Proceedings of the SPIE PHOTONICS EUROPE Conference on Biophotonics in Point-of-Care, 6-10 April 2020, Online Only, France. Proc. SPIE volume 11361

The Arctic Council is well-positioned to play a leadership role in better understanding the impact of Covid-19 in the Arctic and spearheading activities to respond to the pandemic in the short-, medium- and longer-term. This briefing document was prepared to inform initial discussions regarding the coronavirus pandemic in the Arctic at the Senior Arctic Officials’ executive meeting (SAOX) on 24-25 June 2020. It draws together available information – to date (June 2020) – about the impact of Covid-19 in the Arctic: Briefing Document for SAOs June 2020 For public release Page 10 of 83 Covid-19 and the actions taken to respond in the Arctic region. The document draws from a wide spectrum of sources, reflecting the complex and intricate nature of how Covid-19 affects Arctic peoples and communities, including national and subnational statistical databases and tools, peer-reviewed articles, policy statements, technical guidelines, field surveys, and local observations from Arctic communities.

The book contains 19 national reports and a comparative legal analysis of the legal regulations on the procedure of genome editing on the human germline. It is worked out which shared values ​​the different legal systems connect and which differences exist. On this basis, it is examined whether an international regulation of the topic is possible and how it could be designed. In addition, it will be examined to what extent the regulations of other countries can serve as a model for German legislation.

Cancer cells require exogenous methionine for survival and therefore methionine restriction is a promising avenue for treatment. The basis for methionine dependence in cancer cells is still not entirely clear. While the lack of the methionine salvage enzyme methylthioadenosine phosphorylase (MTAP) is associated with methionine auxotrophy in cancer cells, there are other causes for tumors to require exogenous methionine. Restricting methionine by diet or by enzyme depletion, alone or in combination with certain chemotherapeutics, is a promising antitumor strategy.

Preface It’s not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change. —Charles Darwin We live in an era of rapid and unprecedented change. Driven by technological innovation and changes in the way we deliver services, the face of healthcare is undergoing a metamorphosis, shifting into a more person-based, technologically enabled, evidence-based, and responsive system. That is the theory, at least. But are health systems that are changing according to these plans heralding transformative change? And what do some of the best thinkers believe is the prole of their health system over the next 5–15 years? We believe this book represents the best attempt yet to answer those thorny questions. Very few people could reach into the health systems of 152 countries and territories and orchestrate a book of this magnitude. Jeffrey Braithwaite, as series editor, accompanied by regional editors, Russell Mannion, Yukihiro Matsuyama, Paul G. Shekelle, Stuart Whittaker, and Samir Al-Adawi, and supported by an extremely knowledgeable team at Macquarie University, Sydney, Australia, particularly Dr. Wendy James and Kristiana Ludlow, were just the team to accomplish this. The omnibus they have created is an invaluable source of predictions about the future scope and shape of health systems across low-, middle-, and highincome countries. It is a treasure trove of important information. People will use it as a practical guide to the future in many ways: it can be read for benet and learning by region, by theme, and by specic case study exemplars of the kinds of reforms people are enacting in their health systems, extrapolated across the medium-term time horizon. Most books do not do this. The fact that this group has been able to achieve this is an endorsement of the skills, efforts, ingenuity, and expertise of the editors, editorial team, and individual chapter authors. We commend this book and recommend it as a must-read to many stakeholder groups: students of the system, policy-makers, planners, futurists, and groups representing managers, clinicians, and patients—in fact, all those who have an interest in healthcare and its future success. We enjoyed dipping xii Preface into it and thinking about its many learning points. We are sure others will too. Wendy Nicklin RN, BN, MSc(A), CHE, FACHE, FISQua, ICD.D President, International Society for Quality in Health Care Clifford F. Hughes AO, MBBS, DSc, FRACS, FACS, FACC, FIACS (Hon), FAAQHC, FCSANZ, FISQua, AdDipMgt, Immediate Past President, International Society for Quality in Health Care

