Differential RNA-sequencing (dRNA-seq) is indispensable for determination of primary transcriptomes. However, using dRNA-seq data to map transcriptional start sites (TSSs) and promoters genome-wide is a bioinformatics challenge. We performed dRNA-seq of Bradyrhizobium japonicum USDA 110, the nitrogen-fixing symbiont of soybean, and developed algorithms to map TSSs and promoters.
A specialized machine learning procedure for TSS recognition allowed us to map 15,923 TSSs: 14,360 in free-living bacteria, 4329 in symbiosis with soybean and 2766 in both conditions. Further, we provide proteomic evidence for 4090 proteins, among them 107 proteins corresponding to new genes and 178 proteins with N-termini different from the existing annotation (72 and 109 of them with TSS support, respectively). Guided by proteomics evidence, previously identified TSSs and TSSs experimentally validated here, we assign a score threshold to flag 14 % of the mapped TSSs as a class of lower confidence. However, this class of lower confidence contains valid TSSs of low-abundant transcripts. Moreover, we developed a de novo algorithm to identify promoter motifs upstream of mapped TSSs, which is publicly available, and found motifs mainly used in symbiosis (similar to RpoN-dependent promoters) or under both conditions (similar to RpoD-dependent promoters). Mapped TSSs and putative promoters, proteomic evidence and updated gene annotation were combined into an annotation file.
The genome-wide TSS and promoter maps along with the extended genome annotation of B. japonicum represent a valuable resource for future systems biology studies and for detailed analyses of individual non-coding transcripts and ORFs. Our data will also provide new insights into bacterial gene regulation during the agriculturally important symbiosis between rhizobia and legumes.
The genome of Caldithrix abyssi, the first cultivated representative of a phylum-level bacterial lineage, was sequenced within the framework of Genomic Encyclopedia of Bacteria and Archaea (GEBA) project. The genomic analysis revealed mechanisms allowing this anaerobic bacterium to ferment peptides or to implement nitrate reduction with acetate or molecular hydrogen as electron donors. The genome encoded five different [NiFe]- and [FeFe]-hydrogenases, one of which, group 1 [NiFe]-hydrogenase, is presumably involved in lithoheterotrophic growth, three other produce H2 during fermentation, and one is apparently bidirectional. The ability to reduce nitrate is determined by a nitrate reductase of the Nap family, while nitrite reduction to ammonia is presumably catalyzed by an octaheme cytochrome c nitrite reductase εHao. The genome contained genes of respiratory polysulfide/thiosulfate reductase, however, elemental sulfur and thiosulfate were not used as the electron acceptors for anaerobic respiration with acetate or H2, probably due to the lack of the gene of the maturation protein. Nevertheless, elemental sulfur and thiosulfate stimulated growth on fermentable substrates (peptides), being reduced to sulfide, most probably through the action of the cytoplasmic sulfide dehydrogenase and/or NAD(P)-dependent [NiFe]-hydrogenase (sulfhydrogenase) encoded by the genome. Surprisingly, the genome of this anaerobic microorganism encoded all genes for cytochrome c oxidase, however, its maturation machinery seems to be non-operational due to genomic rearrangements of supplementary genes. Despite the fact that sugars were not among the substrates reported when C. abyssi was first described, our genomic analysis revealed multiple genes of glycoside hydrolases, and some of them were predicted to be secreted. This finding aided in bringing out four carbohydrates that supported the growth of C. abyssi: starch, cellobiose, glucomannan and xyloglucan. The genomic analysis demonstrated the ability of C. abyssi to synthesize nucleotides and most amino acids and vitamins. Finally, the genomic sequence allowed us to perform a phylogenomic analysis, based on 38 protein sequences, which confirmed the deep branching of this lineage and justified the proposal of a novel phylum Calditrichaeota.
