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| 11. |
- Abbafati, Cristiana, et al.
(author)
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- 2020
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Journal article (peer-reviewed)
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| 12. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 13. |
- Khatri, C, et al.
(author)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 14. |
- Lozano, Rafael, et al.
(author)
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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
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In: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Journal article (peer-reviewed)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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| 15. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 16. |
- Ademuyiwa, Adesoji O., et al.
(author)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 17. |
- Feigin, Valery L., et al.
(author)
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Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2021
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In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
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Journal article (peer-reviewed)abstract
- Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% [10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% [5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million [6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million [2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million [1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million [67.7-90.8] DALYs or 55.5% [48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million [22.3-48.6] DALYs or 24.3% [15.7-33.2]), high fasting plasma glucose (28.9 million [19.8-41.5] DALYs or 20.2% [13.8-29.1]), ambient particulate matter pollution (28.7 million [23.4-33.4] DALYs or 20.1% [16.6-23.0]), and smoking (25.3 million [22.6-28.2] DALYs or 17.6% [16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.
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| 18. |
- Pennells, Lisa, et al.
(author)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Journal article (peer-reviewed)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 19. |
- Stanaway, Jeffrey D., et al.
(author)
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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
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In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Journal article (peer-reviewed)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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| 20. |
- Tercero, M., et al.
(author)
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5G systems: The mmMAGIC project perspective on use cases and challenges between 6-100 GHz
- 2016
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In: IEEE Wireless Communications and Networking Conference, WCNC. - 1525-3511. ; 2016-September, s. 200-205
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Conference paper (peer-reviewed)abstract
- mmMAGIC (Millimetre-Wave Based Mobile Radio Access Network for Fifth Generation Integrated Communications) is an EU funded 5G-PPP project, whose overall objective is to design and pre-develop a mobile radio access technology (RAT) operating in the 6-100 GHz range, capable of impacting standards and other relevant fora. The focus of the project is on extreme Mobile Broadband, which is expected to drive the 5G requirements for massive increase in capacity and data-rates. This paper elaborates on some 5G key research areas such as: identification of the most compelling use-cases and Key Performance Indicators (KPIs) for future 5G systems, advantages and challenges of millimeter-wave (mmWave) technologies, channel measurements and channel modeling, network architecture; and the design of a new mobile radio interface including multi-node and multi-Antenna transceiver architecture.
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| 21. |
- Aravind, P. V., et al.
(author)
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Negative emissions at negative cost-an opportunity for a scalable niche
- 2022
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In: Frontiers in Energy Research. - : Frontiers Media SA. - 2296-598X. ; 10
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Journal article (peer-reviewed)abstract
- In the face of the rapidly dwindling carbon budgets, negative emission technologies are widely suggested as required to stabilize the Earth's climate. However, finding cost-effective, socially acceptable, and politically achievable means to enable such technologies remains a challenge. We propose solutions based on negative emission technologies to facilitate wealth creation for the stakeholders while helping to mitigate climate change. This paper comes up with suggestions and guidelines on significantly increasing carbon sequestration in coffee farms. A coffee and jackfruit agroforestry-based case study is presented along with an array of technical interventions, having a special focus on bioenergy and biochar, potentially leading to "negative emissions at negative cost. " The strategies for integrating food production with soil and water management, fuel production, adoption of renewable energy systems and timber management are outlined. The emphasis is on combining biological and engineering sciences to devise a practically viable niche that is easy to adopt, adapt and scale up for the communities and regions to achieve net negative emissions. The concerns expressed in the recent literature on the implementation of emission reduction and negative emission technologies are briefly presented. The novel opportunities to alleviate these concerns arising from our proposed interventions are then pointed out. Our analysis indicates that 1 ha coffee jackfruit-based agroforestry can additionally sequester around 10 tonnes of CO2-eq and lead to an income enhancement of up to 3,000-4,000 Euros in comparison to unshaded coffee. Finally, the global outlook for an easily adoptable nature-based approach is presented, suggesting an opportunity to implement revenue-generating negative emission technologies on a gigatonne scale. We anticipate that our approach presented in the paper results in increased attention to the development of practically viable science and technology-based interventions in order to support the speeding up of climate change mitigation efforts.
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| 22. |
- Asplund, Maria E., et al.
(author)
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Water column dynamics of Vibrio in relation to phytoplankton community composition and environmental conditions in a tropical coastal area
- 2011
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In: Environmental Microbiology. - 1462-2912 .- 1462-2920. ; 13:10, s. 2738-2751
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Journal article (peer-reviewed)abstract
- Vibrio abundance generally displays seasonal patterns. In temperate coastal areas, temperature and salinity influence Vibrio growth, whereas in tropical areas this pattern is not obvious. The present study assessed the dynamics of Vibrio in the Arabian Sea, 1-2 km off Mangalore on the south-west coast of India, during temporally separated periods. The two sampling periods were signified by oligotrophic conditions, and stable temperatures and salinity. Vibrio abundance was estimated by culture-independent techniques in relation to phytoplankton community composition and environmental variables. The results showed that the Vibrio density during December 2007 was 10- to 100-fold higher compared with the February-March 2008 period. High Vibrio abundance in December coincided with a diatom-dominated phytoplankton assemblage. A partial least squares (PLS) regression model indicated that diatom biomass was the primary predictor variable. Low nutrient levels suggested high water column turnover rate, which bacteria compensated for by using organic molecules leaking from phytoplankton. The abundance of potential Vibrio predators was low during both sampling periods; therefore it is suggested that resource supply from primary producers is more important than top-down control by predators.
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| 23. |
- Berg, David D., et al.
(author)
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Serial Assessment of High-Sensitivity Cardiac Troponin and the Effect of Dapagliflozin in Patients With Heart Failure With Reduced Ejection Fraction : An Analysis of the DAPA-HF Trial.
- 2022
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In: Circulation. ; 145:3, s. 158-169
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Journal article (peer-reviewed)abstract
- BACKGROUND: Circulating high-sensitivity cardiac troponin T (hsTnT) predominantly reflects myocardial injury, and higher levels are associated with a higher risk of worsening heart failure and death in patients with heart failure with reduced ejection fraction. Less is known about the prognostic significance of changes in hsTnT over time, the effects of dapagliflozin on clinical outcomes in relation to baseline hsTnT levels, and the effect of dapagliflozin on hsTnT levels. METHODS: DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) was a randomized, double-blind, placebo-controlled trial of dapagliflozin (10 mg daily) in patients with New York Heart Association class II to IV symptoms and left ventricular ejection fraction $<$/=40% (median follow-up, 18.2 months). hsTnT (Roche Diagnostics) was measured at baseline in 3112 patients and at 1 year in 2506 patients. The primary end point was adjudicated worsening heart failure or cardiovascular death. Clinical end points were analyzed according to baseline hsTnT and change in hsTnT from baseline to 1 year. Comparative treatment effects on clinical end points with dapagliflozin versus placebo were assessed by baseline hsTnT. The effect of dapagliflozin on hsTnT was explored. RESULTS: Median baseline hsTnT concentration was 20.0 (25th-75th percentile, 13.7-30.2) ng/L. Over 1 year, 67.9% of patients had a $>$/=10% relative increase or decrease in hsTnT concentrations, and 43.5% had a $>$/=20% relative change. A stepwise gradient of higher risk for the primary end point was observed across increasing quartiles of baseline hsTnT concentration (adjusted hazard ratio Q4 versus Q1, 3.44 [95% CI, 2.46-4.82]). Relative and absolute increases in hsTnT over 1 year were associated with higher subsequent risk of the primary end point. The relative reduction in the primary end point with dapagliflozin was consistent across quartiles of baseline hsTnT (P-interaction=0.55), but patients in the top quartile tended to have the greatest absolute risk reduction (absolute risk difference, 7.5% [95% CI, 1.0%-14.0%]). Dapagliflozin tended to attenuate the increase in hsTnT over time compared with placebo (relative least squares mean reduction, -3% [-6% to 0%]; P=0.076). CONCLUSIONS: Higher baseline hsTnT and greater increase in hsTnT over 1 year are associated with worse clinical outcomes. Dapagliflozin consistently reduced the risk of the primary end point, irrespective of baseline hsTnT levels. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
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| 24. |
- Campbell, Brittany B., et al.
(author)
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Comprehensive Analysis of Hypermutation in Human Cancer
- 2017
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In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 171:5
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Journal article (peer-reviewed)abstract
- © 2017 Elsevier Inc. We present an extensive assessment of mutation burden through sequencing analysis of > 81,000 tumors from pediatric and adult patients, including tumors with hypermutation caused by chemotherapy, carcinogens, or germline alterations. Hypermutation was detected in tumor types not previously associated with high mutation burden. Replication repair deficiency was a major contributing factor. We uncovered new driver mutations in the replication-repair-associated DNA polymerases and a distinct impact of microsatellite instability and replication repair deficiency on the scale of mutation load. Unbiased clustering, based on mutational context, revealed clinically relevant subgroups regardless of the tumors' tissue of origin, highlighting similarities in evolutionary dynamics leading to hypermutation. Mutagens, such as UV light, were implicated in unexpected cancers, including sarcomas and lung tumors. The order of mutational signatures identified previous treatment and germline replication repair deficiency, which improved management of patients and families. These data will inform tumor classification, genetic testing, and clinical trial design. A large-scale analysis of hypermutation in human cancers provides insights into tumor evolution dynamics and identifies clinically actionable mutation signatures.
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| 25. |
- Carvalho, F. A., et al.
(author)
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Transient Inability to Manage Proteobacteria Promotes Chronic Gut Inflammation in TLR5-Deficient Mice
- 2012
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In: Cell Host & Microbe. - : Elsevier BV. - 1931-3128. ; 12:2, s. 139-152
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Journal article (peer-reviewed)abstract
- Colitis results from breakdown of homeostasis between intestinal microbiota and the mucosal immune system, with both environmental and genetic influencing factors. Flagellin receptor TLR5-deficient mice (T5KO) display elevated intestinal proinflammatory gene expression and colitis with incomplete penetrance, providing a genetically sensitized system to study the contribution of microbiota to driving colitis. Both colitic and noncolitic T5KO exhibited transiently unstable microbiotas, with lasting differences in colitic T5KO, while their noncolitic siblings stabilized their microbiotas to resemble wild-type mice. Transient high levels of proteobacteria, especially enterobacteria species including E. coli, observed in close proximity to the gut epithelium were a striking feature of colitic microbiota. A Crohn's disease-associated E. coli strain induced chronic colitis in T5KO, which persisted well after the exogenously introduced bacterial species had been eliminated. Thus, an innate immune deficiency can result in unstable gut microbiota associated with low-grade inflammation, and harboring proteobacteria can drive and/or instigate chronic colitis.
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| 26. |
- Goyal, Nitin, et al.
(author)
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Medical Management vs Mechanical Thrombectomy for Mild Strokes: An International Multicenter Study and Systematic Review and Meta-analysis
- 2020
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In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 77:1, s. 16-24
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Journal article (peer-reviewed)abstract
- © 2019 American Medical Association. All rights reserved. Importance: The benefit of mechanical thrombectomy (MT) in patients with stroke presenting with mild deficits (National Institutes of Health Stroke Scale [NIHSS] score <6) owing to emergency large-vessel occlusion (ELVO) remains uncertain. Objective: To assess the outcomes of patients with mild-deficits ELVO (mELVO) treated with MT vs best medical management (bMM). Data Sources: We retrospectively pooled patients with mELVO during a 5-year period from 16 centers. A meta-analysis of studies reporting efficacy and safety outcomes with MT or bMM among patients with mELVO was also conducted. Data were analyzed between 2013 and 2017. Study Selection: We identified studies that enrolled patients with stroke (within 24 hours of symptom onset) with mELVO treated with MT or bMM. Main Outcomes and Measures: Efficacy outcomes included 3-month favorable functional outcome and 3-month functional independence that were defined as modified Rankin Scale scores of 0 to 1 and 0 to 2, respectively. Safety outcomes included 3-month mortality and symptomatic and asymptomatic intracranial hemorrhage (ICH). Results: We evaluated a total of 251 patients with mELVO who were treated with MT (n = 138; 65 women; mean age, 65.2 years; median NIHSS score, 4; interquartile range [IQR], 3-5) or bMM (n = 113; 51 women; mean age, 64.8; median NIHSS score, 3; interquartile range [IQR], 2-4). The rate of asymptomatic ICH was lower in bMM (4.6% vs 17.5%; P =.002), while the rate of 3-month FI (after imputation of missing follow-up evaluations) was lower in MT (77.4% vs 88.5%; P =.02). The 2 groups did not differ in any other efficacy or safety outcomes. In multivariable analyses, MT was associated with higher odds of asymptomatic ICH (odds ratio [OR], 11.07; 95% CI, 1.31-93.53; P =.03). In the meta-analysis of 4 studies (843 patients), MT was associated with higher odds of symptomatic ICH in unadjusted analyses (OR, 5.52; 95% CI, 1.91-15.49; P =.002; I2 = 0%). This association did not retain its significance in adjusted analyses including 2 studies (OR, 2.06; 95% CI, 0.49-8.63; P =.32; I2 = 0%). The meta-analysis did not document any other independent associations between treatment groups and safety or efficacy outcomes. Conclusions and Relevance: Our multicenter study coupled with the meta-analysis suggests similar outcomes of MT and bMM in patients with stroke with mELVO, but no conclusions about treatment effect can be made. The clinical equipoise can further be resolved by a randomized clinical trial.
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| 27. |
- Heard, J. M., et al.
(author)
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Availability, accessibility and delivery to patients of the 28 orphan medicines approved by the European Medicine Agency for hereditary metabolic diseases in the MetabERN network
- 2020
-
In: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 15:1
-
Journal article (peer-reviewed)abstract
- Background The European Medicine Agency granted marketing approval to 164 orphan medicinal products for rare diseases, among which 28 products intended for the treatment of hereditary metabolic diseases. Taking advantage of its privileged connection with 69 healthcare centres of excellence in this field, MetabERN, the European Reference Network for hereditary metabolic diseases, performed a survey asking health care providers from 18 European countries whether these products are available on the market, reimbursed and therefore accessible for prescription, and actually delivered in their centre. Results Responses received from 52 centres (75%) concerned the design of treatment plans, the access to marketed products, and the barriers to delivery. Treatment options are always discussed with patients, who are often involved in their treatment plan. Most products (26/28) are available in most countries (15/18). Among the 15 broadly accessible products (88.5% of the centres), 9 are delivered to most patients (mean 70.1%), and the others to only few (16.5%). Among the 10 less accessible products (40.2% of the centres), 6 are delivered to many patients (66.7%), and 4 are rarely used (6.3%). Information was missing for 3 products. Delay between prescription and delivery is on average one month. Beside the lack of availability or accessibility, the most frequent reasons for not prescribing a treatment are patients' clinical status, characteristic, and personal choice. Conclusions Data collected from health care providers in the MetabERN network indicate that two-third of the orphan medicines approved by EMA for the treatment of hereditary metabolic diseases are accessible to treating patients, although often less than one-half of the patients with the relevant conditions actually received the approved product to treat their disease. Thus, in spite of the remarkable achievement of many products, patients concerned by EMA-approved orphan medicinal products have persistent unmet needs, which deserve consideration. The enormous investments made by the companies to develop products, and the high financial burden for the Member States to purchase these products emphasize the importance of a scrupulous appreciation of treatment value involving all stakeholders at early stage of development, before marketing authorization, and during follow up.
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| 28. |
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| 29. |
- Jackson, Alice M., et al.
(author)
-
Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF.
- 2020
-
In: Circulation. - 1524-4539. ; 142:11, s. 1040-1054
-
Journal article (peer-reviewed)abstract
- BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo. METHODS: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide $<$40, 40, and $>$40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms. RESULTS: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on $<$40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking $>$40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow- up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. CONCLUSIONS: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
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| 30. |
- Joshi, Bhupendra, et al.
(author)
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A comparative survey between cascade correlation neural network (CCNN) and feedforward neural network (FFNN) machine learning models for forecasting suspended sediment concentration
- 2024
-
In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14
-
Journal article (peer-reviewed)abstract
- Suspended sediment concentration prediction is critical for the design of reservoirs, dams, rivers ecosystems, various operations of aquatic resource structure, environmental safety, and water management. In this study, two different machine models, namely the cascade correlation neural network (CCNN) and feedforward neural network (FFNN) were applied to predict daily-suspended sediment concentration (SSC) at Simga and Jondhara stations in Sheonath basin, India. Daily-suspended sediment concentration and discharge data from 2010 to 2015 were collected and used to develop the model to predict suspended sediment concentration. The developed models were evaluated using statistical indices like Nash and Sutcliffe efficiency coefficient (NES), root mean square error (RMSE), Willmott’s index of agreement (WI), and Legates–McCabe’s index (LM), supplemented by a scatter plot, density plots, histograms and Taylor diagram for graphical representation. The developed model was evaluated and compared with CCNN and FFNN. Nine input combinations were explored using different lag-times for discharge (Qt-n) and suspended sediment concentration (St-n) as input variables, with the current suspended sediment concentration as the desired output, to develop CCNN and FFNN models. The CCNN4 model with 4 lagged inputs (St-1, St-2, St-3, St-4) outperformed the other developed models with the lowest RMSE = 95.02 mg/l and the highest NES = 0.0.662, WI = 0.890 and LM = 0.668 for the Jondhara Station while the same CCNN4 model secure as the best with the lowest RMSE = 53.71 mg/l and the highest NES = 0.785, WI = 0.936 and LM = 0.788 for the Simga Station. The result shows the CCNN model was better than the FFNN model for predicting daily-suspended sediment at both stations in the Sheonath basin, India. Overall, CCNN showed better forecasting potential for suspended sediment concentration compared to FFNN at both stations, demonstrating their applicability for hydrological forecasting with complex relationships.
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| 31. |
- Karthick Raaj, R., et al.
(author)
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Exploring grinding and burnishing as surface post-treatment options for electron beam additive manufactured Alloy 718
- 2020
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In: Surface & Coatings Technology. - : Elsevier BV. - 0257-8972 .- 1879-3347. ; 397
-
Journal article (peer-reviewed)abstract
- Numerous additive manufacturing (AM) techniques have been developed over the past decade. Features like immense freedom of intricate part design and shorter lead time make AM routes promising for a wide range of applications spanning aerospace, marine and automobile sectors. Among the various metal AM processes, Electron Beam Additive Manufacturing (EBAM) is being widely explored to realise the potential of Ni-based superalloys and Ti alloys for varied high-performance applications. A novel attempt has been made in this paper to assess the surface integrity of as-built EBAM nickel-based superalloy 718 (AB) subjected to grinding (G), Low Plasticity Burnishing (LPB) and their sequential combination. Apart from their influence on sub-surface microstructures, the effect of process variables during the above post-treatments on the residual stress profiles was also investigated. Results revealed that G + LPB results in about 0.6 ÎŒm lower surface roughness, 17% improved microhardness compared to AB + LPB, and higher compressive surface residual stress as compared to LPB processed EBAM samples. The sequential grinding and LPB - improved microhardness, was also found to extend about 500 ÎŒm more when compared to the LPB process. The G + LPB, which is greatly influenced by the prior grinding, smoothens the surface and thus results in a better surface finish. Highest hardness, superior surface finish, reduced porosity and improved compressive residual stress were observed in samples that adopted the AB + G + LPB sequence over other samples, with the LPB step at 40 MPa yielding the best results. © 2020 Elsevier B.V.
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| 32. |
- Koli, Rohit R., et al.
(author)
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Gram bean extract-mediated synthesis of Fe3O4 nanoparticles for tuning the magneto-structural properties that influence the hyperthermia performance
- 2019
-
In: Journal of the Taiwan Institute of Chemical Engineers / Elsevier. - : Elsevier BV. - 1876-1070 .- 1876-1089. ; 95, s. 357-368
-
Journal article (peer-reviewed)abstract
- A green synthesis of biocompatible magnetite (Fe3O4) nanoparticles (MNPs) using a combination of urea (U) and gram-bean extract (GBE, Cicer arietinum L.) is reported. The particle size of similar to 13 nm and highly stable magnetite phase is observed for GBE-U mediated MNPs. On the other hand, the MNPs synthesized using either U or GBE shows larger particle size and uneven size distribution. Interestingly, the sample with particle size similar to 13 nm shows optimum heat generation capacity (measured in specific absorption rate, i.e., SAR) near to the therapeutic temperature (43 degrees C) with least-variance. To investigate the influence of various factors such as variation in MNPs weight concentration (W-t), applied alternating magnetic field (AMF), saturation magnetization (M-s), magnetization rate (R-m), etc. on SAR, a multiple linear regression model (MLRM) is used. The study reveals a positive correlation of SAR with R-m, and AMF values while the negative correlation with M-s and W-t. Ultimately, the present green synthesis is the affordable approach for preparing stable and tiny MNPs. Moreover, MLRM is found to be a useful theoretical tool for understanding the influence of MNPs on hyperthermia performance.
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| 33. |
- Kumar, Vijay, et al.
(author)
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Amplification of electrolyte uptake in the absorptive glass mat (AGM)separator for valve regulated lead acid (VRLA) batteries
- 2017
-
In: Journal of Power Sources. - : Elsevier BV. - 0378-7753 .- 1873-2755. ; 341, s. 19-26
-
Journal article (peer-reviewed)abstract
- Absorptive glass mat (AGM) separators are widely used for valve regulated lead acid (VRLA) batteries due to their remarkable fiber and structural characteristics. Discharge performance and recharge effectiveness of VRLA batteries essentially rely on the distribution and saturation levels of the electrolyte within the AGM separator. Herein, we report an analytical model for predicting the wicking characteristics of AGM battery separators under unconfined and confined states. The model of wicking behavior of AGM is based upon Fries and Dreyer's approach that included the effect of gravity component which was neglected in classic Lucas-Washburn's model. In addition, the predictive model of wicking accounted for realistic structural characteristics of AGM via orientation averaging approach. For wicking under confined state, the structural parameters have been updated under defined level of compressive stresses based upon the constitutive equation derived for a planar network of fibers in AGM under transverse loading conditions. A comparison has been made between the theoretical models and experimental results of wicking behavior under unconfined and confined states. Most importantly, the presented work has highlighted the questionable validity of classic Lucas-Washburn model for predicting the wicking characteristics of AGM separator over longer time duration.
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| 34. |
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| 35. |
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| 36. |
- Lischka, Matthias, et al.
(author)
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On-Surface Polymerization of 1,6-Dibromo-3,8-diiodpyrene-A Comparative Study on Au(111) Versus Ag(111) by STM, XPS, and NEXAFS
- 2018
-
In: The Journal of Physical Chemistry C. - : AMER CHEMICAL SOC. - 1932-7447 .- 1932-7455. ; 122:11, s. 5967-5977
-
Journal article (peer-reviewed)abstract
- The surface chemistry of 1,6-dibromo-3,8-diiodopyrene (Br2I2Py) is comparatively studied on Au(111) versus Ag(111) surfaces under ultrahigh vacuum conditions by a combination of high-resolution scanning tunneling microscopy (STM) and X-ray spectroscopy. The chemical state of the molecular networks, that is, the dehalogenation and the possible formation of organometallic intermediates, is assessed by X-ray photoelectron spectroscopy. In addition, pyrene tilt angles are quantified by carbon K-edge near edge X-ray absorption fine structure experiments. Upon room-temperature (RT) deposition of Br2I2Py onto Au(111), only partial deiodination was found, and STM revealed the coexistence of ordered arrangements of both intact Br2I2Py molecules and organometallic dimers as well as few larger aggregates. Further annealing to 100 C triggered full deiodination followed by the formation of organometallic chains of otherwise still brominated molecules. By contrast, on Ag(111), iodine is fully and bromine is partly dissociated upon RT deposition of Br2I2Py. The initially disordered organometallic aggregates can be reorganized into more ordered structures by mild annealing at 125 degrees C. Yet, the conversion of the organometallic intermediates into well-defined cross-linked quasi 2D covalent networks was neither possible on Au(111) nor on Ag(111). This is attributed to the large steric hindrance in the covalently linked adsorbed state.
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| 37. |
- Manesso, Erica, et al.
(author)
-
Computational modelling of T-cell formation kinetics: output regulated by initial proliferation-linked deferral of developmental competence.
- 2013
-
In: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5662 .- 1742-5689. ; 10:78
-
Journal article (peer-reviewed)abstract
- Bone-marrow-derived progenitors must continually enter the thymus of an adult mouse to sustain T-cell homeostasis, yet only a few input cells per day are sufficient to support a yield of 5 × 10(7) immature T-cells per day and an eventual output of 1-2 × 10(6) mature cells per day. While substantial progress has been made to delineate the developmental pathway of T-cell lineage commitment, still little is known about the relationship between differentiation competence and the remarkable expansion of the earliest (DN1 stage) T-cell progenitors. To address this question, we developed computational models where the probability to progress to the next stage (DN2) is related to division number. To satisfy differentiation kinetics and overall cell yield data, our models require that adult DN1 cells divide multiple times before becoming competent to progress into DN2 stage. Our findings were subsequently tested by in vitro experiments, where putative early and later-stage DN1 progenitors from the thymus were purified and their progression into DN2 was measured. These experiments showed that the two DN1 sub-populations divided with similar rates, but progressed to the DN2 stage with different rates, thus providing experimental evidence that DN1 cells increase their commitment probability in a cell-intrinsic manner as they undergo cell division. Proliferation-linked shifts in eligibility of DN1 cells to undergo specification thus control kinetics of T-cell generation.
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| 38. |
- Mehta, Shamir R, et al.
(author)
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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
-
In: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 7:11, s. 1091-1099
-
Journal article (peer-reviewed)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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| 39. |
- Menkveld, Albert J., et al.
(author)
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Nonstandard Errors
- 2024
-
In: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
-
Journal article (peer-reviewed)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 40. |
- Menon, Vijay Krishna, et al.
(author)
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A Spark (TM) Based Client for Synchrophasor Data Stream Processing
- 2018
-
In: PROCEEDINGS OF THE 2018 INTERNATIONAL CONFERENCE AND UTILITY EXHIBITION ON GREEN ENERGY FOR SUSTAINABLE DEVELOPMENT (ICUE 2018). - : Institute of Electrical and Electronics Engineers (IEEE). - 9789748257990
-
Conference paper (peer-reviewed)abstract
- The SCADA based monitoring systems, having a very low sampling of one reading per 2-4 seconds is known to produce roughly 4.3 Tera Bytes (TiBs) of data annually. With synchrophasor technology, this will go up at least 100 times more as the rate of streaming is as high as 50/100 (60/120) Hz. Phasor data concentrators (PDCs) transmit byte streams encapsulating a comprehensive list of power system parameter including multiple phasor measurements, instantaneous frequency estimates, rate of change of frequency and several analog and digital quantities; this high volume and velocity of data makes it truly 'Big Data'. This helps in making the power grid a lot more observable, enabling real-time monitoring of crucial grid events such as voltage stability, grid stress and transient oscillations. Synchrophasor technology uses the IEEE C37.118.2-2011 (TM) Phasor Measurement Unit (PMU) /PDC communication protocol for data exchange which has no direct interface with any contemporary big data stream APIs or protocols. In this paper we propose a streaming interface in Apache Spark (TM), a popular big data platform, using Scala programming language, implementing a complete IEEE C37.118.2-2011 (TM) client inside a stream receiver so that we can effortlessly receive synchrophasor data directly to Spark (TM) applications for real-time processing and archiving.
