FULL POPULATION TESTING FOR VALIDATION OF HUMAN RESTRAINT SYSTEMS ON COMMERCIAL AND NON COMMERCIAL ERGOMETERS

Human missions to Mars is one of the main objectives for scientific space international community and major goals on physiological and biomechanical space research is reduction of muscle atrophy (Fitts, 2000; Zange, 1997). MARES (Muscular Atrophy Research and Exercise System) system is an ergometer to be flown and installed in the International Space Station in the year 2007. This system will allow neuromuscular and gravitational physiology research on orbit. MARES consists of a control electronics that drives a motor, to which a subject .is connected by means of a restraining system named HRS (Human Restraint System). This ergometer can be programmed to work in 14 different modes (Isometric, Isotonic, Isokinetic, Spring, Friction, Additional Moment of Inertia/Mass, Pseudogravitational, Position Control, Velocity Control, Torque/Force Control, Power Control, Physical Elements, Extended Torque/Force Control, Quick Release). All of this modes are available for 11 movements, corresponding to main body joints and movements

The Importance of the Stem Cell Marker Prominin-1/CD133 in the Uptake of Transferrin and in Iron Metabolism in Human Colon Cancer Caco-2 Cells

As the pentaspan stem cell marker CD133 was shown to bind cholesterol and to localize in plasma membrane protrusions, we investigated a possible function for CD133 in endocytosis. Using the CD133 siRNA knockdown strategy and non-differentiated human colon cancer Caco-2 cells that constitutively over-expressed CD133, we provide for the first time direct evidence for a role of CD133 in the intracellular accumulation of fluorescently labeled extracellular compounds. Assessed using AC133 monoclonal antibody, CD133 knockdown was shown to improve Alexa488-transferrin (Tf) uptake in Caco-2 cells but had no impact on FITC-dextran or FITC-cholera-toxin. Absence of effect of the CD133 knockdown on Tf recycling established a role for CD133 in inhibiting Tf endocytosis rather than in stimulating Tf exocytosis. Use of previously identified inhibitors of known endocytic pathways and the positive impact of CD133 knockdown on cellular uptake of clathrin-endocytosed synthetic lipid nanocapsules supported that CD133 impact on endocytosis was primarily ascribed to the clathrin pathway. Also, cholesterol extraction with methyl-β-cyclodextrine up regulated Tf uptake at greater intensity in the CD133high situation than in the CD133low situation, thus suggesting a role for cholesterol in the inhibitory effect of CD133 on endocytosis. Interestingly, cell treatment with the AC133 antibody down regulated Tf uptake, thus demonstrating that direct extracellular binding to CD133 could affect endocytosis. Moreover, flow cytometry and confocal microscopy established that down regulation of CD133 improved the accessibility to the TfR from the extracellular space, providing a mechanism by which CD133 inhibited Tf uptake. As Tf is involved in supplying iron to the cell, effects of iron supplementation and deprivation on CD133/AC133 expression were investigated. Both demonstrated a dose-dependent down regulation here discussed to the light of transcriptional and post-transciptional effects. Taken together, these data extend our knowledge of the function of CD133 and underline the interest of further exploring the CD133-Tf-iron network

Use of multidimensional item response theory methods for dementia prevalence prediction : an example using the Health and Retirement Survey and the Aging, Demographics, and Memory Study

Background Data sparsity is a major limitation to estimating national and global dementia burden. Surveys with full diagnostic evaluations of dementia prevalence are prohibitively resource-intensive in many settings. However, validation samples from nationally representative surveys allow for the development of algorithms for the prediction of dementia prevalence nationally. Methods Using cognitive testing data and data on functional limitations from Wave A (2001-2003) of the ADAMS study (n = 744) and the 2000 wave of the HRS study (n = 6358) we estimated a two-dimensional item response theory model to calculate cognition and function scores for all individuals over 70. Based on diagnostic information from the formal clinical adjudication in ADAMS, we fit a logistic regression model for the classification of dementia status using cognition and function scores and applied this algorithm to the full HRS sample to calculate dementia prevalence by age and sex. Results Our algorithm had a cross-validated predictive accuracy of 88% (86-90), and an area under the curve of 0.97 (0.97-0.98) in ADAMS. Prevalence was higher in females than males and increased over age, with a prevalence of 4% (3-4) in individuals 70-79, 11% (9-12) in individuals 80-89 years old, and 28% (22-35) in those 90 and older. Conclusions Our model had similar or better accuracy as compared to previously reviewed algorithms for the prediction of dementia prevalence in HRS, while utilizing more flexible methods. These methods could be more easily generalized and utilized to estimate dementia prevalence in other national surveys

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

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

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. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