The Kets, an ethnic group in the Yenisei River basin, Russia, are considered the last nomadic hunter-gatherers of Siberia, and Ket language has no transparent affiliation with any language family. We investigated connections between the Kets and Siberian and North American populations, with emphasis on the Mal'ta and Paleo-Eskimo ancient genomes, using original data from 46 unrelated samples of Kets and 42 samples of their neighboring ethnic groups (Uralic-speaking Nganasans, Enets, and Selkups). We genotyped over 130,000 autosomal SNPs, identified mitochondrial and Y-chromosomal haplogroups, and performed high-coverage genome sequencing of two Ket individuals. We established that Nganasans, Kets, Selkups, and Yukaghirs form a cluster of populations most closely related to Paleo-Eskimos in Siberia (not considering indigenous populations of Chukotka and Kamchatka). Kets are closely related to modern Selkups and to some Bronze and Iron Age populations of the Altai region, with all these groups sharing a high degree of Mal'ta ancestry. Implications of these findings for the linguistic hypothesis uniting Ket and Na-Dene languages into a language macrofamily are discussed.
A global compilation of glacier advances and retreats for the past two millennia grouped by 17 regions (excluding Antarctica) highlights the nature of glacier fluctuations during the late Holocene. The dataset includes 275 time series of glacier fluctuations based on historical, tree ring, lake sediment, radiocarbon and terrestrial cosmogenic nuclide data. The most detailed and reliable series for individual glaciers and regional compilations are compared with summer temperature and, when available, winter precipitation reconstructions, the most important parameters for glacier mass balance. In many cases major glacier advances correlate with multi-decadal periods of decreased summer temperature. In a few cases, such as in Arctic Alaska and western Canada, some glacier advances occurred during relatively warm wet times. The timing and scale of glacier fluctuations over the past two millennia varies greatly from region to region. However, the number of glacier advances shows a clear pattern for the high, mid and low latitudes and, hence, points to common forcing factors acting at the global scale. Globally, during the first millennium CE glaciers were smaller than between the advances in 13th to early 20th centuries CE. The precise extent of glacier retreat in the first millennium is not well defined; however, the most conservative estimates indicate that during the 1st and 2nd centuries in some regions glaciers were smaller than at the end of 20th/early 21st centuries. Other periods of glacier retreat are identified regionally during the 5th and 8th centuries in the European Alps, in the 3rd–6th and 9th centuries in Norway, during the 10th–13th centuries in southern Alaska, and in the 18th century in Spitsbergen. However, no single period of common global glacier retreat of centennial duration, except for the past century, has yet been identified. In contrast, the view that the Little Ice Age was a period of global glacier expansion beginning in the 13th century (or earlier) and reaching a maximum in 17th–19th centuries is supported by our data. The pattern of glacier variations in the past two millennia corresponds with cooling in reconstructed temperature records at the continental and hemispheric scales. The number of glacier advances also broadly matches periods showing high volcanic activity and low solar irradiance over the past two millennia, although the resolution of most glacier chronologies is not enough for robust statistical correlations. Glacier retreat in the past 100–150 years corresponds to the anthropogenic global temperature increase. Many questions concerning the relative strength of forcing factors that drove glacier variations in the past 2 ka still remain.
In the Northern Caucasus, glacier and climatic variations over the past centuries remain insufficiently documented. In this review, we summarized the high-resolution information on glacier and climate fluctuations in the region for the past millennium and provided a synthesis of these two lines of evidence with respect to regional climate change. The key areas considered in the paper are the Elbrus area, the Teberda and Arkhyz valleys in the Western Caucasus and the Cherek Bezengiisky and Tsey valleys in the Eastern Caucasus, where the most paleoclimatic evidence has been retrieved.
We focused on the fluctuation records of the ten glaciers that are best documented. To reconstruct changes in glacier length in the past, we used aerial photos, optical space images, repeated photographs and old maps. The ages of moraines were defined with the help of instrumental records, historical images, old maps, and tree-ring dating.
Lichenometry was used as a supplementary tool to determine the relative ages of glacial landforms. We reviewed the collection of control points used for the lichenometric curves and determined the time limit of potential use of this method in the Caucasus to be up to one millennium.
