Exposure to air pollution in epidemiological studies in Kuwait: A systematic review (preprint)

Objective To systematically review the epidemiological studies of human exposure to air pollution in Kuwait. Methods Specific keywords related to air pollution and health effects in Kuwait were systematically searched using PubMed and BASE search engines for published research in English language from the year 1990 up to June 2020. Non eligible studies were those which published in non-English studies, studies on animals, plants, exposure to pollutants other that air pollutants, studies related to oil fires caused by Iraqi invasion to Kuwait in 1991. After duplicates were removed, titles and abstracts of eligible studies were screened and full text of publications meeting the inclusion criteria was read. Non-epidemiological studies were included only to compare their numbers to the epidemiological studies, and to help in future studies. Results Total of 85 studies including epidemiological and non-epidemiological studies, only 8 of them found to be an epidemiological study, which 4 of them concerned with mortality and 3 with morbidity, and 1 with both morbidity and mortality. Two of these studies concern with respiratory disease, 1 of them concerned with atopic dermatitis and was the only study measured indoors (i.e. house), and 1 study concerned with rheumatoid arthritis. One study measured ETS, 4 studies measured dust, 2 studies measured PM10 and PM2.5, and 1 study measured NO2, SO2, O3, CO. All studies found that exposure to air pollution has adverse effect on health problems (i.e. respiratory problems, atopic dermatitis, rheumatoid arthritis) and mortality except one study found no significant correlation between exposure to air pollution (i.e. dust) and mortality. Conclusion Epidemiological studies related to human exposure to air pollution in Kuwait are underestimated and insufficient, there are extremely limited studies that cannot be compared to each other. Since currently Kuwait have many major constructions in major roads in and out the capital which alters the air pollution, adding to that the new study which found that the new current global epidemic namely coronavirus COVID-19 is correlated to air pollution (i.e. NO2), new researches need to be done measuring the different pollutants in both indoor and outdoor exposure examining different health problems, these researches need to be done during and after these circumstances for comparison.

Dynamic Vaccine Allocation for Control of Human Transmissible Disease (preprint)

During pandemics, such as COVID-19, supplies of vaccines can be insufficient to meet all needs, particularly when vaccines first become available. Our study develops a dynamic methodology for vaccine allo- cation, segmented by region, age, and timeframe, using a time-sensitive, age-structured compartmental model. Based on the objective of mini- mizing a weighted sum of deaths and cases, we used the Sequential Least Squares Quadratic Programming method to search for a locally opti- mal COVID-19 vaccine allocation for the United States, for the period from December 16, 2020, to June 30, 2021, where regions corresponded to the 50 states in the United States (US). We also compared our solu- tion to actual allocations of vaccines. From our model, we estimate that approximately 1.8 million cases and 9 thousand deaths could have been averted in the US with an improved allocation. When case reduction is prioritized over death reduction, we found that young people (17 and younger) should receive priority over old people due to their potential to expose others. However, if death reduction is prioritized over case reduc- tion, we found that more vaccines should be allocated to older people, due to their propensity for severe disease. While we have applied our methodology to COVID-19, our approach generalizes to other human- transmissible diseases, with potential application to future epidemics.

Educator Perspectives on Stressors and Health: A qualitative study of U.S. K-12 educators in February 2022 (preprint)

