Summary Background 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.
In this paper, the drainage of storm water from traffic roads is analysed by analysing the traditional method of drainage using a separate sewage system, and also by analysing the integral approach to the drainage of rainwater in the urban area. The research objectives for the treatment of the topic in this paper are set and processed for the needs of planning and development of the sewage system for the drainage of rainwater from roads in urban areas, as well as for the evaluation and ranking of conceptual solutions and the elaboration of plans for the general solution for the collection and drainage of surface water from roads. For relevant rain episodes, i.e. rainfall of appropriate duration and intensity, runoff coefficients and flows were considered and analysed according to the rational method, all for the purpose of obtaining data on the amount of rainwater entering the sewage system. According to the set research program, it was necessary to work on defining and establishing the amount of precipitation for the area that was the research polygon, and based on exact measurement data, the optimal transverse and longitudinal drops of the level of the road were determined in order to drain rainwater from the roads as efficiently and quickly as possible, within the framework of the rules that define this area.
Although autism has historically been conceptualized as a condition that emerges in early childhood1,2, many autistic people are diagnosed later in life3, 4–5. It is unknown whether earlier- and later-diagnosed autism have different developmental trajectories and genetic profiles. Using longitudinal data from four independent birth cohorts, we demonstrate that two different socioemotional and behavioural trajectories are associated with age at diagnosis. In independent cohorts of autistic individuals, common genetic variants account for approximately 11% of the variance in age at autism diagnosis, similar to the contribution of individual sociodemographic and clinical factors, which typically explain less than 15% of this variance. We further demonstrate that the polygenic architecture of autism can be broken down into two modestly genetically correlated (rg = 0.38, s.e. = 0.07) autism polygenic factors. One of these factors is associated with earlier autism diagnosis and lower social and communication abilities in early childhood, but is only moderately genetically correlated with attention deficit–hyperactivity disorder (ADHD) and mental-health conditions. Conversely, the second factor is associated with later autism diagnosis and increased socioemotional and behavioural difficulties in adolescence, and has moderate to high positive genetic correlations with ADHD and mental-health conditions. These findings indicate that earlier- and later-diagnosed autism have different developmental trajectories and genetic profiles. Our findings have important implications for how we conceptualize autism and provide a model to explain some of the diversity found in autism. A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.
Considering that two-layer parquet is composed of two lamellas—most commonly 10 mm birch plywood and 4 mm solid oak—bonded together with adhesive, and that profiling is required to create a joint that serves a mechanical function, the process becomes complex and imposes significant demands on the cutting tool. This paper presents an experimental analysis of how the type of cutting tool affects the surface quality, profile stability, and edge wear of the tool after a certain machining length. Two different technological solutions were analyzed: a tool with replaceable tungsten carbide (TC) inserts and a tool with an integrated polycrystalline diamond (PCD) cutting edge. A particular focus of the analysis is the wear of the TC tool in the area of the oak and plywood joint profile, where selective wear of the TC edge occurs, potentially causing profile deformation and a weaker joint. The obtained results show that using PCD tools in two-layer parquet profiling achieves better surface finish, longer tool life, more consistent geometry of the cutting edge, and thus a more stable parquet profile.
Sustainable nutrient management is critical for maintaining soil fertility, improving agricultural productivity and mitigating environmental impacts. This study evaluated the impact of Ireland's Nitrates Action Programme (NAP) on soil pH, phosphorus (P) and potassium (K) dynamics over a 12‐year period across four meso‐scale agricultural catchments. Using a spatially defined field‐scale sampling approach, trends in studied chemical soil parameters were assessed in response to changing agricultural practices and policy interventions. Results indicate a notable increase in optimal soil pH levels (21%), likely as a result of recent targeted advisory efforts. While overall median soil test P (STP) levels decreased by 0.5 mg/L, variability among catchments was evident, with one catchment showing a significant increase due to intensive poultry manure applications. Additionally, the proportion of P Index 1 soils increased by 9%, suggesting uneven P distribution and highlighting challenges in on‐farm nutrient management. Median soil test K (STK) increased by 17.6 mg/L, with notable gains in tillage and dairy enterprises, indicating shifts in nutrient application strategies. The study also identifies critical source areas (CSAs) of P losses, which decreased by 2%, aligning with NAP objectives. However, nearly 80% of soils remain of suboptimal fertility, particularly for P and pH, underscoring the need for targeted advisory efforts, improved nutrient planning and region‐specific management strategies. Findings provide key insights into how regulatory measures influence soil nutrient trends, informing future policies for sustainable nutrient management and environmental protection in Irish agriculture.