High-resolution tree-ring-based hydroclimatic reconstructions in the Northern Caucasus are presented based on the reconstruction of June–September temperature (1595–2012 CE), the mass balance reconstruction of the Garabashi Glacier (1800–2008 CE) and the runoff of the Teberda River (low-frequency variations) for May, July and August for 1850–2005 CE.
The synthesis of all the available paleoclimatic records revealed several distinct climatic periods. Evidence of a warm interval (traditionally referred to as the “Arkhyz break in glaciation”) preceding the Little Ice Age (LIA) in the Caucasus is based on archeological, palynological, geochemical and pedological data. However, the conclusions concerning the duration and magnitude of this warming are still vague due to the low resolution of the data available and ambiguous interpretation of the evidence. The first LIA maximum glacier extent in the past millennium is poorly constrained. According to our data, it occurred prior to the year 1598 CE (tree-ring-based minimum age). Two other major phases of advances occurred in the second half of the 17th century CE and the first half of 19th century CE. General glacier retreat in the Northern Caucasus started in the late 1840s CE, with four to five minor readvances in the 1860s–1880s CE and three readvances or steady states in the 20th century CE (1910s, 1920s and 1970s–1980s). Since the last LIA maximum in the middle of the 19th century CE, most glaciers have decreased in length by more than 1000 m, and the rise in the elevation of the glacier fronts has exceeded 200 m. The glacier advances correspond to summer temperature minima and are generally coherent with the reconstructed mass balance of the Garabashi Glacier. A comparison of a tree-ring-based summer temperature reconstruction in the Northern Caucasus with detailed reconstructions of summer temperature and glacier fluctuations in the Alps shows a pronounced agreement between the records and supports the similarity between the patterns of climatic and glacier variations in the two regions.
Glaciers distinct from the Greenland and Antarctic ice sheets cover an area of approximately 706,000 square kilometres globally1, with an estimated total volume of 170,000 cubic kilometres, or 0.4 metres of potential sea-level-rise equivalent2. Retreating and thinning glaciers are icons of climate change3 and affect regional runoff4 as well as global sea level5,6. In past reports from the Intergovernmental Panel on Climate Change, estimates of changes in glacier mass were based on the multiplication of averaged or interpolated results from available observations of a few hundred glaciers by defined regional glacier areas7,8,9,10. For data-scarce regions, these results had to be complemented with estimates based on satellite altimetry and gravimetry11. These past approaches were challenged by the small number and heterogeneous spatiotemporal distribution of in situ measurement series and their often unknown ability to represent their respective mountain ranges, as well as by the spatial limitations of satellite altimetry (for which only point data are available) and gravimetry (with its coarse resolution). Here we use an extrapolation of glaciological and geodetic observations to show that glaciers contributed 27 ± 22 millimetres to global mean sea-level rise from 1961 to 2016. Regional specific-mass-change rates for 2006–2016 range from −0.1 metres to −1.2 metres of water equivalent per year, resulting in a global sea-level contribution of 335 ± 144 gigatonnes, or 0.92 ± 0.39 millimetres, per year. Although statistical uncertainty ranges overlap, our conclusions suggest that glacier mass loss may be larger than previously reported11. The present glacier mass loss is equivalent to the sea-level contribution of the Greenland Ice Sheet12, clearly exceeds the loss from the Antarctic Ice Sheet13, and accounts for 25 to 30 per cent of the total observed sea-level rise14. Present mass-loss rates indicate that glaciers could almost disappear in some mountain ranges in this century, while heavily glacierized regions will continue to contribute to sea-level rise beyond 2100.
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.
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.
Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset 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.
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.