Background The teaching profession, already characterized by high stress and burnout, experienced exacerbated challenges during the height of the COVID-19 pandemic. While educators faced changing job demands over the course of the pandemic with switches in remote and in-person teaching along with COVID-19 transmission prevention strategies, the demands and resulting impact in the years that follow are still being explored. We sought to understand the stressors and health impacts of U.S. educators in the 2021–2022 school year, 2 years following the acute phase of the pandemic.Methods Thirty-four certified educators based in Connecticut, USA participated in 4 virtual focus groups in February 2022. A semi-structured focus group script, designed by the research team and guided by the job demands-resources model, was administered to understand stress impacts and stressors. Data were transcribed and analyzed using the constant comparative method to identify themes and sub-themes. Themes were summarized by frequency as well as by individuals.Results The majority of respondents reported educator well-being impacts of stress fell into three categories: physical health impacts and behaviors (76%; e.g. poor sleep, physical exhaustion, lack of exercise, unhealthy eating), psychological health impacts (62%; e.g. emotional exhaustion, anxiety, negative self-evaluation); and social well-being impacts and behaviors (68%; e.g. connections with family or friends, connections with others, relationships with coworkers). Sources of reported stressors included the school or district (94%), personal (65%), situational (35%), and to a lesser extent parents (24%), other work factors (15%), community (12%), students (12%), and state or national level (9%) factors. At the school/district level, stressors were related to protocols/expectations (91%, e.g. excessive or increased demands, insufficient or decreased resources) or administrators (38%). Personal level stressors included personal life (41%); other personal factors (20%); and income (17%); situational factors included the pandemic (26%) and safety concerns (9%).Conclusion Focus groups allowed us to assess the health and working conditions of Connecticut’s public education workforce 2 years following the acute phase of the pandemic. Lasting effects are relevant in the post-pandemic era and continue to pose challenges as teacher shortages increase. Targeted interventions are needed to reduce school and district-related demands and to address stress-related educator well-being.

Workplace sustainability or financial resilience? Composite-financial resilience index (preprint)

Due to the variety of corporate risks in turmoil markets and the consequent financial distress especially in COVID-19 time, this paper investigates corporate resilience and compares different types of resilience that can be potential sources of heterogeneity in firms' implied rate of return. Specifically, the novelty is not only to quantify firms' financial resilience but also to compare it with workplace resilience which matters more in the COVID-19 era. The study prepares several pieces of evidence of the necessity and insufficiency of these two main types of resilience by comparing earnings expectations and implied discount rates of high- and low-resilience firms. Particularly, results present evidence of the possible amplification of workplace resilience by the financial status of firms in the COVID-19 era. The paper proposes a novel composite-financial resilience index as a potential measure for disaster risk that significantly and persistently reveals low-resilience characteristics of firms and resilience-heterogeneity in implied discount rates.

Differential Patterns of Cross-Protection against Antigenically Distinct Variants in Small Animal Models of SARS-CoV-2 Infection (preprint)

Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will likely force more future updates of vaccine composition. Based on a series of studies carried out in human ACE2 transgenic mice (K18-hACE2) and Syrian hamsters, we show that immunity at the respiratory tract, acquired through either previous infection or vaccination with an in-house live attenuate virus, offers protection against antigenically distinct variants in the absence of variant spike-specific neutralizing antibodies. Interestingly, immunity acquired through infection of a modern variant (XBB.1.5) was insufficient in preventing brain infection by the ancestral virus (WA1/2020) in K18-hACE2 mice. Similarly, previous infection with WA1/2020 did not protect against brain infection by XBB.1.5. Our results highlight the importance of immune components other than neutralizing antibodies in maintaining protection against new variants in the respiratory tract, but also paint scenarios where a monovalent vaccine based on a contemporary variant may be less effective against the ancestral strain.

Fluoxetine and Sertraline Potently Neutralize the Replication of Distinct SARS-CoV-2 Variants (preprint)

The pandemic caused by SARS-CoV-2 is still a major health problem. Newly emerging variants and long-COVID-19 represent a challenge for the global health system. In particular, individuals in developing countries with insufficient health care need easily accessible, affordable and effective treatments of COVID-19. Previous studies have demonstrated the efficacy of functional inhibitors of acid sphingomyelinase (FIASMA) against infections with various viruses, including early variants of SARS-CoV-2. This work investigated whether the acid sphingomyelinase inhibitors fluoxetine and sertraline, usually used as antidepressant molecules in clinical practice, can inhibit the replication of the former and recently emerged SARS-CoV-2 variants in vitro. Fluoxetine and sertraline potently inhibited the infection with pseudotyped virus like particles and SARS-CoV-2 variants D614G, alpha, delta, omicron BA.1 and omicron BA.5. These results highlight fluoxetine and sertraline as priority candidates for large-scale phase 3 clinical trials at different stages of SARS-CoV-2 infections, either alone or in combination with other medications.

