The osteoarthritis prevention study (TOPS) - A randomized controlled trial of diet and exercise to prevent Knee Osteoarthritis:Design and rationale

Background: Osteoarthritis (OA), the leading cause of disability among adults, has no cure and is associated with significant comorbidities. The premise of this randomized clinical trial is that, in a population at risk, a 48-month program of dietary weight loss and exercise will result in less incident structural knee OA compared to control. Methods/design: The Osteoarthritis Prevention Study (TOPS) is a Phase III, assessor-blinded, 48-month, parallel 2 arm, multicenter randomized clinical trial designed to reduce the incidence of structural knee OA. The study objective is to assess the effects of a dietary weight loss, exercise, and weight-loss maintenance program in preventing the development of structural knee OA in females at risk for the disease. TOPS will recruit 1230 ambulatory, community dwelling females with obesity (Body Mass Index (BMI) ​≥ ​30 ​kg/m2) and aged ≥50 years with no radiographic (Kellgren-Lawrence grade ≤1) and no magnetic resonance imaging (MRI) evidence of OA in the eligible knee, with no or infrequent knee pain. Incident structural knee OA (defined as tibiofemoral and/or patellofemoral OA on MRI) assessed at 48-months from intervention initiation using the MRI Osteoarthritis Knee Score (MOAKS) is the primary outcome. Secondary outcomes include knee pain, 6-min walk distance, health-related quality of life, knee joint loading during gait, inflammatory biomarkers, and self-efficacy. Cost effectiveness and budgetary impact analyses will determine the value and affordability of this intervention. Discussion: This study will assess the efficacy and cost effectiveness of a dietary weight loss, exercise, and weight-loss maintenance program designed to reduce incident knee OA.Trial registration: ClinicalTrials.gov Identifier: NCT05946044.</p

Model for screening of resonant magnetic perturbations by plasma in a realistic tokamak geometry and its impact on divertor strike points

This work addresses the question of the relation between strike-point splitting and magnetic stochasticity at the edge of a poloidally diverted tokamak in the presence of externally imposed magnetic perturbations. More specifically, ad-hoc helical current sheets are introduced in order to mimic a hypothetical screening of the external resonant magnetic perturbations by the plasma. These current sheets, which suppress magnetic islands, are found to reduce the amount of splitting expected at the target, which suggests that screening effects should be observable experimentally. Multiple screening current sheets reinforce each other, i.e. less current relative to the case of only one current sheet is required to screen the perturbation.Comment: Accepted in the Proceedings of the 19th International Conference on Plasma Surface Interactions, to be published in Journal of Nuclear Materials. Version 2: minor formatting and text improvements, more results mentioned in the conclusion and abstrac

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

Helicobacter pylori bab genes during chronic colonization

Helicobacter pylori BabA adhesin metastability could yield variants with potential for periodic activation and deactivation of their mediated adherence. babA/B or babB/A chimeras could play an important role in translational regulation. We investigated the frequency of different bab gene profiles in paired isolates from antrum and corpus recovered from patients with chronic gastritis. Isolates from 174 biopsies from 34 patients were included, and bab genes at the three common chromosomal loci were investigated. Inter-micro-niche variation was found in 1/4 patients, counting duplicate copies of babA or babB, babB/A or babA/B chimeras, opposite location of babA and babB or babC and babB, and absence of babB ATG translational codon. Truncated BabA was identified in 2/34 patients without inter-micro-niche variation. Isolates from 12/34 patients harbored babA/B or babB/A chimeras -either in one, several or all micro-niches indicating that chimera formation is a common mechanism to control BabA expression. To note, babA gene was absent in 11/34 patients, and in this population, babA/B chimeras which lack expression predominated over babB/A, able to exhibit Leb binding phenotype

Combining Inertial Sensors and Machine Learning to Predict vGRF and Knee Biomechanics during a Double Limb Jump Landing Task

(1) Background: Biomechanics during landing tasks, such as the kinematics and kinetics of the knee, are altered following anterior cruciate ligament (ACL) injury and reconstruction. These variables are recommended to assess prior to clearance for return to sport, but clinicians lack access to the current gold-standard laboratory-based assessment. Inertial sensors serve as a potential solution to provide a clinically feasible means to assess biomechanics and augment the return to sport testing. The purposes of this study were to (a) develop multi-sensor machine learning algorithms for predicting biomechanics and (b) quantify the accuracy of each algorithm. (2) Methods: 26 healthy young adults completed 8 trials of a double limb jump landing task. Peak vertical ground reaction force, peak knee flexion angle, peak knee extension moment, and peak sagittal knee power absorption were assessed using 3D motion capture and force plates. Shank- and thigh- mounted inertial sensors were used to collect data concurrently. Inertial data were submitted as inputs to single- and multiple- feature linear regressions to predict biomechanical variables in each limb. (3) Results: Multiple-feature models, particularly when an accelerometer and gyroscope were used together, were valid predictors of biomechanics (R2 = 0.68–0.94, normalized root mean square error = 4.6–10.2%). Single-feature models had decreased performance (R2 = 0.16–0.60, normalized root mean square error = 10.0–16.2%). (4) Conclusions: The combination of inertial sensors and machine learning provides a valid prediction of biomechanics during a double limb landing task. This is a feasible solution to assess biomechanics for both clinical and real-world settings outside the traditional biomechanics laboratory

RF heating systems evolution for the WEST project

Tore Supra is dedicated to long pulse operation at high power, with a record in injected energy of 1 GJ (2.8 MW × 380 s) and an achieved capability of 12 MW injected power delivered by 3 RF systems: Lower Hybrid Current Drive (LHCD), Ion Cyclotron Resonance Heating (ICRH) and Electron Cyclotron Resonance Heating (ECRH). The new WEST project (W [tungsten] Environment in Steady-state Tokamak) aims at fitting Tore Supra with an actively cooled tungsten coated wall and a bulk tungsten divertor. This new device will offer to ITER a test bed for validating the relevant technologies for actively cooled metallic components, with D-shaped H-mode plasmas. For WEST operation, different scenarii able to reproduce ITER relevant conditions in terms of steady state heat loads have been identified, ranging from a high RF power scenario (15 MW, 30 s) to a high fluence scenario (10 MW, 1000 s). This paper will focus on the evolution of the RF systems required for WEST. For the ICRH system, the main issues are its ELM resilience and its CW compatibility, three new actively cooled antennas are being designed, with the aim of reducing their sensitivity to the load variations induced by ELMs. The LH system has been recently upgraded with new klystrons and the PAM antenna, the possible reshaping of the antenna mouths is presently studied for matching with the magnetic field line in the WEST configuration. For the ECRH system, the device for the poloidal movement of the mirrors of the antenna is being changed for higher accuracy and speed