Abstract: Background The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis and malaria through the formulation of Millennium Development Goal 6 (MDG 6). The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation 1990 to 2013, and an opportunity to assess if there has been accelerated progress since the Millennium Declaration. Methods To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of the literature on mortality with and without out antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalized epidemics, we minimized a loss function to select epidemic curves most consistent with prevalence data and demographic data on all-cause mortality. We analyzed counterfactual scenarios for HIV to assess years of life saved through prevention of mother to child transmission (PMTCT) and anti-retroviral therapy (ART). For tuberculosis, we analyzed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modeling. We analyzed data on corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys and estimated cause-specific mortality using Bayesian metaregression to generate consistent trends in all parameters. Malaria mortality and incidence were analyzed using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria and recent literature on incidence, drug resistance and coverage of insecticide treated bed nets. Findings Globally in 2013, there were 1.8 million new HIV infections (95% uncertainty interval 1.7 million to 2.1 million), 29.0 million prevalent HIV cases (27.9 to 31.4) and 1.3 million HIV deaths (1.2 to 1.5). At the peak of the epidemic in 2005, HIV caused 1.7 million deaths (1.6 to 1.9). Concentrated epidemics in Latin America and Eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19.3 million life years have been saved, 68.9% in the developing world. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was $4,647-$7,137 in the developing world. All-forms tuberculosis (including Individuals who are HIV-positive) incidence, prevalence and death numbers in 2013 were 6.6 million (6.4 to 6.7), 10.1 million (9.8 to 10.4) and 1.4 million (1.3 to 1.5), the same figures in Individuals who are HIV-negative were 6.1 million (6.0 to 6.3), 9.5 million (9.2 to 9.8) and 1.3 million
Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.Methods
We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores.Findings
We generated 9·3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17·2 billion, 95% uncertainty interval [UI] 15·4–19·2 billion) and diarrhoeal diseases (2·39 billion, 2·30–2·50 billion). Eight causes of chronic disease and injury each affected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-deficiency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that affected the greatest number of people in 2015 was anaemia, with 2·36 billion (2·35–2·37 billion) individuals affected. The second and third leading impairments by number of individuals affected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20–30% of total disability, largely attributable to nutritional deficiencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-deficiency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo.Interpretation
Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profile driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available.
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.
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).
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.
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.
Established in 2000, Millennium Development Goal 4 (MDG4) catalysed extraordinary political, financial, and social commitments to reduce under-5 mortality by two-thirds between 1990 and 2015. At the country level, the pace of progress in improving child survival has varied markedly, highlighting a crucial need to further examine potential drivers of accelerated or slowed decreases in child mortality. The Global Burden of Disease 2015 Study (GBD 2015) provides an analytical framework to comprehensively assess these trends for under-5 mortality, age-specific and cause-specific mortality among children under 5 years, and stillbirths by geography over time.
Drawing from analytical approaches developed and refined in previous iterations of the GBD study, we generated updated estimates of child mortality by age group (neonatal, post-neonatal, ages 1–4 years, and under 5) for 195 countries and territories and selected subnational geographies, from 1980–2015. We also estimated numbers and rates of stillbirths for these geographies and years. Gaussian process regression with data source adjustments for sampling and non-sampling bias was applied to synthesise input data for under-5 mortality for each geography. Age-specific mortality estimates were generated through a two-stage age–sex splitting process, and stillbirth estimates were produced with a mixed-effects model, which accounted for variable stillbirth definitions and data source-specific biases. For GBD 2015, we did a series of novel analyses to systematically quantify the drivers of trends in child mortality across geographies. First, we assessed observed and expected levels and annualised rates of decrease for under-5 mortality and stillbirths as they related to the Soci-demographic Index (SDI). Second, we examined the ratio of recorded and expected levels of child mortality, on the basis of SDI, across geographies, as well as differences in recorded and expected annualised rates of change for under-5 mortality. Third, we analysed levels and cause compositions of under-5 mortality, across time and geographies, as they related to rising SDI. Finally, we decomposed the changes in under-5 mortality to changes in SDI at the global level, as well as changes in leading causes of under-5 deaths for countries and territories. We documented each step of the GBD 2015 child mortality estimation process, as well as data sources, in accordance with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).