Effects of COVID-19 on the provision of Water, Sanitation, and Hygiene (WASH) services in health care facilities in the Far-North Region of Cameroon (preprint)

Background Worldwide, the Joint Monitoring Program reports that one in four health care facilities (HCFs) lack functional water supply on premises, one in three lack hand hygiene facilities, and one in three lack adequate infectious waste disposal. The COVID-19 pandemics shed light on the lack of investments, the absence of infrastructures, education and policies related to WASH as well as revealed insufficient investment in healthcare safety; and has brought WASH services as non-negotiable for HCFs.Methods This study used a cross-sectional pre-post COVID-19 framework to determine the proportion of HCFs: meeting basic WASH services and, which WASH services improved post-COVID-19 in the Far-North Region of Cameroon.Results A total of 97 (23.04%) HCFs among the 421 that are found in the Far-North region were surveyed and located in eight (25%) of the 32 Health Districts. They corresponded to the integrated health centers category (79.4%) and the survey’s respondent was the chief of the HCF (92.8%). Approximately 75.3%, 0.0%, 48.5%, 46.4%, and 6.2% of HCFs respectively met thresholds for basic water, sanitation, hygiene, waste management, and environment cleaning services. When comparing pre- vs. post COVID-19 periods, a significant increase (8%) was noted in the proportion of HCFs as of optimal handwashing practices-related services (P = 0.0026). There was also a significant increase (p = 0.007) in the proportion of HCFs with cleaning protocols available. Further, none of the HCFs fulfilled all the criteria to meet basic services for all the five WASH services.Conclusions In conclusion, the response to the COVID-19 pandemics only partially improved WASH services-related infrastructures in HCFs of the Far-North Region of Cameroon. The COVID-19 pandemics was a missed opportunity to strengthen WASH services. There should be a continuing encouragement of governments and funding agencies in planning and budgeting WASH in healthcare-related research and issues, and enabling the maintenance of existing WASH infrastructures in healthcare settings.

Effects of COVID-19 on the provision of Water, Sanitation, and Hygiene (WASH) services in health care facilities in the Far-North Region of Cameroon (preprint)

Worldwide, the Joint Monitoring Program reports that one in four health care facilities (HCFs) lack functional water supply on premises, one in three lack hand hygiene facilities, and one in three lack adequate infectious waste disposal. The COVID-19 pandemics shed light on the lack of investments, the absence of infrastructures, education and policies related to WASH as well as revealed insufficient investment in healthcare safety and has brought WASH services as non-negotiable for HCFs. This study used a cross-sectional pre-post COVID-19 framework to determine the proportion of HCFs: meeting basic WASH services and, which WASH services improved post-COVID-19 in the Far-North Region of Cameroon. A total of 97 (23.04%) HCFs among the 421 that are found in the Far-North region were surveyed and located in eight (25%) of the 32 Health Districts. They corresponded to the integrated health centers category (79.4%) and the surveys respondent was the chief of the HCF (92.8%). Approximately 75.3%, 0.0%, 48.5%, 46.4%, and 6.2% of HCFs respectively met thresholds for basic water, sanitation, hygiene, waste management, and environment cleaning services. When comparing pre- vs. post COVID-19 periods, a significant increase (8%) was noted in the proportion of HCFs as of optimal handwashing practices-related services (P=0.0026). There was also a significant increase (p=0.007) in the proportion of HCFs with cleaning protocols available. Further, none of the HCFs fulfilled all the criteria to meet basic services for all the five WASH services. In conclusion, the response to the COVID-19 pandemics only partially improved WASH services-related infrastructures in HCFs of the Far-North Region of Cameroon. The COVID-19 pandemics was a missed opportunity to strengthen WASH services. There should be a continuing encouragement of governments and funding agencies in planning and budgeting WASH in healthcare-related research and issues, and enabling the maintenance of existing WASH infrastructures in healthcare settings.

