| 1. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
- Birney, Ewan, et al.
(författare)
-
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
-
Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
|
|
| 3. |
- Chng, Kern Rei, et al.
(författare)
-
Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment
- 2020
-
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26, s. 941-951
-
Tidskriftsartikel (refereegranskat)abstract
- Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections. Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.
|
|
| 4. |
- Kassebaum, Nicholas J., et al.
(författare)
-
Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
-
Tidskriftsartikel (refereegranskat)abstract
- Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
|
|
| 5. |
- Wang, Haidong, et al.
(författare)
-
Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
|
|
| 6. |
- Lin, Yan-Shih, et al.
(författare)
-
Optimal stomatal behaviour around the world
- 2015
-
Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 5, s. 459-464
-
Tidskriftsartikel (refereegranskat)abstract
- Stomatal conductance (gs) is a key land-surface attribute as it links transpiration, the dominant component of global land evapotranspiration, and photosynthesis, the driving force of the global carbon cycle. Despite the pivotal role of gs in predictions of global water and carbon cycle changes, a globalscale database and an associated globally applicable model of gs that allow predictions of stomatal behaviour are lacking. Here,we present a database of globally distributed gs obtained in the field for a wide range of plant functional types (PFTs) and biomes. We find that stomatal behaviour differs among PFTs according to their marginal carbon cost of water use, as predicted by the theory underpinning the optimal stomatal model1 and the leaf and wood economics spectrum2,3.We also demonstrate a global relationship with climate. These findings provide a robust theoretical framework for understanding and predicting the behaviour of gs across biomes and across PFTs that can be applied to regional, continental and global-scale modelling of ecosystem productivity, energy balance and ecohydrological processes in a future changing climate.
|
|
| 7. |
- Lin, Yan-Shih, et al.
(författare)
-
Optimal stomatal behaviour around the world
- 2015
-
Ingår i: Nature Climate Change. - 1758-6798 .- 1758-678X. ; 5:5, s. 459-464
-
Tidskriftsartikel (refereegranskat)abstract
- Stomatal conductance (g(s)) is a key land-surface attribute as it links transpiration, the dominant component of global land evapotranspiration, and photosynthesis, the driving force of the global carbon cycle. Despite the pivotal role of g(s) in predictions of global water and carbon cycle changes, a global-scale database and an associated globally applicable model of g(s) that allow predictions of stomatal behaviour are lacking. Here, we present a database of globally distributed g(s) obtained in the field for a wide range of plant functional types (PFTs) and biomes. We find that stomatal behaviour differs among PFTs according to their marginal carbon cost of water use, as predicted by the theory underpinning the optimal stomatal model(1) and the leaf and wood economics spectrum(2,3). We also demonstrate a global relationship with climate. These findin g(s) provide a robust theoretical framework for understanding and predicting the behaviour of g(s) across biomes and across PFTs that can be applied to regional, continental and global-scale modelling of ecosystem productivity, energy balance and ecohydrological processes in a future changing climate.
|
|
| 8. |
- Danko, David, et al.
(författare)
-
A global metagenomic map of urban microbiomes and antimicrobial resistance
- 2021
-
Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 184:13, s. 3376-3393
-
Tidskriftsartikel (refereegranskat)abstract
- We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.
|
|
| 9. |
- Domingo, Nina G.G., et al.
(författare)
-
Ozone-related acute excess mortality projected to increase in the absence of climate and air quality controls consistent with the Paris Agreement
- 2024
-
Ingår i: One Earth. - : Elsevier. - 2590-3330 .- 2590-3322. ; 7:2, s. 325-335
-
Tidskriftsartikel (refereegranskat)abstract
- Short-term exposure to ground-level ozone in cities is associated with increased mortality and is expected to worsen with climate and emission changes. However, no study has yet comprehensively assessed future ozone-related acute mortality across diverse geographic areas, various climate scenarios, and using CMIP6 multi-model ensembles, limiting our knowledge on future changes in global ozone-related acute mortality and our ability to design targeted health policies. Here, we combine CMIP6 simulations and epidemiological data from 406 cities in 20 countries or regions. We find that ozone-related deaths in 406 cities will increase by 45 to 6,200 deaths/year between 2010 and 2014 and between 2050 and 2054, with attributable fractions increasing in all climate scenarios (from 0.17% to 0.22% total deaths), except the single scenario consistent with the Paris Climate Agreement (declines from 0.17% to 0.15% total deaths). These findings stress the need for more stringent air quality regulations, as current standards in many countries are inadequate.
