| 1. |
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| 2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 4. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Sbarra, AN, et al.
(författare)
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Mapping routine measles vaccination in low- and middle-income countries
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
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Tidskriftsartikel (refereegranskat)abstract
- The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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| 9. |
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| 10. |
- Lozano, Rafael, et al.
(författare)
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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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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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| 11. |
- Stanaway, Jeffrey D., et al.
(författare)
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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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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Tidskriftsartikel (refereegranskat)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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| 12. |
- Murray, Christopher J. L., et al.
(författare)
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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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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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| 13. |
- Feigin, Valery L., et al.
(författare)
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Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2019
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:5, s. 459-480
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.Funding: Bill & Melinda Gates Foundation.
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| 14. |
- Feigin, Valery L., et al.
(författare)
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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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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
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Tidskriftsartikel (refereegranskat)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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| 15. |
- Mokdad, Ali H., et al.
(författare)
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Adolescent health in the Eastern Mediterranean Region : findings from the global burden of disease 2015 study
- 2018
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Ingår i: International Journal of Public Health. - : SPRINGER BASEL AG. - 1661-8556 .- 1661-8564. ; 63, s. 79-96
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Tidskriftsartikel (refereegranskat)abstract
- The 22 countries of the East Mediterranean Region (EMR) have large populations of adolescents aged 10-24 years. These adolescents are central to assuring the health, development, and peace of this region. We described their health needs. Using data from the Global Burden of Disease Study 2015 (GBD 2015), we report the leading causes of mortality and morbidity for adolescents in the EMR from 1990 to 2015. We also report the prevalence of key health risk behaviors and determinants. Communicable diseases and the health consequences of natural disasters reduced substantially between 1990 and 2015. However, these gains have largely been offset by the health impacts of war and the emergence of non-communicable diseases (including mental health disorders), unintentional injury, and self-harm. Tobacco smoking and high body mass were common health risks amongst adolescents. Additionally, many EMR countries had high rates of adolescent pregnancy and unmet need for contraception. Even with the return of peace and security, adolescents will have a persisting poor health profile that will pose a barrier to socioeconomic growth and development of the EMR.
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| 16. |
- Mokdad, Ali H., et al.
(författare)
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Diabetes mellitus and chronic kidney disease in the Eastern Mediterranean Region : findings from the Global Burden of Disease 2015 study
- 2018
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Ingår i: International Journal of Public Health. - : SPRINGER BASEL AG. - 1661-8556 .- 1661-8564. ; 63, s. 177-186
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Tidskriftsartikel (refereegranskat)abstract
- We used findings from the Global Burden of Disease 2015 study to update our previous publication on the burden of diabetes and chronic kidney disease due to diabetes (CKD-DM) during 1990-2015. We extracted GBD 2015 estimates for prevalence, mortality, and disability-adjusted life years (DALYs) of diabetes (including burden of low vision due to diabetes, neuropathy, and amputations and CKD-DM for 22 countries of the EMR from the GBD visualization tools. In 2015, 135,230 (95% UI 123,034-148,184) individuals died from diabetes and 16,470 (95% UI 13,977-18,961) from CKD-DM, 216 and 179% increases, respectively, compared to 1990. The total number of people with diabetes was 42.3 million (95% UI 38.6-46.4 million) in 2015. DALY rates of diabetes in 2015 were significantly higher than the expected rates based on Socio-demographic Index (SDI). Our study showed a large and increasing burden of diabetes in the region. There is an urgency in dealing with diabetes and its consequences, and these efforts should be at the forefront of health prevention and promotion.
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| 17. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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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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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)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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| 18. |
- Ibrahim, Mahmoud A. A., et al.
