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Sökning: WFRF:(Mehran R)

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1.
  • Abbafati, Cristiana, et al. (författare)
  • 2020
  • Tidskriftsartikel (refereegranskat)
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  • Lozano, Rafael, et al. (författare)
  • Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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3.
  • Stanaway, Jeffrey D., et al. (författare)
  • Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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  • Murray, Christopher J. L., et al. (författare)
  • Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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  • Feigin, Valery L., et al. (författare)
  • Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016
  • 2019
  • Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:5, s. 459-480
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.Funding: Bill & Melinda Gates Foundation.
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7.
  • Griswold, Max G., et al. (författare)
  • Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
  • 2018
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 392:10152, s. 1015-1035
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.Methods: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.Findings: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week.Interpretation: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.
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  • Ekhtiari, Hamed, et al. (författare)
  • A methodological checklist for fMRI drug cue reactivity studies : development and expert consensus
  • 2022
  • Ingår i: Nature Protocols. - : Nature Portfolio. - 1754-2189 .- 1750-2799. ; 17:3, s. 567-595
  • Tidskriftsartikel (refereegranskat)abstract
    • Cue reactivity measured by functional magnetic resonance imaging is used in studies of substance-use disorders. This Consensus Statement is the result of a Delphi process to arrive at parameters that should be reported in describing these studies. Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, the interpretability and reproducibility of these studies is limited by incomplete reporting of participants characteristics, task design, craving assessment, scanning preparation and analysis decisions in fMRI drug cue reactivity (FDCR) experiments. This hampers clinical translation, not least because systematic review and meta-analysis of published work are difficult. This consensus paper and Delphi study aims to outline the important methodological aspects of FDCR research, present structured recommendations for more comprehensive methods reporting and review the FDCR literature to assess the reporting of items that are deemed important. Forty-five FDCR scientists from around the world participated in this study. First, an initial checklist of items deemed important in FDCR studies was developed by several members of the Enhanced NeuroImaging Genetics through Meta-Analyses (ENIGMA) Addiction working group on the basis of a systematic review. Using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist, and then to rate the importance of each item in subsequent rounds. The reporting status of the items in the final checklist was investigated in 108 recently published FDCR studies identified through a systematic review. By the final round, 38 items reached the consensus threshold and were classified under seven major categories: Participants Characteristics, General fMRI Information, General Task Information, Cue Information, Craving Assessment Inside Scanner, Craving Assessment Outside Scanner and Pre- and Post-Scanning Considerations. The review of the 108 FDCR papers revealed significant gaps in the reporting of the items considered important by the experts. For instance, whereas items in the General fMRI Information category were reported in 90.5% of the reviewed papers, items in the Pre- and Post-Scanning Considerations category were reported by only 44.7% of reviewed FDCR studies. Considering the notable and sometimes unexpected gaps in the reporting of items deemed to be important by experts in any FDCR study, the protocols could benefit from the adoption of reporting standards. This checklist, a living document to be updated as the field and its methods advance, can help improve experimental design, reporting and the widespread understanding of the FDCR protocols. This checklist can also provide a sample for developing consensus statements for protocols in other areas of task-based fMRI.
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  • Sangchooli, Arshiya, et al. (författare)
  • Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity
  • 2024
  • Ingår i: JAMA psychiatry. - : AMER MEDICAL ASSOC. - 2168-6238 .- 2168-622X.
  • Forskningsöversikt (refereegranskat)abstract
    • Importance In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.
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  • Ahsant, Mehran, et al. (författare)
  • Streamlining Grid Operations : Definition and Deployment of a Portal-based User Registration Service
  • 2006
  • Ingår i: Journal of Grid Computing. - : Springer Science and Business Media LLC. - 1572-9184 .- 1570-7873. ; 4:2, s. 135-144
  • Tidskriftsartikel (refereegranskat)abstract
    • Manual management of public key credentials can be a significant and often off-putting obstacle to Grid use, particularly for casual users. We describe the Portal-based User Registration Service (PURSE), a set of tools for automating user registration, credential creation, and credential management tasks. PURSE provides the system developer with a set of customizable components, suitable for integration with portals, that can be used to address the full lifecycle of Grid credential management. We describe the PURSE design and its use in portals for two systems, the Earth System Grid data access system and the Swegrid computational Grid. In both cases, the user is entirely freed from the need to create or manage public key credentials, thus simplifying the Grid experience and reducing opportunities for error. We argue that this capturing of common use cases in a reusable ‘solution’ can be a model for how Grid ease-of-use can be addressed in other domains as well.
