1.25 (most dependent) to 13 (independent), were based on the patient's ability to perform each activity with or without assistance. Logistic regression was used to estimate the odds ratio (OR; 95% confidence interval [CI]) of a FS score < 11 comparing each country with the United States (US). Cox regression was used to estimate the hazard ratio (HR; 95% CI) for the effect of a low FS score on mortality and transfer to hemodialysis, adjusting for case mix. RESULTS: Of 2,593 patients with complete data on FS, 48% were fully independent (FS = 13), 32% had a FS score 11 to < 13, 14% had a FS score 8 to < 11, and 6% had a FS score < 8. Relative to the US, low FS scores (< 11; more dependent) were more frequent in Thailand (OR = 10.48, 5.90 - 18.60) and the United Kingdom (UK) (OR = 3.29, 1.77 - 6.08), but similar in other PDOPPS countries. The FS score was inversely and monotonically associated with mortality but not with transfer to hemodialysis; the HR, comparing a FS score < 8 vs 13, was 4.01 (2.44 - 6.61) for mortality and 0.91 (0.58 - 1.43) for transfer to hemodialysis. CONCLUSION: Regional differences in FS scores observed across PDOPPS countries may have been partly due to differences in regional patient selection for PD. Functional impairment was associated with mortality but not with permanent transfer to hemodialysis

    Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017 : a systematic analysis for the Global Burden of Disease Study 2017

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    Background Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. Methods The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODErn), to generate cause fractions and cause specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised. Findings At the broadest grouping of causes of death (Level 1), non-communicable diseases (NC Ds) comprised the greatest fraction of deaths, contributing to 73.4% (95% uncertainty interval [UI] 72.5-74.1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 186% (17.9-19.6), and injuries 8.0% (7.7-8.2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22.7% (21.5-23.9), representing an additional 7.61 million (7. 20-8.01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7.9% (7.08.8). The number of deaths for CMNN causes decreased by 222% (20.0-24.0) and the death rate by 31.8% (30.1-33.3). Total deaths from injuries increased by 2.3% (0-5-4-0) between 2007 and 2017, and the death rate from injuries decreased by 13.7% (12.2-15.1) to 57.9 deaths (55.9-59.2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000-289 000) globally in 2007 to 352 000 (334 000-363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118.0% (88.8-148.6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36.4% (32.2-40.6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33.6% (31.2-36.1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respirator}, infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990 neonatal disorders, lower respiratory infections, and diarrhoeal diseases were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases. Interpretation Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.Peer reviewe
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