This volume contains proceedings of the first Workshop on Data Analysis in Medicine held in May 2017 at the National Research University Higher School of Economics, Moscow. The volume contains one invited paper by Dr. Svetla Boytcheva, 6 regular contributions and 2 project proposals, carefully selected and reviewed by at least two reviewers from the international program commit- tee. The papers accepted for publication report on different aspects of analysis of medical data, among them treatment of data on particular diseases (Consoli- dated mathematical growth model of Breast Cancer CoMBreC, Artificial neural networks for prediction of final height in children with growth hormone deficiency), methods of data analysis (analysis of rare diseases, methods of machine learning and Big Data, subgroup discovery for treatment optimization), and instrumental tools (explanation-oriented methods of data analysis in medicine, information support features of the medical research process, modeling frame- work for medical data semantic transformations, radiology quality management and peer-review system). Organizers of the workshop would like to thank the reviewers for their careful work and all contributors and participants of the workshop.

This book examines how Russia, the world’s most complicated country, is governed. As it resumes its place at the centre of global affairs, the book explores Russia’s overarching strategies, and how it organizes itself (or not) in policy areas ranging from foreign policy and national security to health care, education, immigration, science, sport, agriculture, the environment and criminal justice. The book also discusses the structures and institutions on which Russia relies in order to deliver its goals in these areas of national life, as well as what’s to be done, in policy terms, to improve the country’s performance in its first post-Soviet century. Edited by Irvin Studin, the book includes contributions from a tremendous list of Russia’s leading thinkers and specialists, including Alexei Kudrin, Vladimir Mau, Alexander Auzan, Simon Kordonsky, Fyodor Lukyanov, Natalia Zubarevich and Andrey Melville.

This overview report is based upon the scientific report for the Bering-Chukchi-Beaufort (BCB) region, which comprises parts of Canada, the United States and Russia. The scientific report describes current regional environmental conditions, global and regional drivers of change, and the human and ecological impacts of this change. It also emphasises is the diverse, inter-linked environmental, social and economic challenges that residents are already, or likely will be, experiencing from climate change and other regional and global-scale drivers. It considers the environmental and socio-economic changes to which inhabitants in the region are and will be adapting to. Finally, it provides a number of observations intended to help inform decision makers about how they might help their communities adapt to future changes.

The authors proposed and mathematically described model of a new type of the Fermi-Pasta-Ulam recurrence (the FPU auto recurrence) and hypothesized an adequate description of the heart's electrical dynamics within the observed phenomenon. The dynamics of the FPU auto recurrence making appropriate electrical dynamics of the normal functioning of the heart in the form of an electrocardiogram (ECG) was obtained by a computer model study. The model solutions in the form of the FPU auto recurrence – ECG Fourier spectrum were evaluated for resistance to external disturbances in the form of random effects, as well as periodic perturbation at a frequency close to the heart beating rate of about 1 Hz. In addition, in order to simulate the dynamics of myocardial infarction model, studied the effect of the surface area of the myocardium on the stability and shape of the auto recurrence – ECG spectrum. It has been found that the intense external disturbing periodic impacts at a frequency of about 1 Hz lead to a sharp disturbance spectrum shape FPU auto recurrence – ECG structure. In addition, the decrease in the surface of the myocardium by 50% in the model led to the destruction of structures of the auto recurrence – ECG, which corresponds to the state of atrial myocardium. Research models have revealed a hypothetical basis of coronary heart disease in the form of increasing the energy of high-frequency harmonics spectrum of the auto recurrence by reducing the energy of low-frequency harmonic spectrum of the auto recurrence, which ultimately leads to a sharp decrease in myocardial contractility. In order to test the hypothesis has been studied more than 20,000 ECGs both healthy people and patients with cardiovascular disease. As a result of these studies, it was found that the dynamics of the electrical activity of normal functioning of the heart can be interpreted by the display of the detected by authors the FPU auto recurrence, and coronary heart disease is a violation of the energy ratio between the low and high frequency harmonics of the FPU auto recurrence Fourier spectrum equal to the ECG spectrum. Thus, the hypothesis has been confirmed.