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| 41. |
- Micah, Angela E., et al.
(author)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
-
In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
-
Research review (peer-reviewed)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 42. |
- Mudedla, S. K., et al.
(author)
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Enhancement of Internal Motions of Lysozyme through Interaction with Gold Nanoclusters and its Optical Imaging
- 2015
-
In: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 119:1, s. 653-664
-
Journal article (peer-reviewed)abstract
- Understanding the interaction of gold nanoclusters with proteins has important ramifications in various fields. We present a study of the interaction between gold nanoclusters and lysozyme investigated using classical molecular dynamics and center-of-mass pulling simulations. The results reveal that the gold nanoclusters induce significant structural changes in lysozyme. Because the internal motions of lysozyme are related to its function, the changes in these internal motions have been quantified using principal component analysis of the molecular dynamics trajectories. The internal motions of lysozyme that are important for its function have been altered because of the interaction with the gold nanocluster. We have also explored how these induced changes in the lysozyme structure affect specific optical properties of the gold nanocluster using the complex polarization propagator method within the time-dependent density functional theory framework, which is of relevance for studies of the optical imaging of lysozyme using gold nanoclusters as molecular probes.
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| 43. |
- Narayana, Sujay, et al.
(author)
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Hummingbird : energy efficient GPS receiver for small satellites
- 2020
-
In: MobiCom '20. - New York, NY, USA : ACM. - 9781450370851 ; , s. 1-13
-
Conference paper (peer-reviewed)abstract
- Global Positioning System is a widely adopted localization technique. With the increasing demand for small satellites, the need for a low-power GPS for satellites is also increasing. To enable many state-of-the-art applications, the exact position of the satellites is necessary. However, building low-power GPS receivers which operate in low earth orbit pose significant challenges. This is mainly due to the high speed (~7.8 km/s) of small satellites. While duty-cycling the receiver is a possible solution, the high relative Doppler shift between the GPS satellites and the small satellite contributes to the increase in Time To First Fix (TTFF), thus increasing the energy consumption. Further, if the GPS receiver is tumbling along with the small satellite on which it is mounted, longer TTFF may lead to no GPS fix due to disorientation of the receiver antenna. In this paper, we elucidate the design of a low-cost, low-power GPS receiver for small satellite applications. We also propose an energy optimization algorithm called F3to improve the TTFF which is the main contributor to the energy consumption during cold start. With simulations and in-orbit evaluation from a launched nanosatellite with our μGPS and high-end GPS simulators, we show that up to 96.16% of energy savings (consuming only ~ 1/25th energy compared to the state of the art) can be achieved using our algorithm without compromising much (~10 m) on the navigation accuracy. The TTFF achieved is at most 33 s.
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| 44. |
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| 45. |
- Petrie, Mark C, et al.
(author)
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Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes.
- 2020
-
In: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 323:14, s. 1353-1368
-
Journal article (peer-reviewed)abstract
- Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes.To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes.Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019.Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy.The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%.Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (P value for interaction=.80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (P value for interaction=.72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes.In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status.ClinicalTrials.gov Identifier: NCT03036124.
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| 46. |
- Poelstra, Jelmer W., et al.
(author)
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The genomic landscape underlying phenotypic integrity in the face of gene flow in crows
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 344:6190, s. 1410-1414
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Journal article (peer-reviewed)abstract
- The importance, extent, and mode of interspecific gene flow for the evolution of species has long been debated. Characterization of genomic differentiation in a classic example of hybridization between all-black carrion crows and gray-coated hooded crows identified genome-wide introgression extending far beyond the morphological hybrid zone. Gene expression divergence was concentrated in pigmentation genes expressed in gray versus black feather follicles. Only a small number of narrow genomic islands exhibited resistance to gene flow. One prominent genomic region (<2 megabases) harbored 81 of all 82 fixed differences (of 8.4 million single-nucleotide polymorphisms in total) linking genes involved in pigmentation and in visual perception-a genomic signal reflecting color-mediated prezygotic isolation. Thus, localized genomic selection can cause marked heterogeneity in introgression landscapes while maintaining phenotypic divergence.
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| 47. |
- Rahmathullah, Abu Sajana, 1986, et al.
