13 research outputs found
A protein-dependent side-chain rotamer library
No full textAbstract Background Protein side-chain packing problem has remained one of the key open problems in bioinformatics. The three main components of protein side-chain prediction methods are a rotamer library, an energy function and a search algorithm. Rotamer libraries summarize the existing knowledge of the experimentally determined structures quantitatively. Depending on how much contextual information is encoded, there are backbone-independent rotamer libraries and backbone-dependent rotamer libraries. Backbone-independent libraries only encode sequential information, whereas backbone-dependent libraries encode both sequential and locally structural information. However, side-chain conformations are determined by spatially local information, rather than sequentially local information. Since in the side-chain prediction problem, the backbone structure is given, spatially local information should ideally be encoded into the rotamer libraries. Methods In this paper, we propose a new type of backbone-dependent rotamer library, which encodes structural information of all the spatially neighboring residues. We call it protein-dependent rotamer libraries. Given any rotamer library and a protein backbone structure, we first model the protein structure as a Markov random field. Then the marginal distributions are estimated by the inference algorithms, without doing global optimization or search. The rotamers from the given library are then re-ranked and associated with the updated probabilities. Results Experimental results demonstrate that the proposed protein-dependent libraries significantly outperform the widely used backbone-dependent libraries in terms of the side-chain prediction accuracy and the rotamer ranking ability. Furthermore, without global optimization/search, the side-chain prediction power of the protein-dependent library is still comparable to the global-search-based side-chain prediction methods.</p
Arabic nominals in HPSG: A verbal noun perspective
No full textSemitic languages exhibit rich nonconcatenative morphological operations, which can generate a myriad of
derived lexemes. Especially, the feature rich, root-driven morphology in the Arabic language demonstrates the
construction of several verb-derived nominals (verbal nouns) such as gerunds, active participles, passive
participles, locative participles, etc. Although HPSG is a successful syntactic theory, it lacks the
representation of complex nonconcatenative morphology. In this paper, we propose a novel HPSG representation for
Arabic nominals and various verb-derived nouns. We also present the lexical type hierarchy and derivational rules
for generating these verb-derived nominals using the HPSG framework
Bridging the Last Mile: Unpacking the Rural Digital Divide in Bangladesh
No full textPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/198755/1/3715335.3735463.pd
Burden of disease scenarios by state in the USA, 2022–50: a forecasting analysis for the Global Burden of Disease Study 2021
No full textBackgroundThe capacity to anticipate future health issues is important for both policy makers and practitioners in the USA, as such insights can facilitate effective planning, investment, and implementation strategies. Forecasting trends in disease and injury burden is not only crucial for policy makers but also garners substantial interest from the general populace and leads to a better-informed public. Through the integration of new data sources, the refinement of methodologies, and the inclusion of additional causes, we have improved our previous forecasting efforts within the scope of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to produce forecasts at the state and national levels for the USA under various possible scenarios. MethodsWe developed a comprehensive framework for forecasting life expectancy, healthy life expectancy (HALE), cause-specific mortality, and disability-adjusted life-years (DALYs) due to 359 causes of disease and injury burden from 2022 to 2050 for the USA and all 50 states and Washington, DC. Using the GBD 2021 Future Health Scenarios modelling framework, we forecasted drivers of disease, demographic drivers, risk factors, temperature and particulate matter, mortality and years of life lost (YLL), population, and non-fatal burden. In addition to a reference scenario (representing the most probable future trajectory), we explored various future scenarios and their potential impacts over the next several decades on human health. These alternative scenarios comprised four risk elimination scenarios (including safer environment, improved behavioural and metabolic risks, improved childhood nutrition and vaccination, and a combined scenario) and three USA-specific scenarios based on risk exposure or attributable burden in the best-performing US states (improved high adult BMI and high fasting plasma glucose [FPG], improved smoking, and improved drug use [encompassing opioids, cocaine, amphetamine, and others]). FindingsLife expectancy in the USA is projected to increase from 78·3 years (95% uncertainty interval 78·1–78·5) in 2022 to 79·9 years (79·5–80·2) in 2035, and to 80·4 years (79·8–81·0) in 2050 for all sexes combined. This increase is forecasted to be modest compared with that in other countries around the world, resulting in the USA declining in global rank over the 2022–50 forecasted period among the 204 countries and territories in GBD, from 49th to 66th. There is projected to be a decline in female life expectancy in West Virginia between 1990 and 2050, and little change in Arkansas and Oklahoma. Additionally, after 2023, we projected