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Owing to its high magnetic field, high power, and compact size, the SPARC experiment will operate with divertor conditions at or above those expected in reactor-class tokamaks. Power exhaust at this scale remains one of the key challenges for practical fusion energy. Based on empirical scalings, the peak unmitigated divertor parallel heat flux is projected to be greater than 10 GW m−2. This is nearly an order of magnitude higher than has been demonstrated to date. Furthermore, the divertor parallel Edge-Localized Mode (ELM) energy fluence projections (~11–34 MJ m−2) are comparable with those for ITER. However, the relatively short pulse length (~25 s pulse, with a ~10 s flat top) provides the opportunity to consider mitigation schemes unsuited to long-pulse devices including ITER and reactors. The baseline scenario for SPARC employs a ~1 Hz strike point sweep to spread the heat flux over a large divertor target surface area to keep tile surface temperatures within tolerable levels without the use of active divertor cooling systems. In addition, SPARC operation presents a unique opportunity to study divertor heat exhaust mitigation at reactor-level plasma densities and power fluxes. Not only will SPARC test the limits of current experimental scalings and serve for benchmarking theoretical models in reactor regimes, it is also being designed to enable the assessment of long-legged and X-point target advanced divertor magnetic configurations. Experimental results from SPARC will be crucial to reducing risk for a fusion pilot plant divertor design.

ObjectivesTo evaluate the efficacy and safety of different doses and regimens of filgotinib, an oral Janus kinase 1 inhibitor, as add-on treatment to methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and inadequate response to MTX.MethodsIn this 24-week phase IIb study, patients with moderate-to-severe active RA receiving a stable dose of MTX were randomised (1:1:1:1:1:1:1) to receive placebo or 50, 100 or 200 mg filgotinib, administered once daily or twice daily. Primary end point was the percentage of patients achieving a week 12 American College of Rheumatology (ACR)20 response.ResultsOverall, 594 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib 100 mg once daily or 200 mg daily (both regimens) achieved an ACR20 response versus placebo. For other key end points at week 12 (ACR50, ACR-N, Disease Activity Score based on 28 joints and C reactive protein value, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index), differences in favour of 100  or 200 mg filgotinib daily were seen versus placebo; responses were maintained or improved through to week 24. Rapid onset of action and dose-dependent responses were observed for most efficacy end points and were associated with an increased haemoglobin concentration. No significant differences between once-daily and twice-daily regimens were seen. Treatment-emergent adverse event rates were similar in placebo and filgotinib groups. Serious infections occurred in one and five patients in the placebo and filgotinib groups, respectively. No tuberculosis or opportunistic infections were reported.ConclusionsFilgotinib as add-on to MTX improved the signs and symptoms of active RA over 24 weeks and was associated with a rapid onset of action. Filgotinib was generally well tolerated.Trial registration number:NCT01888874.

ObjectivesTo evaluate the efficacy and safety of different doses of filgotinib, an oral Janus kinase 1 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA) and previous inadequate response to methotrexate (MTX).MethodsIn this 24-week phase IIb study, patients with moderately to severely active RA were randomised (1:1:1:1) to receive 50, 100 or 200 mg filgotinib once daily, or placebo, after a ≥4-week washout from MTX. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR)20 response at week 12.ResultsOverall, 283 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib at any dose achieved ACR20 responses versus placebo (≥65% vs 29%, p<0.001). For other key end points at week 12 (ACR50, ACR70, ACR-N, Disease Activity Score based on 28 joints and C reactive protein, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index) significant differences from baseline in favour of filgotinib 100 and 200 mg versus placebo were seen; responses were maintained or improved through week 24. Rapid onset of action was observed for most efficacy end points. Dose-dependent increases in haemoglobin were observed. The percentage of patients with treatment-emergent adverse events (TEAE) was similar in the placebo and filgotinib groups (∼40%). Eight patients on filgotinib and one on placebo had a serious TEAE, and four patients, all of whom received filgotinib, experienced a serious infection. No tuberculosis or opportunistic infections were reported.ConclusionsOver 24 weeks, filgotinib as monotherapy was efficacious in treating the signs and symptoms of active RA, with a rapid onset of action. Filgotinib was generally well tolerated.Trial registration numberNCT01894516.