(författare)
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In silico drug discovery of major metabolites from spices as SARS-CoV-2 main protease inhibitors
- 2020
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Ingår i: Computers in Biology and Medicine. - : Elsevier BV. - 0010-4825 .- 1879-0534. ; 126
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus Disease 2019 (COVID-19) is an infectious illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), originally identified in Wuhan, China (December 2019) and has since expanded into a pandemic. Here, we investigate metabolites present in several common spices as possible inhibitors of COVID-19. Specifically, 32 compounds isolated from 14 cooking seasonings were examined as inhibitors for SARS-CoV-2 main protease (MPrn), which is required for viral multiplication. Using a drug discovery approach to identify possible antiviral leads, in silico molecular docking studies were performed. Docking calculations revealed a high potency of salvianolic acid A and curcumin as MPr inhibitors with binding energies of 9.7 and 9.2 kcal/mol, respectively. Binding mode analysis demonstrated the ability of salvianolic acid A and curcumin to form nine and six hydrogen bonds, respectively with amino acids proximal to MPr 's active site. Stabilities and binding affinities of the two identified natural spices were calculated over 40 ns molecular dynamics simulations and compared to an antiviral protease inhibitor (lopinavir). Molecular mechanics-generalized Born surface area energy calculations revealed greater salvianolic acid A affinity for the enzyme over curcumin and lopinavir with energies of 44.8, 34.2 and 34.8 kcal/mol, respectively. Using a STRING database, protein-protein interactions were identified for salvianolic acid A included the biochemical signaling genes ACE, MAPK14 and ESR1; and for curcumin, EGFR and TNF. This study establishes salvianolic acid A as an in silico natural product inhibitor against the SARS-CoV-2 main protease and provides a promising inhibitor lead for in vitro enzyme testing.
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| 19. |
- Abosedera, Dalia A., et al.
(författare)
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Metabolomic profile and in vitro evaluation of the cytotoxic activity of Asphodelus microcarpus against human malignant melanoma cells A375
- 2022
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Ingår i: Arabian Journal of Chemistry. - : Elsevier. - 1878-5352 .- 1878-5379. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- Melanoma is a huge worldwide health problem that must be handled more effectively with better therapeutic options. As a result, new treatment drugs are required to treat this condition. The goal of this study was to investigate the cytotoxic activity of the anthraquinone-rich fractions obtained from Asphodelus microcarpus against human melanoma cell A375. On these melanoma cell lines; the cytotoxicity of these fractions had never been studied before. Liquid chromatography linked to mass spectrometry (LC-MS-MS) and Nuclear Magnetic Resonance was used to determine the chemical profiles of these fractions. The cytotoxicity of the fractions studied was determined by measuring cell viability and calculating IC50 values. Both ethyl acetate (EtOAC) and the precipitate fractions (PPT) exhibited selective cytotoxicity on human melanoma A 375 cell line with IC50 values of 83 and 65 mu g/mL, respectively. The antiproliferative properties of EtOAc fraction and PPT were supported by a noticeable decrease in cell numbers during the G2/M cell cycle arrest. Our findings suggest that the anthraquinone content of A. microcarpus tubers is responsible for its anti-proliferative and apoptotic properties and that further in vivo investigations should be conducted to establish the viability of using them to treat human melanomas.
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| 20. |
- Hamed, A. N. E., et al.
