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.

Blood groups, erythrocyte antigens, and transfusion are fundamental areas of medicine and are related to many disciplines of science like hematology, immunology, surgery, and genetics. This book is a collection of information related to blood groups and transfusion, and a practical resource for all concerned physicians. The book is divided into two sections. The first section includes chapters on blood transfusion reactions and hemolytic disease of the fetus. The second section includes information for the future perspectives of blood group antigens. This book will be a stepping stone for scientists who are rapidly advancing their science journey.

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.

In humans, trophoblast hypoxia during placental development can be a cause of serious pregnancy complications, such as preeclampsia and fetal growth restriction. The pathogenesis of these conditions is not fully clear and may be associated with changed expression of some genes and regulatory molecules, including miRNA, in trophoblast cells. The aim of this study was to analyze miRNA profiles and measure the expression of their target genes in a model of trophoblast hypoxia. Human choriocarcinoma BeWo b30 cells were used as a trophoblast model. Hypoxia was induced by cobalt chloride (CoCl2) and an oxyquinoline derivative. MRNA and miRNA expression profiles were evaluated by means of next generation sequencing (NGS); the expression of individual genes was analyzed by PCR. We studied the secondary structure of mRNAs of target genes for those miRNAs whose expression had changed significantly and analyzed potential competition between these miRNAs for the binding site. The observed changes in the expression of the key genes involved in the response to hypoxia confirmed the feasibility of using CoCl2 and the oxyquinoline derivative as hypoxia inducers. The analysis revealed an increase in miR-374 levels following the activation of the hypoxia pathway in our trophoblast model. The changes were accompanied by a reduction in FOXM1 mRNA expression; this mRNA is a target for hsa-miR-374a-5p and hsa-miR374b-5p, which can compete with hsa-miR-21-5p for the binding sites on FOXM1 mRNA. The involvement of FOXM1 in the regulation of the invasive cell potential suggests the role of miR-374 and FOXM1 in the pathogenesis of disrupted trophoblast invasion during placental development as predisposing for fetal growth restriction and preeclampsia.

Background

Ending the global tobacco epidemic is a defining challenge in global health. Timely and comprehensive estimates of the prevalence of smoking tobacco use and attributable disease burden are needed to guide tobacco control efforts nationally and globally.

Methods

We estimated the prevalence of smoking tobacco use and attributable disease burden for 204 countries and territories, by age and sex, from 1990 to 2019 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study. We modelled multiple smoking-related indicators from 3625 nationally representative surveys. We completed systematic reviews and did Bayesian meta-regressions for 36 causally linked health outcomes to estimate non-linear dose-response risk curves for current and former smokers. We used a direct estimation approach to estimate attributable burden, providing more comprehensive estimates of the health effects of smoking than previously available.

Findings

Globally in 2019, 1·14 billion (95% uncertainty interval 1·13–1·16) individuals were current smokers, who consumed 7·41 trillion (7·11–7·74) cigarette-equivalents of tobacco in 2019. Although prevalence of smoking had decreased significantly since 1990 among both males (27·5% [26·5–28·5] reduction) and females (37·7% [35·4–39·9] reduction) aged 15 years and older, population growth has led to a significant increase in the total number of smokers from 0·99 billion (0·98–1·00) in 1990. Globally in 2019, smoking tobacco use accounted for 7·69 million (7·16–8·20) deaths and 200 million (185–214) disability-adjusted life-years, and was the leading risk factor for death among males (20·2% [19·3–21·1] of male deaths). 6·68 million [86·9%] of 7·69 million deaths attributable to smoking tobacco use were among current smokers.

Interpretation

In the absence of intervention, the annual toll of 7·69 million deaths and 200 million disability-adjusted life-years attributable to smoking will increase over the coming decades. Substantial progress in reducing the prevalence of smoking tobacco use has been observed in countries from all regions and at all stages of development, but a large implementation gap remains for tobacco control. Countries have a clear and urgent opportunity to pass strong, evidence-based policies to accelerate reductions in the prevalence of smoking and reap massive health benefits for their citizens.