The Role of perceived value and emotions in the satisfaction and future intentions of spectators in sporting events

The quality of service offered by sports entities has become a good predictor of user satisfaction and also future intentions. To know the future intentions of customers of any service is a key objective to develop service improvement and retention strategies. This need has also become apparent to professional sports clubs. In this study, the relationship between perceived quality (tangibles, staff, complementary services and outcome quality), perceived value, emotions, satisfaction and future intentions of spectators are analyzed for a sporting event. Consequently, the main objectives proposed in this study were to test a model of causal relationships whereby the perceived value is a function of perceived quality, satisfaction is a consequence of quality, perceived value and emotions, and future intentions are a function of satisfaction and perceived value, and to know the importance of perceived value in predicting future intentions of the spectator. The research was conducted on a basketball club of the Spanish premier league, where 563 spectators were surveyed with a self-administered questionnaire. The original scale used for the analysis of perceived quality consisted of 9 items with an alternative seven-point response and was called Eventqual-R, that is the short version of Eventqual which is used in the regular leagues of professional basketball. Results indicate that perceived value is the best predictor of the satisfaction and future intentions of spectators, while quality and emotions have limited relevance as predictors of spectator satisfactio

Role of Perceived Value and Emotions in the Satisfaction and Future Intentions of Spectators in Sporting Events

The quality of service offered by sports entities has become a good predictor of user satisfaction and also future intentions. To know the future intentions of customers of any service is a key objective to develop service improvement and retention strategies. This need has also become apparent to professional sports clubs. In this study, the relationship between perceived quality (tangibles, staff, complementary services and outcome quality), perceived value, emotions, satisfaction and future intentions of spectators are analyzed for a sporting event. Consequently, the main objectives proposed in this study were to test a model of causal relationships whereby the perceived value is a function of perceived quality, satisfaction is a consequence of quality, perceived value and emotions, and future intentions are a function of satisfaction and perceived value, and to know the importance of perceived value in predicting future intentions of the spectator. The research was conducted on a basketball club of the Spanish premier league, where 563 spectators were surveyed with a self-administered questionnaire. The original scale used for the analysis of perceived quality consisted of 9 items with an alternative seven-point response and was called Eventqual-R, that is the short version of Eventqual which is used in the regular leagues of professional basketball. Results indicate that perceived value is the best predictor of the satisfaction and future intentions of spectators, while quality and emotions have limited relevance as predictors of spectator satisfaction

Surgical Site Infection a major risk factor of pseudarthrosis in adult spinal deformity surgery

BACKGROUND CONTEXT: Despite the evidence in appendicular skeletal surgery, the effect of infection on spinal fusion remains unclear, particularly after Adult Spinal Deformity (ASD) surgery. PURPOSE: The purpose of this study was to determine the impact of surgical site infection (SSI) in ASD surgery fusion rates and its association with other risks factors of pseudarthrosis. STUDY DESIGN: We conducted an international multicenter retrospective study on a prospective cohort of patients operated for spinal deformity. PATIENT SAMPLE: A total of 956 patients were included (762 females and 194 males). OUTCOME MEASURES: Patient's preoperative characteristics, pre- and postoperative spinopelvic parameters, surgical variables, post-operative complications and were recorded. Surgical site infections were asserted in case of clinical signs associated with positive surgical samples. Each case was treated with surgical reintervention for debridement and irrigation. Presence of pseudarthrosis was defined by the association of clinical symptoms and radiological signs of non-fusion (either direct evidence on CT-scan or indirect radiographic clues such as screw loosening, rod breakage, screw pull out or loss of correction). Each iterative surgical intervention was collected. METHODS: Univariate and multivariate analysis with logistic regression models were performed to evaluate the role of risk factors of pseudarthrosis. RESULTS: 956 surgical ASD patients with more than two years of follow-up were included in the study. 65 of these patients were treated for SSI (6.8%), 138 for pseudarthrosis (14.4%), and 28 patients for both SSI and pseudarthrosis. On multivariate analysis, SSI was found to be a major risk factor of pseudarthrosis (OR = 4.4; 95% CI = 2.4,7.9) as well as other known risks factors: BMI (OR = 1.1; 95% CI = 1.0,1.1), smoking (OR = 1.6; 95% CI = 1.1,2.9), performance of Smith-Petersen osteotomy (OR = 1.6; 95% CI 1.0,2.6), number of vertebrae instrumented (OR = 1.1; 95% CI = 1.1,1.2) and the caudal level of fusion, with a distal exponential increment of the risk (OR max for S1 = 6, 95% CI = 1.9,18.6). CONCLUSION: SSI significantly increases the risk of pseudarthrosis with an OR of 4.4