Attitudes and concerns of nursing students against the COVID-19 vaccine, willingness to be vaccinated: A cross-sectional study (preprint)

Background: COVID-19 vaccine acceptance by the nurses of the future is important to increase the population immunity. Aim: This study aimed to determine the attitudes and concerns of nursing students towards the coronavirus disease-2019 (COVID-19) vaccine, their willingness to be vaccinated, and the factors affecting their willingness in the second wave of the COVID-19 pandemic. Method: This cross-sectional study was conducted between February 1, 2021, to March 30, 2021, using an online questionnaire in 498 nursing students in Turkey. Results: While 64.5% of nursing students had the intention to be vaccinated against COVID-19, 35.5% had no intention to be vaccinated (29.3% hesitant and 6.2% unwilling). Students expressed their attitudes and concerns on the lack of COVID-19 vaccine information (65.7%), its effectiveness (41.6%), safety (45.8%), and side effects (50.8%). Students did not intend to be vaccinated due to insufficient trust in the vaccine effectiveness (84%), the continuous COVID-19 mutation, vaccines side effects (68.9%), and not trusting the supplied vaccine (55.4%). Students’ high education level, high family income perception, previous vaccine rejection, family members with COVID-19 infection, COVID-19 information from official institutions, trusting health professionals’ COVID-19 explanations, and attitudes and concerns toward vaccines for their intention to be vaccinated are the affecting factors (p < 0.05). Conclusions: Nursing students are known to be future healthcare professionals and play a decisive role in counseling individuals in the community on the risks of COVID-19 and the benefits of the vaccine. Therefore, focusing on training that is aimed at increasing vaccine knowledge, eliminating their negative attitudes and concerns, and building confidence in vaccines is necessary.

Cohort Profile of the Chilean COVID-19 Biorepository: a Multicentric initiative for multi-omics research on COVID-19 and LONG-COVID in a Latin American population. (preprint)

PurposeMolecular mechanisms underlying COVID-19 susceptibility and severity are still poorly understood. The presence of genetic risk factors associated with ethnic background has been suggested, highlighting non-European ancestry as a risk factor for hospitalization in the United States. However, the representation of non-European populations in genomic case-control and cohort studies remains insufficient, and Latin American populations have been significantly understudied. Addressing this gap, we established The Chilean COVID-19 Biorepository, a multicentric endeavor comprising high-quality biological samples and associated data collected throughout Chile under stringent biobanking standards that ensure high quality, reproducibility, and interoperability. ParticipantsThe Chilean COVID-19 Biorepository was established by a network of nine nodes distributed in five macro-zones nationwide. The study enrolled adult participants living in Chile who had tested positive for SARS-CoV-2 infection and provided broad written informed consent. Blood samples were collected with EDTA and processed to store blood, plasma, buffy-coat, and DNA. Quality control measures, such as Standard Preanalytical Code (SPREC), incident reporting, DNA concentration, and absorbance ratio (260/280), were implemented to ensure the reliability and quality of the collected samples. Sociodemographic data, habits, clinical information, use of medications, and preexisting pathologies were registered. A weekly iterative workflow was implemented to ensure the quality and integrity of specimens and data. Findings to dateBetween October 2020 and February 2021, 2262 participants were recruited, pseudonymized, and categorized by disease severity into six categories, from asymptomatic to lethal. Notably, the Biorepository exhibited high compliance rates (>90%) across all quality control assessed items, reflecting high adherence to biobanking standards. A noteworthy feature of this cohort is the self-identification of 279 participants (12.3%) into thirteen different ethnic groups. Amerindian ancestry from genome-wide genetic data was 44.0%[SD15.5%] and increased to 61.2%[SD19.5%] when considering participants who identified as Native South Americans. As a data-contributor partner of the COVID-19 Host Genetics Initiative, the Chilean COVID-19 Biorepository has contributed to the publication of a second updated genome-wide association study, further enhancing our knowledge of the role of host genetics in susceptibility and severity to SARS-CoV-2. Future plansThe Chilean COVID-19 Biorepository, under the leadership of Latin American researchers from a Latin American country, substantially adds to the integration of Latin American populations in the global collections landscape. Just as ocurred with the COVID-19 Host Genetics Initiative, we expect that this repository will attract global network collaborations for comparative studies on the effects of COVID-19 across diverse populations, including exploring potential genetic advantages or disadvantages in the context of SARS-CoV-2 infection. Researchers involved in establishing this biorepository are currently associated within a collaborative initiative known as COVID-19 Genomics Network (C19-GenoNet), aimed to accelerate the identification of genetic factors in both hosts and pathogens that influence the short and long-term outcomes of SARS-CoV-2 infection. The broad informed consent utilized enables longitudinal cohort follow-up, thereby allowing for investigating the long-term consequences of SARS-CoV-2 infection, particularly concerning long-COVID. Thus, participants of this cohort were re-contacted to assess the development of long-COVID through a survey-based approach. The re-contact and recruitment procedures yielded a high response rate (82.11%), demonstrating strong participant engagement. In this case as well, this cohort has been leveraged by collaboration with the COVID-19 Host Genetics Initiative for the forthcoming publication of a genome-wide association study on long-COVID. The concerted endeavors invested in this Chilean initiative have led to the establishment and consolidation of C19-GenoNet as both a research network and a biobanking network. A comprehensive catalog of the C19-GenoNet biobank network has been created and is accessible online at https://redcovid.uchile.cl/. STRENGHT AND LIMITATIONS OF THIS STUDYO_LIThis study is one of the largest cohorts of COVID-19 patients with associated Biobank reported so far in Latin America. C_LIO_LIThe studys design and rigorous weekly monitoring ensured effective collection of high-quality simples and maximized the quality and completeness of data, with the ability to re-contact participants in case of problematic information. C_LIO_LIThere were no control or reliable information about the time between the infection and the sampling, which may hamper the comparison of some parameters among cases due to transcriptional dynamics after SARS-CoV-2 infection. C_LIO_LIThe study is based on a self-reported survey, which may represent a bias when analyzing specific clinical phenotypes. C_LI