Objective: To validate a novel artificial-intelligence electrocardiogram algorithm(AI-ECG) to detect left ventricular systolic dysfunction (LVSD) in an external population. Background: LVSD, even when asymptomatic, confers increased morbidity and mortality. We recently derived AI-ECG to detect LVSD using ECGs based on a large sample of patients treated at the Mayo Clinic. Methods: We performed an external validation study with subjects from the Know Your Heart Study, a crosssectional study of adults aged 35–69 years residing in two cities in Russia, who had undergone both ECG and transthoracic echocardiography. LVSD was defined as left ventricular ejection fraction ≤ 35%. We assessed the performance of the AI-ECG to identify LVSD in this distinct patient population. Results: Among 4277 subjects in this external population-based validation study, 0.6% had LVSD (compared to 7.8% of the original clinical derivation study). The overall performance of the AI-ECG to detect LVSD was robust with an area under the receiver operating curve of 0.82.When using the LVSD probability cut-off of 0.256 from the original derivation study, the sensitivity, specificity, and accuracy in this population were 26.9%, 97.4%, 97.0%, respectively. Other probability cut-offs were analysed for different sensitivity values. Conclusions: The AI-ECG detected LVSDwith robust test performance in a population thatwas very different from that used to develop the algorithm. Population-specific cut-offs may be necessary for clinical implementation. Differences in population characteristics, ECG and echocardiographic data quality may affect test performance.

Exclusive breastfeeding (EBF)—giving infants only breast-milk for the first 6 months of life—is a component of optimal breastfeeding practices effective in preventing child morbidity and mortality. EBF practices are known to vary by population and comparable subnational estimates of prevalence and progress across low- and middle-income countries (LMICs) are required for planning policy and interventions. Here we present a geospatial analysis of EBF prevalence estimates from 2000 to 2018 across 94 LMICs mapped to policy-relevant administrative units (for example, districts), quantify subnational inequalities and their changes over time, and estimate probabilities of meeting the World Health Organization’s Global Nutrition Target (WHO GNT) of ≥70% EBF prevalence by 2030. While six LMICs are projected to meet the WHO GNT of ≥70% EBF prevalence at a national scale, only three are predicted to meet the target in all their district-level units by 2030.

This article addresses two unresolved methodological issues related to prior research on Russia that was based on census-unlinked data and did not account for the substantial increase in the share of death records with missing information on education. The study uses a proportional mortality analysis method relying on a case–control framework, together with a plausible imputation-based solution for the redistribution of the unknown education on death records. The new results suggest that high levels of inequality persist, but they do not support recent findings indicating that the educational gap in life expectancy has substantially widened.

The research note focuses on the issues of eating behaviour of young people in Arkhangelsk. The authors analyze the dynamics of general indicators of morbidity and mortality from diseases of the digestive system in the regions of the Arctic zone and substantiate the relevance of nutrition studies in these regions. Based on the results of the survey conducted in 2018 at schools, colleges and universities in Arkhangelsk, the authors show that a significant part of the youth have irregular eating habits and characterise the structure of their own nutrition as unsatisfactory. University students show a greater commitment to balanced nutrition than college students, but it is college and university students that disregard frequency of nutrition, which can be a consequence of inadequate catering arrangement and its affordability at local schools.

Objectives

Clinical practice is developing under influence of the evidence-based clinical practice guidelines (EBCPG). In Russia development of the documents prescribing the content of care is connected with the idea that they may be used as well for estimation of the cost of care. The outcome is the national healthcare legislation of 2011. It dictates that care should be planned, funded, provided, and evaluated in agreement with standards of healthcare (SHC)—documents prescribing the content of care. The objective of this study was to evaluate how the correction of the SHC with the relevant EBCPG may change the cost of the prescribed care.

Methods

We selected the random sample of the SHC from the approved by the Ministry of Health for primary healthcare (SPHC) and specialized healthcare (SSHC). We analyzed interventions comparing SHC to the relevant EBCPG. Not recommended interventions were considered unnecessary. If the recommended by EBCPG intervention was missed in the SHC, then it increased the cost. We take the drug costs and the costs of interventions from the relevant ministerial registries. We calculated the total cost of the SHC by summing up the cost of each medical intervention/medications specified in the SHC.

Results

SPHC and SSHC both contain medical interventions and drugs that should not be provided. The total cost of all SHC included became lower: SPHC cost decreased by 66%, SSHC by 19%. The smaller change of the cost of SSHC is explained by the fact that the major part of the total cost of SSHC is the stay in a hospital.

Conclusion

Correction of the SHC using EBCPG may reduce the cost of care

The Keap1-Nrf2 signaling axis is a validated and promising target for cellular defense and survival pathways. This minireview discusses the potential off-target effects and their impact on future drug development originating from Keap1-targeting small molecules that function as displacement activators of the redox-sensitive transcription factor Nrf2. We argue that small-molecule displacement activators, similarly to electrophiles, will release both Nrf2 and other Keap1 client proteins from the ubiquitin ligase complex. This non-specificity is likely unavoidable and may result in off-target effects during Nrf2 activation by targeting Keap1. The small molecule displacement activators may also target Kelch domains in proteins other than Keap1, causing additional off-target effects unless designed to ensure specificity for the Kelch domain only in Keap1. A potentially promising and alternative therapeutic approach to overcome this non-specificity emerging from targeting Keap1 is to inhibit the Nrf2 repressor Bach1 for constitutive activation of the Nrf2 pathway and bypass the Keap1-Nrf2 complex.