(författare)
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Chemical constituents from Carica papaya Linn. leaves as potential cytotoxic, EGFR(wt) and aromatase (CYP19A) inhibitors; a study supported by molecular docking
- 2022
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Ingår i: Rsc Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 12:15, s. 9154-9162
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Tidskriftsartikel (refereegranskat)abstract
- The phytochemical investigation of the hydromethanolic extract of Carica papaya Linn. leaves (Caricaceae) resulted in the isolation and characterization of ten compounds, namely; carpaine (1), methyl gallate (2), loliolide (3), rutin (4), clitorin (5), kaempferol-3-O-neohesperidoside (6), isoquercetin (7), nicotiflorin (8) and isorhamnetin-3-O-beta-D-gluacopyranoside (9). The compounds 2, 3, 5-7 and 9 were isolated for the first time from the genus Carica. An in vitro breast cancer cytotoxicity study was evaluated with an MCF-7 cell line using the MTT assay. Methyl gallate and ditorin demonstrated the most potent cytotoxic activities with an IC50 of 1.11 +/- 0.06 and 2.47 +/- 0.14 mu M, respectively. Moreover, methyl gallate and nicotiflorin exhibited potential EGFR(wt) kinase inhibition activities with an IC50 of 37.3 +/- 1.9 and 41.08 +/- 2.1 nM, respectively, compared with the positive control erlotinib (IC50 = 35.94 +/- 1.8 nM). On the other hand, clitorin and nicotiflorin displayed the strongest aromatase kinase inhibition activities with an IC50 of 77.41 +/- 4.53 and 92.84 +/- 5.44 nM, respectively. Clitorin was comparable to the efficacy of the standard drug letrozole (IC50 = 77.72 +/- 4.55). Additionally, molecular docking simulations of the isolated compounds to EGFR and human placental aromatase cytochrome P450 (CYP19A1) were evaluated. Methyl gallate linked with the EGFR receptor through hydrogen bonding with a pose score of -4.5287 kcal mol(-1) and RMSD value of 1.69 angstrom. Ditorin showed the strongest interaction with aromatase (CYP19A1) for the breast cancer receptor with a posing score of -14.2074 and RMSD value of 1.56 angstrom. Compounds (1-3) possessed a good bioavallability score with a 0.55 value.
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| 21. |
- Moreau, Thomas, et al.
(författare)
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Benchopt : Reproducible, efficient and collaborative optimization benchmarks
- 2022
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Ingår i: Advances in Neural Information Processing Systems 35 - 36th Conference on Neural Information Processing Systems, NeurIPS 2022. - 1049-5258. - 9781713871088 ; 35, s. 25404-25421
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Konferensbidrag (refereegranskat)abstract
- Numerical validation is at the core of machine learning research as it allows to assess the actual impact of new methods, and to confirm the agreement between theory and practice. Yet, the rapid development of the field poses several challenges: researchers are confronted with a profusion of methods to compare, limited transparency and consensus on best practices, as well as tedious re-implementation work. As a result, validation is often very partial, which can lead to wrong conclusions that slow down the progress of research. We propose Benchopt, a collaborative framework to automate, reproduce and publish optimization benchmarks in machine learning across programming languages and hardware architectures. Benchopt simplifies benchmarking for the community by providing an off-the-shelf tool for running, sharing and extending experiments. To demonstrate its broad usability, we showcase benchmarks on three standard learning tasks: ℓ2-regularized logistic regression, Lasso, and ResNet18 training for image classification. These benchmarks highlight key practical findings that give a more nuanced view of the state-of-the-art for these problems, showing that for practical evaluation, the devil is in the details. We hope that Benchopt will foster collaborative work in the community hence improving the reproducibility of research findings.
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| 22. |
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| 23. |
- Al-Melh, M. A., et al.
