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.

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.

Background: Creating visualizations that include multiple dimensions of the data while preserving spatial structure and readability is challenging. Here we demonstrate the use of geofaceting to meet this challenge.

Objective: Using data on young adult mortality in the 32 Mexican states from 1990 to 2015, we demonstrate how aligning small multiples for territorial units, often regions, according to their approximate geographical location – geofaceting – can be used to depict complex multi-dimensional phenomena.

Methods: The idea is to align small-multiples for territorial units, often regions, according to approximate geographical location. We illustrate the technique using data on young adult mortality in the 32 Mexican states from 1990 to 2015.

Results: Geofaceting reveals the macro-level spatial pattern while preserving the flexibility of choosing any visualization techniques for the small multiples. Creating geofaceted visualizations gives all the advantages of standard plots in which one can adequately display multiple dimensions of a dataset.

Contribution: Compared to other ways of small-multiples' arrangement, geofaceting improves the speed of regions' identification and exposes the broad spatial pattern.

Objectives To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016.Design Systematic analysis.Main outcome measures Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education).Results The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%).Conclusions Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.

The present study reports alterations of task-based functional brain connectivity in a group of 11 cosmonauts after a long-duration spaceflight, compared to a healthy control group not involved in the space program. To elicit the postural and locomotor sensorimotor mechanisms that are usually most significantly impaired when space travelers return to Earth, a plantar stimulation paradigm was used in a block design fMRI study. The motor control system activated by the plantar stimulation involved the pre-central and post-central gyri, SMA, SII/operculum, and, to a lesser degree, the insular cortex and cerebellum. While no post-flight alterations were observed in terms of activation, the network-based statistics approach revealed task-specific functional connectivity modifications within a broader set of regions involving the activation sites along with other parts of the sensorimotor neural network and the visual, proprioceptive, and vestibular systems. The most notable findings included a post-flight increase in the stimulation-specific connectivity of the right posterior supramarginal gyrus with the rest of the brain; a strengthening of connections between the left and right insulae; decreased connectivity of the vestibular nuclei, right inferior parietal cortex (BA40) and cerebellum with areas associated with motor, visual, vestibular, and proprioception functions; and decreased coupling of the cerebellum with the visual cortex and the right inferior parietal cortex. The severity of space motion sickness symptoms was found to correlate with a post- to pre-flight difference in connectivity between the right supramarginal gyrus and the left anterior insula. Due to the complex nature and rapid dynamics of adaptation to gravity alterations, the post-flight findings might be attributed to both the long-term microgravity exposure and to the readaptation to Earth’s gravity that took place between the landing and post-flight MRI session. Nevertheless, the results have implications for the multisensory reweighting and gravitational motor system theories, generating hypotheses to be tested in future research.

Long-duration spaceflight induces detrimental changes in human physiology. Its residual effects and mechanisms remain unclear. We prospectively investigated the changes in cerebrospinal fluid (CSF) volume of the brain ventricular regions in space crew by means of a region of interest analysis on structural brain scans. Cosmonaut MRI data were investigated preflight (n = 11), postflight (n = 11), and at long-term follow-up 7 mo after landing (n = 7). Post hoc analyses revealed a significant difference between preflight and postflight values for all supratentorial ventricular structures, i.e., lateral ventricle (mean % change ± SE = 13.3 ± 1.9), third ventricle (mean % change ± SE = 10.4 ± 1.1), and the total ventricular volume (mean % change ± SE = 11.6 ± 1.5) (all P < 0.0001), with higher volumes at postflight. At follow-up, these structures did not quite reach baseline levels, with still residual increases in volume for the lateral ventricle (mean % change ± SE = 7.7 ± 1.6; P = 0.0009), the third ventricle (mean % change ± SE = 4.7 ± 1.3; P = 0.0063), and the total ventricular volume (mean % change ± SE = 6.4 ± 1.3; P = 0.0008). This spatiotemporal pattern of CSF compartment enlargement and recovery points to a reduced CSF resorption in microgravity as the underlying cause. Our results warrant more detailed and longer longitudinal follow-up. The clinical impact of our findings on the long-term cosmonauts’ health and their relation to ocular changes reported in space travelers requires further prospective studies.

This article examines the role of physicians within the managerial structure of Russian hospitals. A comparative qualitative methodology with a structured assessmentframework is used to conduct case studies that allow for international comparison. The research is exploratory in nature and comprises 63 individual interviews and 49 focus groups with key informants in 15 hospitals, complemented by document analysis. The material was collected between February and April 2017 in five different regions of the Russian Federation. The results reveal three major problems of hospital management in the Russian Federation. First, hospitals exhibit a leaky system of coordination with a lack of structures for horizontal exchange of information within the hospitals (meso-level). Second, at the macro-level, the governance system includes implementation gaps, lacking mechanisms for coordination between hospitals that may reinforce existing inequalities in service provision. Third, there is little evidence of a learning culture, and consequently, a risk that the same mistakes could be made repeatedly. We argue for a new approach to governing hospitals that can guide implementation of structures and processes that allow systematic and coherent coordination within and among Russian hospitals, based on modern approaches to accountability and organisational learning. 

Calcium plays a role of universal cellular regulator in the living cell and one of the crucial regulators of proper fetal development during gestation. Mitochondria are important for intracellular calcium handling and signaling. Mitochondrial calcium uniporter (mtCU) is a multiprotein complex of the mitochondrial inner membrane responsible for the transport of calcium to the mitochondrial matrix. In the present study, we analyzed the expression level of mtCU components in two parts of the feto-maternal system - placenta and myometrium at full-term delivery and at preterm birth (PTB) on different stages: 22-27, 28-32, 33-36 weeks of gestation (n = 50). A gradual increase of mRNA expression and changes in protein content of MCU and MICU1 subunits were revealed in the placenta during gestation. We also observed slower depolarization rate of isolated placental mitochondria induced by Ca2+ titration at PTB. In myometrium at PTB relative gene expression level of MCU, MCUb and SMDT1 increased as compared to full-term pregnancy, but the tendency to gradual increase of MCU protein simultaneous with MCUb increase and MICU1 decline was shown in gestational dynamics. Changes observed in the present study might be considered both natural dynamics as well as possible pathological mechanisms underlying preterm birth.

The aim of this work is to investigate the optimal vaccine sharing between two SIR centres in the presence of migration fluxes of susceptibles and infected individuals during the mumps outbreak. Optimality of the vaccine allocation means the minimisation of the total number of lost working days during the whole period of epidemic outbreak $[0,t_f]$, which can be described by the functional $Q=\int_0^{t_f}I(t){\rm d}t$ where $I(t)$ stands for the number of infectives at time $t$. We explain the behaviour of the optimal allocation, which depends on the model parameters and the amount of vaccine available $V$.

Background

Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries.

Methods

We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories—government, out-of-pocket, and prepaid private health spending—and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more resources for health.

Findings

Between 1995 and 2016, health spending grew at a rate of 4·00% (95% uncertainty interval 3·89–4·12) annually, although it grew slower in per capita terms (2·72% [2·61–2·84]) and increased by less than $1 per capita over this period in 22 of 195 countries. The highest annual growth rates in per capita health spending were observed in upper-middle-income countries (5·55% [5·18–5·95]), mainly due to growth in government health spending, and in lower-middle-income countries (3·71% [3·10–4·34]), mainly from DAH. Health spending globally reached $8·0 trillion (7·8–8·1) in 2016 (comprising 8·6% [8·4–8·7] of the global economy and $10·3 trillion [10·1–10·6] in purchasing-power parity-adjusted dollars), with a per capita spending of US$5252 (5184–5319) in high-income countries, $491 (461–524) in upper-middle-income countries, $81 (74–89) in lower-middle-income countries, and $40 (38–43) in low-income countries. In 2016, 0·4% (0·3–0·4) of health spending globally was in low-income countries, despite these countries comprising 10·0% of the global population. In 2018, the largest proportion of DAH targeted HIV/AIDS ($9·5 billion, 24·3% of total DAH), although spending on other infectious diseases (excluding tuberculosis and malaria) grew fastest from 2010 to 2018 (6·27% per year). The leading sources of DAH were the USA and private philanthropy (excluding corporate donations and the Bill & Melinda Gates Foundation). For the first time, we included estimates of China's contribution to DAH ($644·7 million in 2018). Globally, health spending is projected to increase to $15·0 trillion (14·0–16·0) by 2050 (reaching 9·4% [7·6–11·3] of the global economy and $21·3 trillion [19·8–23·1] in purchasing-power parity-adjusted dollars), but at a lower growth rate of 1·84% (1·68–2·02) annually, and with continuing disparities in spending between countries. In 2050, we estimate that 0·6% (0·6–0·7) of health spending will occur in currently low-income countries, despite these countries comprising an estimated 15·7% of the global population by 2050. The ratio between per capita health spending in high-income and low-income countries was 130·2 (122·9–136·9) in 2016 and is projected to remain at similar levels in 2050 (125·9 [113·7–138·1]). The decomposition analysis identified governments’ increased prioritisation of the health sector and economic development as the strongest factors associated with increases in government health spending globally. Future government health spending scenarios suggest that, with greater prioritisation of the health sector and increased government spending, health spending per capita could more than double, with greater impacts in countries that currently have the lowest levels of government health spending.

Interpretation

Financing for global health has increased steadily over the past two decades and is projected to continue increasing in the future, although at a slower pace of growth and with persistent disparities in per-capita health spending between countries. Out-of-pocket spending is projected to remain substantial outside of high-income countries. Many low-income countries are expected to remain dependent on development assistance, although with greater government spending, larger investments in health are feasible. In the absence of sustained new investments in health, increasing efficiency in health spending is essential to meet global health targets

Background: Chromosomal rearrangements are the typical phenomena in cancer genomes causing gene disruptions and fusions, corruption of regulatory elements, damage to chromosome integrity. Among the factors contributing to genomic instability are non-B DNA structures with stem-loops and quadruplexes being the most prevalent. We aimed at investigating the impact of specifically these two classes of non-B DNA structures on cancer breakpoint hotspots using machine learning approach.

Methods: We developed procedure for machine learning model building and evaluation as the considered data are extremely imbalanced and it was required to get a reliable estimate of the prediction power. We built logistic regression models predicting cancer breakpoint hotspots based on the densities of stem-loops and quadruplexes, jointly and separately. We also tested Random Forest models varying different resampling schemes (leave-one-out cross validation, train-test split, 3-fold cross-validation) and class balancing techniques (oversampling, stratification, synthetic minority oversampling).

Results: We performed analysis of 487,425 breakpoints from 2234 samples covering 10 cancer types available from the International Cancer Genome Consortium. We showed that distribution of breakpoint hotspots in different types of cancer are not correlated, confirming the heterogeneous nature of cancer. It appeared that stem-loop- based model best explains the blood, brain, liver, and prostate cancer breakpoint hotspot profiles while quadruplex- based model has higher performance for the bone, breast, ovary, pancreatic, and skin cancer. For the overall cancer profile and uterus cancer the joint model shows the highest performance. For particular datasets the constructed models reach high predictive power using just one predictor, and in the majority of the cases, the model built on both predictors does not increase the model performance.

Conclusion: Despite the heterogeneity in breakpoint hotspots’ distribution across different cancer types, our results demonstrate an association between cancer breakpoint hotspots and stem-loops and quadruplexes. Approximately for half of the cancer types stem-loops are the most influential factors while for the others these are quadruplexes. This fact reflects the differences in regulatory potential of stem-loops and quadruplexes at the tissue-specific level, which yet to be discovered at the genome-wide scale. The performed analysis demonstrates that influence of stem- loops and quadruplexes on breakpoint hotspots formation is tissue-specific.

The aim of this work is to investigate the optimal vaccine sharing between two SIR centers in the presence of migration fluxes of susceptibles and infected individuals during the mumps outbreak. Optimality of the vaccine allocation means the minimization of the total number of lost working days during the whole period of epidemic outbreak [0,tf], which can be described by the functional Q=∫tf0I(t)dt where I(t) stands for the number of infectives at time t. We explain the behavior of the optimal allocation, which depends on the model parameters and the amount of available vaccine.

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.