Causal Model Analysis of the Effect of Policy Formalism, Equipment Insufficiency, Covid-19 Fear and Job Insecurity on Construction Workers’ Insomnia during the Epidemic (preprint)

This study mainly explores the effect of policy formalism, equipment insufficiency, covid-19 fear and job insecurity on construction workers’ insomnia during the epidemic. The main contribution of this article is to introduce policy formalism into the exploration of the causes of insomnia among construction site workers during the epidemic. This study collected 733 valid samples of construction site workers. We tested the established hypotheses using confirmatory factor analysis and structural equation modeling. The research results found that equipment insufficiency positively affects Covid-19 fear. Policy formalism and Covid-19 fear positively affect job burnout. Social support negatively affects job burnout. Job burnout and job insecurity positively affect insomnia.

Dissecting Clinical Features of COVID-19 in a Cohort of 21,312 Acute Care Patients (preprint)

COVID-19 has resulted in over 645 million hospitalization and 7 million deaths globally. However, many questions still remain about clinical complications in COVID-19 and if these complications changed with different circulating SARS-CoV-2 strains. We analyzed a 2.5-year retrospective cohort of 47,063 encounters for 21,312 acute care patients at five Central Texas hospitals and define distinct trajectory groups (TGs) with latent class mixed modeling, based on the World Health Organization COVID-19 Ordinal Scale. Using this TG framework, we evaluated the association of demographics, diagnoses, vitals, labs, imaging, consultations, and medications with COVID-19 severity and broad clinical outcomes. Patients within 6 distinct TGs differed in manifestations of multi-organ disease and multiple clinical factors. The proportion of mild patients increased over time, particularly during Omicron waves. Age separated mild and fatal patients, though did not distinguish patients with severe versus critical disease. Male and Hispanic/Latino demographics were associated with more severe/critical TGs. More severe patients had a higher rate of neuropsychiatric diagnoses, consultations, and brain imaging, which did not change significantly in severe patients across SARS-CoV-2 variant waves. More severely affected patients also demonstrated an immunological signature of high neutrophils and immature granulocytes, and low lymphocytes and monocytes. Interestingly, low albumin was one of the best lab predictors of COVID-19 severity in association with higher malnutrition in severe/critical patients, raising concern of nutritional insufficiency influencing COVID-19 outcomes. Despite this, only a small fraction of severe/critical patients had nutritional labs checked (pre-albumin, thiamine, Vitamin D, B vitamins) or received targeted interventions to address nutritional deficiencies such as vitamin replacement. Our findings underscore the significant link between COVID-19 severity, neuropsychiatric complications, and nutritional insufficiency as key risk factors of COVID-19 outcomes and raise the question of the need for more widespread early assessment of patients neurological, psychiatric, and nutritional status in acute care settings to help identify those at risk of severe disease outcomes.