The machinability of wood is an insufficiently researched problem that is mainly related to the machinability of metals. The machinability of a material is a technological property that expresses the ability to remove the maximum amount of crisps from the machined surface in the shortest possible time with satisfactory machining quality and the lowest possible cutting forces and tool wear. The quality and efficiency of the production process when milling solid wood is influenced by the following factors: type of wood, density and moisture content of the wood, temperatures and dimensions of the workpiece as well as the hardness and strength of the wood. The parameters of the milling mode, such as the main and auxiliary motion, the cutting force and power and the power of the drive unit, have a direct effect on the milling process and are related to the milling tool, i.e. the type and quality of the material from which it is made, the number of cutting edges, the geometry of the cutting edge and the sharpness of the tool. In this work, the influence of significant input parameters on the machinability of solid wood in flat peripheral milling is analysed as a function of the cutting force as an output parameter by planning an experiment. The experimental results are mathematically modelled with the aim of obtaining a mathematical model of the process of large-scale milling of solid wood, i.e. its parameters as a function of the cutting force. The results of the experimental part and the results of the models are analysed and compared in order to draw appropriate conclusions and
The genus Temnostoma comprises saproxylic hoverflies whose larvae develop by boring into wet, decaying wood, where they feed on microorganisms. Records of these species in the northwestern Balkans are sparse in the literature and nearly absent from openaccess databases. To enhance knowledge of their distribution in the region, we present new records of four Temnostoma species from Croatia, Bosnia and Herzegovina, and Serbia. Three species were recorded in all three countries, while T. apiforme was found exclusively in Croatia. This discovery marks not only the first record of this species in the country but also the first for the entire Balkan Peninsula. Furthermore, Temnostomameridionale was documented in Bosnia and Herzegovina for the first time. Given thatthese hoverflies are large and visually striking, we hope this study will inspire interestamong citizen scientists and encourage future contributions to the documentation ofthis genus in the region.
Alien species Trichopoda (Galactomyia) pictipennis Bigot, 1876 was found in southeasternBosnia and Herzegovina and Croatia in June and August 2024. This is the first recordof this species for Bosnia and Herzegovina and the southeastern part of Croatia.Additionally, this report includes the records from Montenegro and Bulgaria obtainedfrom the online data platform iNaturalist representing the first observations of T.pictipennis for Montenegro and the Black Sea coast in Bulgaria.
Background and objectives: Melanocytic nevi are among the most common skin lesions, yet their relationship with the peripheral nervous system has remained understudied. Given the neural crest origin of melanocytes and Schwann cells, and the neurotrophic signaling capabilities of pigment cells, this study aimed to investigate the density of nerve fibers within nevi and assess how it varies with respect to histological subtype and anatomical location. Materials and Methods: A total of 90 nevi were analyzed, including junctional, compound, and intradermal types, distributed across the head, trunk, and limbs. Immunofluorescence staining for the pan-neuronal marker PGP 9.5 and for CGRP were performed and nerve fiber density was quantified. Statistical evaluation using two-way ANOVA revealed that both nevus type and anatomical site significantly influenced the degree of total innervation. Results: Junctional nevi demonstrated the highest total nerve fiber density, significantly exceeding that of compound and intradermal nevi. Likewise, nevi located on the head exhibited a significantly greater density of PGP 9.5-positive nerve fibers compared to those on the trunk and limbs. No significant correlation was observed between nevus type and location, suggesting that both factors contribute independently to the differences in innervation. CGRP-positive innervation was uniform regardless of the histological type of nevus and anatomical location. Conclusions: These findings likely reflect the facts that junctional nevi reside at the dermo-epidermal junction, where nerve fibers are most abundant, while the skin of the head and neck is well known to be more richly innervated than other regions. In contrast, analysis of CGRP-positive fibers suggests that the heterogeneity detected with PGP 9.5 is primarily driven by other neuronal populations. The results support the hypothesis of a dynamic relationship between nevi and the peripheral nervous system, potentially mediated by neurotrophic factors. Understanding this interaction may provide insight into nevus biology, sensory symptoms reported in some lesions, and the evolving role of nerves in the tumor microenvironment.
Introduction: Vitamin D (VD) deficiency has become a global epidemic in the past 2 decades. Cardiac troponin is a specific biomarker for detecting myocardial injury, particularly in the context of myocardial infarction (MI), where elevated levels are indicative of myocardial necrosis. This study aimed to investigate the relationship between VD levels and troponin values in patients admitted to the Intensive Care Unit under suspicion of acute coronary syndrome, including comparisons with patients ultimately not diagnosed with ACS. Materials and Methods: This cross-sectional study included a group of 69 patients who were hospitalized in the Intensive Care Unit of the Hospital under suspicion of acute coronary syndrome. The control consisted of patients without ACS. The content of VD-(25[OH]D) in blood plasma was measured by enzyme-linked immunosorbent assay during June–August 2024. Blood samples were taken in tubes with ethylenediaminetetraacetic acid anticoagulant. The tubes without anticoagulant were used for collecting blood for VD, fibrinogen, D-dimer, and lipid parameter measurement. Results: A statistically significant difference in total cholesterol levels was observed between patients with angina pectoris and those with MI (P < 0.05). Pearson correlation analysis also demonstrated a moderate negative correlation between VD levels and troponin values in patients diagnosed with MI (P < 0.05), indicating that lower VD concentrations may be associated with greater myocardial injury. Conclusions: Based on the data obtained, the medical community is inclined to believe that correction of VD deficiency has great prognostic significance. Further clinical and experimental studies are needed to study in more detail the mechanisms of the negative effects of VD deficiency on the cardiovascular system.
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