(författare)
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Comparison between Topical and Injection Anesthetics on Pain Related to Orthodontic Miniscrew Placement : A Split-mouth Study
- 2021
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Ingår i: Journal of Contemporary Dental Practice. - : Jaypee Brothers Medical Publishers (P) Ltd. - 1526-3711. ; 22:6, s. 637-643
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Tidskriftsartikel (refereegranskat)abstract
- Aims and objectives: The aims of this study were to compare the anesthetic effect of a lidocaine/prilocaine (L/P) topical anesthetic with placebo on pain from needle sticks and to compare the anesthetic effect of the L/P topical anesthetic with an infiltrative anesthetic on pain from orthodontic miniscrew placement. Materials and methods: Pain elimination was analyzed from two interventions: (a) needle stick and (b) miniscrew insertion. When assessing pain from needle stick, one side of the mandible received 2.5% lidocaine/2.5% prilocaine topical anesthetic, and the other side received placebo. When evaluating pain from miniscrew placement, one side of the mandible received L/P topical anesthetic and the other side received infiltrative anesthetic. The findings were recorded on a Visual Analogue Scale after needle stick and after miniscrew placement. Subjective assessment was analyzed by a questionnaire. Results: The L/P topical anesthetic significantly eliminated the pain from needle stick (Mann–Whitney test of medians, 29.0 vs 0.0, respectively, p<0.001). However, the injection anesthetic eliminated the pain from the miniscrew placement better than the L/P topical anesthetic (Mann–Whitney test of medians, 0.0 vs 5.5, respectively, p<0.001). Eighty percent of the subjects felt more comfortable with L/P topical anesthetic than injection anesthetic. Pain from needle stick pain was reported to be the most uncomfortable part of the study. Conclusion: The L/P topical anesthetic efficiently eliminated pain from needle stick. The L/P topical anesthetic did not completely eliminate pain from miniscrew placement as the injection anesthesia, but it did reduce pain to tolerable levels. Clinical significance: L/P topical anesthetics can significantly eliminate pain from needle stick injections, and L/P topical anesthetics can reduce pain from orthodontic miniscrew placement to tolerable levels. © Jaypee Brothers Medical Publishers. 2021 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated
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| 24. |
- Awoyera, Paul O., et al.
(författare)
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Structural retrofitting of RC slabs using bamboo fibre laminate: Flexural performance and crack patterns
- 2024
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Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Enhancing the durability of structural elements is a viable approach to promote sustainability in civil engineering. Research has shown that well-maintained slabs outperform degraded ones, which deteriorate rapidly due to insufficient upkeep. The occurrence of cracking and deformation in slabs subjected to sustained loads significantly impacts their functionality. However, the implementation of appropriate retrofitting techniques utilizing locally available materials can effectively minimize deflection and crack propagation while also improving flexural capacity. This particular study aimed to evaluate the flexural performance of slabs that were retrofitted using bamboo fibre laminate (BFL). Also, the study investigated two alternative replacement methods alongside the conventional mix; one involved replacing all fine aggregates with ceramic fine aggregate and the other involved a complete replacement of coarse aggregates with ceramic coarse aggregate. These mixes were represented in both the retrofitted and non-retrofitted samples. The retrofitting process included using the combined external bonding and near surface-mounted method. Twelve slab samples were made, with six being non-retrofitted and the other six retrofitted with BFL. Each of the samples had dimensions of 300 mm × 300 mm × 50 mm for reinforced concrete (RC) slabs. The slabs were tested employing the three point-bending system, and the retrofitted slabs with the conventional mix exhibited the highest ultimate failure load and flexural strength (62.1 kN), which compared to the non-retrofitted slabs of the same mix was a 60.76% increase. Additionally, the study did a thorough analysis of the presence of flexural and diagonal shear cracks, as well as the occurrence of debonding between BFL and the slabs. Non-destructive tests were also conducted on the slab samples to further confirm accurate results. These findings offer helpful insights into the development and application of a sustainable retrofitting material that can remarkably improve RC slabs.
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| 25. |
- Badr, Christian E, et al.
(författare)
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Lanatoside C sensitizes glioblastoma cells to tumor necrosis factor-related apoptosis-inducing ligand and induces an alternative cell death pathway.
- 2011
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Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1522-8517 .- 1523-5866. ; 13:11, s. 1213-1224
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Tidskriftsartikel (refereegranskat)abstract
- Human glioblastoma (GBM) cells are notorious for their resistance to apoptosis-inducing therapeutics. We have identified lanatoside C as a sensitizer of GBM cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death partly by upregulation of the death receptor 5. We show that lanatoside C sensitizes GBM cells to TRAIL-induced apoptosis in a GBM xenograft model in vivo. Lanatoside C on its own serves as a therapeutic agent against GBM by activating a caspase-independent cell death pathway. Cells treated with lanatoside C showed necrotic cell morphology with absence of caspase activation, low mitochondrial membrane potential, and early intracellular ATP depletion. In conclusion, lanatoside C sensitizes GBM cells to TRAIL-induced cell death and mitigates apoptosis resistance of glioblastoma cells by inducing an alternative cell death pathway. To our knowledge, this is one of the first examples of use of caspase-independent cell death inducers to trigger tumor regression in vivo. Activation of such mechanism may be a useful strategy to counter resistance of cancer cells to apoptosis.