The materials of The International Scientific – Practical Conference is presented below. The Conference reflects the modern state of innovation in education, science, industry and social-economic sphere, from the standpoint of introducing new information technologies.

It is interesting for a wide range of researchers, teachers, graduate students and professionals in the field of innovation and information technologies.

Background and aims. This research reported here presents findings from an evaluation of the development and implementation of the Healthy Community Challenge Fund (otherwise known as the ‘Healthy Towns’ programme). A key aim of the research has been to inform the development of future environmental and systems‐based ‘whole town’ approaches to obesity prevention. The overall aim of the Healthy Towns programme was to pilot and stimulate novel ‘whole town’ approaches that tackle the ‘obesogenic’ environment in order to reduce obesity, with a particular focus on improving diet and increasing physical activity. Through a competitive tender process, nine towns were selected that represented urban areas across England ranging from small market towns to areas of large cities. The fund provided £30 million over the period 2008‐2011, divided amongst the nine towns. The amounts awarded ranged from £900,000 to £4.85 million. Towns were instructed to be innovative and were given freedom to develop a locally‐specific programme of interventions. This report supplements local process and impact evaluations undertaken by each town (not reported here) by taking an overall view of the programme’s development and implementation. Our evaluation therefore addressed the following research questions: 1. What kinds of interventions were delivered across the Healthy Towns programme? 2. Were environmental and infrastructural interventions equitably delivered? 3. How was the Healthy Towns programme theorised and translated into practice? 4. How was evidence used in the selection and design of interventions? 5. What are the barriers and facilitators to the implementation of a systems approach to obesity prevention?

Adequate assessment of individual functional motor potentials is important for developing appropriate rehabilitation strategies in ischemic stroke [1]. Microstructural changes in corticospinal tract (CST) and corpus callosum (CC) were repeatedly correlated to post-stroke outcome [2, 3]. However, relationship between them and functional recovery remains unclear. Here we investigated relationship between integrity of CST and CC assessed with diffusion tensor imaging (DTI) and brain functional state assessed with navigated transcranial magnetic stimulation (nTMS) in chronic ischemic supratentorial stroke.

The present volume is the fourth issue of the Yearbook series entitled ‘Evolution’. The title of the present volume is ‘From Big Bang to Nanorobots’. In this way we demonstrate that all phases of evolution and Big History are covered in the articles of the present Yearbook. Several articles also present the forecasts about future development.

The main objective of our Yearbook as well as of the previous issues is the creation of a unified interdisciplinary field of research in which the scientists specializing in different disciplines could work within the framework of unified or similar paradigms, using the common terminology and searching for common rules, tendencies and regularities. At the same time for the formation of such an integrated field one should use all available opportunities: theories, laws and methods. In the present volume, a number of such approaches are used.

The volume consists of four sections: Universal Evolutionary Principles; Biosocial Evolution, Ecological Aspects, and Consciousness; Projects for the Future; In Memoriam.

This Yearbook will be useful both for those who study interdisciplinary macroproblems and for specialists working in focused directions, as well as for those who are interested in evolutionary issues of Cosmology, Biology, History, Anthropology, Economics and other areas of study. More than that, this edition will challenge and excite your vision of your own life and the new discoveries going on around us!