Globally, 5·8 million (95% uncertainty interval [UI] 5·7–6·0) children younger than 5 years died in 2015, representing a 52·0% (95% UI 50·7–53·3) decrease in the number of under-5 deaths since 1990. Neonatal deaths and stillbirths fell at a slower pace since 1990, decreasing by 42·4% (41·3–43·6) to 2·6 million (2·6–2·7) neonatal deaths and 47·0% (35·1–57·0) to 2·1 million (1·8-2·5) stillbirths in 2015. Between 1990 and 2015, global under-5 mortality decreased at an annualised rate of decrease of 3·0% (2·6–3·3), falling short of the 4·4% annualised rate of decrease required to achieve MDG4. During this time, 58 countries met or exceeded the pace of progress required to meet MDG4. Between 2000, the year MDG4 was formally enacted, and 2015, 28 additional countries that did not achieve the 4·4% rate of decrease from 1990 met the MDG4 pace of decrease. However, absolute levels of under-5 mortality remained high in many countries, with 11 countries still recording rates exceeding 100 per 1000 livebirths in 2015. Marked decreases in under-5 deaths due to a number of communicable diseases, including lower respiratory infections, diarrhoeal diseases, measles, and malaria, accounted for much of the progress in lowering overall under-5 mortality in low-income countries. Compared with gains achieved for infectious diseases and nutritional deficiencies, the persisting toll of neonatal conditions and congenital anomalies on child survival became evident, especially in low-income and low-middle-income countries. We found sizeable heterogeneities in comparing observed and expected rates of under-5 mortality, as well as differences in observed and expected rates of change for under-5 mortality. At the global level, we recorded a divergence in observed and expected levels of under-5 mortality starting in 2000, with the observed trend falling much faster than what was expected based on SDI through 2015. Between 2000 and 2015, the world recorded 10·3 million fewer under-5 deaths than expected on the basis of improving SDI alone.
Gains in child survival have been large, widespread, and in many places in the world, faster than what was anticipated based on improving levels of development. Yet some countries, particularly in sub-Saharan Africa, still had high rates of under-5 mortality in 2015. Unless these countries are able to accelerate reductions in child deaths at an extraordinary pace, their achievement of proposed SDG targets is unlikely. Improving the evidence base on drivers that might hasten the pace of progress for child survival, ranging from cost-effective intervention packages to innovative financing mechanisms, is vital to charting the pathways for ultimately ending preventable child deaths by 2030.
Transforming the housing stock to a low energy performance is a key priority in the context of sustainable development and a post-carbon transition. However, in terms of its practical implementation it, firstly, faces a number of complex institutional barriers, while, secondly, involves a risk of being dominated by a narrow technocratic agenda for energy/carbon reduction that may overtake the socially progressive pursuits of housing policy. Energy efficiency strategies for the residential sector must, therefore, be multidimensional, fully synergised with housing policy, and incorporating the principles of equity, access and a balanced geographical development. This paper discusses a strategic policy framework, which was designed by the United Nations Economic Commission for Europe (UNECE) to address those important needs in international policy. The document – Action Plan for Energy-efficient Housing in the UNECE Region – outlines a number of goals, targets and actions structured at three dimensions: (i) governance and finance, (ii) technological advancement, and (iii) access and affordability. The Action Plan provides a comprehensive and integrated framework, based on which governments can shape their own pathways towards a sustainable low-energy residential sector.
The aim of the study was to assess temporal trends in health risks related to most common persistent contaminants, including polychlorinated biphenyls (PCBs), dichloro-diphenyltrichloroethanes (DDTs), lead (Pb), as well as mercury (Hg) among indigenous peoples living in coastal areas of Chukotka in Arctic Russia. This is examined in relation to exposure pathways and a range of social and behavioral factors capable of modifying the exposure to these contaminants, including place of residence, income, traditional subsistence, alcohol consumption, and awareness of risk prevention. The primary exposure pathway for PCBs is shown to be the intake of traditional foods, which explained as much as 90% of the total health risk calculated employing established risk guidelines. Nearly 50% of past DDT-related health risks also appear to have been contributed by contaminated indoor surfaces involving commonly used DDT-containing insecticides. Individuals who practiced traditional activities are shown to have experienced a 4.4-fold higher risk of exposure to PCBs and a 1.3-fold higher risk for DDTs, Pb, and Hg. Low income, high consumption of marine mammal fat, alcohol consumption, and lack of awareness of health risk prevention are attributed to a further 2- to 6-fold increase in the risk of PCBs exposure. Low socioeconomic status enhances the health risks associated with exposure to the persistent contaminants examined.