Large, open-source datasets, such as the Human Connectome Project and the Autism Brain Imaging Data Exchange, have spurred the development of new and increasingly powerful machine learning approaches for brain connectomics. However, one key question remains: are we capturing biologically relevant and generalizable information about the brain, or are we simply overfitting to the data? To answer this, we organized a scientific challenge, the Connectomics in NeuroImaging Transfer Learning Challenge (CNI-TLC), held in conjunction with MICCAI 2019. CNI-TLC included two classification tasks: (1) diagnosis of Attention-Deficit/Hyperactivity Disorder (ADHD) within a pre-adolescent cohort; and (2) transference of the ADHD model to a related cohort of Autism Spectrum Disorder (ASD) patients with an ADHD comorbidity. In total, 240 resting-state fMRI (rsfMRI) time series averaged according to three standard parcellation atlases, along with clinical diagnosis, were released for training and validation (120 neurotypical controls and 120 ADHD). We also provided Challenge participants with demographic information of age, sex, IQ, and handedness. The second set of 100 subjects (50 neurotypical controls, 25 ADHD, and 25 ASD with ADHD comorbidity) was used for testing. Classification methodologies were submitted in a standardized format as containerized Docker images through ChRIS, an open-source image analysis platform. Utilizing an inclusive approach, we ranked the methods based on 16 metrics: accuracy, area under the curve, F1-score, false discovery rate, false negative rate, false omission rate, false positive rate, geometric mean, informedness, markedness, Matthew’s correlation coefficient, negative predictive value, optimized precision, precision, sensitivity, and specificity. The final rank was calculated using the rank product for each participant across all measures. Furthermore, we assessed the calibration curves of each methodology. Five participants submitted their method for evaluation, with one outperforming all other methods in both ADHD and ASD classification. However, further improvements are still needed to reach the clinical translation of functional connectomics. We have kept the CNI-TLC open as a publicly available resource for developing and validating new classification methodologies in the field of connectomics.

As an effort to help contain the COVID-19 pandemic, large numbers of SARS-CoV-2 genomes have been sequenced from all continents. More than one million viral sequences are publicly available as of April 2021. Many studies estimate viral genealogies from these sequences, as these can provide valuable information about the spread of the pandemic across time and space. Additionally such data are a rich source of information about molecular evolutionary processes including natural selection, for example allowing the identification and investigating the spread of new variants conferring transmissibility and immunity evasion advantages to the virus. To validate new methods and to verify results resulting from these vast datasets, one needs an efficient simulator able to simulate the pandemic to approximate world-scale scenarios and generate viral genealogies of millions of samples. Here, we introduce a new fast simulator VGsim which addresses this problem. The simulation process is split into two phases. During the forward run the algorithm generates a chain of events reflecting the dynamics of the pandemic using an hierarchical version of the Gillespie algorithm. During the backward run a coalescent-like approach generates a tree genealogy of samples conditioning on the events chain generated during the forward run. Our software can model complex population structure, epistasis and immunity escape. The code is freely available at https://github.com/Genomics-HSE/VGsim.

The spatial accuracy of TMS may be as small as a few millimeters. Despite such great potential, navigated TMS (nTMS) mapping is still underused for the assessment of motor plasticity, particularly in clinical settings. Here we investigate the within-limb somatotopy gradient as well as absolute and relative reliability of three hand muscle cortical representations (MCRs) using a comprehensive grid-based sulcus-informed nTMS motor mapping. We enrolled 22 young healthy male volunteers. Two nTMS mapping sessions were separated by 5-10 days. Motor evoked potentials were obtained from abductor pollicis brevis (APB), abductor digiti minimi, and extensor digitorum communis. In addition to individual MRI-based analysis, we studied MNI normalized MCRs. For the reliability assessment, we calculated intra-class correlation and the smallest detectable change. Our results revealed a somatotopy gradient reflected by APB MCR having the most lateral location. Reliability analysis showed that the commonly used metrics of MCRs, such as areas, volumes, centers of gravity (COGs), and hotspots had a high relative and low absolute reliability for all three muscles. For within-limb TMS somatotopy, the most common metrics such as the shifts between MCR COGs and hotspots had poor relative reliability. However, overlaps between different muscle MCRs were highly reliable. We thus provide novel evidence that inter-muscle MCR interaction can be reliably traced using MCR overlaps while shifts between the COGs and hotspots of different MCRs are not suitable for this purpose. Our results have implications for the interpretation of nTMS motor mapping results in healthy subjects and patients with neurological conditions.

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.