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| 26. |
- Badr, Hussein O., et al.
(författare)
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Bottom-up, scalable synthesis of anatase nanofilament-based two-dimensional titanium carbo-oxide flakes
- 2022
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Ingår i: Materials Today. - : ELSEVIER SCI LTD. - 1369-7021 .- 1873-4103. ; 54
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Tidskriftsartikel (refereegranskat)abstract
- Two-dimensional (2D) materials offer advantages that their 3D counterparts do not. The conventional method for the bulk synthesis of 2D materials has predominantly been through etching layered solids. Herein, we convert - through a bottom-up approach - 10 binary and ternary titanium carbides, nitrides, borides, phosphides, and silicides into 2D flakes by immersing them in a tetramethylammonium hydroxide solution at temperatures in the 25-85 degrees C range. Based on X-ray diffraction, density functional theory, X-ray photoelectron, electron energy loss, Raman, X-ray absorption near edge structure spectroscopies, transmission and scanning electron microscope images and selected area diffraction, we conclude that the resulting flakes are carbon containing anatase-based layers that are, in turn, comprised of approximate to 6 x 10 angstrom(2) nanofilaments in cross-section some of which are few microns long. Electrodes made from some of these films performed well in lithium-ion and lithium-sulphur systems. These materials also reduce the viability of cancer cells thus showing potential in biomedical applications. Synthesizing 2D materials, at near ambient conditions, with non-layered, inexpensive, green precursors (e.g., TiC) is paradigm shifting and will undoubtedly open new and exciting avenues of research and applications.
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| 27. |
- Hanner, Luke A., et al.
(författare)
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Synthesis, characterization and first principle modelling of the MAB phase solid solutions: (Mn1-xCrx)(2)AlB2 and (Mn1-xCrx)(3)AlB4
- 2021
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Ingår i: Materials Research Letters. - : Taylor & Francis. - 2166-3831. ; 9:2, s. 112-118
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Tidskriftsartikel (refereegranskat)abstract
- The MAB phases are a family of layered ternary transition metal borides, with atomically laminated crystal structures comprised of transition metal boride (M-B) layers interleaved by single, or double, Al (A) layers. Herein, density functional theory is implemented to evaluate the thermodynamic stability of disordered (Mn1-xCrx)(2)AlB2, and disordered and ordered (Mn1-xCrx)(3)AlB4 quaternaries. The (Mn1-xCrx)(2)AlB2 solid solutions were synthesized over the entire range of substitution. A (Mn1-xCrx)(3)AlB4 solid solution was produced, on the base of Cr3AlB4, to form (Mn0.33Cr0.66)(3)AlB4. Powder X-ray diffraction shows lattice parameter shifts and unit cell expansions indicative of successful solid solution formations.
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| 28. |
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| 29. |
- Lycke, Jan, 1956, et al.
(författare)
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Acyclovir treatment of relapsing-remitting multiple sclerosis. A randomized, placebo-controlled, double-blind study.
