(R1488) Transformation of Glucokinase under Variable Rate Constants and Thermal Conditions: A Mathematical Model

The glucokinase (GK) in cells plays a pivotal role in the regulation of carbohydrate metabolism and acts as a sensor of glucose. It helps us to control glucose levels during fast and food intake conditions through triggering shifts in metabolism or cell functions. Various forms of hypoglycaemia and hyperglycaemia occur due to the transformations of the gene of the Glucokinase. The mathematical modelling of enzyme dynamics is an emerging research area to serve its role in biological investigations. Thus, it is imperative to establish a mathematical model to understand the kinetics of native and denatured forms of enzyme-GK under thermal stress with respect to time. The formulation of the current model is based on the number of non-linear ordinary differential equations with suitable initial and boundary conditions. The transformations of glucokinase were studied using mathematical and computational simulations in order to estimate the concentration of native and denatured enzyme forms with respect to different rate constants and under various thermal changes. The results obtained in this model were verified with the empirical outcome of Sanchez Ruiz et al. and Weinhouse for the validity and efficacy of the formulated model

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 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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Отношения между Ираном и Турцией после 11 сентября 2001 г.

In contemporary Middle East politics, Iran and Turkey are the two important countries. The two countries are among the ancient civilisations and are also old competitors for playing a dominant role in the Middle East power structure as well. Further the US invasion of Afghanistan and Iraq in 2001 and 2003 added extra fuel to their competition by created a power vacuum in the power structure of the region. However despite ideological differences between the two countries maintained peaceful relations as there are certain concerns like geopolitical realities and economic interests, energy, Iran’s isolation in world politics due to US led sanctions etc that compelled the two nations to work together. Even Turkey played very active role in mediating between Iran and US for resolving the Iranian nuclear issue peacefully. However the upspring in Middles Eastern countries once again brought their difference to forefront particularly with respect to ongoing Syrian crisis. Both the countries alleged one another for adding fuel to the crises in the region in order to safeguard their national interests. In this situation of uncertainties, this paper would try to look into the changing nature of Iran-Turkey relationship in post 9/11 era and try to analyse and pinpoint the areas of competition between the two countries and its effects on regional peace and stabilityИран и Турция являются двумя важными странами в современной политике Ближнего Востока. Обе страны относятся к древним цивилизациям и с давних пор соперничают за право играть ведущую роль в распределении сил на Ближнем Востоке. Вторжение США в Афганистан и Ирак в 2001 и 2003 гг. добавили масла в огонь, создав тем самым определенный вакуум в структуре власти региона. Тем не менее, несмотря на идеологические разногласия, Турция и Иран сохраняли мирные отношения ввиду определённой заинтересованности в геополитических событиях и наличии экономических интересов, в том числе в сфере энергетики. Кроме того, исключение Ирана из мировой политики из-за санкций, введенных США, также способствовало тому, что обе страны были вынуждены действовать сообща. Турция принимала активное участие в переговорах между Ираном и США, касающихся мирного разрешения ядерного вопроса для Ирана. Однако текущая ситуация на Ближнем Востоке, и сирийский кризис в частности, вновь обострили разногласия между странами. Обе страны обвиняют друг друга в подогревании кризиса в регионе с целью защиты своих национальных интересов. Ситуация неоднозначная, и данная статья посвящена рассмотрению изменчивой природы иранско-турецких отношений в период после террористических атак 11 сентября 2001 г., а также анализу и определению конфликтных сфер для двух стран и их влиянию на стабильность регион

Отношения между Ираном и Турцией после 11 сентября 2001 г.

In contemporary Middle East politics, Iran and Turkey are the two important countries. The two countries are among the ancient civilisations and are also old competitors for playing a dominant role in the Middle East power structure as well. Further the US invasion of Afghanistan and Iraq in 2001 and 2003 added extra fuel to their competition by created a power vacuum in the power structure of the region. However despite ideological differences between the two countries maintained peaceful relations as there are certain concerns like geopolitical realities and economic interests, energy, Iran’s isolation in world politics due to US led sanctions etc that compelled the two nations to work together. Even Turkey played very active role in mediating between Iran and US for resolving the Iranian nuclear issue peacefully. However the upspring in Middles Eastern countries once again brought their difference to forefront particularly with respect to ongoing Syrian crisis. Both the countries alleged one another for adding fuel to the crises in the region in order to safeguard their national interests. In this situation of uncertainties, this paper would try to look into the changing nature of Iran-Turkey relationship in post 9/11 era and try to analyse and pinpoint the areas of competition between the two countries and its effects on regional peace and stabilityИран и Турция являются двумя важными странами в современной политике Ближнего Востока. Обе страны относятся к древним цивилизациям и с давних пор соперничают за право играть ведущую роль в распределении сил на Ближнем Востоке. Вторжение США в Афганистан и Ирак в 2001 и 2003 гг. добавили масла в огонь, создав тем самым определенный вакуум в структуре власти региона. Тем не менее, несмотря на идеологические разногласия, Турция и Иран сохраняли мирные отношения ввиду определённой заинтересованности в геополитических событиях и наличии экономических интересов, в том числе в сфере энергетики. Кроме того, исключение Ирана из мировой политики из-за санкций, введенных США, также способствовало тому, что обе страны были вынуждены действовать сообща. Турция принимала активное участие в переговорах между Ираном и США, касающихся мирного разрешения ядерного вопроса для Ирана. Однако текущая ситуация на Ближнем Востоке, и сирийский кризис в частности, вновь обострили разногласия между странами. Обе страны обвиняют друг друга в подогревании кризиса в регионе с целью защиты своих национальных интересов. Ситуация неоднозначная, и данная статья посвящена рассмотрению изменчивой природы иранско-турецких отношений в период после террористических атак 11 сентября 2001 г., а также анализу и определению конфликтных сфер для двух стран и их влиянию на стабильность регион

Synthesis, characterization, stability and thermal conductivity of multi-walled carbon nanotubes (MWCNTs) and eco-friendly jatropha seed oil based nanofluid: An experimental investigation and modeling approach

Despite the remarkable nanofluids potential in energy storage applications, the long-term dispersion stability of the nanoparticles in a base fluid along with improved thermal conductivity is a significant challenge towards their commercialization. Therefore, a novel surfactant MWCNTs and eco-friendly Jatropha seed oil based nanofluid are synthesized via one-step synthesis method and subjected to characterization via visual analysis, FTIR, Zeta potential, pore size distribution, thermogravimetric analysis (TGA), and UV analysis to investigate MWCNTs dispersion stability along with thermal conductivity measurement. The results showed the excellent MWCNTs dispersion stability in Jatropha seed oil and thermal conductivity improvement from 2.29% to 6.76% over the temperature within the range of 25–65 °C and nanoparticle weight fraction in the range of 0.2–0.8 wt%. Furthermore, two new correlations are proposed based on multiple non-linear regression analysis and dimensionless group analysis in the replacement of classical models which are failed to accurate prediction of thermal conductivity. The developed models showed remarkable thermal conductivity prediction accuracy with the value of R2 > 0.991. © 201