The book presents the most important aspects of safe digital image workflows, starting from the basic practical implications and gradually uncovering the underlying concepts and algorithms. With an easy-to-follow, down-to-earth presentation style, the text helps you to optimize your diagnostic imaging projects and connect the dots of medical informatics.​

In the context of global efforts to move towards universal coverage in health systems, this report reviews health financing reforms in the Republic of Moldova and looks in particular at how the population´s access to health services has been affected. In 2004, as has been widely documented elsewhere, wholesale reforms were made to the way in which government funds were used to fund health services, shifting the system overnight from a highly fragmented and inflexible one, to one in which funds for the health sector were pooled nationally, allowing improved risk-sharing as a result of greater flexibility to allocate funds in line with health needs. A new source of funding in the form of a payroll tax for health was also introduced directly leading to a growth in total levels of government health spending. A second phase of reforms starting in 2009 addressed the issue of gaps in population coverage under mandatory health insurance, with legislative measures taken to ensure that all citizens of Moldova had access to primary health care, and to ensure that the poor receive subsidized health insurance. Fiscal constraints have limited the full implementation of these reforms however. Moldova has shown that it is prepared to tackle difficult policy issues head on and has articulated clear goals for the sector. In particular, the Roadmap “Accelerating Reforms: addressing the needs of the health area through investment policies” approved on 1 March 2012, lays a clear agenda for the next phase or priority reforms focusing on principally on service delivery reorganization but also on health financing. This is the correct focus given that progress on a number of priority indicators such as equity in access to services and financial protection has been limited in recent years. This report summarizes the main impact of health financing reforms to date and agrees with the Roadmap about the major challenges for the coming decade, in particular the need to address inefficiencies in service delivery, but also to ensure that the close link between guaranteed benefits and available funding is maintained in future policy decisions.

Fish muscle may constitute one of the main sources of iodine (I) for the indigenous peoples of the Russian Arctic, although limited information is available about its content in commonly consumed fish species. In the current study, bromine (Br), I, the essential elements (copper, selenium and zinc) and other non-essential elements — specifically mercury, arsenic (As), cadmium, lead and nickel — have been quantified in 10 fish species consumed by people living in the Nenets and Chukotka Regions. Fish muscle was analysed by ICP-MS after nitric acid or tetramethylammonium hydroxide digestion. Certified reference materials were employed and concentrations are reported as geometric means (GMs). Atlantic cod (6.32 mg/kg) and navaga (0.934 mg/kg) contained substantially higher amounts of I than all other fish species, while broad whitefish had the lowest (0.033 mg/kg). By comparison, navaga contained more Br (14.5 mg/kg) than the other fish species, ranging 7.45 mg/kg in Atlantic cod to 2.39 mg/kg in northern pike. A significant inter-fish association between As and I in freshwater and marine fish was observed, suggesting common sources and perhaps parallel absorption patterns. Only Atlantic cod and, to lesser extent, navaga constituted significant dietary sources of I.

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3·5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.

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 development 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.

Background

Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease.

Methods

GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk–outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk–outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk–outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden.

Findings

The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10·8 million (95% uncertainty interval [UI] 9·51–12·1) deaths (19·2% [16·9–21·3] of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8·71 million (8·12–9·31) deaths (15·4% [14·6–16·2] of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253–350) DALYs (11·6% [10·3–13·1] of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0–9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10–24 years, alcohol use for those aged 25–49 years, and high systolic blood pressure for those aged 50–74 years and 75 years and older.

Interpretation

Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public.

Background

Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages.

Methods

Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0–100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—we estimated additional population equivalents with UHC effective coverage from 2018 to 2023.

Findings

Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2–47·5) in 1990 to 60·3 (58·7–61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9–3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010–2019 relative to 1990–2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6–421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0–3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5–1040·3]) residing in south Asia.

Interpretation

The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people—the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close—or how far—all populations are in benefiting from UHC.

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.

Interpretation

Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring.

