Research papers

Biology of glucose metabolization in cancer cells

Adewale Oluwaseun Fadaka, Basiru Olaitan Ajiboye, Oluwafemi Adeleke Ojo, Olusola Bolaji Adewale, Israel Olayide, Rosemary Em…

Cancer is a disease at the cellular level involving heritable disorders in cellular control mechanism. Cancer cells also need to adapt their metabolism to survive and multiply under the metabolically compromised conditions provided by the tumor microenvironment. Tumor cells alter their metabolism to maintain unregulated cellular proliferation and survival, but this transformation leaves them reliant on constant supply of nutrients and energy. They alter their metabolism to support their rapid proliferation and expansion across the body. After the discovery of based on the altered cancer cell metabolism in 1930, loads of studies have shed light on several aspects of cancer metabolism with a common goal to find new ways for effectively eliminating tumor cells by targeting their energy metabolism. Research has directed most of its resources to elucidate the causes, prevention and possible cure for cancer, yet the process has been elusive claiming human lives more than ever. This disease is a manifestation of etiological and pathological disturbances of mechanisms that control cell division, differentiation and metabolism. 50% of all human tumors carry genetic alterations that lead to the inactivation of some tumor suppressor proteins. Cancer cells are shown to experience characteristic changes in their metabolic programs, including increased uptake of glucose, enhanced rates of glutaminolysis and fatty acids synthesis, suggesting that metabolic shifts supports tumor cells growth and survival. In this review, we summarized the major concepts of glucose metabolization and explore the molecular basis of aerobic glycolysis of cancer cells.

Artificial intelligence in healthcare: past, present and future

Fei Jiang, Yong Jiang, Hui Zhi, Yi Dong, Hao Li, Sufeng Ma, Yilong Wang, Qiang Dong, Haipeng Shen, Yongjun Wang

Artificial intelligence (AI) aims to mimic human cognitive functions. It is bringing a paradigm shift to healthcare, powered by increasing availability of healthcare data and rapid progress of analytics techniques. We survey the current status of AI applications in healthcare and discuss its future. AI can be applied to various types of healthcare data (structured and unstructured). Popular AI techniques include machine learning methods for structured data, such as the classical support vector machine and neural network, and the modern deep learning, as well as natural language processing for unstructured data. Major disease areas that use AI tools include cancer, neurology and cardiology. We then review in more details the AI applications in stroke, in the three major areas of early detection and diagnosis, treatment, as well as outcome prediction and prognosis evaluation. We conclude with discussion about pioneer AI systems, such as IBM Watson, and hurdles for real-life deployment of AI.

The Use of Cronbach’s Alpha When Developing and Reporting Research Instruments in Science Education

Keith S. Taber

Cronbach’s alpha is a statistic commonly quoted by authors to demonstrate that tests and scales that have been constructed or adopted for research projects are fit for purpose. Cronbach’s alpha is regularly adopted in studies in science education: it was referred to in 69 different papers published in 4 leading science education journals in a single year (2015)—usually as a measure of reliability. This article explores how this statistic is used in reporting science education research and what it represents. Authors often cite alpha values with little commentary to explain why they feel this statistic is relevant and seldom interpret the result for readers beyond citing an arbitrary threshold for an acceptable value. Those authors who do offer readers qualitative descriptors interpreting alpha values adopt a diverse and seemingly arbitrary terminology. More seriously, illustrative examples from the science education literature demonstrate that alpha may be acceptable even when there are recognised problems with the scales concerned. Alpha is also sometimes inappropriately used to claim an instrument is unidimensional. It is argued that a high value of alpha offers limited evidence of the reliability of a research instrument, and that indeed a very high value may actually be undesirable when developing a test of scientific knowledge or understanding. Guidance is offered to authors reporting, and readers evaluating, studies that present Cronbach’s alpha statistic as evidence of instrument quality.