Many studies in Western societies have shown that women prefer relatively taller men as potential partners, whereas men prefer women who are slightly shorter than themselves. Here, we discuss possible limitations of previous results within the context of the stimuli used (i.e., differences in the perceived body size of female silhouettes). Our results show that, at least in a Polish sample (N= 231), modified stimuli did not essentially change the observed male-taller preferences. In contrast, we report height preferences in a traditional ethnic group, the Datoga people from Tanzania (N= 107), in which men and women preferred extreme sexual dimorphism in stature (SDS) sets (i.e., men and women chose women much taller or much shorter than themselves). Thus, our data do not accord with the suggestion of a universal preference for taller men, but rather suggests that height preferences may be influenced by cultural, environmental, and ecological conditions.
Phylogenetic models of primate social behaviour posit that core social traits are inherent species characteristics that depend largely on phylogenetic histories of species rather than on adaptation to current socioecological conditions. These models predict that aspects of social structure will vary more between species than within species and that they will display strong phylogenetic signals. We tested these predictions in macaques focusing on dominance gradients, a relatively little studied, yet central, aspect of social structure.We used data from 14 social groups representing nine macaque species living in a variety of conditions. We examined proportions of counteraggression and two recently developed measures of dominance gradients (hierarchical steepness) for phylogenetic signals in nine phylogenetic trees constructed using (1) available genetic data sets and (2) Bayesian Markov Chain Monte Carlo (MCMC) and maximum likelihood algorithms. Hierarchical steepness and counteraggression showed significant variation between species but inconsistent variation within species. Both steepness and counteraggression showed evidence of phylogenetic signals, with results being particularly strong for one steepness measure and for counteraggression. Our results suggest that between-species variation in some core aspects of social structure are shaped by species’ evolutionary relationships, despite differences in living conditions. As such, they provide broad support for the phylogenetic model.
Despite some success for small molecules, elucidating structure–function relationships for biologically active peptides — the ligands for various targets in the organism — remains a great challenge and calls for the development of novel approaches. Some of us recently proposed the Protein Surface Topography (PST) approach, which benefits from a simplified representation of biomolecules’ surface as projection maps, which enables the exposure of the structure–function dependencies. Here, we use PST to uncover the “activity pattern” in α-conotoxins — neuroactive peptides that effectively target nicotinic acetylcholine receptors (nAChRs). PST was applied in order to design several variants of the α-conotoxin PnIA, which were synthesized and thoroughly studied. Among the best was PnIA[R9, L10], which exhibits nanomolar affinity for the α7 nAChR, selectivity and a slow wash-out from this target. Importantly, these mutations could hardly be delineated by “standard” structure-based drug design. The proposed combination of PST with a set of experiments proved very efficient for the rational construction of new bioactive molecules.