A novel potent analog of the branched tail oxyquinoline group of hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors, neuradapt, has been studied in two treatment regimes in an in vitro hypoxia model on murine primary hippocampal cultures. Neuradapt activates the expression of HIF1 and HIF2 target genes and shows no toxicity up to 20 μM, which is more than an order of magnitude higher than its biologically active concentration. Cell viability, functional activity, and network connectivity between the elements of neuronal networks have been studied using a pairwise correlation analysis of the intracellular calcium fluctuations in the individual cells. An immediate treatment with 1 μM and 15 μM neuradapt right at the onset of hypoxia not only protects from the death, but also maintains the spontaneous calcium activity in nervous cells at the level of the intact cultures. A similar neuroprotective effect in the post-treatment scenario is observed for 15 μM, but not for 1 μM neuradapt. Network connectivity is better preserved with immediate treatment using 1 μM neuradapt than with 15 μM, which is still beneficial. Post-treatment with neuradapt did not restore the network connectivity despite the observation that neuradapt significantly increased cell viability at 1 μM and functional activity at 15 μM. The preservation of cell viability and functional activity makes neuradapt promising for further studies in a post-treatment scenario, since it can be combined with other drugs and treatments restoring the network connectivity of functionally competent cells.

Objective: To describe the features of HIV-associated chronic lung disease (CLD) in older children and adolescents living with HIV and to examine the clinical factors associated with CLD. This is a post-hoc analysis of baseline data from the BREATHE clinical trial (ClinicalTrials.gov, NCT02426112). Methods: Children and adolescents aged 6-19 years were screened for CLD (defined as a FEV1 z-score <-1 with no reversibility post-bronchodilation with salbutamol) at two HIV clinics in Harare, Zimbabwe and Blantyre, Malawi. Eligible participants with CLD (cases) were enrolled, together with a control group without CLD (frequency-matched by age group and duration on ART) in a 4:1 allocation ratio. A clinical history and examination was undertaken. The association between CLD and a priori-defined demographic and clinical covariates was investigated using multivariable logistic regression. Results: Of the 1,585 participants screened, 419 (32%) had a FEV1 z- score <-1, of whom 347 were enrolled as cases (median age 15.3 years [IQR 12.7 -17.7]; 48.9% female), and 74 with FEV1 z-score>0 as controls (median age 15.6 years [IQR 12.1 -18.2]; 62.2% female). Amongst cases, current respiratory symptoms including cough and shortness of breath were reported infrequently (9.3% and 1.8%, respectively). However, 152 (43.8%) of cases had a respiratory rate above the 90th centile for their age. Wasting and taking second-line antiretroviral treatment (ART) were independently associated with CLD. Conclusions: The presence of CLD indicates the need to address additional treatment support for youth living with HIV, alongside ART provision, to ensure a healthier adulthood.

Increased carotid intima-media thickness (cIMT) is reported in both adults and children with human immunodeficiency virus (HIV) in high income settings and is associated with an increased risk of cardiovascular disease, but data from sub-Saharan Africa is lacking.We assessed cIMT using ultrasound in perinatally HIV-infected children aged 6 to 16 years taking antiretroviral therapy (ART) for ≥6 months compared with HIV-uninfected controls in Harare, Zimbabwe. Groups were compared using unpaired t test and potential predictors of cIMT were assessed using multiple linear regression.A total of 117 participants with HIV, of whom 55 (45%) were female and 75 healthy uninfected controls were included. Participants with HIV were younger than uninfected controls, 10.7 (2.4) years versus 11.9 (2.6) years (P = .001). Mean cIMT was 0.40 (0.05) mm in those with HIV versus 0.40 (0.04) mm in healthy controls (P = .377). There was no association between cluster of differentiation 4 count, HIV viral load, and duration on ART and cIMT.Children with HIV taking ART have similar cIMT to uninfected children. Increasing numbers of children with HIV are reaching adulthood and longitudinal studies to assess the effect of long-term HIV and ART on vascular changes are required.

The ongoing pandemic of SARS-CoV-2 presents novel challenges and opportunities for the use of phylogenetics to understand and control its spread. Here, we analyze the emergence of SARS-CoV-2 in Russia in March and April 2020. Combining phylogeographic analysis with travel history data, we estimate that the sampled viral diversity has originated from 67 closely timed introductions into Russia, mostly in late February to early March. All but one of these introductions came from non-Chinese sources, suggesting that border closure with China has helped delay establishment of SARS-CoV-2 in Russia. These introductions resulted in at least 9 distinct Russian lineages corresponding to domestic transmission. A notable transmission cluster corresponded to a nosocomial outbreak at the Vreden hospital in Saint Petersburg; phylodynamic analysis of this cluster reveals multiple (2-4) introductions each giving rise to a large number of cases, with a high initial effective reproduction number of 3.7 (2.5-5.0).

