| 1. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 3. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- 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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| 8. |
- 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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| 9. |
- Murray, Christopher J. L., et al.
(author)
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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
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In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
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Journal article (peer-reviewed)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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| 10. |
- Abbafati, Cristiana, et al.
(author)
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- 2020
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Journal article (peer-reviewed)
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| 11. |
- 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
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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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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| 12. |
- 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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| 13. |
- Khetan, A. K., et al.
(author)
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Variations in the financial impact of the COVID-19 pandemic across 5 continents: A cross-sectional, individual level analysis
- 2022
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In: eClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 44
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Journal article (peer-reviewed)abstract
- Background: COVID-19 has caused profound socio-economic changes worldwide. However, internationally comparative data regarding the financial impact on individuals is sparse. Therefore, we conducted a survey of the financial impact of the pandemic on individuals, using an international cohort that has been well-characterized prior to the pandemic. Methods: Between August 2020 and September 2021, we surveyed 24,506 community-dwelling participants from the Prospective Urban-Rural Epidemiology (PURE) study across high (HIC), upper middle (UMIC)-and lower middle (LMIC)-income countries. We collected information regarding the impact of the pandemic on their self-reported personal finances and sources of income. Findings: Overall, 32.4% of participants had suffered an adverse financial impact, defined as job loss, inability to meet financial obligations or essential needs, or using savings to meet financial obligations. 8.4% of participants had lost a job (temporarily or permanently); 14.6% of participants were unable to meet financial obligations or essential needs at the time of the survey and 16.3% were using their savings to meet financial obligations. Participants with a post-secondary education were least likely to be adversely impacted (19.6%), compared with 33.4% of those with secondary education and 33.5% of those with pre-secondary education. Similarly, those in the highest wealth tertile were least likely to be financially impacted (26.7%), compared with 32.5% in the middle tertile and 30.4% in the bottom tertile participants. Compared with HICs, financial impact was greater in UMIC [odds ratio of 2.09 (1.88–2.33)] and greatest in LMIC [odds ratio of 16.88 (14.69–19.39)]. HIC participants with the lowest educational attainment suffered less financial impact (15.1% of participants affected) than those with the highest education in UMIC (22.0% of participants affected). Similarly, participants with the lowest education in UMIC experienced less financial impact (28.3%) than those with the highest education in LMIC (45.9%). A similar gradient was seen across country income categories when compared by pre-pandemic wealth status. Interpretation: The financial impact of the pandemic differs more between HIC, UMIC, and LMIC than between socio-economic categories within a country income level. The most disadvantaged socio-economic subgroups in HIC had a lower financial impact from the pandemic than the most advantaged subgroup in UMIC, with a similar disparity seen between UMIC and LMIC. Continued high levels of infection will exacerbate financial inequity between countries and hinder progress towards the sustainable development goals, emphasising the importance of effective measures to control COVID-19 and, especially, ensuring high vaccine coverage in all countries. Funding: Funding for this study was provided by the Canadian Institutes of Health Research and the International Development Research Centre. © 2022 The Author(s)
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| 14. |
- Mente, A., et al.
(author)
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Diet, cardiovascular disease, and mortality in 80 countries
- 2023
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In: European Heart Journal. - 0195-668X. ; 44:28, s. 2560-2579
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Journal article (peer-reviewed)abstract
- Aims To develop a healthy diet score that is associated with health outcomes and is globally applicable using data from the Prospective Urban Rural Epidemiology (PURE) study and replicate it in five independent studies on a total of 245 000 people from 80 countries. Methods and results A healthy diet score was developed in 147 642 people from the general population, from 21 countries in the PURE study, and the consistency of the associations of the score with events was examined in five large independent studies from 70 countries. The healthy diet score was developed based on six foods each of which has been associated with a significantly lower risk of mortality [i.e. fruit, vegetables, nuts, legumes, fish, and dairy (mainly whole-fat); range of scores, 0-6]. The main outcome measures were all-cause mortality and major cardiovascular events [cardiovascular disease (CVD)]. During a median follow-up of 9.3 years in PURE, compared with a diet score of & LE;1 points, a diet score of & GE;5 points was associated with a lower risk of mortality [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.63-0.77)], CVD (HR 0.82; 0.75-0.91), myocardial infarction (HR 0.86; 0.75-0.99), and stroke (HR 0.81; 0.71-0.93). In three independent studies in vascular patients, similar results were found, with a higher diet score being associated with lower mortality (HR 0.73; 0.66-0.81), CVD (HR 0.79; 0.72-0.87), myocardial infarction (HR 0.85; 0.71-0.99), and a non-statistically significant lower risk of stroke (HR 0.87; 0.73-1.03). Additionally, in two case-control studies, a higher diet score was associated with lower first myocardial infarction [odds ratio (OR) 0.72; 0.65-0.80] and stroke (OR 0.57; 0.50-0.65). A higher diet score was associated with a significantly lower risk of death or CVD in regions with lower than with higher gross national incomes (P for heterogeneity <0.0001). The PURE score showed slightly stronger associations with death or CVD than several other common diet scores (P < 0.001 for each comparison). Conclusion A diet comprised of higher amounts of fruit, vegetables, nuts, legumes, fish, and whole-fat dairy is associated with lower CVD and mortality in all world regions, especially in countries with lower income where consumption of these foods is low.
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| 15. |
- Boakye, K., et al.
(author)
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Perceived built environment characteristics associated with walking and cycling across 355 communities in 21 countries
- 2023
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In: Cities. - : Elsevier BV. - 0264-2751. ; 132
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Journal article (peer-reviewed)abstract
- Research examining built environment (BE) characteristics and walking/cycling behaviors has been conducted primarily in high-income countries and conclusions cannot be applied directly to low- and middle-income countries. We evaluated perceived BE characteristics and walking/cycling behaviors across 355 urban communities in 21 low-, middle-, and high- income countries using individual data for 39,908 adults in the Prospective Urban and Rural Epidemiology study. The 1-week long-form International Physical Activity Questionnaire was used to measure walking/cycling behaviors. Perceived BE characteristics were measured using the Neighborhood Environment Walkability Scale. Mixed effects logistic regression models examined associations between BE measures and walking for transport (≥150 min/wk), walking for leisure (≥150 min/wk), and any cycling for transport, controlling for individual, household, and community factors. Land-use mix diversity, land-use mix access, and street connectivity were associated with higher odds of walking for transport. Land-use mix diversity, land-use mix access, safety from traffic and safety from crime were associated with higher odds of walking for leisure. Land-use mix diversity, land-use mix access, and aesthetics were associated with higher odds of cycling. Differences in associations were observed by country-income status. Our findings can help guide policy makers globally to implement BE design to encourage walking and cycling behaviors.
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| 16. |
- Mente, A., et al.
(author)
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Association of dietary nutrients with blood lipids and blood pressure in 18 countries: a cross-sectional analysis from the PURE study
- 2017
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In: Lancet Diabetes & Endocrinology. - : Elsevier BV. - 2213-8587. ; 5:10, s. 774-787
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Journal article (peer-reviewed)abstract
- Background The relation between dietary nutrients and cardiovascular disease risk markers in many regions worldwide is unknown. In this study, we investigated the effect of dietary nutrients on blood lipids and blood pressure, two of the most important risk factors for cardiovascular disease, in low-income, middle-income, and high-income countries. Methods We studied 125 287 participants from 18 countries in North America, South America, Europe, Africa, and Asia in the Prospective Urban Rural Epidemiology (PURE) study. Habitual food intake was measured with validated food frequency questionnaires. We assessed the associations between nutrients (total fats, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, carbohydrates, protein, and dietary cholesterol) and cardiovascular disease risk markers using multilevel modelling. The effect of isocaloric replacement of saturated fatty acids with other fats and carbohydrates was determined overall and by levels of intakes by use of nutrient density models. We did simulation modelling in which we assumed that the effects of saturated fatty acids on cardiovascular disease events was solely related to their association through an individual risk marker, and then compared these simulated risk markerbased estimates with directly observed associations of saturated fatty acids with cardiovascular disease events. Findings Participants were enrolled into the study from Jan 1, 2003, to March 31, 2013. Intake of total fat and each type of fat was associated with higher concentrations of total cholesterol and LDL cholesterol, but also with higher HDL cholesterol and apolipoprotein A1 (ApoA1), and lower triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein B (ApoB) to ApoA1 (all p(trend) < 0.0001). Higher carbohydrate intake was associated with lower total cholesterol, LDL cholesterol, and ApoB, but also with lower HDL cholesterol and ApoA1, and higher triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ApoB-to-ApoA1 ratio (all p(trend) < 0.0001, apart from ApoB [p(trend) = 0.0014]). Higher intakes of total fat, saturated fatty acids, and carbohydrates were associated with higher blood pressure, whereas higher protein intake was associated with lower blood pressure. Replacement of saturated fatty acids with carbohydrates was associated with the most adverse effects on lipids, whereas replacement of saturated fatty acids with unsaturated fats improved some risk markers (LDL cholesterol and blood pressure), but seemed to worsen others (HDL cholesterol and triglycerides). The observed associations between saturated fatty acids and cardiovascular disease events were approximated by the simulated associations mediated through the effects on the ApoB-to-ApoA1 ratio, but not with other lipid markers including LDL cholesterol. Interpretation Our data are at odds with current recommendations to reduce total fat and saturated fats. Reducing saturated fatty acid intake and replacing it with carbohydrate has an adverse effect on blood lipids. Substituting saturated fatty acids with unsaturated fats might improve some risk markers, but might worsen others. Simulations suggest that ApoB-to-ApoA1 ratio probably provides the best overall indication of the effect of saturated fatty acids on cardiovascular disease risk among the markers tested. Focusing on a single lipid marker such as LDL cholesterol alone does not capture the net clinical effects of nutrients on cardiovascular risk.
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| 17. |
- Tedersoo, Leho, et al.
(author)
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Global patterns in endemicity and vulnerability of soil fungi.
- 2022
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In: Global change biology. - : Wiley. - 1365-2486 .- 1354-1013. ; 28:22, s. 6696-6710
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Journal article (peer-reviewed)abstract
- Fungi are highly diverse organisms, which provide multiple ecosystem services. However, compared with charismatic animals and plants, the distribution patterns and conservation needs of fungi have been little explored. Here, we examined endemicity patterns, global change vulnerability and conservation priority areas for functional groups of soil fungi based on six global surveys using a high-resolution, long-read metabarcoding approach. We found that the endemicity of all fungi and most functional groups peaks in tropical habitats, including Amazonia, Yucatan, West-Central Africa, Sri Lanka, and New Caledonia, with a negligible island effect compared with plants and animals. We also found that fungi are predominantly vulnerable to drought, heat and land-cover change, particularly in dry tropical regions with high human population density. Fungal conservation areas of highest priority include herbaceous wetlands, tropical forests, and woodlands. We stress that more attention should be focused on the conservation of fungi, especially root symbiotic arbuscular mycorrhizal and ectomycorrhizal fungi in tropical regions as well as unicellular early-diverging groups and macrofungi in general. Given the low overlap between the endemicity of fungi and macroorganisms, but high conservation needs in both groups, detailed analyses on distribution and conservation requirements are warranted for other microorganisms and soil organisms.
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| 18. |
- Masood, KI, et al.
(author)
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Upregulated type I interferon responses in asymptomatic COVID-19 infection are associated with improved clinical outcome
- 2021
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 22958-
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Journal article (peer-reviewed)abstract
- Understanding key host protective mechanisms against SARS-CoV-2 infection can help improve treatment modalities for COVID-19. We used a blood transcriptome approach to study biomarkers associated with differing severity of COVID-19, comparing severe and mild Symptomatic disease with Asymptomatic COVID-19 and uninfected Controls. There was suppression of antigen presentation but upregulation of inflammatory and viral mRNA translation associated pathways in Symptomatic as compared with Asymptomatic cases. In severe COVID-19, CD177 a neutrophil marker, was upregulated while interferon stimulated genes (ISGs) were downregulated. Asymptomatic COVID-19 cases displayed upregulation of ISGs and humoral response genes with downregulation of ICAM3 and TLR8. Compared across the COVID-19 disease spectrum, we found type I interferon (IFN) responses to be significantly upregulated (IFNAR2, IRF2BP1, IRF4, MAVS, SAMHD1, TRIM1), or downregulated (SOCS3, IRF2BP2, IRF2BPL) in Asymptomatic as compared with mild and severe COVID-19, with the dysregulation of an increasing number of ISGs associated with progressive disease. These data suggest that initial early responses against SARS-CoV-2 may be effectively controlled by ISGs. Therefore, we hypothesize that treatment with type I interferons in the early stage of COVID-19 may limit disease progression by limiting SARS-CoV-2 in the host.
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| 19. |
- Nasir, A. A., et al.
(author)
-
DSTBC based DF cooperative networks in the presence of timing and frequency offsets
- 2013
-
In: Signal Processing Advances in Wireless Communications (SPAWC), 2013 IEEE 14th Workshop on. ; , s. 86-90
-
Conference paper (peer-reviewed)abstract
- n decode-and-forward (DF) relaying networks, the received signal at the destination may be affected by multiple impairments such as multiple channel gains, multiple timing offsets (MTOs), and multiple carrier frequency offsets (MCFOs). This paper proposes novel optimal and sub-optimal minimum mean-square error (MMSE) receiver designs at the destination node to detect the signal in the presence of these impairments. Distributed space-time block codes (DSTBCs) are used at the relays to achieve spatial diversity. The proposed sub-optimal receiver uses the estimated values of multiple channel gains, MTOs, and MCFOs, while the optimal receiver assumes perfect knowledge of these impairments at the destination and serves as a benchmark performance measure. To achieve robustness to estimation errors, the estimates statistical properties are exploited at the destination. Simulation results show that the proposed optimal and sub-optimal MMSE compensation receivers achieve full diversity gain in the presence of channel and synchronization impairments in DSTBC based DF cooperative networks
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| 20. |
- Nasir, A. A., et al.
(author)
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Optimal Training Sequences for Joint Timing Synchronization and Channel Estimation in Distributed Communication Networks
- 2013
-
In: IEEE Transactions on Communications. - 0090-6778 .- 1558-0857. ; 61:7, s. 3002-3015
-
Journal article (peer-reviewed)abstract
- For distributed multi-user and multi-relay cooperative networks, the received signal may be affected by multiple timing offsets (MTOs) and multiple channels that need to be jointly estimated for successful decoding at the receiver. This paper addresses the design of optimal training sequences for efficient estimation of MTOs and multiple channel parameters. A new hybrid Cramer-Rao lower bound (HCRB) for joint estimation of MTOs and channels is derived. Subsequently, by minimizing the derived HCRB as a function of training sequences, three training sequence design guidelines are derived and according to these guidelines, two training sequences are proposed. In order to show that the proposed design guidelines also improve estimation accuracy, the conditional Cramer-Rao lower bound (ECRB), which is a tighter lower bound on the estimation accuracy compared to the HCRB, is also derived. Numerical results show that the proposed training sequence design guidelines not only lower the HCRB, but they also lower the ECRB and the mean-square error of the proposed maximum a posteriori estimator. Moreover, extensive simulations demonstrate that application of the proposed training sequences significantly lowers the bit-error rate performance of multi-relay cooperative networks when compared to training sequences that violate these design guidelines.
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| 21. |
- Nasir, A. A., et al.
(author)
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Transceiver Design for Distributed STBC Based AF Cooperative Networks in the Presence of Timing and Frequency Offsets
- 2013
-
In: IEEE Transactions on Signal Processing. - 1053-587X .- 1941-0476. ; 61:12, s. 3143-3158
-
Journal article (peer-reviewed)abstract
- In multi-relay cooperative systems, the signal at the destination is affected by impairments such as multiple channel gains, multiple timing offsets (MTOs), and multiple carrier frequency offsets (MCFOs). In this paper we account for all these impairments and propose a new transceiver structure at the relays and a novel receiver design at the destination in distributed space-time block code (DSTBC) based amplify-and-forward (AF) cooperative networks. The Cramer-Rao lower bounds and a least squares (LS) estimator for the multi-parameter estimation problem are derived. In order to significantly reduce the receiver complexity at the destination, a differential evolution (DE) based estimation algorithm is applied and the initialization and constraints for the convergence of the proposed DE algorithm are investigated. In order to detect the signal from multiple relays in the presence of unknown channels, MTOs, and MCFOs, novel optimal and sub-optimal minimum mean-square error receiver designs at the destination node are proposed. Simulation results show that the proposed estimation and compensation methods achieve full diversity gain in the presence of channel and synchronization impairments in multi-relay AF cooperative networks.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Smith, Stuart W., et al.
(author)
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Tree species that 'live slow, die older' enhance tropical peat swamp restoration : Evidence from a systematic review
- 2022
-
In: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 59:8, s. 1950-1966
-
Research review (peer-reviewed)abstract
- 1. Degraded tropical peatlands lack tree cover and are often subject to seasonal flooding and repeated burning. These harsh environments for tree seedlings to survive and grow are therefore challenging to revegetate. Knowledge on species performance from previous plantings represents an important evidence base to help guide future tropical peat swamp forest (TPSF) restoration efforts.2. We conducted a systematic review of the survival and growth of tree species planted in degraded peatlands across Southeast Asia to examine (1) species differences, (2) the impact of seedling and site treatments on survival and growth and (3) the potential use of plant functional traits to predict seedling survival and growth rates.3. Planted seedling monitoring data were compiled through a systematic review of journal articles, conference proceedings, reports, theses and unpublished datasets. In total, 94 study-sites were included, spanning three decades from 1988 to 2019, and including 141 indigenous peatland tree and palm species. Accounting for variable planting numbers and monitoring durations, we analysed three measures of survival and growth: (1) final survival weighted by the number of seedlings planted, (2) half-life, that is, duration until 50% mortality and (3) relative growth rates (RGR) corrected for initial planting height of seedlings.4. Average final survival was 62% and half-life was 33 months across all species, sites and treatments. Species differed significantly in survival and half-life. Seedling and site treatments had small effects with the strongest being higher survival of mycorrhizal fungi inoculated seedlings; lower survival, half-life and RGR when shading seedlings; and lower RGR and higher survival when fertilising seedlings. Leaf nutrient and wood density traits predicted TPSF species survival, but not half-life and RGR. RGR and half-life were negatively correlated, meaning that slower growing species survived for longer.5. Synthesis and applications. To advance tropical peat swamp reforestation requires expanding the number and replication of species planted and testing treatments by adopting control vs. treatment experimental designs. Species selection should involve slower growing species (e.g. Lophopetalum rigidum, Alstonia spatulata, Madhuca motleyana) that survive for longer and explore screening species based on functional traits associated with nutrient acquisition, flooding tolerance and recovery from fire.
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| 26. |
- Tronnier, Volker M., et al.
(author)
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The appropriate management of persisting pain after spine surgery : a European panel study with recommendations based on the RAND/UCLA method
- 2019
-
In: European spine journal. - : Springer. - 0940-6719 .- 1432-0932. ; 28:1, s. 31-45
-
Journal article (peer-reviewed)abstract
- Purpose: Management of patients with persisting pain after spine surgery (PPSS) shows significant variability, and there is limited evidence from clinical studies to support treatment choice in daily practice. This study aimed to develop patient-specific recommendations on the management of PPSS.Methods: Using the RAND/UCLA appropriateness method (RUAM), an international panel of 6 neurosurgeons, 6 pain specialists, and 6 orthopaedic surgeons assessed the appropriateness of 4 treatment options (conservative, minimally invasive, neurostimulation, and re-operation) for 210 clinical scenarios. These scenarios were unique combinations of patient characteristics considered relevant to treatment choice. Appropriateness had to be expressed on a 9-point scale (1 = extremely inappropriate, 9 = extremely appropriate). A treatment was considered appropriate if the median score was ≥ 7 in the absence of disagreement (≥ 1/3 of ratings in each of the opposite sections 1–3 and 7–9).Results: Appropriateness outcomes showed clear and specific patterns. In 48% of the scenarios, exclusively one of the 4 treatments was appropriate. Conservative treatment was usually considered appropriate for patients without clear anatomic abnormalities and for those with new pain differing from the original symptoms. Neurostimulation was considered appropriate in the case of (predominant) neuropathic leg pain in the absence of conditions that may require surgical intervention. Re-operation could be considered for patients with recurrent disc, spinal/foraminal stenosis, or spinal instability.Conclusions: Using the RUAM, an international multidisciplinary panel established criteria for appropriate treatment choice in patients with PPSS. These may be helpful to educate physicians and to improve consistency and quality of care.
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| 27. |
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| 28. |
- Assarsson, A., et al.
(author)
-
Kinetic and thermodynamic study of the interactions between human carbonic anhydrase variants and polystyrene nanoparticles of different size
- 2016
-
In: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 6:42, s. 35868-35874
-
Journal article (peer-reviewed)abstract
- The activity and adsorption of three variants of human carbonic anhydrase (HCA) with similar topology but variation in charge and stability were studied in the presence of carboxyl-modified polystyrene nanoparticles of different sizes ranging from 25 nm to 114 nm. The balance of forces driving the adsorption of carbonic anhydrase variants is affected by the physicochemical properties of the protein and the nanoparticle size. All enzymes are totally inhibited upon adsorption due to the transition towards a molten globule like state that lacks enzymatic activity. The size of the particle affects the adsorption of human carbonic anhydrase I and N-terminal truncated human carbonic anhydrase II. Investigations on pH effects indicate that the size of the particle modulates the lateral interactions at the protein layer for these particular variants whose adsorption is mainly driven by electrostatic forces. A third variant, human carbonic anhydrase II, instead shows no strong influence of nanoparticle size which supports an adsorption process mainly driven by the hydrophobic effect.
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| 29. |
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| 30. |
- Dimov, Aleksandar, et al.
(author)
-
Mutation testing framework for software reliability model analysis and reliability estimation
- 2010
-
In: Central and Eastern European Software Engineering Conference (CEE-SECR). - 9781457706066 ; , s. 163-169
-
Conference paper (peer-reviewed)abstract
- After several years of research, even today estimation of software reliability is extremely challenging. The undeterministic nature of the factors that contribute to the reliability estimation has led to the development of numerous statistical models for this purpose. One of the important factors that contribute to software reliability is testing. The aim of this paper is to use mutation testing for estimating the „true” reliability of a system and provide a framework for estimation of uncertainty bounds associated with testing and a measure for factors such as test coverage, time between failures and code coverage that contribute to the estimation of reliability and use mutation testing as a tool to create a software failure dataset. The approach is experimented with an open source search tool.
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| 31. |
- Fakhar-E-Alam, M., et al.
(author)
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Anticancer effects of nanometallic oxides and their ligands with photosensitizers in osteosarcoma cells
- 2015
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In: Journal of Optoelectronics and Advanced Materials. - : NATL INST OPTOELECTRONICS. - 1454-4164 .- 1841-7132. ; 17:11-12, s. 1808-1815
-
Journal article (peer-reviewed)abstract
- We studied the cytotoxic effects in Osteosarcoma (U2OS) cells to different nanosized metallic oxides e.g. zinc oxide nanowires (ZnO-NRs), manganese di-oxide nanowires (MnO2 NWs), ferric oxide nanoparticles (Fe2O3 NPs) individually and their connplexed forms with photosensitizers photofrin (R), 5-Aminolevulinic acid (5-ALA), and protoporphyrin IX (Pp IX). Cellular toxicity was assayed by cellular morphology, reactive oxygen species (ROS) detection, MTT assay under ultraviolet (UV), visible light and laser exposed conditions. Prominent cell death with above cited nanomaterials in their complexed forms with Photosensitizer was observed in labeled U2OS cells. This cell death might be due to their synergetic effect via the release of singlet oxygen species in Osteosarcoma cells showing their anticancer-cell effects.
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| 32. |
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| 33. |
- Isikman, Arif Onder, 1988, et al.
(author)
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Joint phase noise estimation and data detection in coded multi-input-multi-output systems
- 2014
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In: IET Communications. - : Institution of Engineering and Technology (IET). - 1751-8628 .- 1751-8636. ; 8:7, s. 981-989
-
Journal article (peer-reviewed)abstract
- The problem of joint oscillator phase noise (PHN) estimation and data detection for multi-input multi-output (MIMO) systems using bit-interleaved-coded modulation is analysed. A new MIMO receiver that iterates between the estimator and the detector, based on the expectation-maximisation (EM) framework, is proposed. It is shown that at high signal-to-noise ratios, a maximum a posteriori (MAP) estimator can be used to carry out the maximisation step of the EM algorithm. Moreover, to reduce the computational complexity of the proposed EM algorithm, a soft decision-directed extended Kalman filter-smoother (EKFS) is applied instead of the MAP estimator to track the PHN parameters. The numerical results show that by combining the proposed EKFS-based approach with an iterative detector that employs low-density parity check codes, PHN can be accurately tracked. The simulations also demonstrate that compared to the existing algorithms, the proposed iterative receiver can significantly enhance the performance of MIMO systems in the presence of PHN.
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| 34. |
- Johnson, Benjamin B., et al.
(author)
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Perlecan (HSPG2) promotes structural, contractile, and metabolic development of human cardiomyocytes
- 2024
-
In: Cell Reports. - : Elsevier. - 2211-1247. ; 43:1
-
Journal article (peer-reviewed)abstract
- Perlecan (HSPG2), a heparan sulfate proteoglycan similar to agrin, is key for extracellular matrix (ECM) maturation and stabilization. Although crucial for cardiac development, its role remains elusive. We show that perlecan expression increases as cardiomyocytes mature in vivo and during human pluripotent stem cell differentiation to cardiomyocytes (hPSC-CMs). Perlecan-haploinsuffient hPSCs (HSPG2(+/-)) differentiate efficiently, but late-stage CMs have structural, contractile, metabolic, and ECM gene dysregulation. In keeping with this, late -stage HSPG2(+/-) hPSC-CMs have immature features, including reduced alpha-actinin expression and increased glycolytic metabolism and proliferation. Moreover, perlecan-haploinsuffient engineered heart tissues have reduced tissue thickness and force generation. Conversely, hPSC-CMs grown on a perlecanpeptide substrate are enlarged and display increased nucleation, typical of hypertrophic growth. Together, perlecan appears to play the opposite role of agrin, promoting cellular maturation rather than hyperplasia and proliferation. Perlecan signaling is likely mediated via its binding to the dystroglycan complex. Targeting perlecan-dependent signaling may help reverse the phenotypic switch common to heart failure.
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| 35. |
- Kamat, Nasir, et al.
(author)
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Chemotherapy induced microsatellite instability and loss of heterozygosity in chromosomes 2, 5, 10, and 17 in solid tumor patients
- 2014
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In: Cancer Cell International. - : Springer Science and Business Media LLC. - 1475-2867. ; 14, s. 118-
-
Journal article (peer-reviewed)abstract
- Background: The inevitable side effects of the currently used chemotherapy are associated with serious syndromes. Genotoxic effects and consequent genetic instability may play an important role in these syndromes. The aim of the study was to evaluate chemotherapy-related microsatellite instability (MSI), loss of heterozygosity (LOH), and loss of mismatch repair (MMR) expression in solid tumor patients. Methods: Samples were collected from 117 de novo patients with solid tumors of different origins. Specimens, taken pre- and post-treatment, were screened for MSI and LOH in 10 microsatellite sequences in blood, and expression of five MMR proteins were analyzed in cancer tissues using immunohistochemistry. Statistical analysis included the use of; Fisher's exact test, Chi Square, and an inter-rater reliability test using Cohen's kappa coefficient. Results: Microsatellite analysis showed that 66.7% of the patients had MSI, including 23.1% high-positive MSI and 43.6% low-positive MSI. A large portion (41%) of the patients exhibited LOH in addition to MSI. MSI and LOH were detected in seven loci in which incidence rates ranged from 3.8% positive for Bat-26 to 34.6% positive for Tp53-Alu. Immunohistochemistry revealed that human mutL homolog 1 (hMLH1) expression was deficient in 29.1% of the patients, whereas 18.8%, 23.9%, 13.4%, and 9.7% were deficient for human mutS homolog 2 (hMSH2), P53, human mutS homolog 6 (hMSH6) and human post-meiotic segregation increased 2 (hPMS2), respectively. There was a significant correlation between MSI and LOH incidence in Tp53-Alu, Mfd41, and APC with low or deficient expression of hMLH1, hMSH2, and P53. A significant association between MSI and LOH, and incidence of secondary tumors was also evident. Conclusions: The negative correlation between MMR expression, MSI, and LOH and increased resistance to anti-cancer drugs and development of secondary cancers demonstrates a useful aid in early detection of potential chemotherapy-related side-effects. The diagnostic value demonstrated in our earlier study on breast cancer patients was confirmed for other solid tumors.
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| 36. |
- Kamat, Nasir, et al.
(author)
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High incidence of microsatellite instability and loss of heterozygosity in three loci in breast cancer patients receiving chemotherapy : a prospective study
- 2012
-
In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12, s. 373-
-
Journal article (peer-reviewed)abstract
- Background: The aim of the study was to evaluate potential chemotherapy-induced microsatellite instability, loss of heterozygosity, loss of expression in mismatch repair proteins and associations with clinical findings in breast cancer patients, especially resistance to chemotherapy and/or development of other tumors in the four years following chemotherapy treatment. Methods: A comprehensive study of chemotherapy-related effects with a follow-up period of 48 months post treatment was conducted. A total of 369 peripheral blood samples were collected from 123 de novo breast cancer patients. Microsatellite instability and loss of heterozygosity in five commonly used marker loci (including Tp53-Alu of the tumor suppressor gene TP53) were analyzed in blood samples. Sampling was conducted on three occasions; 4-5 weeks prior to the first chemotherapy session (pre-treatment), to serve as a baseline, followed by two consecutive draws at 12 weeks intervals from the first collection. Mismatch repair protein expression was evaluated in cancer tissues using immunohistochemistry for three mismatch-repair related proteins. Results: A total of 70.7% of the patients showed microsatellite instability for at least one locus, including 18.6% marked as high-positive and 52.1% as low-positive; 35.8% showed loss of heterozygosity in addition to microsatellite instability, while 29.3% exhibited microsatellite stability. The following incidence rates for microsatellite instability and loss of heterozygosity were detected: 39.1% positive for Tp53-Alu, 31.1% for locus Mfd41, and 25.3% for locus Mfd28. A higher occurrence of loss of heterozygosity was noted with alleles 399 and 404 of Tp53-Alu. The mismatch repair protein expression analysis showed that the chemotherapy caused a loss of 29.3% in hMLH1 expression, and 18.7% and 25.2% loss in hMSH2 and P53 expression, respectively. A strong correlation between low or deficient hMSH2 protein expression and occurrence of mismatch repair/loss of heterozygosity events in Mfd41, Tp53-Alu, and Mfd28 was evident. A significant association between mismatch repair/loss of heterozygosity and incidence of secondary tumors was also established. Conclusion: Our results suggest that microsatellite instability, loss of heterozygosity, and deficiency in mismatch repair may serve as early prognostic factors for potential chemotherapy-related side effects in breast cancer patients.
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| 37. |
- Kamat, Nasir, et al.
(author)
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Microsatellite instability and loss of heterozygosity detected in middle-aged patients with sporadic colon cancer : A retrospective study
- 2013
-
In: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 6:5, s. 1413-1420
-
Journal article (peer-reviewed)abstract
- Microsatellite instability (MSI) is a mutator phenotype that results from a defective mismatch repair (MMR) pathway. The present study examined the incidence of MSI and loss of heterozygosity (LOH) according to five markers from the panel of the National Cancer Institute (NCI) in 38 colorectal cancer (CRC) patients from the United Arab Emirates (UAE). MSI and LOH were analyzed using fragment analyses in a multiplex PCR setting on a capillary array electrophoresis platform. The expression of the MMR proteins, hMLH1 and hMSH2, was analyzed using immunohistochemistry. The cohort consisted of 17 females (44.7%) and 21 males (55.3%) with mean ages of 59.9 and 63.3 years, respectively. The overall MSI incidence was 31.3% (95% CI, 16.1-50.0), and included three patients with high MSI (MSI-H; 9.4%; 95% CI, 2.0-25.0) and seven patients with low MSI (MSI-L; 21.9%; 95% CI, 10.7-39). LOH was detected in three patients, while the remaining 25 patients (65.8%) showed no instability and were therefore classified as microsatellite stable (MSS). MSI was detected in the following screened markers: Bat25 in seven patients, Bat26 in three patients, adenomatous polyposis coli (APC; D5S346) in five patients, AFM093xh3 (D2S123) in two patients and Mfd15 (D17S250) in three patients. Of the five MSI-positive patients, four (80%) were evidently younger, aged 38, 48, 49 and 59 years, respectively. The MSI-H incidence (9.4%) was lower compared with that of other ethnic groups. In terms of the MMR proteins, hMLH1 expression was deficient in seven patients, of whom three were MSI-H patients, and hMSH2 was deficient in three patients. Fisher's exact test showed significant associations between hMLH1 and MSI when classified as MSS, MSI-L or MSI-H (P=0.0003). No such association was observed with abnormal MMR protein expression, age, cancer stage or gender.
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| 38. |
- Keck, Michaela Kristina, et al.
(author)
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Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification
- 2023
-
In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 145:1, s. 49-69
-
Journal article (peer-reviewed)abstract
- Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0–14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.
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| 39. |
- Lubcke, M., et al.
(author)
-
Twisted plasma column
- 2002
-
In: Phys. Lett.. ; B534, s. 195-200
-
Journal article (peer-reviewed)abstract
- We inspect a particular gauge field theory model that describes the properties of a variety of physical systems, including a charge neutral two-component plasma, a Gross-Pitaevskii functional of two charged Cooper pair condensates, and a limiting case of the bosonic sector in the Salam-Weinberg model. It has been argued that this field theory model also admits stable knot-like solitons. Here we produce numerical evidence in support for the existence of these solitons, by considering stable axis-symmetric solutions that can be thought of as straight twisted vortex lines clamped at the two ends. We compute the energy of these solutions as a function of the amount of twist per unit length. The result can be described in terms of a energy spectral function. We find that this spectral function acquires a minimum which corresponds to a nontrivial twist per unit length, strongly suggesting that the model indeed supports stable toroidal solitons.
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| 40. |
- Majid, Farzana, et al.
(author)
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Exploration of magnesium based MgX2O4 (X = Rh, Bi) spinels for thermoelectric applications using density functional theory (DFT)
- 2020
-
In: Journal of Materials Research and Technology. - : Elsevier. - 2238-7854. ; 9:3, s. 6135-6142
-
Journal article (peer-reviewed)abstract
- By using WIEN2k code, we investigated the mechanical and thermoelectric properties of magnesium based MgX2O4 (X = Rh and Bi) spinels. To compute the mechanical behavior of MgX2O4 (X = Rh and Bi), the Perdew-Bruke-Ernzerhof (PBEsol) flavor of generalized gradient approximation is used. From structural optimization, ground state lattice constant (a0) show a comparable with the previously evaluated theoretical and experimental values. The Born stability criterion represents that the investigated spinels are stable in the cubic phase and their ductile behaviors are observed by calculating Pugh’s ratio as well as Poisson ratio. Besides, thermodynamic behavior is concluded in terms of the Debye temperature. To investigate the electronic and thermoelectric behavior, the modified Becke and Johnson (mBJ) potential is employed. Finally, we investigated the thermoelectric behavior to represent the importance of studied spinels in thermoelectric appliances by calculating the figure of merit (ZT). High values of the See-beck coefficient and ZT at room temperature explores the potential of the studied spinels in thermoelectric devices.
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| 41. |
- Nasir, Ali Arshad, et al.
(author)
-
Estimation of Synchronization Parameters in AF Cooperative Networks
- 2012
-
In: IEEE International Conference on Communications. - 1550-3607. - 9781457720529 ; , s. 3713-3717
-
Conference paper (peer-reviewed)abstract
- In cooperative networks, multiple carrier frequencyoffsets (MCFOs) and multiple timing offsets (MTOs) originate due to multiple distributed nodes. In this paper, algorithms for joint estimation of these parameters and channels in amplify-and-forward (AF) relaying networks are proposed. A new training model and transceiver structure at the relays for achieving synchronization throughout the network is devised. New exact closed-form expressions for the Cram´er-Rao lower bounds (CRLBs) for the multi-parameter estimation problem are derived. An estimation method is proposed for jointly estimating MCFOs, MTOs, and channel gains at the destination based on space-alternating generalized expectation maximization (SAGE) and compared to a computationally-intensiveleast squares (LS) approach. The proposed estimator’s performance is shown to be close to the CRLB at mid-to-high signal-to-noise ratio (SNR) resulting in significant cooperative performance gains in the presence of practical impairments.
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| 42. |
- Nasir, Ali Arshad, et al.
(author)
-
Timing and Carrier Synchronization with Channel Estimation in Multi-Relay Cooperative Networks
- 2012
-
In: IEEE Transactions on Signal Processing. - 1941-0476 .- 1053-587X. ; 60:2, s. 793-811
-
Journal article (peer-reviewed)abstract
- Multiple distributed nodes in cooperative networksgenerally are subject to multiple carrier frequency offsets (MCFOs)and multiple timing offsets (MTOs), which result in time varying channels and erroneous decoding. This paper seeks to develop estimation and detection algorithms that enable cooperative communications for both decode-and-forward (DF) and amplify-and-forward (AF) relaying networks in the presence of MCFOs, MTOs, and unknown channel gains. A novel transceiver structure at the relays for achieving synchronization in AF-relaying networks is proposed. New exact closed-form expressions for the Cramér-Rao lower bounds (CRLBs) for the multi-parameter estimation problem are derived. Next, two iterative algorithms based on the expectation conditional maximization (ECM) and space-alternating generalized expectation-maximization (SAGE) algorithms are proposed for jointly estimating MCFOs, MTOs, and channel gains at the destination. Though the global convergence of the proposed ECM and SAGE estimators cannot be shown analytically, numerical simulations indicate that through appropriate initialization the proposed algorithms can estimate channel and synchronization impairments in a few iterations. Finally, a maximum likelihood (ML) decoder is devised for decoding the received signal at the destination in the presence of MCFOs and MTOs. Simulation results show that through the application of the proposed estimation and decoding methods, cooperative systems result in significant performance gains even in presence of impairments.
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| 43. |
- Nasir, Irem, 1987, et al.