This paper presents the results of long-term remote monitoring of tree overgrowth on abandoned agricultural lands. This monitoring is based on multi-temporal satellite images with ultra-high spatial resolution and highly-detailed optical survey from Unmanned Air Vehicles (UAVs). Successful use of photogrammetric dense point clouds was demonstrated for three-dimensional reconstruction of tree canopy structure on abandoned agricultural lands by using the tree canopy height digital model. Spatial data were obtained on tree expansion on the fallow in 2005–2018, current tree canopy heights and its vertical growth, stem density, and canopy closure. The study revealed distinct spatio-temporal heterogeneity of tree overgrowth on the fallow. In the first years after land abandonment the most rapid regeneration and dispersal of trees occurred from the forests resulting in very dense but low tree cover adjacent to the forest. Later, tree overgrowth occurred in isolated hotspots and was characterized by very intensive vertical growth of the tree canopy. Original Russian Text © 2019 A.A. Medvedev, N.O. Telnova, A.V. Kudikov, published in Forest Science Issues Vol. 2, No. 3, pp. 1-12
Three-dimensional (3D) organization of genomes affects critical cellular processes such as transcription, replication, and deoxyribo nucleic acid (DNA) repair. While previous studies have investigated the natural role, the 3D organization plays in limiting a possible set of genomic rearrangements following DNA repair, the influence of specific organizational principles on this process, particularly over longer evolutionary time scales, remains relatively unexplored. In budding yeast S.cerevisiae, chromosomes are organized into a Rabl-like configuration, with clustered centromeres and telomeres tethered to the nuclear periphery. Hi-C data for S.cerevisiae show that a consequence of this Rabl-like organization is that regions equally distant from centromeres are more frequently in contact with each other, between arms of both the same and different chromosomes. Here, we detect rearrangement events in Saccharomyces species using an automatic approach, and observe increased rearrangement frequency between regions with higher contact frequencies. Together, our results underscore how specific principles of 3D chromosomal organization can influence evolutionary events.
A series of dates of unfolding of the first leaves and duration of the season of vegetation in the silver birch (Betula pendula Roth. (B. verrucosa Ehrh.)), as well as the duration of flowering of the bird cherry (Padus avium), mountain ash (Sorbus aucuparia), and smallleaved lime (Tilia cordata Mill.) for the period 1970–2010 in the central part of European Russia were studied in order to assess the trends. Differences in phenological responses to homogeneous climate changes in the trees of the same species from the northernand southern parts of the range were revealed. If spring events occur 3–7 days earlier in the northern part, nosuch effect is observed in the south. This fact can be interpreted as a manifestation of the different mechanisms of homeostasis in different populations determined by their biological characteristics (in particular, by the need to pass successfully the periods of organic rest and vegetation).
In conditions of intense spatial transformation of the Moscow agglomeration (MA) driven by housing construction and migration from Russian regions, study of how these processes are interrelated has become an urgent task. In the article a new model of spatial equilibrium in MA is developed. Model includes three blocks: (1) a spatial equilibrium model for the labor and housing markets in the MA; (2) a model of dynamic equilibrium between migration and housing construction in the MA; (3) a model of housing construction distribution by zones of the MA. In block 1, for three zones of the MA (the central business district, urban zone, and zone of new construction) the equilibrium values of population, employment, and wages are determined with allowance for commuting. In block 2, equilibrium is determined between the migration level and housing construction in the MA, which replicates the gap in real incomes between the MA and other Russian regions. Deviation from equilibrium leads to an adjustment of incentives for migration and a change in its level restores equilibrium. In block 3, it is shown that the behavior of developers owing to land price adjustment determines the location of construction by the MA zones. Despite the generic nature of the model, it is able to reproduce a number of trends in the spatial evolution of the MA, including the transition from an extensive stage of development with sprawling construction and hyperdensity of the center to an intense stage with in-depth development of the main “body” of the city. The model stresses how tightly related the processes in the largest agglomeration of the country and the national settlement system are. The model shows how the political and economic processes, via changes in rent and agglomeration economies, change incentives for work, living, and housing construction in different zones of the agglomeration and determine the fate of urban territories. The model also describes the influence of the internal structure of the MA on interregional migration. By increasing construction, especially of affordable housing in greenfield projects at the periphery of the agglomeration,
The generation of huge amplitude internal waves by the barotropic tide in the Barents Sea at high latitudes is examined using the numerical model of the Euler 2D equations for incompressible stratified fluid. The considered area is located between the Spitsbergen (Svalbard) Island and the Franz-VictoriaTrough as cross-section of 350 km length. There are two underwater hills of heights about 100 - 150 m on the background depth about 300 m. It is shown that intensive nonlinear internal waves with amplitudes up to 50 m and lengths about 6-12 km are generated in this zone. The total height of such waves is huge and they must be considered as a significant factor of the environment in this basin.