Background and Purpose Despite the continuing efforts in multimodal assessment of the motor system after stroke, conclusive findings on the complementarity of functional and structural metrics of the corticospinal tract (CST) integrity and the role of the contralesional hemisphere are still missing. The aim of this work was to find the best combination of the motor system parameters, allowing classification of patients into three predefined groups of upper limb motor recovery. Methods 35 chronic ischemic stroke patients (47 [26–66] y.o., 29 [6–58] months post-stroke) with only supratentorial lesion and unilateral upper extremity weakness were enrolled. Patients were divided into three groups depending on the upper limb motor recovery. Non-parametric statistical tests and regression analysis were used to investigate the relationships among structural and functional motor system parameters, probed by diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS). In addition, stratification rules were tested, using a decision tree classifier to identify parameters explaining motor recovery. Results Fractional anisotropy (FA) ratio in the internal capsule (IC) and absence/presence of motor evoked potentials (MEPs), were equally discriminative of the worst motor outcome group (96% accuracy). MEP presence diverged for two investigated hand muscles. Concurrently, for the three recovery groups’ classification, the best parameter combination was: IC FA ratio and Fréchet distance between the contralesional and ipsilesional CST FA profiles (91% accuracy). No other metrics had any additional value for patients’ classification. Conclusions This study demonstrates that IC FA ratio and MEPs absence are equally important markers for poor recovery. Importantly, we found that MEPs should be controlled in more than one hand muscle. Finally, we show that better separation between different motor recovery groups may be achieved when considering the whole CST FA profile.

Human genetic variability is thought to account for a substantial fraction of individual biochemical characteristics — in biomedical sense, of individual drug response. However, only a handful of human genetic variants have been linked to medication outcomes. Here, we combine data on drug-protein interactions and human genome sequences to assess the impact of human variation on their binding affinity. Using data from the complexes of FDA-drugs and drug-like compounds, we predict SNPs substantially affecting the protein-ligand binding affinities. We estimate that an average individual carries ~6 SNPs affecting ~5 different FDA-approved drugs from among all of the approved compounds. SNPs affecting drug-protein binding affinity have low frequency in the population indicating that the genetic component for many ADEs may be highly personalized with each individual carrying a unique set of relevant SNPs. The reduction of ADEs, therefore, may primarily rely on the application of computational genome analysis in the clinic rather than the experimental study of common SNPs.

The paper examines the changes in the physician’s motivation at work during the period of reforms the salary system started since 2008. These reforms have included a shift from fixed salary system to pay for performance remuneration as well as sufficient increase of salary. The data of six surveys of health workers implemented in 2007-2016 were used to reveal the hierarchy of physician’s motives at work and to track their changes during the period of time under consideration. The changes were minor, and the directions of these changes were rather opposite to the expected strengthening of financial motivation at work: the importance of the motive of earning money has moved from the first place. The share of doctors willing to work more and better on the condition of linking salary with labor contribution did not increase. In contrast, almost two-thirds of physicians believe that they are working on a high level of quality and performance. The majority of physicians desire to increase not a stimulating part of the salary but a base, fixed one. Doctors who receive bonuses for the intensity, quality and performance, and who have a higher amount of salary wish to see the share of fixed part of salary higher than it is now available. This is a clear indication of orientation of this professional to strengthening the protective function of the salary rather than to use increased opportunities for earning money.

The paper explores primary health care models in Russia and in Central and Eastern European (CEE) countries. Starting with the similar model, they have taken totally different ways of primary health care transformation, including the role of general practitioner, multispecialty polyclinics and private sector. The comparison of this diversity, based on the conceptual framework of Primary Health Care Activity Monitor in Europe, demonstrated that the scores of primary care in Russia are relatively lower, particularly in the dimensions of accessibility, comprehensiveness, continuity and coordination of care. The score of the selected efficiency indicators is also relatively low. The major reasons for this are discussed, including the lack of strategic vision on the role of primary care, an excessive specialization of primary care and the delay with a shift to a general practitioner model. A debatable issue of primary care extended composition (the involvement of a growing number of specialists) is also addressed. The conceptual presumption that an extended composition presents new opportunities for more integrated care and better performance has not been supported by the evidence. Big multispecialty policlinics in Russia don’t demonstrate advantages over solo and group GP practices that dominate in CEE countries. The potential of polyclinics is not used because of the lack of specific activities for integration. It is argued that new specialists in the practices can strengthen primary care only when they support generalists rather than replace them. The lesson learnt from CEE countries is that substantial changes are needed to overcome the lagging status of primary care in Russia, including overcoming the excessive specialization of primary care, the replacement of district physicians by general practitioners, developing the forms of independent practices operating in parallel with polyclinics and competing with them.

In this work, we present a family of operational semantics that gradually approximates the realistic program behaviors in the C/C++11 memory model. Each semantics in our framework is built by elaborating and combining two simple ingredients: viewfronts and operation buffers. Viewfronts allow us to express the spatial aspect of thread interaction, i.e., which values a thread can read, while operation buffers enable manipulation with the temporal execution aspect, i.e., determining the order in which the results of certain operations can be observed by concurrently running threads.  Starting from a simple abstract state machine, through a series of gradual refinements of the abstract state, we capture such language aspects and synchronization primitives as release/acquire atomics, sequentially-consistent and non-atomic memory accesses, also providing a semantics for relaxed atomics, while avoiding the Out-of-Thin-Air problem. To the best of our knowledge, this is the first formal and executable operational semantics of C11 capable of expressing all essential concurrent aspects of the standard.  We illustrate our approach via a number of characteristic examples, relating the observed behaviors to those of standard litmus test programs from the literature. We provide an executable implementation of the semantics in PLT Redex, along with a number of implemented litmus tests and examples, and showcase our prototype on a large case study: randomized testing and debugging of a realistic Read-Copy-Update data structure.

Having one of the highest physician-population ratios in the world, Russia – paradoxically – also faces shortages of physicians. This paper explores the reasons for this paradox through examining the structural characteristics of the Russian health workforce and its development. In comparing Russia with mainstream European countries and in particular the ‘new” EU countries we argue that the shortage of physicians is determined mostly by the prevailing model of health workforce development with its enduring emphasis on quantitative rather than structural indicators. First, the traditional perception of physicians as inexpensive health resources determines the long-term growth of their jobs – irrespective of the new opportunities for substitution and other structural innovations. Second, there is a persistent distortion in the composition of physician supply, of which the most important is the very low share and narrow remit of primary health care providers in comparison to European standards. Third, the international trends in the division of labor between physicians, medical nurses and allied health personnel are not followed in Russia with the result of an inevitable overburden of physicians, the reproduction of a large supply of physicians, while also the paradoxical shortage. Fourth, the system of professional development of physicians does not match international standards. Although with a substantial delay, Russia has now started transition to a workforce model focused on structural characteristics of human resources and so, in the final part of the paper, these new initiatives of the Government are critically assessed.

