Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

Predictors of Academic Performance in High School Students: The Longitudinal ASAP Study

International Journal of Exercise Science 15(4): 616-631, 2022. Academic performance is influenced by multitude factors. However, little is known about their relative importance and how they evolve over time. The purpose of the present study was to determine the relative importance of cognitive control, physical, psychological and sociological factors as well as lifestyle habits in predicting academic performance in high school students using cross sectional and longitudinal approaches. One hundred and eighty-five grade seventh to ninth students (mean age: 13.1 ± 1.0 years old) from a single high school completed a 3-year prospective study. Academic performance, cognitive control, physical, psychological and sociological factors as well as lifestyle habits were assessed every year during the 3-year study. Results showed that different combinations of factors were found to predict academic performance measures in both male and female students at baseline and after a 3-year period. For example, in female students, screen time and VO2 max were found to be important predictors of academic performance, whereas working memory was the only recurring factor in predicting academic performance in male students. Moreover, our models were able to explain between 6.1 to 52.2% of the variation in the change of the different measures of academic performance. Results of the present study show that academic performance may be predicted by a wide range of multiple factors in high school students. Indeed, the factors that predicted academic performance varied between school subjects, sex and study design, highlighting the complexity of predicting academic performance in high school students

Biomarkers of Sarcopenia in Clinical Trials—Recommendations from the International Working Group on Sarcopenia

Sarcopenia, the age-related skeletal muscle decline, is associated with relevant clinical and socioeconomic negative outcomes in older persons. The study of this phenomenon and the development of preventive/therapeutic strategies represent public health priorities. The present document reports the results of a recent meeting of the International Working Group on Sarcopenia (a task force consisting of geriatricians and scientists from academia and industry) held on June 7–8, 2011 in Toulouse (France). The meeting was specifically focused at gaining knowledge on the currently available biomarkers (functional, biological, or imaging-related) that could be utilized in clinical trials of sarcopenia and considered the most reliable and promising to evaluate age-related modifications of skeletal muscle. Specific recommendations about the assessment of aging skeletal muscle in older people and the optimal methodological design of studies on sarcopenia were also discussed and finalized. Although the study of skeletal muscle decline is still in a very preliminary phase, the potential great benefits derived from a better understanding and treatment of this condition should encourage research on sarcopenia. However, the reasonable uncertainties (derived from exploring a novel field and the exponential acceleration of scientific progress) require the adoption of a cautious and comprehensive approach to the subject

Brasilia, distrito federal

Les photographies en noir et blanc présentées dans cet ouvrage témoignent des itinéraires urbains, des mouvements qui traversent la ville et lui donnent sa physionomie. L'image, langage visuel qui permet de comparer, interpréter, réfléchir est ici utilisée comme élément de recherche à part entièr

A black‐box automated approach to calibrate numerical simulations and optimize cover design: Application to a flow control layer constructed on an experimental waste rock pile

Mining operations often produce large volumes of waste rock to access economically valuable mineralized zones. Waste rock is usually stored in surface piles, the construction and reclamation of which represent a challenge for the industry. A flow control layer (FCL) made of crushed waste rock or sand and constructed on top of each waste rock bench could contribute to control water infiltration, thus improving waste rock pile stability and limiting contamination. An experimental waste rock pile was built and instrumented at the Tio mine (Rio Tinto Fer et Titane, Canada) to evaluate the performance of an FCL in field conditions. Large infiltration tests and rainfall monitoring were carried out, and measured outflow and water contents were used to calibrate numerical simulations. However, data were noisy and sometimes incomplete, and the models were difficult to calibrate. A new automated calibration approach was therefore proposed. An algorithm was developed to automate the numerical simulation calibration, using a black-box method that involves solving an optimization problem on a function without an analytic form. The approach was applied on measurements obtained from large-scale infiltration tests and validated using 2 yr of field monitoring data. Finally, the automated approach was adapted to optimize the design of the FCL, and an optimal design (material properties and layer thickness) was recommended based on local climate conditions. The proposed automated method could contribute to reduce the bias induced by manual calibration and allows for rapid multivariable calibration and optimization for a broad spectrum of mine waste cover system applications