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  • Bainey, Kevin R., et al. (författare)
  • Complete vs Culprit-Lesion-Only Revascularization for ST-Segment Elevation Myocardial Infarction A Systematic Review and Meta-analysis
  • 2020
  • Ingår i: JAMA cardiology. - : AMER MEDICAL ASSOC. - 2380-6583 .- 2380-6591. ; 5:8, s. 881-888
  • Forskningsöversikt (refereegranskat)abstract
    • IMPORTANCE Recently, the Complete vs Culprit-Only Revascularization to Treat Multi vessel Disease After Early PCI (percutaneous coronary intervention) for STEMI (ST-segment elevation myocardial infarction [MI]) (COMPLETE) trial showed that angiography-guided PCI of the nonculprit lesion with the goal of complete revascularization reduced cardiovascular (CV) death or new MI compared with PCI of the culprit lesion only in STEMI. Whether complete revascularization also reduces CV mortality is uncertain. Moreover, whether the association of complete revascularization with hard clinical outcomes is consistent when fractional flow reserve (FFR)- and angiography-guided strategies are used is unknown. OBJECTIVE To determine through a systematic review and meta-analysis (1) whether complete revascularization is associated with decreased CV mortality and (2) whether heterogeneity in the association occurs when FFR- and angiography-guided PCI strategies for nonculprit lesions are performed. DATA SOURCES A systematic search of MEDLINE, Embase, ISI Web of Science, and CENTRAL (Cochrane Central Register of Controlled Trials) from database inception to September 30, 2019, was performed. Conference proceedings were also reviewed from January 1, 2002, to September 30, 2019. STUDY SELECTION English-language randomized clinical trials comparing complete revascularization vs culprit-lesion-only PCI in patients with STEMI and multivessel disease were included. DATA EXTRACTION AND SYNTHESIS The combined odds ratio (OR) was calculated with the random-effects model using the Mantel-Haenszel method (sensitivity with fixed-effects model). Heterogeneity was measured using the I-2 statistic. Publication bias was evaluated using the inverted funnel plot approach. Data were analyzed from October 2019 to January 2020. MAIN OUTCOMES AND MEASURES Cardiovascular death and the composite of CV death or new MI. RESULTS Ten randomized clinical trials involving 7030 unique patients were included. The weighted mean follow-up time was 29.5 months. Complete revascularization was associated with reduced CV death compared with culprit-lesion-only PCI (80 of 3191 [2.5%] vs 106 of 3406 [3]%1 OR, 0.69 [95% CI, 0.48-0.99]; P =.05; fixed-effects model OR, 0.74 [95% CI, 0.55-0.99]; P =.04). All-cause mortality occurred in 153 of 3426 patients (4.5%) in the complete revascularization group vs 177 of 3604 (4.9%) in the culprit-lesion-only group (OR, 0.84 [95% [I, 0.67-1.05]; P =.13; I-2 = 0%). Complete revascularization was associated with a reduced composite of CV death or new MI (192 of 2616 [7.3%] vs 266 of 2586 [10.3%]; OR, 0.69 [95% [I, 0.55-0.87]; P =.001; fixed-effects model OR, 0.69 [95% [I, 0.57-0.84]; P <.001), with no heterogeneity in this outcome when complete revascularization was performed using an FFR-guided strategy (OR, 0.78 [95% CI, 0.43-1.44]) or an angiography-guided strategy (OR, 0.61 [95% CI, 0.38-0.97]; P =.52 for interaction). CONCLUSIONS AND RELEVANCE In patients with STEMI and multivessel disease, complete revascularization was associated with a reduction in CV mortality compared with culprit-lesion-only PCI. There was no differential association with treatment between FFR- and angiography-guided strategies on major CV outcomes.