ImageNet classification with deep convolutional neural networks

Alex Krizhevsky, Ilya Sutskever, Geoffrey E. Hinton

We trained a large, deep convolutional neural network to classify the 1.2 million high-resolution images in the ImageNet LSVRC-2010 contest into the 1000 different classes. On the test data, we achieved top-1 and top-5 error rates of 37.5% and 17.0%, respectively, which is considerably better than the previous state-of-the-art. The neural network, which has 60 million parameters and 650,000 neurons, consists of five convolutional layers, some of which are followed by max-pooling layers, and three fully connected layers with a final 1000-way softmax. To make training faster, we used non-saturating neurons and a very efficient GPU implementation of the convolution operation. To reduce overfitting in the fully connected layers we employed a recently developed regularization method called "dropout" that proved to be very effective. We also entered a variant of this model in the ILSVRC-2012 competition and achieved a winning top-5 test error rate of 15.3%, compared to 26.2% achieved by the second-best entry.

Study habit and its impact on secondary school students academic performance in biology in the Federal Capital Territory, Abuja

Uju F. Ebele, Paul Agbade Olofu

Study habits is how one studies. That is, the habits which students form during their school years. Without good study habits, a student cannot succeed. Thus, this study investigated the impact of study habits on secondary school students’ academic performance in the Federal Capital Territory, Abuja. The study was guided by one null hypothesis. The study adopted a descriptive survey research design as its plan. The sample of the study constituted of 1050 senior secondary school students drawn from the Federal Capital Territory, Abuja. The instrument used for data collection was questionnaire. Chi-square was used for data analysis. The finding of the study revealed that there is significant relationship between study habits and students’ academic performance. It was recommended that teachers and school guidance counselors should collaboratively guide students on how to develop good study habits; thereby enhancing their academic success. Key words: Habits, study habits, biology, impact and academic performance.

A Unified Approach to Interpreting Model Predictions

Scott Lundberg, Su‐In Lee

Understanding why a model makes a certain prediction can be as crucial as the prediction's accuracy in many applications. However, the highest accuracy for large modern datasets is often achieved by complex models that even experts struggle to interpret, such as ensemble or deep learning models, creating a tension between accuracy and interpretability. In response, various methods have recently been proposed to help users interpret the predictions of complex models, but it is often unclear how these methods are related and when one method is preferable over another. To address this problem, we present a unified framework for interpreting predictions, SHAP (SHapley Additive exPlanations). SHAP assigns each feature an importance value for a particular prediction. Its novel components include: (1) the identification of a new class of additive feature importance measures, and (2) theoretical results showing there is a unique solution in this class with a set of desirable properties. The new class unifies six existing methods, notable because several recent methods in the class lack the proposed desirable properties. Based on insights from this unification, we present new methods that show improved computational performance and/or better consistency with human intuition than previous approaches.

Gender Inequality and Role-strained among Male Nursing Students in Selected Nursing Institution, Lagos, Nigeria

Florence F. Folami

Gender discrimination remains problem in the world as a whole and unfortunately, nursing profession is not immune to this problem. Gender discrimination is rejection or restriction made on the basis of socially constructed gender roles which prevents a person from relishing full human rights. Role strain has been defined as when an individual is likely to experience tension in coping with the rations of dissenting roles. Role strain can occur when the men in nursing are observed by lecturers and peers to occupy a female role distinct with their masculine gender which may lead to diminishment of their individual contribution. Simple random sampling method was used to select nursing institutions that was included in the study and convenience sampling method was used to select the respondents that partook in the study. The study population is male nursing students from 200 level-500 level of the selected nursing institutions. A questionnaire including measures of gender role identity and perceived gender relevance of careers was administered to 205 male student nurses from three nursing institutions. The results showed that 32% of the respondents had not experienced gender bias during nursing school, whereas 68% reported gender bias from the lecturers and the nursing staff. This study has implications for nursing profession that address the current predicament in the nursing field caused by discrimination and social isolation that man face. Therefore, Nursing and Midwifery council of Nigeria should develop a strategic plan to addresses the eradication of discrimination and racism in and by the nursing profession.

Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015

Gregory A. Roth, Catherine O. Johnson, Amanuel Alemu Abajobir, Foad Abd-Allah, Semaw Ferede Abera, Gebre Yitayih Abyu, Mukta…

BACKGROUND: The burden of cardiovascular diseases (CVDs) remains unclear in many regions of the world. OBJECTIVES: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden. METHODS: CVD mortality was estimated from vital registration and verbal autopsy data. CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries. Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights. Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. RESULTS: In 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths). Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0.75. CONCLUSIONS: CVDs remain a major cause of health loss for all regions of the world. Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI, but only a gradual decrease or no change in most regions. Future updates of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD.

The biology and the importance of Photobacterium species

Ibrahim Musa Moi, Noordiyanah Nadhirah Roslan, Thean Chor Leow, Mohd Shukuri Mohamad Ali, Raja Noor Zaliha Raja Abd Rahman, …

Statistical physics of human cooperation

Matjaž Perc, Jillian Jordan, David G. Rand, Zhen Wang, Stefano Boccaletti, Attila Szolnoki

Posttraumatic stress disorder in the World Mental Health Surveys

Karestan C. Koenen, Andrew Ratanatharathorn, L. Ng, Katie A. McLaughlin, Evelyn J. Bromet, Dan J. Stein, Elie G. Karam, Ayel…

BACKGROUND: Traumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking. METHODS: Data were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics. RESULTS: The cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed. CONCLUSIONS: PTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.

Smoking prevalence and attributable disease burden in 195 countries and territories, 1990–2015: a systematic analysis from the Global Burden of Disease Study 2015

Marissa B Reitsma, Nancy Fullman, Marie Ng, Joseph S Salama, Amanuel Alemu Abajobir, Kalkidan Hassen Abate, Cristiana Abbafa…

BACKGROUND: The scale-up of tobacco control, especially after the adoption of the Framework Convention for Tobacco Control, is a major public health success story. Nonetheless, smoking remains a leading risk for early death and disability worldwide, and therefore continues to require sustained political commitment. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) offers a robust platform through which global, regional, and national progress toward achieving smoking-related targets can be assessed. METHODS: We synthesised 2818 data sources with spatiotemporal Gaussian process regression and produced estimates of daily smoking prevalence by sex, age group, and year for 195 countries and territories from 1990 to 2015. We analysed 38 risk-outcome pairs to generate estimates of smoking-attributable mortality and disease burden, as measured by disability-adjusted life-years (DALYs). We then performed a cohort analysis of smoking prevalence by birth-year cohort to better understand temporal age patterns in smoking. We also did a decomposition analysis, in which we parsed out changes in all-cause smoking-attributable DALYs due to changes in population growth, population ageing, smoking prevalence, and risk-deleted DALY rates. Finally, we explored results by level of development using the Socio-demographic Index (SDI). FINDINGS: Worldwide, the age-standardised prevalence of daily smoking was 25·0% (95% uncertainty interval [UI] 24·2-25·7) for men and 5·4% (5·1-5·7) for women, representing 28·4% (25·8-31·1) and 34·4% (29·4-38·6) reductions, respectively, since 1990. A greater percentage of countries and territories achieved significant annualised rates of decline in smoking prevalence from 1990 to 2005 than in between 2005 and 2015; however, only four countries had significant annualised increases in smoking prevalence between 2005 and 2015 (Congo [Brazzaville] and Azerbaijan for men and Kuwait and Timor-Leste for women). In 2015, 11·5% of global deaths (6·4 million [95% UI 5·7-7·0 million]) were attributable to smoking worldwide, of which 52·2% took place in four countries (China, India, the USA, and Russia). Smoking was ranked among the five leading risk factors by DALYs in 109 countries and territories in 2015, rising from 88 geographies in 1990. In terms of birth cohorts, male smoking prevalence followed similar age patterns across levels of SDI, whereas much more heterogeneity was found in age patterns for female smokers by level of development. While smoking prevalence and risk-deleted DALY rates mostly decreased by sex and SDI quintile, population growth, population ageing, or a combination of both, drove rises in overall smoking-attributable DALYs in low-SDI to middle-SDI geographies between 2005 and 2015. INTERPRETATION: The pace of progress in reducing smoking prevalence has been heterogeneous across geographies, development status, and sex, and as highlighted by more recent trends, maintaining past rates of decline should not be taken for granted, especially in women and in low-SDI to middle-SDI countries. Beyond the effect of the tobacco industry and societal mores, a crucial challenge facing tobacco control initiatives is that demographic forces are poised to heighten smoking's global toll, unless progress in preventing initiation and promoting cessation can be substantially accelerated. Greater success in tobacco control is possible but requires effective, comprehensive, and adequately implemented and enforced policies, which might in turn require global and national levels of political commitment beyond what has been achieved during the past 25 years. FUNDING: Bill & Melinda Gates Foundation and Bloomberg Philanthropies.

Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart

Derek J. Hausenloy, David García‐Dorado, Hans Erik Bøtker, Sean M. Davidson, James M. Downey, Felix B. Engel, Robert B. Jenn…

Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury (IRI). During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic-however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing. Therefore, in this Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart, we critically analyse the current state of ischaemic conditioning in both the experimental and clinical settings, provide recommendations for improving its translation into the clinical setting, and highlight novel therapeutic targets and new treatment strategies for reducing acute myocardial IRI.

Model-Agnostic Meta-Learning for Fast Adaptation of Deep Networks

Chelsea Finn, Pieter Abbeel, Sergey Levine

We propose an algorithm for meta-learning that is model-agnostic, in the sense that it is compatible with any model trained with gradient descent and applicable to a variety of different learning problems, including classification, regression, and reinforcement learning. The goal of meta-learning is to train a model on a variety of learning tasks, such that it can solve new learning tasks using only a small number of training samples. In our approach, the parameters of the model are explicitly trained such that a small number of gradient steps with a small amount of training data from a new task will produce good generalization performance on that task. In effect, our method trains the model to be easy to fine-tune. We demonstrate that this approach leads to state-of-the-art performance on two few-shot image classification benchmarks, produces good results on few-shot regression, and accelerates fine-tuning for policy gradient reinforcement learning with neural network policies.

Distribution and importance of microplastics in the marine environment: A review of the sources, fate, effects, and potential solutions

Helen Shnada Auta, Chijioke Emenike, S. H. Fauziah

Assessing Climate Driven Malaria Variability in Ghana Using a Regional Scale Dynamical Model

Ernest O. Asare, Leonard K. Amekudzi

Malaria is a major public health challenge in Ghana and adversely affects the productivity and economy of the country. Although malaria is climate driven, there are limited studies linking climate variability and disease transmission across the various agro-ecological zones in Ghana. We used the VECTRI (vector-borne disease community model of the International Centre for Theoretical Physics, Trieste) model with a new surface hydrology scheme to investigate the spatio-temporal variability in malaria transmission patterns over the four agro-ecological zones in Ghana. The model is driven using temperature and rainfall datasets obtained from the GMet (Ghana Meteorological Agency) synoptic stations between 1981 and 2010. In addition, the potential of the VECTRI model to simulate seasonal pattern of local scale malaria incidence is assessed. The model results reveal that the simulated malaria transmission follows rainfall peaks with a two-month time lag. Furthermore, malaria transmission ranges from eight to twelve months, with minimum transmission occurring between February and April. The results further reveal that the intra- and inter-agro-ecological variability in terms of intensity and duration of malaria transmission are predominantly controlled by rainfall. The VECTRI simulated EIR (Entomological Inoculation Rate) tends to agree with values obtained from field surveys across the country. Furthermore, despite being a regional model, VECTRI demonstrates useful skill in reproducing monthly variations in reported malaria cases from Emena hospital (a peri urban town located within Kumasi metropolis). Although further refinements in this surface hydrology scheme may improve VECTRI performance, VECTRI still possesses the potential to provide useful information for malaria control in the tropics.

SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules

Antoine Daina, Olivier Michielin, Vincent Zoete

To be effective as a drug, a potent molecule must reach its target in the body in sufficient concentration, and stay there in a bioactive form long enough for the expected biologic events to occur. Drug development involves assessment of absorption, distribution, metabolism and excretion (ADME) increasingly earlier in the discovery process, at a stage when considered compounds are numerous but access to the physical samples is limited. In that context, computer models constitute valid alternatives to experiments. Here, we present the new SwissADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar. Easy efficient input and interpretation are ensured thanks to a user-friendly interface through the login-free website http://www.swissadme.ch. Specialists, but also nonexpert in cheminformatics or computational chemistry can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavours.

Can chaos be observed in quantum gravity?

Bianca Dittrich, Philipp A. Höhn, Tim Koslowski, Mike I. Nelson

Full general relativity is almost certainly ‘chaotic’. We argue that this entails a notion of non-integrability: a generic general relativistic model, at least when coupled to cosmologically interesting matter, likely possesses neither differentiable Dirac observables nor a reduced phase space. It follows that the standard notion of observable has to be extended to include non-differentiable or even discontinuous generalized observables. These cannot carry Poisson-algebraic structures and do not admit a standard quantization; one thus faces a quantum representation problem of gravitational observables. This has deep consequences for a quantum theory of gravity, which we investigate in a simple model for a system with Hamiltonian constraint that fails to be completely integrable. We show that basing the quantization on standard topology precludes a semiclassical limit and can even prohibit any solutions to the quantum constraints. Our proposed solution to this problem is to refine topology such that a complete set of Dirac observables becomes continuous. In the toy model, it turns out that a refinement to a polymer-type topology, as e.g. used in loop gravity, is sufficient. Basing quantization of the toy model on this finer topology, we find a complete set of quantum Dirac observables and a suitable semiclassical limit. This strategy is applicable to realistic candidate theories of quantum gravity and thereby suggests a solution to a long-standing problem which implies ramifications for the very concept of quantization. Our work reveals a qualitatively novel facet of chaos in physics and opens up a new avenue of research on chaos in gravity which hints at deep insights into the structure of quantum gravity.

Understanding the Intersections between Metabolism and Cancer Biology

Matthew G. Vander Heiden, Ralph J. DeBerardinis

Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen

Felicity J. Burt, Weiqiang Chen, Jonathan J. Miner, Deborah J. Lenschow, Andres Merits, Esther Schnettler, Alain Kohl, Penny…

Integrated genomic and molecular characterization of cervical cancer

Robert D. Burk, Zigui Chen, Saller Cf, Katherine Tarvin, André L. Carvalho, Cristovam Scapulatempo-Neto, Henrique C. Silveir…

Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers. This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types. Cervical cancer is one of the main causes of cancer-related deaths worldwide, and 95% of cases result from human papilloma virus (HPV) infection. The Cancer Genome Atlas Research Network now reports the genomic and molecular characterization of 228 primary cervical cancers. The authors identify significantly mutated genes and pathways that differ by cervical cancer subtype, and find that keratin-low squamous, keratin-high squamous and adenocarcinoma-rich clusters are marked by different HPV types and molecular features.

Artificial intelligence in medicine

Pavel Hamet, Johanne Tremblay

Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015

Mohammad H. Forouzanfar, Patrick Liu, Gregory A. Roth, Marie Ng, Stan Biryukov, Laurie B. Marczak, Lily Alexander, Kara Este…

Importance: Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. Objective: To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. Design: A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Main Outcomes and Measures: Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year. Results: Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). For loss of DALYs associated with systolic blood pressure of 140 mm Hg or higher, the loss increased from 95.9 million (95% uncertainty interval [UI], 87.0-104.9 million) to 143.0 million (95% UI, 130.2-157.0 million) [corrected], and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. Conclusions and Relevance: In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.

Realistic friction coefficient model between a rolling cylindrical element and a deformable flat surface

Francis Davis, M. N. Sackey, Anthony Andrews, S.P. Owusu-Ofori