Impacts of Remote Physical Exercises on Functional Status and Mobility among Community-Dwelling Pre-Disabled Seniors during the Covid-19 Lockdown

peer reviewedObjectives: To assess whether remote physical exercise interventions helped maintain function in daily life, level of physical activities, basic mobility and frailty status in pre-disabled seniors during the first Covid-19 lockdown. Design: This is an interventional study conducted from May 2020 to May 2021. Setting: Community-dwelling older adults in 2 Canadian cities. Participants: 84 pre-disabled seniors. Intervention: 12-week physical exercise programs (1 hour/ 3 times/ week) in kinesiologist-guided groups using Zoom or phone-supervised individual booklet-based home-program (n=44) vs. Control (usual life habits; n=40). Measurements: Functional status in daily activities (OARS scale); Daily level of aerobic (TAPA-1) and strengthening/flexibility (TAPA-2) physical activities; Basic mobility abilities (SPPB: balance, lower limbs strength, walking speed; Timed Up-and-Go) and Frailty (SOF index) were assessed at baseline and at 3, 6, 9 and 12-month follow-ups. Results: The participants’ mean age was 78.5 ± 7.2 and 76.5 % were women. There was a group * time effect for the OARS scale (p=0.02), the TAPA-1 (p=0.06) and the TAPA-2 (p=0.007) scores. For these outcomes, scores significantly improved during the first 3 months of follow-up and then stabilised in the intervention group whereas they remained constant in the control group over time. There was an overall time effect for the SPPB (p=0.004), the 4-m walking speed (p=0.02) and for the SOF index (p=0.004), with no between-group differences. Finally, no effect was observed for the TUG. Conclusion: Remote home-based physical exercise interventions and monitoring during the first Covid-19 lockdown seemed to have helped maintain seniors’ level of physical activities without impacting on basic mobility abilities. Further studies are needed to identify parameters of remote exercise programs that can improve daily function and mobility in this population

Synthesis of Polyhydroxylated Pyrano-Pyrrole Derivatives from Carbohydrate Precursors

The efficient synthesis of novel polyhydroxy‐tetrahydropyrano‐pyrroles from acetylenic carbohydrate precursors in three to four steps is described. The methodology involves, as key steps, the ring contraction of pyridazine intermediates obtained by an inverse‐demand Diels–Alder reaction and subsequent intramolecular lactonization

Is there a role for menopausal hormone therapy in the management of postmenopausal osteoporosis?

We provide an evidence base and guidance for the use of menopausal hormone therapy (MHT) for the maintenance of skeletal health and prevention of future fractures in recently menopausal women. Despite controversy over associated side effects, which has limited its use in recent decades, the potential role for MHT soon after menopause in the management of postmenopausal osteoporosis is increasingly recognized. We present a narrative review of the benefits versus risks of using MHT in the management of postmenopausal osteoporosis. Current literature suggests robust anti-fracture efficacy of MHT in patients unselected for low BMD, regardless of concomitant use with progestogens, but with limited evidence of persisting skeletal benefits following cessation of therapy. Side effects include cardiovascular events, thromboembolic disease, stroke and breast cancer, but the benefit-risk profile differs according to the use of opposed versus unopposed oestrogens, type of oestrogen/progestogen, dose and route of delivery and, for cardiovascular events, timing of MHT use. Overall, the benefit-risk profile supports MHT treatment in women who have recently (< 10 years) become menopausal, who have menopausal symptoms and who are less than 60 years old, with a low baseline risk for adverse events. MHT should be considered as an option for the maintenance of skeletal health in women, specifically as an additional benefit in the context of treatment of menopausal symptoms, when commenced at the menopause, or shortly thereafter, in the context of a personalized benefit-risk evaluation

International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent