Optical flow analysis reveals that Kinesin-mediated advection impacts on the orientation of microtubules in the Drosophila oocyte.

The orientation of microtubule networks is exploited by motors to deliver cargoes to specific intracellular destinations, and is thus essential for cell polarity and function. Reconstituted in vitro systems have largely contributed to understanding the molecular framework regulating the behavior of microtubule filaments. In cells however, microtubules are exposed to various biomechanical forces that might impact on their orientation, but little is known about it. Oocytes, which display forceful cytoplasmic streaming, are excellent model systems to study the impact of motion forces on cytoskeletons in vivo. Here we implement variational optical flow analysis as a new approach to analyze the polarity of microtubules in the Drosophila oocyte, a cell that displays distinct Kinesin-dependent streaming. After validating the method as robust for describing microtubule orientation from confocal movies, we find that increasing the speed of flows results in aberrant plus end growth direction. Furthermore, we find that in oocytes where Kinesin is unable to induce cytoplasmic streaming, the growth direction of microtubule plus ends is also altered. These findings lead us to propose that cytoplasmic streaming - and thus motion by advection - contributes to the correct orientation of MTs in vivo. Finally, we propose a possible mechanism for a specialised cytoplasmic actin network (the actin mesh) to act as a regulator of flow speeds; to counteract the recruitment of Kinesin to microtubules. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]

Oral cholera vaccine use in Zanzibar: socioeconomic and behavioural features affecting demand and acceptance

Cholera remains a serious public health problem in low-income countries despite efforts in the past to promote oral rehydration therapy as major treatment. In 2007, the majority of worldwide cases (94%) and deaths (99%) were reported from Africa. To improve cholera control efforts in addition to maintaining and improving existing water supply, sanitation and hygiene behaviour measures, the World Health Organization has recently started to consider the use of vaccines as an additional public health tool. To assess this new approach in endemic settings, a project was launched in Zanzibar to vaccinate 50,000 individuals living in communities at high risk of cholera with an oral two-dose vaccine (Dukoral). Immunisation programmes in low-income countries have suffered a reduced coverage or were even brought to a halt because of an ignorance of local realities. To ensure the success of vaccination campaigns, implementers have to consider community-held perceptions and behaviours regarding the infectious disease and the vaccine of interest. The main aim of this study is to provide advice to the Ministry of Health and Social Welfare of Zanzibar regarding routine introduction of an oral cholera vaccine from a socioeconomic and behavioural perspective as part of a long-term development for a sustained cholera prevention strategy. Qualitative and quantitative methods of health social science research will be applied on four stakeholder levels before and after the mass vaccination campaign. Rapid assessment individual interviews and focus groups will be used to describe cholera- and vaccine-related views of policy makers, health care professionals and community representatives. The cultural epidemiological approach will be employed on the individual household resident level in a repeated cross-sectional design to estimate determinants of anticipated and actual oral cholera vaccine acceptance. The study presented here is designed to inform about people's perceptions regarding cholera and about socioeconomic and behavioural factors determining anticipated and actual oral cholera vaccine acceptance in Zanzibar. Its pre- and post-intervention design using a mixed-methods approach on different stakeholder levels in communities at high risk of cholera outbreaks will ensure the collection of locally valid data relevant for public health action and planning

Diseases, Injuries, and Risk Factors in Child and Adolescent Health, 1990 to 2017: Findings From the Global Burden of Diseases, Injuries, and Risk Factors 2017 Study.

Importance:Understanding causes and correlates of health loss among children and adolescents can identify areas of success, stagnation, and emerging threats and thereby facilitate effective improvement strategies. Objective:To estimate mortality and morbidity in children and adolescents from 1990 to 2017 by age and sex in 195 countries and territories. Design, Setting, and Participants:This study examined levels, trends, and spatiotemporal patterns of cause-specific mortality and nonfatal health outcomes using standardized approaches to data processing and statistical analysis. It also describes epidemiologic transitions by evaluating historical associations between disease indicators and the Socio-Demographic Index (SDI), a composite indicator of income, educational attainment, and fertility. Data collected from 1990 to 2017 on children and adolescents from birth through 19 years of age in 195 countries and territories were assessed. Data analysis occurred from January 2018 to August 2018. Exposures:Being under the age of 20 years between 1990 and 2017. Main Outcomes and Measures:Death and disability. All-cause and cause-specific deaths, disability-adjusted life years, years of life lost, and years of life lived with disability. Results:Child and adolescent deaths decreased 51.7% from 13.77 million (95% uncertainty interval [UI], 13.60-13.93 million) in 1990 to 6.64 million (95% UI, 6.44-6.87 million) in 2017, but in 2017, aggregate disability increased 4.7% to a total of 145 million (95% UI, 107-190 million) years lived with disability globally. Progress was uneven, and inequity increased, with low-SDI and low-middle-SDI locations experiencing 82.2% (95% UI, 81.6%-82.9%) of deaths, up from 70.9% (95% UI, 70.4%-71.4%) in 1990. The leading disaggregated causes of disability-adjusted life years in 2017 in the low-SDI quintile were neonatal disorders, lower respiratory infections, diarrhea, malaria, and congenital birth defects, whereas neonatal disorders, congenital birth defects, headache, dermatitis, and anxiety were highest-ranked in the high-SDI quintile. Conclusions and Relevance:Mortality reductions over this 27-year period mean that children are more likely than ever to reach their 20th birthdays. The concomitant expansion of nonfatal health loss and epidemiological transition in children and adolescents, especially in low-SDI and middle-SDI countries, has the potential to increase already overburdened health systems, will affect the human capital potential of societies, and may influence the trajectory of socioeconomic development. Continued monitoring of child and adolescent health loss is crucial to sustain the progress of the past 27 years

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings: In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding: Bill & Melinda Gates Foundation

The overlapping burden of the three leading causes of disability and death in sub-Saharan African children

Despite substantial declines since 2000, lower respiratory infections (LRIs), diarrhoeal diseases, and malaria remain among the leading causes of nonfatal and fatal disease burden for children under 5 years of age (under 5), primarily in sub-Saharan Africa (SSA). The spatial burden of each of these diseases has been estimated subnationally across SSA, yet no prior analyses have examined the pattern of their combined burden. Here we synthesise subnational estimates of the burden of LRIs, diarrhoea, and malaria in children under-5 from 2000 to 2017 for 43 sub-Saharan countries. Some units faced a relatively equal burden from each of the three diseases, while others had one or two dominant sources of unit-level burden, with no consistent pattern geographically across the entire subcontinent. Using a subnational counterfactual analysis, we show that nearly 300 million DALYs could have been averted since 2000 by raising all units to their national average. Our findings are directly relevant for decision-makers in determining which and targeting where the most appropriate interventions are for increasing child survival. © 2022, The Author(s).Funding text 1: This work was primarily supported by grant OPP1132415 from the Bill & Melinda Gates Foundation. ; Funding text 2: This study was funded by the Bill & Melinda Gates Foundation. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. The non-consortium authors have no competing interests . Competing interests for consortium authors is as follows: Robert Ancuceanu reports receiving consultancy or speaker feeds from UCB, Sandoz, Abbvie, Zentiva, Teva, Laropharm, CEGEDIM, Angelini, Biessen Pharma, Hofigal, AstraZeneca, and Stada. Jacek Jerzy Jozwiak reports personal fees from Amgen, ALAB Laboratories, Teva, Synexus, Boehringer Ingelheim, and Zentiva, all outside the submitted work. Kewal Krishan reports non-financial support from UGC Centre of Advanced Study, CAS II, Department of Anthropology, Panjab University, Chandigarh, India, outside the submitted work. Walter Mendoza is a Program Analyst in Population and Development at the United Nations Population Fund-UNFPA Country Office in Peru, which does not necessarily endorse or support these findings. Maarten J Postma reports grants and personal fees from MSD, GSK, Pfizer, Boehringer Ingelheim, Novavax, BMS, Seqirus, Astra Zeneca, Sanofi, IQVIA, grants from Bayer, BioMerieux, WHO, EU, FIND, Antilope, DIKTI, LPDP, Budi, personal fees from Novartis, Quintiles, Pharmerit, owning stock options in Health-Ecore and PAG Ltd, and being advisor to Asc Academics, all outside the submitted work. Jasviner A Singh reports personal fees from Crealta/Horizon, Medisys, Fidia, UBM LLC, Trio health, Medscape, WebMD, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, Practice Point communications, the National Institutes of Health, the American College of Rheumatology, and Simply Speaking, owning stock options in Amarin, Viking, Moderna, Vaxart pharmaceuticals and Charlotte’s Web Holdings, being a member of FDA Arthritis Advisory Committee, the steering committee of OMERACT, an international organization that develops measures for clinical trials and receives arm’s length funding from 12 pharmaceutical companies, and the Veterans Affairs Rheumatology Field Advisory Committee, and acting as Editor and Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis, all outside the submitted work. Era Upadhyay has a patent A system and method of reusable filters for anti-pollution mask pending, and a patent A system and method for electricity generation through crop stubble by using microbial fuel cells pending

Global, regional, and national mortality among young people aged 10–24 years, 1950–2019: a systematic analysis for the Global Burden of Disease Study 2019

Summary: Background Documentation of patterns and long-term trends in mortality in young people, which reflect huge changes in demographic and social determinants of adolescent health, enables identification of global investment priorities for this age group. We aimed to analyse data on the number of deaths, years of life lost, and mortality rates by sex and age group in people aged 10–24 years in 204 countries and territories from 1950 to 2019 by use of estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods We report trends in estimated total numbers of deaths and mortality rate per 100 000 population in young people aged 10–24 years by age group (10–14 years, 15–19 years, and 20–24 years) and sex in 204 countries and territories between 1950 and 2019 for all causes, and between 1980 and 2019 by cause of death. We analyse variation in outcomes by region, age group, and sex, and compare annual rate of change in mortality in young people aged 10–24 years with that in children aged 0–9 years from 1990 to 2019. We then analyse the association between mortality in people aged 10–24 years and socioeconomic development using the GBD Socio-demographic Index (SDI), a composite measure based on average national educational attainment in people older than 15 years, total fertility rate in people younger than 25 years, and income per capita. We assess the association between SDI and all-cause mortality in 2019, and analyse the ratio of observed to expected mortality by SDI using the most recent available data release (2017). Findings In 2019 there were 1·49 million deaths (95% uncertainty interval 1·39–1·59) worldwide in people aged 10–24 years, of which 61% occurred in males. 32·7% of all adolescent deaths were due to transport injuries, unintentional injuries, or interpersonal violence and conflict; 32·1% were due to communicable, nutritional, or maternal causes; 27·0% were due to non-communicable diseases; and 8·2% were due to self-harm. Since 1950, deaths in this age group decreased by 30·0% in females and 15·3% in males, and sex-based differences in mortality rate have widened in most regions of the world. Geographical variation has also increased, particularly in people aged 10–14 years. Since 1980, communicable and maternal causes of death have decreased sharply as a proportion of total deaths in most GBD super-regions, but remain some of the most common causes in sub-Saharan Africa and south Asia, where more than half of all adolescent deaths occur. Annual percentage decrease in all-cause mortality rate since 1990 in adolescents aged 15–19 years was 1·3% in males and 1·6% in females, almost half that of males aged 1–4 years (2·4%), and around a third less than in females aged 1–4 years (2·5%). The proportion of global deaths in people aged 0–24 years that occurred in people aged 10–24 years more than doubled between 1950 and 2019, from 9·5% to 21·6%. Interpretation Variation in adolescent mortality between countries and by sex is widening, driven by poor progress in reducing deaths in males and older adolescents. Improving global adolescent mortality will require action to address the specific vulnerabilities of this age group, which are being overlooked. Furthermore, indirect effects of the COVID-19 pandemic are likely to jeopardise efforts to improve health outcomes including mortality in young people aged 10–24 years. There is an urgent need to respond to the changing global burden of adolescent mortality, address inequities where they occur, and improve the availability and quality of primary mortality data in this age group

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Mapping inequalities in exclusive breastfeeding in low- and middle-income countries, 2000–2018

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 work was primarily supported by grant no. OPP1132415 from the Bill & Melinda Gates Foundation. Co-authors used by the Bill & Melinda Gates Foundation (E.G.P. and R.R.3) provided feedback on initial maps and drafts of this manuscript. L.G.A. has received support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil (CAPES), Código de Financiamento 001 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (grant nos. 404710/2018-2 and 310797/2019-5). O.O.Adetokunboh acknowledges the National Research Foundation, Department of Science and Innovation and South African Centre for Epidemiological Modelling and Analysis. M.Ausloos, A.Pana and C.H. are partially supported by a grant from the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project no. PN-III-P4-ID-PCCF-2016-0084. P.C.B. would like to acknowledge the support of F. Alam and A. Hussain. T.W.B. was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. K.Deribe is supported by the Wellcome Trust (grant no. 201900/Z/16/Z) as part of his international intermediate fellowship. C.H. and A.Pana are partially supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project no. PN-III-P2-2.1-SOL-2020-2-0351. B.Hwang is partially supported by China Medical University (CMU109-MF-63), Taichung, Taiwan. M.Khan acknowledges Jatiya Kabi Kazi Nazrul Islam University for their support. A.M.K. acknowledges the other collaborators and the corresponding author. Y.K. was supported by the Research Management Centre, Xiamen University Malaysia (grant no. XMUMRF/2020-C6/ITM/0004). K.Krishan is supported by a DST PURSE grant and UGC Centre of Advanced Study (CAS II) awarded to the Department of Anthropology, Panjab University, Chandigarh, India. M.Kumar would like to acknowledge FIC/NIH K43 TW010716-03. I.L. is a member of the Sistema Nacional de Investigación (SNI), which is supported by the Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT), Panamá. M.L. was supported by China Medical University, Taiwan (CMU109-N-22 and CMU109-MF-118). W.M. is currently a programme analyst in Population and Development at the United Nations Population Fund (UNFPA) Country Office in Peru, which does not necessarily endorses this study. D.E.N. acknowledges Cochrane South Africa, South African Medical Research Council. G.C.P. is supported by an NHMRC research fellowship. P.Rathi acknowledges support from Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India. Ramu Rawat acknowledges the support of the GBD Secretariat for supporting the reviewing and collaboration of this paper. B.R. acknowledges support from Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal. A.Ribeiro was supported by National Funds through FCT, under the programme of ‘Stimulus of Scientific Employment—Individual Support’ within the contract no. info:eu-repo/grantAgreement/FCT/CEEC IND 2018/CEECIND/02386/2018/CP1538/CT0001/PT. S.Sajadi acknowledges colleagues at Global Burden of Diseases and Local Burden of Disease. A.M.S. acknowledges the support from the Egyptian Fulbright Mission Program. F.S. was supported by the Shenzhen Science and Technology Program (grant no. KQTD20190929172835662). A.Sheikh is supported by Health Data Research UK. B.K.S. acknowledges Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal for all the academic support. B.U. acknowledges support from Manipal Academy of Higher Education, Manipal. C.S.W. is supported by the South African Medical Research Council. Y.Z. was supported by Science and Technology Research Project of Hubei Provincial Department of Education (grant no. Q20201104) and Outstanding Young and Middle-aged Technology Innovation Team Project of Hubei Provincial Department of Education (grant no. T2020003). The funders of the study had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. All maps presented in this study are generated by the authors and no permissions are required to publish them