The Human Microglia Atlas (HuMicA) Unravels Changes in Homeostatic and Disease-Associated Microglia Subsets across Neurodegenerative Conditions (preprint)

Dysregulated microglia activation, leading to neuroinflammation, is currently considered to be of major relevance in the development and progression of neurodegenerative diseases. The initial M1/M2 dual activation classification for microglia is now considered outdated. Even the "disease-associated microglia" (DAM) phenotype, firstly described in mice, has proven insufficient to precisely represent the multitude of microglia phenotypes in pathology. In this study, we have constructed a transcriptomic atlas of human brain immune cells by integrating single-nucleus (sn)RNA-seq datasets from multiple neurodegenerative conditions. Sixteen datasets were included, comprising 295 samples from patients with Alzheimer's disease, autism spectrum disorder, epilepsy, multiple sclerosis, Lewy body diseases, COVID-19, and healthy controls. The integrated Human Microglia Atlas (HuMicA) dataset included 60,557 nuclei and revealed 11 microglial subpopulations distributed across all pathological and healthy conditions. Among these, we identified four different homeostatic clusters as well as pathological phenotypes. These included two stages of early and late activation of the DAM phenotype and the disease-inflammatory macrophage (DIM) phenotype, which was recently described in mice, and is also present in human microglia, as indicated by our analysis. The high versatility of microglia is evident through changes in subset distribution across various pathologies, suggesting their contribution to the establishment of pathological phenotypes. Our analysis showed overall depletion of four substates of homeostatic microglia, and expansion of niche subpopulations within the DAM and DIM spectrum across distinct neurodegenerative pathologies. The HuMicA is an invaluable resource tool used to support further advances in the study of microglia biology through healthy and disease settings.

ВЫГОДЫ И РИСКИ ДЛЯ РОССИЙСКИХ ОТРАСЛЕЙ И ОТДЕЛЬНЫХ ПРЕДПРИЯТИЙ ОТ РЕАЛИЗАЦИИ ТОРГОВО-ЭКОНОМИЧЕСКИХ СОГЛАШЕНИЙ СТРАН СНГ (Benefits and Risks for Russian Industries and Individual Enterprises from the Implementation of Trade and Economic Agreements of the CIS Countries) (preprint)