Objective: To assess the efficacy and safety of 100 mg daily anakinra (Kineret), a recombinant form of the naturally occurring interleukin 1 receptor antagonist, plus methotrexate (MTX) in reducing the signs and symptoms of rheumatoid arthritis (RA). Methods: Patients with active RA (n = 506) despite current treatment with MTX were enrolled in this multicentre, double blind, randomised, placebo controlled study. Patients received subcutaneous injections of anakinra 100 mg/day or placebo. They were assessed monthly for 6 months for improvement in signs and symptoms of RA and for adverse events. The primary efficacy measure was the percentage of patients attaining ACR20 response at week 24. Results: Significantly greater proportions of patients treated with anakinra compared with placebo achieved ACR20 (38% v 22%; p<0.001), ACR50 (17% v 8%; p<0.01), and ACR70 (6% v 2%; p<0.05) responses. The response to anakinra was rapid; the proportion of patients with an ACR20 response at the first study assessment (4 weeks) was twice as high with anakinra as with placebo (p<0.005). Clinically meaningful and statistically significant responses were also seen in individual components of the ACR response (for example, Health Assessment Questionnaire, pain, C reactive protein levels, and erythrocyte sedimentation rate). Anakinra was well tolerated, with a safety profile, similar to that of placebo with one exception: mild to moderate injection site reactions were more common with anakinra than with placebo (65% v 24%). Conclusions: This study confirms previous observations from a dose-ranging study showing that anakinra, in combination with MTX, is an effective and safe treatment for patients with RA who have inadequate responses to MTX alone.

An important problem in nuclear fusion plasmas is the prediction and control of turbulence which drives the cross-field transport, thus leading to energy loss from the system and deteriorating confinement. Turbulence, being a highly nonlinear and multiscale process, is challenging to theoretically describe and computationally model. Most advanced computational models fall into one of the two categories: fluid or gyro-kinetic. They both come at a high computational cost and cannot be applied for routine simulation of plasma discharge evolution and control. Development of reduced models based on (physics informed) artificial neural networks could potentially fulfil the need for affordable simulations of plasma turbulence. However, the training requires an extensive data base and the obtained models lack extrapolation capability to scenarios not originally encountered during training. This leads to reduced models of limited validity which may not prove adequate for predicting scenarios in future machines. In contrast, we explore a data-driven model discovery approach based on sparse regression to infer governing nonlinear partial differential equations directly from the data. Our input data are generated by simulations of drift-wave turbulence according to the Hasegawa–Wakatani and modified Hasegawa–Wakatani models. Balancing model accuracy and complexity enables the reconstruction of the systems of partial differential equations accurately describing the dynamics simulated in the input data sets. Sparse regression is not data hungry and can be extrapolated to unexplored parameter ranges. We explore and demonstrate the potential of this approach for fusion plasma turbulence modelling. The findings show that the methodology is promising for the development of reduced and computationally efficient turbulence models as well as for existing model cross-validation.

Environmental DNA (eDNA) is an increasingly useful method for detecting pelagic animals in the ocean but typically requires large water volumes to sample diverse assemblages. Ship-based pelagic sampling programs that could implement eDNA methods generally have restrictive water budgets. Studies that quantify how eDNA methods perform on low water volumes in the ocean are limited, especially in deep-sea habitats with low animal biomass and poorly described species assemblages. Using 12S rRNA and COI gene primers, we quantified assemblages comprised of micronekton, coastal forage fishes, and zooplankton from low volume eDNA seawater samples (n = 436, 380–1800 mL) collected at depths of 0–2200 m in the southern California Current. We compared diversity in eDNA samples to concurrently collected pelagic trawl samples (n = 27), detecting a higher diversity of vertebrate and invertebrate groups in the eDNA samples. Differences in assemblage composition could be explained by variability in size-selectivity among methods and DNA primer suitability across taxonomic groups. The number of reads and amplicon sequences variants (ASVs) did not vary substantially among shallow (<200 m) and deep samples (>600 m), but the proportion of invertebrate ASVs that could be assigned a species-level identification decreased with sampling depth. Using hierarchical clustering, we resolved horizontal and vertical variability in marine animal assemblages from samples characterized by a relatively low diversity of ecologically important species. Low volume eDNA samples will quantify greater taxonomic diversity as reference libraries, especially for deep-dwelling invertebrate species, continue to expand.