- 1996
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Ingår i: Journal of neurology. - 0340-5354. ; 243:3, s. 214-24
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Tidskriftsartikel (refereegranskat)abstract
- Acyclovir treatment was used in a randomized, double-blind, placebo-controlled clinical trial with parallel groups to test the hypothesis that herpes virus infections are involved in the pathogenesis of multiple sclerosis (MS). Sixty patients with the relapsing-remitting form of MS were randomized to either oral treatment with 800 mg acyclovir or placebo tablets three times daily for 2 years. The clinical effect was investigated by an extensive test battery consisting of neurological examinations, neuro-ophthalmological and neuropsychological tests, and evoked potentials. Results were based on "intent-to-treat" data and the primary outcome measure was the exacerbation rate. In the acyclovir group (n = 30), 62 exacerbations were recorded during the treatment period, yielding an annual exacerbation rate of 1.03. The placebo group (n = 30) had 94 exacerbations and an annual exacerbation rate of 1.57. Thus, 34% fewer exacerbations were encountered during acyclovir treatment. This difference in exacerbation rate between the treatment groups was not significant (P = 0.083). However, this trend to a lower disease activity in acyclovir-treated patients was supported in subsequent data analysis. If the patients were grouped according to exacerbation frequencies, i.e. into low (0-2), medium (3-5) and high (6-8) rate groups, the difference between acyclovir and placebo treatment was significant (P = 0.017). Moreover, in a subgroup of the population with a duration of the disease of at least 2 years providing an exacerbation rate base-line before entry, individual differences in exacerbation rates were compared between the 2-year pre-study period and the study period in acyclovir-treated (n = 19) and placebo (n = 20) patients and acyclovir-treated patients showed a significant reduction of exacerbations (P = 0.024). Otherwise, neurological parameters were essentially unaffected by acyclovir treatment and there were no convincing signs of reduced neurological deterioration in the acyclovir group. This study indicates that acyclovir treatment might inhibit the triggering of MS exacerbations and thus suggests that acyclovir-susceptible viruses might be involved in the pathogenesis of MS. This possibility warrants further investigation.
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| 30. |
- Manee, Manee M, et al.
(författare)
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Omics in the Red Palm Weevil Rhynchophorus ferrugineus (Olivier) (Coleoptera : Curculionidae)
- 2023
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Ingår i: Insects. - : MDPI AG. - 2075-4450. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- The red palm weevil (RPW), Rhynchophorus ferrugineus (Coleoptera: Curculionidae), is the most devastating pest of palm trees worldwide. Mitigation of the economic and biodiversity impact it causes is an international priority that could be greatly aided by a better understanding of its biology and genetics. Despite its relevance, the biology of the RPW remains poorly understood, and research on management strategies often focuses on outdated empirical methods that produce sub-optimal results. With the development of omics approaches in genetic research, new avenues for pest control are becoming increasingly feasible. For example, genetic engineering approaches become available once a species's target genes are well characterized in terms of their sequence, but also population variability, epistatic interactions, and more. In the last few years alone, there have been major advances in omics studies of the RPW. Multiple draft genomes are currently available, along with short and long-read transcriptomes, and metagenomes, which have facilitated the identification of genes of interest to the RPW scientific community. This review describes omics approaches previously applied to RPW research, highlights findings that could be impactful for pest management, and emphasizes future opportunities and challenges in this area of research.
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| 31. |
- Monstein, Hans-Jurg, 1946-, et al.
(författare)
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Identification of enterococcal isolates by temperature gradient gel electrophoresis and partial sequence analysis of PCR-amplified 16S rDNA variable V6 regions
- 2001
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - 0903-4641 .- 1600-0463. ; 109:3, s. 209-216
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Tidskriftsartikel (refereegranskat)abstract
- Based on partial sequence analysis of PCR-amplified 16S rDNA variable V6 regions of 14 enterococcal type strains, Enterococcus faecalis, Enterococcus mundtii, Enterococcus gallinarum, Enterococcus avium, Enterococcus raffinosus and Enterococcus saccharolyticus showed characteristic sequence motifs which made it possible to separate them into six individual species lines. Furthermore, two species cluster groups could be identified, including (i) Enterococcus faecium, Enterococcus durans, Enterococcus hirae, Enterococcus malodoratus, and (ii) Enterococcus casseliflavus/Enterococcus flavescens, Enterococcus pseudoavium, Enterococcus dispar and Enterococcus sulfureus. There were identical DNA sequences in the V6 region within each group. Temporal temperature gradient gel electrophoresis (TTGE) of the PCR products from 16 type strains, 12 enterococcal reference strains and 8 clinical isolates revealed that a single nucleotide divergence in DNA sequences was sufficient for separation, identification and division of the studied enterococcal strains into corresponding TTGE profiles. It was concluded that partial DNA sequence analysis and TTGE profiling of PCR-amplified 16S rDNA variable V6 regions provide useful tools for the identification of clinically important Enterococcus spp.