Russian abstract: Страны СНГ, или более широко – бывшие республики СССР, фактически делают выбор между европейской (ЕС) и евразийской интеграцией (ЕАЭС), что приводит к определенным выгодам и рискам для всех стран СНГ+ (с учётом Украины и Грузии), в особенности для России. В первую очередь интерес представляют случаи Украины, Грузии и Молдовы. Прекращение торгово-экономического сотрудничества, нарушение цепочек добавленной стоимости и т.д. влечет за собой серьезную опасность для промышленного развития для российских отраслей и отдельных предприятий. Кризисные явления, к примеру, такие как пандемия коронавируса, только усиливают данные тенденции. Исследовательский интерес также представляет факт выхода Великобритании из ЕС (Brexit) в конце января 2020 г.Тематика стран постсоветского пространства и их торгово-экономического сотрудничества с разными странами изучается различными авторами с момента развала СССР. В последние десять лет наблюдается рост активности изучения данных проблем, в связи с развитием европейской политики соседства с одной стороны и евразийской интеграции с другой. Можно выделить следующих зарубежных и отечественных авторов по группам исследований:1)Анализ, в том числе количественный, различных интеграционных сценариев для стран СНГ+.2)Противостояние европейской и евразийской интеграций, а также проблемы ЕАЭС.3)Проблемы кооперации между Россией и странами постсоветского пространства, в том числе на уровне предприятий.English abstract: The CIS countries, or more broadly the former republics of the USSR, are effectively making a choice between European (EU) and Eurasian (EAEU) integration, which leads to certain benefits and risks for all CIS+ countries (including Ukraine and Georgia), especially for Russia. The cases of Ukraine, Georgia and Moldova are of primary interest. Termination of trade and economic cooperation, disruption of value chains, etc. entail a serious threat to industrial development for Russian industries and individual enterprises. Crisis phenomena such as the COVID-19 pandemic, for example, only exacerbate these trends. Great Britain’s departure from the EU (Brexit) at the end of January 2020 is also of research interest.The topics of the post-Soviet countries and their trade and economic cooperation with different countries have been studied by various authors since the collapse of the USSR. In the past ten years, there has been an increase in the activity of studying these problems, in connection with the development of the European Neighborhood Policy on the one hand and Eurasian integration on the other. Research by foreign and domestic authors can be distinguished into the following groups:1) Analysis, including quantitative analysis, of various integration scenarios for the CIS+ countries.2) The confrontation between European and Eurasian integrations, as well as the problems of the EAEU.3) Problems of cooperation between Russia and the post-Soviet countries, including at the level of individual enterprises.However, the issue of assessing the risks and possible consequences at the enterprise level for the EAEU countries from the implementation of the agreements of the CIS member states remains insufficiently studied, especially taking into account the participation in value chains and the importance of industrial recovery after the COVID-19 pandemic, etc.

Understanding the impact of numerical solvers on inference for differential equation models (preprint)

Most ordinary differential equation (ODE) models used to describe biological or physical systems must be solved approximately using numerical methods. Perniciously, even those solvers which seem sufficiently accurate for the forward problem, i.e., for obtaining an accurate simulation, may not be sufficiently accurate for the inverse problem, i.e., for inferring the model parameters from data. We show that for both fixed step and adaptive step ODE solvers, solving the forward problem with insufficient accuracy can distort likelihood surfaces, which may become jagged, causing inference algorithms to get stuck in local "phantom" optima. We demonstrate that biases in inference arising from numerical approximation of ODEs are potentially most severe in systems involving low noise and rapid nonlinear dynamics. We reanalyze an ODE changepoint model previously fit to the COVID-19 outbreak in Germany and show the effect of the step size on simulation and inference results. We then fit a more complicated rainfall-runoff model to hydrological data and illustrate the importance of tuning solver tolerances to avoid distorted likelihood surfaces. Our results indicate that when performing inference for ODE model parameters, adaptive step size solver tolerances must be set cautiously and likelihood surfaces should be inspected for characteristic signs of numerical issues.

Energy security and corruption in Central Asia as the main challenges for the European Union energy diversification policy (preprint)

Background The main goal of the paper is to define, analyze and assess the basic security, development and institutional challenges faced by the Central Asian countries after 2022. Following the Covid-19 pandemic, and with the outbreak of the Ukrainian crisis, Europe faced the need to find other sources of energy supply outside the Russian Federation. The Central Asian region is rich in energy resources and is therefore of special importance, but at the same time it is also a region of special geopolitical interest of often conflicting parties - the region for which there are limited information and insufficient academic literature about development, various aspects of security, internal specificities and future challenges.Methods The research included qualitative and quantitative analyses carried out for Kazakhstan, the Kyrgyz Republic, Turkmenistan, Uzbekistan and Tajikistan. Data processing was performed on the basis of 16 selected indicators in the fields of economy, energy, governance and climate change, for the time period from 2011 to 2021. Data processing was performed using the correlation and regression analysis (ANOVA).Results The results showed that energy policy and corruption represent one of the biggest problems faced by the countries of Central Asia, which strongly affects the energy security and sustainable development, not only of the countries of Central Asia, but also of all countries that are supplied with energy products from this region, or plan to do so. Correlation analysis shows that the countries of Central Asia have certain similarities when it comes to economic and social policy. Energy security is positive only in the case of Turkmenistan. Regression analysis shows that Kazakhstan reported the best positive trend for most indicators. Data for Germany show consistent values over the observed period.Conclusions The main conclusions of the paper indicate that the countries of Central Asia have made little progress when it comes to overall sustainable development, with energy security, corruption and government efficiency being the biggest problems. The European Union and Europe as a whole must find ways and mechanisms to overcome these and many other impediments if they are to get energy products from the aforementioned region.