(author)
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A low-complexity algorithm for intrusion detection in a PIR-based Wireless Sensor Network
- 2009
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In: Intelligent Sensors, Sensor Networks and Information Processing (ISSNIP), 2009, Melbourne, Australia. - 9781424435173 ; , s. 337 - 342
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Conference paper (peer-reviewed)abstract
- We present a low-complexity algorithm for intrusion detection in the presence of clutter arising from wind-blown vegetation, using passive infra-red (PIR) sensors in a wireless sensor network (WSN). The algorithm is based on a combination of Haar transform (HT) and support-vector-machine (SVM) based training and was field tested in a network setting comprising of 15-20 sensing nodes. Also contained in this paper is a closed-form expression for the signal generated by an intruder moving at a constant velocity. It is shown how this expression can be exploited to determine the direction of motion information and the velocity of the intruder from the signals of three well-positioned sensors.
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| 48. |
- Rao, P. V. Kameswara, et al.
(author)
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Compression-recovery model of absorptive glass mat (AGM) separator guided by X-ray micro-computed tomography analysis
- 2017
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In: Journal of Power Sources. - : Elsevier. - 0378-7753 .- 1873-2755. ; 365, s. 389-398
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Journal article (peer-reviewed)abstract
- Absorptive glass mat (AGM) separators play a key role in enhancing the cycle life of the valve regulated lead acid (VRLA) batteries by maintaining the elastic characteristics under a defined level of compression force with the plates of the electrodes. Inevitably, there are inherent challenges to maintain the required level of compression characteristics of AGM separators during the charge and discharge of the battery. Herein, we report a three-dimensional (3D) analytical model for predicting the compression-recovery behavior of AGM separators by formulating a direct relationship with the constituent fiber and structural parameters. The analytical model of compression-recovery behavior of AGM separators has successfully included the fiber slippage criterion and internal friction losses. The presented work uses, for the first time, 3D data of fiber orientation from X-ray micro-computed tomography, for predicting the compression-recovery behavior of AGM separators. A comparison has been made between the theoretical and experimental results of compression-recovery behavior of AGM samples with defined fiber orientation characteristics. In general, the theory agreed reasonably well with the experimental results of AGM samples in both dry and wet states. Through theoretical modeling, fiber volume fraction was established as one of the key structural parameters that modulates the compression hysteresis of an AGM separator.
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| 49. |
- Serenelli, Matteo, et al.
(author)
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Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).
- 2020
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In: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 41:36, s. 3402-3418
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Journal article (peer-reviewed)abstract
- Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).Key inclusion criteria were: New York Heart Association Class II-IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP <110mmHg; 981≥110<120; 1149≥120<130; and 1409≥130mmHg. The placebo-corrected reduction in SBP from baseline to 2weeks with dapagliflozin was -2.54 (-3.33 to -1.76) mmHg (P<0.001), with a smaller between-treatment difference in patients in the lowest compared to highest SBP category. Patients in the lowest SBP category had a much higher rate (per 100 person-years) of the primary outcome [20.6, 95% confidence interval (95% CI) 17.6-24.2] than those in the highest SBP category (13.8, 11.7-16.4). The benefit and safety of dapagliflozin was consistent across the range of SBP; hazard ratio (95% CI) in each SBP group, lowest to highest: 0.76 (0.60-0.97), 0.76 (0.57-1.02), 0.81 (0.61-1.08), and 0.67 (0.51-0.87), P interaction = 0.78. Study drug discontinuation did not differ between dapagliflozin and placebo across the SBP categories examined.Dapagliflozin had a small effect on SBP in patients with HFrEF and was superior to placebo in improving outcomes, and well tolerated, across the range of SBP included in DAPA-HF.ClinicalTrials.gov NCT03036124.
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| 50. |
- Siddharth, Shukla, et al.
(author)
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Probing the three-dimensional porous and tortuous nature of absorptive glass mat (AGM) separators
- 2020
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In: Journal of Energy Storage. - : Elsevier BV. - 2352-152X .- 2352-1538. ; 2017:101003
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Journal article (peer-reviewed)abstract
- The valve regulated lead acid (VRLA) battery is a predominant electrochemical storage system that stores energy in a cheap, reliable and recyclable manner for innumerable applications. The absorptive glass mat (AGM) separator is a key component, which is pivotal for the successful functioning of the VRLA battery. Herein, the intricate three-dimensional (3D) porous structure of AGM separators has been unveiled using X-ray micro-computed tomography (microCT) analysis. X-ray microCT has quantified a variety of fiber and structural parameters including fiber orientation, porosity, tortuosity, pore size distribution, pore interconnectivity and pore volume distribution. A predictive model of hydraulic tortuosity has been developed based upon some of these fiber and structural parameters. Moreover, the pore size distribution extracted via X-ray microCT analysis has served as a benchmark for making a comparison with the existing analytical model of the pore size distribution of AGM separators. Pore size distributions obtained via the existing analytical model and through X-ray microCT analysis are in close agreement.
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