(author)
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Ratiometric Single-Molecule FRET Measurements to Probe Conformational Subpopulations of Intrinsically Disordered Proteins
- 2020
-
In: Current protocols in chemical biology. - : Wiley. - 2160-4762 .- 2160-4762. ; 12:1
-
Journal article (peer-reviewed)abstract
- Over the past few decades, numerous examples have demonstrated that intrinsic disorder in proteins lies at the heart of many vital processes, including transcriptional regulation, stress response, cellular signaling, and most recently protein liquid-liquid phase separation. The so-called intrinsically disordered proteins (IDPs) involved in these processes have presented a challenge to the classic protein "structure-function paradigm," as their functions do not necessarily involve well-defined structures. Understanding the mechanisms of IDP function is likewise challenging because traditional structure determination methods often fail with such proteins or provide little information about the diverse array of structures that can be related to different functions of a single IDP. Single-molecule fluorescence methods can overcome this ensemble-average masking, allowing the resolution of subpopulations and dynamics and thus providing invaluable insights into IDPs and their function. In this protocol, we describe a ratiometric single-molecule Förster resonance energy transfer (smFRET) routine that permits the investigation of IDP conformational subpopulations and dynamics. We note that this is a basic protocol, and we provide brief information and references for more complex analysis schemes available for in-depth characterization. This protocol covers optical setup preparation and protein handling and provides insights into experimental design and outcomes, together with background information about theory and a brief discussion of troubleshooting. © 2020 by John Wiley & Sons, Inc. Basic Protocol: Ratiometric smFRET detection and analysis of IDPs Support Protocol 1: Fluorophore labeling of a protein through maleimide chemistry Support Protocol 2: Sample chamber preparation Support Protocol 3: Determination of direct excitation of acceptor by donor excitation and leakage of donor emission to acceptor emission channel.
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| 44. |
- Nasir, Irem, 1987, et al.
(author)
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Single-molecule fluorescence studies of intrinsically disordered proteins and liquid phase separation
- 2019
-
In: Biochimica et Biophysica Acta - Proteins and Proteomics. - : Elsevier BV. - 1878-1454 .- 1570-9639. ; 1867:10, s. 980-987
-
Research review (peer-reviewed)abstract
- Intrinsically disordered proteins (IDPs) are ubiquitous in proteomes and serve in a range of cellular functions including signaling, regulation, transport and enzyme function. IDP misfunction and aggregation are also associated with several diseases including neurodegenerative diseases and cancer. During the past decade, single-molecule methods have become popular for detailed biophysical and structural studies of these complex proteins. This work has included recent applications to cellular liquid-liquid phase separation (LLPS), relevant for functional dynamics of membraneless organelles such as the nucleolus and stress granules. In this concise review, we cover the conceptual motivations for development and application of single-molecule fluorescence methods for such IDP studies. We follow with a few key examples of systems and biophysical problems that have been addressed, and conclude with thoughts for emerging and future directions.
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| 45. |
- Nasir, Muhammad Anis Uddin, et al.
(author)
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Fully dynamic algorithm for top-k densest subgraphs
- 2017
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In: CIKM '17 Proceedings of the 2017 ACM on Conference on Information and Knowledge Management. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450349185 ; , s. 1817-1826
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Conference paper (peer-reviewed)abstract
- Given a large graph, the densest-subgraph problem asks to find a subgraph with maximum average degree. When considering the top-k version of this problem, a nattive solution is to iteratively find the densest subgraph and remove it in each iteration. However, such a solution is impractical due to high processing cost. The problem is further complicated when dealing with dynamic graphs, since adding or removing an edge requires re-running the algorithm. In this paper, we study the top-k densest-subgraph problem in the sliding-window model and propose an efficient fully-dynamic algorithm. The input of our algorithm consists of an edge stream, and the goal is to find the node-disjoint subgraphs that maximize the sum of their densities. In contrast to existing state-of-the-art solutions that require iterating over the entire graph upon any update, our algorithm profits from the observation that updates only affect a limited region of the graph. Therefore, the top-k densest subgraphs are maintained by only applying local updates. We provide a theoretical analysis of the proposed algorithm and show empirically that the algorithm offen generates denser subgraphs than state-of-the-art competitors. Experiments show an improvement in efficiency of up to five orders of magnitude compared to state-of-the-art solutions.
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| 46. |
- Nasir, Mehwish Huma, et al.
(author)
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Calcium-, magnesium-, and yttrium-doped lithium nickel phosphate nanomaterials as high-performance catalysts for electrochemical water oxidation reaction
- 2024
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In: Nanotechnology Reviews. - : Walter de Gruyter. - 2191-9089 .- 2191-9097. ; 13:1
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Journal article (peer-reviewed)abstract
- Electrochemical water oxidation reaction (WOR) lies among the most forthcoming approaches toward eco-conscious manufacturing of green hydrogen owing to its environmental favors and high energy density values. Its vast commoditization is restricted by high-efficiency and inexpensive catalysts that are extensively under constant research. Herein, calcium, magnesium, and yttrium doped lithium nickel phosphate olivines (LiNi1-xMxPO, LNMP; x = 0.1-0.9; M = Ca2+, Mg2+, and Y3+) were synthesized via non-aqueous sol-gel method and explored for catalytic WOR. Lithium nickel phosphates (LNP) and compositions were characterized via Fourier transform infrared, scanning electron microscopy, X-ray diffraction, and energy dispersive X-ray diffraction techniques for the structural and morphological analyses. Glassy carbon electrode altered with the LNMPs when studied in a standard redox system of 5 mM KMnO4, displayed that yttrium doped LNP, i.e. LNYP-3 exhibits the highest active surface area (0.0050 cm(2)) displaying the lowest average crystallite size (D-avg) i.e. similar to 7 nm. Electrocatalytic behavior monitored in KOH showed that LNMP-2 offers the highest rate constant "k(o)," value, i.e. 3.9 10(-2) cm s(-1) and the largest diffusion coefficient "D-o," i.e. 5.2 x 10(-5) cm(2) s(-1). Kinetic and thermodynamic parameters demonstrated the facilitated electron transfer and electrocatalytic properties of proposed nanomaterials. Water oxidation peak current density values were indicative of the robust catalysis and facilitated water oxidation process besides lowering the Faradic onset potential signifying the transformation of less LNP into more conducive LNMP toward water oxidation.
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| 47. |
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