Background: With the rapid growth of online social network sites (SNS), the issue of health-related online communities and its social and behavioral implications have become increasingly important for public health and healthcare. Unfortunately, online communities often become vehicles for promotion of pernicious misinformation, for example, alleged harm of vaccination or that HIV-virus is a myth (AIDS-denialism). This study seeks to explore the social structure and participants' behavior of the AIDS-denialists online community to identify and estimate the those who potentially are most susceptible to AIDS-denialists arguments  - “the risk group” in terms of becoming AIDS-denialists. Methods: Social network analysis was used for examining the most numerous AIDS-denialist community in the most popular Russian SNA “VKontakte”, which numbered 13000 – 15 000 members during the various stage of analysis. Qualitative content analysis was also used for collecting relevant for this study members’ attributes, such as HIV status and the extent of belief in AIDS-denialists arguments. Two datasets were collected to analyze friendship  relations between community members and their communication relations. Results: Using social network analysis combined with content-analysis we have identified the core of online community - cohesive and dedicated AIDS-denialists, and the risk group, which is not equal in composition to all peripheral members appeared in the online group. The risk group is the circle of users who engage with core members through online communication and may be more susceptible the AIDS-denialist propaganda. Analysis allowed to significantly reduce the target audience for possible intervention campaign and simultaneously increase the accuracy of user selection into the risk group (1369 users from the risk group is more than 10 times less than whole online group population counting over 15,000 users). Thus, online information interventions should be aimed at this risk group audience in the first place to prevent their adoption of AIDS-denialism beliefs, further spread of AIDS-denialism, and pernicious health consequences associated with being an HIV-positive AIDS-denialist. Conclusion: More research on influence of AIDS-denialism on HIV-positive online group members is needed. Of particular interest are longitudinal or case control studies that could detect the size of effect of AIDS-denialist propaganda that is communicated from hard-core denialists to the risk group, different factors associated with higher or lower susceptibility to AIDS-denialist views, and real health behavior change that occurs with becoming an AIDS-denialist.

The article is based on the preliminary results of author’s current study of the implementation of electronic health records in one of Russian outpatient clinics. Interviews with doctors, developers, managers of the State Department of Healthcare, IT-specialists, and clinic’s head, as well as observations of doctors’ everyday work, show that one of the key problems in the transition from paper to electronic record-keeping is how new information system transforms (or fails to transform) doctors’ routine, habitual activities. The article suggests that the widespread view of habitual action as an action in accordance with a preliminary scheme — a view that forms a basis for the majority of medical information systems — does not describe the actual structure of healthcare activities. The analysis of how doctors perceive and use electronic health records in their daily practice demonstrates that a situational approach to routine actions is more adequate. For example, the use of so-called “templates” that are created by doctors within the electronic health records cannot be understood without reference to the situational context of professional activities. Doctors, creating and using various “templates,” do this in such ways that allow them to make these health records circumstantially understandable. The view of routine activities as situated, concerted achievements not only proves the possibility of a new approach to the description of habitual actions’ role and place in the structure of social action, but can be important for the design and evaluation of professional information systems.

The article focuses on four major assumptions that underlie the alternative conceptualization of public recreation marketing. It explains (1) the redistribution system within recreation resources are allocated; (2) the organizational structure of recreation agencies; (3) the ways in which public recreation agencies interact with local governments and citizens; and (4) the code of ethics and its influence on the behavior of recreation professionals. Finally, the article attempts to integrate these assumptions into an alternative definition of public recreation marketing that is termed “administered marketing.”

This paper presents a method and computational technology for forecasting ambulance trips. We used statistical information about the number of the trips in 2009-2013, the meteorological archive, and the corresponding archive of the meteorological forecasts for the same period. We take into account social and meteorological predictors simultaneously. The method may be used operatively for planning in the ambulance service. It may be applied for all trips and for specific subgroups of diseases. The method and the technology may be applied for any megalopolis if the corresponding medical and meteorological information is available.

The paper considers the changes in major proximate determinants of fertility in Russia within the framework of demographic transition theory and Bongaarts approach to fertility analysis. After World War II Russian fertility became fully controlled process. The complex interplay of abortion and contraception during the Soviet period resulted in a very high abortion level. Russian government has almost never supported and promoted family planning as alternative to abortion. However couple's preferences of small offspring appeared more powerful than the will of authorities. Current trends show that albeit lack of governmental support the society itself is evolving towards more humanistic and effective birth control. Estimates made upon recent surveys' data confirm the validity of official statistics and thus the reality of favorable trend of abortion decline.