almost no change in female life expectancy in many states, notably in Oklahoma, South Dakota, Utah, Iowa, Maine, and Wisconsin. Female HALE is projected to decline between 1990 and 2050 in 20 states and to remain unchanged in three others. Drug use disorders and low back pain are projected to be the leading Level 3 causes of age-standardised DALYs in 2050. The age-standardised DALY rate due to drug use disorders is projected to increase considerably between 2022 and 2050 (19·5% [6·9–34·1]). Our combined risk elimination scenario shows that the USA could gain 3·8 additional years (3·6–4·0) of life expectancy and 4·1 additional years (3·9–4·3) of HALE in 2050 versus the reference scenario. Using our USA-specific scenarios, we forecasted that the USA could gain 0·4 additional years (0·3–0·6) of life expectancy and 0·6 additional years (0·5–0·8) of HALE in 2050 under the improved drug use scenario relative to the reference scenario. Life expectancy and HALE are likewise projected to be 0·4–0·5 years higher in 2050 under the improved adult BMI and FPG and improved smoking scenarios compared with the reference scenario. However, the increases in these scenarios would not substantially improve the USA's global ranking in 2050 (from 66th of 204 in life expectancy in the reference scenario to 63rd–64th in each of the three USA-specific scenarios), indicating that the USA's best-performing states are still lagging behind other countries in their rank throughout the forecasted period. Regardless, an estimated 12·4 million (11·3–13·5) deaths could be averted between 2022 and 2050 if the USA were to follow the combined scenario trajectory rather than the reference scenario. There would also be 1·4 million (0·7–2·2) fewer deaths over the 28-year forecasted period with improved adult BMI and FPG, 2·1 million (1·3–2·9) fewer deaths with improved exposure to smoking, and 1·2 million (0·9–1·5) fewer deaths with lower rates of drug use deaths. InterpretationOur findings highlight the alarming trajectory of health challenges in the USA, which, if left unaddressed, could lead to a reversal of the health progress made over the past three decades for some US states and a decline in global health standing for all states. The evidence from our alternative scenarios along with other published studies suggests that through collaborative, evidence-based strategies, there are opportunities to change the trajectory of health outcomes in the USA, such as by investing in scientific innovation, health-care access, preventive health care, risk exposure reduction, and education. Our forecasts clearly show that the time to act is now, as the future of the country's health and wellbeing—as well as its prosperity and leadership position in science and innovation—are at stake. FundingBill & Melinda Gates Foundation
Global burden of 292 causes of death in 204 countries and territories and 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023
No full textBackground: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. Methods: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. Findings: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. Interpretation: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. Funding: Gates Foundation
Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050
No full textBackground
Antimicrobial resistance (AMR) poses an important global health challenge in the 21st century. A previous study has quantified the global and regional burden of AMR for 2019, followed with additional publications that provided more detailed estimates for several WHO regions by country. To date, there have been no studies that produce comprehensive estimates of AMR burden across locations that encompass historical trends and future forecasts.
Methods
We estimated all-age and age-specific deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 22 pathogens, 84 pathogen–drug combinations, and 11 infectious syndromes in 204 countries and territories from 1990 to 2021. We collected and used multiple cause of death data, hospital discharge data, microbiology data, literature studies, single drug resistance profiles, pharmaceutical sales, antibiotic use surveys, mortality surveillance, linkage data, outpatient and inpatient insurance claims data, and previously published data, covering 520 million individual records or isolates and 19 513 study-location-years. We used statistical modelling to produce estimates of AMR burden for all locations, including those with no data. Our approach leverages the estimation of five broad component quantities: the number of deaths involving sepsis; the proportion of infectious deaths attributable to a given infectious syndrome; the proportion of infectious syndrome deaths attributable to a given pathogen; the percentage of a given pathogen resistant to an antibiotic of interest; and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden attributable to and associated with AMR, which we define based on two counterfactuals; respectively, an alternative scenario in which all drug-resistant infections are replaced by drug-susceptible infections, and an alternative scenario in which all drug-resistant infections were replaced by no infection. Additionally, we produced global and regional forecasts of AMR burden until 2050 for three scenarios: a reference scenario that is a probabilistic forecast of the most likely future; a Gram-negative drug scenario that assumes future drug development that targets Gram-negative pathogens; and a better care scenario that assumes future improvements in health-care quality and access to appropriate antimicrobials. We present final estimates aggregated to the global, super-regional, and regional level.