|
|
| 10. |
- Egondi, Thaddaeus Wandera, 1978-
(författare)
-
Making visible the invisible : Health risks from environmental exposures among socially deprived populations of Nairobi, Kenya
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Most countries of sub-Saharan Africa (SSA) are experiencing a high rate of urbanization accompanied with unplanned development resulting into sprawl of slums. The weather patterns and air pollution sources in most urban areas are changing with significant effects on health. Studies have established a link between environmental exposures, such as weather variation and air pollution, and adverse health outcomes. However, little is known about this relationship in urban populations of SSA where more than half the population reside in slums, or slum like conditions. A major reason for this is the lack of systematic collection of data on exposure and health outcomes. High quality prospective data collection and census registers still remain a great challenge. However, within small and spatially defined areas, dynamic cohorts have been established with continuous monitoring of health outcomes. Collection of environmental exposure data can complement cohort studies to investigate health effects in relation to environmental exposures. The objective of this research was to study the health effects of selected environmental exposure among the urban poor population in Nairobi, Kenya.Methods: We used the platform of the Nairobi Urban Health and Demographic Surveillance System (NUHDSS), including two nested research studies, to provide data on mortality and morbidity. The NUHDSS was established in two areas of Nairobi, Korogocho and Viwandani, in 2003 and provides a unique opportunity for access to longitudinal population data. In addition, we conducted real-time measurements of particulate matter (PM2.5) in the areas from February to October in 2013. We obtained meteorological measurements from the Moi Air Base and Nairobi airport weather stations for the study period. We also conducted a cross-sectional survey to establish the communities’ perceptions about air pollution and its related health risks. Time series regression models with a distributed lag approach were used to model the relationship between weather and mortality. A semi-ecological study with group level exposure assignment to individuals was used to assess the relationship between child health (morbidity and mortality) and the extent of PM2.5 exposure.Results: There was a significant association between daily mean temperature and all-cause mortality with minimum mortality temperature (MMT) in the range of 18 to 20 °C. Both mortality risk and years of life lost analysis showed risk increases in relation to cold temperatures, with pronounced effect among children under-five. Overall, mortality risks were found to be high during cold periods of the year, rising with lower temperature from MMT to about 40% in the 0–4 age group, and by about v 20% among all ages. The results from air pollution assessment showed high levels of PM2.5 concentration exceeding World Health Organization (WHO) guideline limits in the two study areas. The air pollution concentration showed similar seasonal and diurnal variation in the two slums. The majority of community residents reported to be exposed to air pollution at work, with 66% reporting to be exposed to different sources of air pollution. Despite the observed high level of exposure, residents had poor perception of air pollution levels and associated health risks. Children in the high-pollution areas (PM2.5≥ 25 μg⁄m3) were at significantly higher risk for morbidity (OR = 1.30, 95% CI: 1.13-1.48) and cough as the only form of morbidity (OR = 1.33, 95% CI: 1.15-1.53) compared to those in low-pollution areas. In addition, exposure to high levels of pollution was associated with high child mortality from all-causes (IRR=1.15, 95% CI: 1.03-1.28), and indicated a positive association to respiratory related mortality (IRR=1.10, 95% CI: 0.91-1.33).Conclusion: The study findings extend our knowledge on health impacts related to environmental exposure by providing novel evidence on the risks in disadvantaged urban populations in Africa. More specifically, the study illustrates the invisible health burden that the urban poor population are facing in relation to weather and air pollution exposures. The effect of cold on population is preventable. This is manifested by the effective adaptation to cold conditions in high-latitude Nordic countries by housing standards and clothing, as well as a well-functioning health system. Further, awareness and knowledge of consequences, and reductions in exposure to air pollution, are necessary to improve public health in the slum areas. In conclusion, adverse health impacts caused by environmental stressors are critical to assess further in disadvantaged populations, and should be followed by development of mitigation measures leading to improved health and well being in SSA.
|
|