Newly diagnosed autoimmune Addison's disease in a patient with COVID-19 with autoimmune disseminated encephalomyelitis.

A man in his 20s with a history of acute disseminated encephalomyelitis (ADEM) was brought into the emergency department (ED) after his family found him at home collapsed on the floor unresponsive with a blood glucose of 28 mg/dL at the field. In the ED, the patient was tachycardic, tachypnoeic and hypotensive, requiring pressors and intubation at 9 hours and 12 hours after arrival, respectively. Laboratory results revealed a positive COVID-19 test, serum sodium of 125 mmol/L and persistent hypoglycaemia. The patient was given a high dose of dexamethasone for COVID-19 treatment 1 hour before pressors were started. He was then continued on a stress dose of intravenous hydrocortisone with rapid clinical improvement leading to his extubation, and discontinuation of vasopressors and glucose on day 2 of admission. The patient received his last dose of intravenous hydrocortisone on day 4 in the early afternoon with the plan to order adrenal testing the following morning prior to discharge. On day 5, the aldosterone <3.0 ng/dL, adrenocorticotropic hormone (ACTH) level >1250 pg/mL, and ACTH stimulation test showed cortisol levels of 3 and 3 µg/dL at 30 and 60 min, respectively. The anti-21-hydroxylase antibody was positive. The patient was discharged on hydrocortisone and fludrocortisone. The patient's symptoms, elevated ACTH, low cortisol and presence of 21-hydroxylase antibodies are consistent with autoimmune Addison's disease. This is the first case reporting autoimmune Addison's disease in a patient with COVID-19 with a history of ADEM. The case highlights the importance of considering adrenal insufficiency as a diagnostic differential in haemodynamically unstable patients with COVID-19.

Self-management and hospitalization in 615 Swedish patients with Addison's disease during the coronavirus disease 2019 pandemic: a retrospective study.

OBJECTIVE: Autoimmune Addison's disease (AAD) entails a chronic adrenal insufficiency and is associated with an increased risk of severe infections. It is, however, unknown how patients with AAD were affected by the coronavirus disease 2019 (COVID-19) pandemic of 2020-2021. This study was aimed at investigating the incidence of COVID-19 in patients with AAD in Sweden, the self-adjustment of medications during the disease, impact on social aspects, and treatment during hospitalization. Additionally, we investigated if there were any possible risk factors for infection and hospitalization. DESIGN AND METHODS: Questionnaires were sent out from April to October 2021 to 813 adult patients with AAD in the Swedish Addison Registry. The questionnaires included 55 questions inquiring about COVID-19 sickness, hospital care, medications, and comorbidities, focusing on the pre-vaccine phase. RESULTS: Among the 615 included patients with AAD, COVID-19 was reported in 17% of which 8.5% required hospital care. Glucocorticoid treatment in hospitalized patients varied. For outpatients, 85% increased their glucocorticoid dosage during sickness. Older age (P = .002) and hypertension (P = .014) were associated with an increased risk of hospital care, while younger age (P < .001) and less worry about infection (P = .030) were correlated with a higher risk of COVID-19. CONCLUSIONS: In the largest study to date examining AAD during the COVID-19 pandemic, we observed that although one-fifth of the cohort contracted COVID-19, few patients required hospital care. A majority of the patients applied general recommended sick rules despite reporting limited communication with healthcare during the pandemic.