Djelotvornost komercijalne biljne mješavine u liječenju i kontroli kokcidioze peradi

Coccidiosis, a protozoal disease caused by a species of the Eimeria genus, causes tremendous economic damage to the poultry industry. Numerous natural remedies have been developed to combat emerging drug-resistant Eimeria species and mitigate public concerns about anticoccidial drug residues in poultry products. In the current study, the anticoccidial efficacy was evaluated of a commercial mixed botanical product, administered in two concentrations, in the treatment and control of a mixed coccidian infection. In this respect, 120 newly hatched broiler chickens were randomly allocated into five equal groups: Cox500, Cox1000, Positive control (PC), Negative control (NC), and Control (C). The first three groups were exposed to oocysts of several Eimeria species, Cox500 and Cox1000, and then received the two concentrations of a botanical blend (500 and 1,000 ml of formula per 1,000 L of drinking water, respectively) for five consecutive days. The positive control also received toltrazuril (7 mg/kg of live weight) through drinking water for two consecutive days. The negative control and control were the challenged-unmedicated and unchallenged-unmedicated groups, respectively. The chicks were monitored for clinical signs, intestinal lesions, performance indices, and oocyst shedding. The results indicated that the tested botanical formula in both concentrations improved the growth performance of the birds. However, the higher concentration prompted lower oocyst shedding and, likewise, toltrazuril in the positive control, healed cecal lesions more rapidly. In summary, the blended botanical formula, particularly in the higher concentration (1,000 ml per 1,000 L of drinking water), could successfully be incorporated into therapeutic strategies against coccidiosis in broiler flocks.Kokcidioza, protozoarna bolest uzrokovana vrstom parazita iz roda Eimeria, uzrokuje veliku gospodarsku štetu u peradarskoj industriji. Razvijen je niz prirodnih pripravaka za borbu protiv novih vrsta Eimeria otpornih na lijekove i ublažavanje zabrinutosti javnosti u pogledu rezidua antikokcidijskih lijekova u proizvodima od peradi. U ovom istraživanju procijenjena je antikokcidijska djelotvornost komercijalne biljne mješavine, primijenjene u dvije koncentracije, za liječenje i kontrolu miješane infekcije kokcidijama. S tom svrhom, 120 novoizvaljenih brojlera nasumično je raspoređeno u pet jednakih skupina: Cox500, Cox1000, pozitivna kontrola (PC), negativna kontrola (NC) i kontrola (C). Prve dvije skupine, Cox500 i Cox1000, bile su izložene oocistima nekoliko vrsta Eimeria, a zatim su primile dvije koncentracije biljne mješavine (500 odnosno 1000 ml formule na 1000 L vode za piće) tijekom pet uzastopnih dana. PC skupina također je dobivala toltrazuril (7 mg/kg žive tjelesne mase) putem vode za piće, dva uzastopna dana. NC skupina je poslužila kao skupina s izazvanom-neliječenom kokcidiozom a C skupina kao skupina s neizazvanom-neliječenom kokcidiozom. Kod pilića su nadzirani klinički znakovi, crijevne lezije, pokazatelji proizvodnosti i izlučivanje oocista. Rezultati su pokazali da je testirana biljna formula u obje koncentracije poboljšala pokazatelje rasta pilića. Veća koncentracija potaknula je manje izlučivanje oocista, dok je toltrazuril u PC skupini ubrzao cijeljenje lezija crijeva. Istražena biljna mješavina mogla bi se, posebno u višoj koncentraciji (1000 ml na 1000 L vode za piće), uspješno ugraditi u terapijske strategije protiv kokcidioze u jatima brojlera

Thermodynamic Optimization of a Geothermal Power Plant with a Genetic Algorithm in Two Stages

Due to the harmful effects and depletion of non-renewable energy resources, the major concerns are focused on using renewable energy resources. Among them, the geothermal energy has a high potential in volcano regions such as the Middle East. The optimization of an organic Rankine cycle with a geothermal heat source is investigated based on a genetic algorithm having two stages. In the first stage, the optimal variables are the depth of the well and the extraction flow rate of the geothermal fluid mass. The optimal value of the depth of the well, extraction mass flow rate, and the geothermal fluid temperature is found to be 2100 m, 15 kg/s, and 150 °C. In the second stage, the efficiency and output power of the power plant are optimized. To achieve maximum output power as well as cycle efficiency, the optimization variable is the maximum organic fluid pressure in the high-temperature heat exchanger. The optimum values of energy efficiency and cycle power production are equal to 0.433 MW and 14.1%, respectively

Energy, Exergy, Economic, and Exergoenvironmental Analyses of a Novel Hybrid System to Produce Electricity, Cooling, and Syngas

Efficient solar and wind energy to electricity conversion technologies are the best alternatives to reduce the use of fossil fuels and to evolve towards a green and decarbonized world. As the conventional photovoltaic systems use only the 600–1100 nm wavelength range of the solar radiation spectrum for electricity production, hybrid systems taking advantage of the overall solar radiation spectrum are gaining increasing interest. Moreover, such hybrid systems can produce, in an integrated and combined way, electricity, heating, cooling, and syngas through thermochemical processes. They have thus the huge potential for use in residential applications. The present work proposes a novel combined and integrated system for residential applications including wind turbines and a solar dish collector for renewables energy harvesting, an organic Rankine cycle for power production, an absorption chiller for cold production, and a methanation plant for CH4 production from captured CO2. This study deals with the energy, exergy, economic, and exergoenvironmental analyses of the proposed hybrid combined system, to assess its performance, viability, and environmental impact when operating in Tehran. Additionally, it gives a clear picture of how the production pattern of each useful product depends on the patterns of the collection of available renewable energies. Results show that the rate of methane production of this hybrid system changes from 42 up to 140 Nm3/month, due to CO2 consumption from 44 to 144 Nm3/month during a year. Moreover, the energy and exergy efficiencies of this hybrid system vary from 24.7% and 23% to 9.1% and 8%, respectively. The simple payback period of this hybrid system is 15.6 and the payback period of the system is 21.4 years

Analyzing the Impacts of a Successful Diffusion of Shared E-Scooters and Other Micromobility Devices and Efficient Management Strategies for Successful Operations in Illinois

Active transportation can play an important role in promoting more physically active and positive public health outcomes. While walking and biking provide significant physical health benefits, their modal share remains low. As a new form of micromobility service, shared e-scooters can enhance the suite of options available in cities to promote active transportation and fill in the gaps when walking or biking are not preferred. Although e-scooters show potential as a mode of transportation, it is unclear whether people will adopt the technology for everyday use. Furthermore, shared micromobility (e.g., electric scooters) is gaining attention as a complementary mode to public transit and is expected to offer a solution to access/egress for public transit. However, few studies have analyzed integrated usage of shared e-scooters and public transit systems while using panel data to measure spatial and temporal characteristics. This study aims to examine the adoption and frequency of shared e-scooter usage and provide policy implementation. To do so, the researchers launched a survey in the Chicago region in late 2020 and collected a rich data set that includes residents’ sociodemographic details and frequency of shared e-scooter use. To characterize the frequency, the researchers used an ordered probit structure. The findings show that respondents who are male, low income, Millennials and Generation Z, or do not have a vehicle are associated with a higher frequency of shared e-scooter use. Furthermore, this study utilizes shared e-scooter trips for a 35-day measurement period from 10 shared e-scooter operators in Chicago, where the researchers used a random-parameter negative binomial modeling approach to analyze panel effects. The findings highlight the critical role of spatial and temporal characteristics in the integration of shared e-scooters with transit.IDOT-R27-215Ope

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017 : A systematic analysis for the global burden of disease study

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.Peer reviewe

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Effects of 3, 4-Dihydroxyflavone on Cryopreserved Testicular Tissue of Neonatal Mouse

Background and Aim: Infertility is a side effect of cancer treatment because of chemotherapy or radiotherapy. Cryopreservation of testicular tissue or spermatogonial stem cells before cancer treatment and their transplantation may preserve the natural fertility. Cryopreservation is a damaging process due to free radicals and toxic effect of frozen solution. The purpose of this paper is to study the antioxidant and antiapoptotic effects of 3',4'-dihydroxyflavone on the structure of frozen-thawed testicular tissue of neonatal mouse. Materials and Methods: Testes of 6-day-old NMRI mice (N = 20) were isolated. Testicles were randomly divided into four groups: two groups as control groups for quick and slow freezing-melting process, and two others as treatment groups that underwent quick and slow freezing-melting with addition of 3',4'-dihydroxyflavone (10µM) in frozen solution. For the assessment of structural changes and apoptosis in the frozen-thawed testes, the hematoxylin-eosin staining and tunnel pod kits were used respectively. In order to analyze the data, we used Kruskal-Wallis Test and Mann-Whitney Test. The statistical analysis was entirely done by SPSS software. Results: Histopathological changes and apoptosis rate were significantly decreased after thawing in both treatment groups in comparison with control groups. Conclusion: Adding 3',4'-dihydroxyflavone (10µM) to freezing-melting environment and the use of quick freezing-melting method can reduce the histopathological and apoptotic changes