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| 32. |
- Shavalieva, Gulnara, 1987, et al.
(författare)
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Sustainability assessment using local lazy learning: The case of post-combustion CO2 capture solvents
- 2018
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Ingår i: Computer Aided Chemical Engineering. - 1570-7946. ; 44, s. 823-828
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The consideration of sustainability is very important for the assessment of life cycle, environmental, health and safety properties of chemicals used in various applications. The screening of wide ranges of molecular structures, prior to the identification of the optimum and most sustainable options, requires the use of efficient and inclusive predictive models. Group contribution (GC) models are popular for the evaluation of numerous molecular options, but they support the calculation of few properties related to sustainability, while their predictive capabilities are often limited by significant data gaps. To address such challenges, we propose the use of a local learning approach as a means of evaluating sustainability properties for a wide range of molecular structures. Supplementing GC methods with data mining ones, such as local lazy learning approaches and exploiting molecular similarities has a potential to improve the predictive capacity of sustainability indices and offers an alternative when GC methods or empirical models are not available for life cycle assessment (LCA) and environmental, health and safety (EHS) hazard assessment indicators. The proposed approach is applied to predict a set of properties (bioaccumulation, persistence and acute aquatic toxicity) of 101 commercial solvents for post-combustion CO2capture.
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| 33. |
- Shokry, Dina M., et al.
(författare)
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Moringa oleifera leaves extract enhances fresh and cryopreserved semen characters of Barki rams
- 2020
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Ingår i: Theriogenology. - : ELSEVIER SCIENCE INC. - 0093-691X .- 1879-3231. ; 153, s. 133-142
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Tidskriftsartikel (refereegranskat)abstract
- This study was carried out to evaluate the efficacy of Moringa oleifera leaves extract (MOLE) to improve the characters of fresh and cryopreserved semen of Barki rams compared to vitamin E and Selenium combination. Twenty-four mature Barki rams (50-70 Kg) were randomly assigned into three groups, eight rams each. The first group was given distilled water orally. The second group was given MOLE orally daily at a dose of 40 mg/kg. The third group was injected with a combination of vitamin E and selenium at a dose of 3 ml (4.5 mg sodium selenite and 204 mg vitamin E)/head i.m twice a week for 64 days. Moringa oleifera leaves extract increased semen volume, sperm concentration, activities of seminal plasma catalase, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), alkaline phosphatase (ALP), acid phosphatase (ACP), levels of ascorbic acid and total antioxidant capacity (TAC). In addition, it significantly increased post thawing sperms motility, viability index, membrane integrity, and the activities of post thawing semen antioxidant enzymes. While it decreased seminal plasma concentration of malondialdehyde (MDA) and acrosomal defects and DNA fragmentation of sperm in cryopreserved semen. Vitamin E and selenium decreased semin volume, sperm concentration, seminal plasma ascorbic acid, TAC concentrations and activities of antioxidant enzymes while it increased sperm abnormalities, DNA fragmentation and MDA concentration in seminal plasma. This study indicated that Moringa oleifera leaves extract improved the characters of the fresh and cryopreserved semen of Barki rams via improving seminal plasma antioxidant defense mechanism. (C) 2020 Elsevier Inc. All rights reserved.
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