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  • Mehta, Shamir R, et al. (författare)
  • Complete Revascularization vs Culprit Lesion-Only Percutaneous Coronary Intervention for Angina-Related Quality of Life in Patients With ST-Segment Elevation Myocardial Infarction : Results From the COMPLETE Randomized Clinical Trial
  • 2022
  • Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 7:11, s. 1091-1099
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: In patients with multivessel coronary artery disease (CAD) presenting with ST-segment elevation myocardial infarction (STEMI), complete revascularization reduces major cardiovascular events compared with culprit lesion-only percutaneous coronary intervention (PCI). Whether complete revascularization also improves angina-related health status is unknown.OBJECTIVE: To determine whether complete revascularization improves angina status in patients with STEMI and multivessel CAD.DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a randomized, multinational, open label trial of patient-reported outcomes took place in 140 primary PCI centers in 31 countries. Patients presenting with STEMI and multivessel CAD were randomized between February 1, 2013, and March 6, 2017. Analysis took place between July 2021 and December 2021.INTERVENTIONS: Following PCI of the culprit lesion, patients with STEMI and multivessel CAD were randomized to receive either complete revascularization with additional PCI of angiographically significant nonculprit lesions or to no further revascularization.MAIN OUTCOMES AND MEASURES: Seattle Angina Questionnaire Angina Frequency (SAQ-AF) score (range, 0 [daily angina] to 100 [no angina]) and the proportion of angina-free individuals by study end.RESULTS: Of 4041 patients, 2016 were randomized to complete revascularization and 2025 to culprit lesion-only PCI. The mean (SD) age of patients was 62 (10.7) years, and 3225 (80%) were male. The mean (SD) SAQ-AF score increased from 87.1 (17.8) points at baseline to 97.1 (9.7) points at a median follow-up of 3 years in the complete revascularization group (score change, 9.9 [95% CI, 9.0-10.8]; P < .001) compared with an increase of 87.2 (18.4) to 96.3 (10.9) points (score change, 8.9 [95% CI, 8.0-9.8]; P < .001) in the culprit lesion-only group (between-group difference, 0.97 points [95% CI, 0.27-1.67]; P = .006). Overall, 1457 patients (87.5%) were free of angina (SAQ-AF score, 100) in the complete revascularization group compared with 1376 patients (84.3%) in the culprit lesion-only group (absolute difference, 3.2% [95% CI, 0.7%-5.7%]; P = .01). This benefit was observed mainly in patients with nonculprit lesion stenosis severity of 80% or more (absolute difference, 4.7%; interaction P = .02).CONCLUSIONS AND RELEVANCE: In patients with STEMI and multivessel CAD, complete revascularization resulted in a slightly greater proportion of patients being angina-free compared with a culprit lesion-only strategy. This modest incremental improvement in health status is in addition to the established benefit of complete revascularization in reducing cardiovascular events.
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20.
  • Asad Ayoubi, Mehran, et al. (författare)
  • Morphological Investigation of Polydisperse Asymmetric Block Copolymer Systems of Poly(styrene) and Poly(methacrylic acid) in the Strong Segregation Regime
  • 2013
  • Ingår i: Journal of Polymer Science. Part B, Polymer Physics. - : Wiley. - 0887-6266. ; 51:23, s. 1657-1671
  • Tidskriftsartikel (refereegranskat)abstract
    • Samples of compositionally (highly) asymmetric diblock copolymers and, also, mixtures of diblock and triblock copolymers (the latter obtained as end-coupling products of two diblock molecules of the mixture), composed of (a) monodisperse majority block(s) of poly(styrene) (PS) and a polydisperse minority block of poly(methacrylic acid) (PMAA), microphase separate into spherical PMAA microdomains, either in disordered liquid-like state or body-centered-cubic (BCC) arrangement, at various annealing temperatures T, in the strong segregation regime SSR. We found that (i) the microphase separated state is favored over an anticipated molecularly homogenous state, (ii) the spherical microdomain morphology (with BCC symmetry) is favored over an anticipated hexagonally packed cylindrical morphology, (iii) the extent of the dissolution of short PMAA blocks in the PS material can be quantified, (iv) the spherical microdomains are dilated, and (v) despite molecular-weight (and architectural) polydispersity, well-ordered BCC structures can be obtained. (c) 2013 Wiley Periodicals, Inc.
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21.
  • Ashraf, Samaneh, et al. (författare)
  • Compounding effects of human activities and climatic changes on surface water availability in Iran
  • 2019
  • Ingår i: Climatic Change. - : Springer Science and Business Media LLC. - 0165-0009 .- 1573-1480. ; 152:3-4, s. 379-391
  • Tidskriftsartikel (refereegranskat)abstract
    • By combining long-term ground-based data on water withdrawal with climate model projections, this study quantifies the compounding effects of human activities and climate change on surface water availability in Iran over the twenty-first century. Our findings show that increasing water withdrawal in Iran, due to population growth and increased agricultural activities, has been the main source of historical water stress. Increased levels of water stress across Iran are expected to continue or even worsen over the next decades due to projected variability and change in precipitation combined with heightened water withdrawals due to increasing population and socio-economic activities. The greatest rate of decreased water storage is expected in the Urmia Basin, northwest of Iran, (varying from -8.3mm/year in 2010-2039 to -61.6mm/year in 2070-2099 compared with an observed rate of 4mm/year in 1976-2005). Human activities, however, strongly dominate the effects of precipitation variability and change. Major shifts toward sustainable land and water management are needed to reduce the impacts of water scarcity in the future, particularly in Iran's heavily stressed basins like Urmia Basin, which feeds the shrinking Lake Urmia.
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22.
  • Azizi, F, et al. (författare)
  • Sustainability of a well-monitored salt iodization program in Iran: marked reduction in goiter prevalence and eventual normalization of urinary iodine concentrations without alteration in iodine content of salt.
  • 2008
  • Ingår i: Journal of Endocrinological Investigation. - 0391-4097 .- 1720-8386. ; 31:5, s. 422-31
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE:Two yr after legislation of salt iodization of 40 parts per million (ppm) in 1994, goiter was still endemic and urinary iodine concentration (UIC) remained elevated in many provinces of Iran. Goiter prevalence and UIC were compared 2 and 7 yr after sustained consumption of uniformly iodized salt by Iranian households.METHODS:Schoolchildren (7-10 yr) of all provinces were randomly selected by cluster sampling from December 2000 to June 2001. Goiter rate, UIC, and household salt iodine values were compared to those in 1996. Factory salt iodine was also compared in 2001 vs 1996. Ultrasonographically determined thyroid volumes of 7-10 yr old children were compared in 2001 vs 1999.RESULTS:In 2001 (no.=33600) vs 1996 (no.=36178), total, grade 1, and grade 2 goiter rates were 13.9 vs 53.8%, 11.0 vs 44.8%, and 2.9 vs 9.0%, respectively (p<0.0001). Weighted total goiter rate was 9.8% in 2001. Median (range) UIC in 2001 (no.=3329) was 165 (18-499) microg/l and in 1996 (no.=2917) was 205 (10-2300) microg/l (p<0.0001). In 2001 vs 1996, mean+/-SD for iodine salt content was 32.7+/-10.1 vs 33.0+/-10.2 ppm (p=0.68) in households and was 33.2+/-13.4 and 33.8+/-13.2 ppm (p=0.57) in factories, respectively. Among 7-10 yr old children in 2001 (no.=400) vs 1999 (no.=396), only 7-yr-old children in 2001 (the only group with probably no history of iodine deficiency) showed significant smaller thyroid volumes by ultrasonography compared to those in 1999.CONCLUSIONS:After 7 yr of optimized iodized-salt supplementation in Iran, adequate UIC values and marked reduction in goiter rate have been achieved.
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23.
  • Bergmann, Olaf, et al. (författare)
  • Dynamics of Cell Generation and Turnover in the Human Heart.
  • 2015
  • Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 161:7, s. 1566-1575
  • Tidskriftsartikel (refereegranskat)abstract
    • The contribution of cell generation to physiological heart growth and maintenance in humans has been difficult to establish and has remained controversial. We report that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood. Analysis of the integration of nuclear bomb test-derived (14)C revealed a high turnover rate of endothelial cells throughout life (>15% per year) and more limited renewal of mesenchymal cells (<4% per year in adulthood). Cardiomyocyte exchange is highest in early childhood and decreases gradually throughout life to <1% per year in adulthood, with similar turnover rates in the major subdivisions of the myocardium. We provide an integrated model of cell generation and turnover in the human heart. VIDEO ABSTRACT.
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24.
  • Binzer-Panchal, Amrei, et al. (författare)
  • Integrated Molecular Analysis of Undifferentiated Uterine Sarcomas Reveals Clinically Relevant Molecular Subtypes
  • 2019
  • Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 25:7, s. 2155-2165
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Undifferentiated uterine sarcomas (UUS) are rare, extremely deadly, sarcomas with no effective treatment. The goal of this study was to identify novel intrinsic molecular UUS subtypes using integrated clinical, histopathologic, and molecular evaluation of a large, fully annotated, patient cohort.Experimental Design: Fifty cases of UUS with full clinicopathologic annotation were analyzed for gene expression (n = 50), copy-number variation (CNV, n = 40), cell morphometry (n = 39), and protein expression (n = 22). Gene ontology and network enrichment analysis were used to relate over-and underexpressed genes to pathways and further to clinicopathologic and phenotypic findings.Results: Gene expression identified four distinct groups of tumors, which varied in their clinicopathologic parameters. Gene ontology analysis revealed differential activation of pathways related to genital tract development, extracellular matrix (ECM), muscle function, and proliferation. A multivariable, adjusted Cox proportional hazard model demonstrated that RNA group, mitotic index, and hormone receptor expression influence patient overall survival (OS). CNV arrays revealed characteristic chromosomal changes for each group. Morphometry demonstrated that the ECM group, the most aggressive, exhibited a decreased cell density and increased nuclear area. A cell density cutoff of 4,300 tumor cells per mm(2) could separate ECM tumors from the remaining cases with a sensitivity of 83% and a specificity of 94%. IHC staining of MMP-14, Collagens 1 and 6, and Fibronectin proteins revealed differential expression of these ECM-related proteins, identifying potential new biomarkers for this aggressive sarcoma subgroup. Conclusions: Molecular evaluation of UUS provides novel insights into the biology, prognosis, phenotype, and possible treatment of these tumors.
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25.
  • Bueno, Hector, et al. (författare)
  • Report of the European Society of Cardiology Cardiovascular Round Table regulatory workshop update of the evaluation of new agents for the treatment of acute coronary syndrome : Executive summary
  • 2019
  • Ingår i: European Heart Journal. - : SAGE PUBLICATIONS LTD. - 2048-8726 .- 2048-8734. ; 8:8, s. 745-754
  • Tidskriftsartikel (refereegranskat)abstract
    • Regulatory authorities interpret the results of randomized controlled trials according to published principles. The European Medicines Agency (EMA) is planning a revision of the 2000 and 2003 guidance documents on clinical investigation of new medicinal products for the treatment of acute coronary syndrome (ACS) to achieve consistency with current knowledge in the field. This manuscript summarizes the key output from a collaborative workshop, organized by the Cardiovascular Round Table and the European Affairs Committee of the European Society of Cardiology, involving clinicians, academic researchers, trialists, European and US regulators, and pharmaceutical industry researchers. Specific questions in four key areas were selected as priorities for changes in regulatory guidance: patient selection, endpoints, methodologic issues and issues related to the research for novel agents. Patients with ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) should be studied separately for therapies aimed at the specific pathophysiology of either condition, particularly for treatment of the acute phase, but can be studied together for other treatments, especially long-term therapy. Unstable angina patients should be excluded from acute phase ACS trials. In general, cardiovascular death and reinfarction are recommended for primary efficacy endpoints; other endpoints may be considered if specifically relevant for the therapy under study. New agents or interventions should be tested against a background of evidence-based therapy with expanded follow-up for safety assessment. In conclusion, new guidance documents for randomized controlled trials in ACS should consider changes regarding patient and endpoint selection and definitions, and trial designs. Specific requirements for the evaluation of novel pharmacological therapies need further clarification.
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