Findings
In 2021, we estimated 4·71 million (95% UI 4·23–5·19) deaths were associated with bacterial AMR, including 1·14 million (1·00–1·28) deaths attributable to bacterial AMR. Trends in AMR mortality over the past 31 years varied substantially by age and location. From 1990 to 2021, deaths from AMR decreased by more than 50% among children younger than 5 years yet increased by over 80% for adults 70 years and older. AMR mortality decreased for children younger than 5 years in all super-regions, whereas AMR mortality in people 5 years and older increased in all super-regions. For both deaths associated with and deaths attributable to AMR, meticillin-resistant Staphylococcus aureus increased the most globally (from 261 000 associated deaths [95% UI 150 000–372 000] and 57 200 attributable deaths [34 100–80 300] in 1990, to 550 000 associated deaths [500 000–600 000] and 130 000 attributable deaths [113 000–146 000] in 2021). Among Gram-negative bacteria, resistance to carbapenems increased more than any other antibiotic class, rising from 619 000 associated deaths (405 000–834 000) in 1990, to 1·03 million associated deaths (909 000–1·16 million) in 2021, and from 127 000 attributable deaths (82 100–171 000) in 1990, to 216 000 (168 000–264 000) attributable deaths in 2021. There was a notable decrease in non-COVID-related infectious disease in 2020 and 2021. Our forecasts show that an estimated 1·91 million (1·56–2·26) deaths attributable to AMR and 8·22 million (6·85–9·65) deaths associated with AMR could occur globally in 2050. Super-regions with the highest all-age AMR mortality rate in 2050 are forecasted to be south Asia and Latin America and the Caribbean. Increases in deaths attributable to AMR will be largest among those 70 years and older (65·9% [61·2–69·8] of all-age deaths attributable to AMR in 2050). In stark contrast to the strong increase in number of deaths due to AMR of 69·6% (51·5–89·2) from 2022 to 2050, the number of DALYs showed a much smaller increase of 9·4% (–6·9 to 29·0) to 46·5 million (37·7 to 57·3) in 2050. Under the better care scenario, across all age groups, 92·0 million deaths (82·8–102·0) could be cumulatively averted between 2025 and 2050, through better care of severe infections and improved access to antibiotics, and under the Gram-negative drug scenario, 11·1 million AMR deaths (9·08–13·2) could be averted through the development of a Gram-negative drug pipeline to prevent AMR deaths.
Interpretation
This study presents the first comprehensive assessment of the global burden of AMR from 1990 to 2021, with results forecasted until 2050. Evaluating changing trends in AMR mortality across time and location is necessary to understand how this important global health threat is developing and prepares us to make informed decisions regarding interventions. Our findings show the importance of infection prevention, as shown by the reduction of AMR deaths in those younger than 5 years. Simultaneously, our results underscore the concerning trend of AMR burden among those older than 70 years, alongside a rapidly ageing global community. The opposing trends in the burden of AMR deaths between younger and older individuals explains the moderate future increase in global number of DALYs versus number of deaths. Given the high variability of AMR burden by location and age, it is important that interventions combine infection prevention, vaccination, minimisation of inappropriate antibiotic use in farming and humans, and research into new antibiotics to mitigate the number of AMR deaths that are forecasted for 2050.
Funding
UK Department of Health and Social Care's Fleming Fund using UK aid, and the Wellcome Trust
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a systematic analysis for the Global Burden of Disease Study 2019
No full textFunding: J A Loureiro reports support for the present manuscript from Scientific Employment Stimulus (FCT; CEECINST/00049/2018) as support to their salary and from UIDB/00511/2020 of the LEPABE, funded by national funds through the FCT/MCTES (PIDDAC) as research support.BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01-4·94) deaths and 105 million (95·0-116) DALYs for both sexes combined, representing 44·4% (41·3-48·4) of all cancer deaths and 42·0% (39·1-45·6) of all DALYs. There were 2·88 million (2·60-3·18) risk-attributable cancer deaths in males (50·6% [47·8-54·1] of all male cancer deaths) and 1·58 million (1·36-1·84) risk-attributable cancer deaths in females (36·3% [32·5-41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6-28·4) and DALYs by 16·8% (8·8-25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9-42·8] and 33·3% [25·8-42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. FUNDING: Bill & Melinda Gates Foundation.publishersversionpublishe