Measuring head impact exposure is a critical step toward understanding the mechanism and prevention of sport-related mild traumatic brain (concussion) injury, as well as the possible effects of repeated subconcussive impacts. To quantify the frequency and location of head impacts that individual players received in 1 season among 3 collegiate teams, between practice and game sessions, and among player positions. Cohort study. Collegiate football field. One hundred eighty-eight players from 3 National Collegiate Athletic Association football teams. Participants wore football helmets instrumented with an accelerometer-based system during the 2007 fall season. The number of head impacts greater than 10 g and location of the impacts on the player's helmet were recorded and analyzed for trends and interactions among teams (A, B, or C), session types, and player positions using Kaplan-Meier survival curves. The total number of impacts players received was nonnormally distributed and varied by team, session type, and player position. The maximum number of head impacts for a single player on each team was 1022 (team A), 1412 (team B), and 1444 (team C). The median number of head impacts on each team was 4.8 (team A), 7.5 (team B), and 6.6 (team C) impacts per practice and 12.1 (team A), 14.6 (team B), and 16.3 (team C) impacts per game. Linemen and linebackers had the largest number of impacts per practice and per game. Offensive linemen had a higher percentage of impacts to the front than to the back of the helmet, whereas quarterbacks had a higher percentage to the back than to the front of the helmet. The frequency of head impacts and the location on the helmet where the impacts occur are functions of player position and session type. These data provide a basis for quantifying specific head impact exposure for studies related to understanding the biomechanics and clinical aspects of concussion injury, as well as the possible effects of repeated subconcussive impacts in football.

The SPARC tokamak is a critical next step towards commercial fusion energy. SPARC is designed as a high-field ($B_0 = 12.2$ T), compact ($R_0 = 1.85$ m, $a = 0.57$ m), superconducting, D-T tokamak with the goal of producing fusion gain $Q>2$ from a magnetically confined fusion plasma for the first time. Currently under design, SPARC will continue the high-field path of the Alcator series of tokamaks, utilizing new magnets based on rare earth barium copper oxide high-temperature superconductors to achieve high performance in a compact device. The goal of $Q>2$ is achievable with conservative physics assumptions ($H_{98,y2} = 0.7$) and, with the nominal assumption of $H_{98,y2} = 1$, SPARC is projected to attain $Q \\approx 11$ and $P_{\\textrm {fusion}} \\approx 140$ MW. SPARC will therefore constitute a unique platform for burning plasma physics research with high density ($\\langle n_{e} \\rangle \\approx 3 \\times 10^{20}\\ \\textrm {m}^{-3}$), high temperature ($\\langle T_e \\rangle \\approx 7$ keV) and high power density ($P_{\\textrm {fusion}}/V_{\\textrm {plasma}} \\approx 7\\ \\textrm {MW}\\,\\textrm {m}^{-3}$) relevant to fusion power plants. SPARC's place in the path to commercial fusion energy, its parameters and the current status of SPARC design work are presented. This work also describes the basis for global performance projections and summarizes some of the physics analysis that is presented in greater detail in the companion articles of this collection.

The aims of this study were to quantify the sensitivity of various biomechanical measures (linear acceleration, rotational acceleration, impact duration, and impact location) of head impact to the clinical diagnosis of concussion in United States football players and to develop a novel measure of head impact severity combining these measures into a single score that better predicts the incidence of concussion. On-field head impact data were collected from 449 football players at 13 organizations (n = 289,916) using in-helmet systems of six single-axis accelerometers. Concussions were diagnosed by medical staff and later associated with impact data. Principal component analysis and a weighting coefficient based on impact location were used to transform correlated head impact measures into a new composite variable, weighted principal component score (wPCS). The predictive power of linear acceleration, rotational acceleration, head injury criterion, and wPCS was quantified using receiver operating characteristic curves. The null hypothesis, that a measure was no more predictive than guessing, was tested (alpha = 0.05). In addition, receiver operating characteristic curves for wPCS and classical measures were directly compared to test the hypothesis that wPCS was more predictive of concussion than were classic measures (alpha = 0.05). When all of the impacts were considered, every biomechanical measure evaluated was statistically more predictive of concussion than guessing (P < 0.005). However, for the top 1 and 2% of impacts based on linear acceleration, a subset that consisted of 82% of all diagnosed concussions, only wPCS was significantly more predictive of concussion than guessing (P < 0.03); when compared with each other, wPCS was more predictive of concussion than were classical measures for the top 1 and 2% of all of the data (P < 0.04). A weighted combination of several biomechanical inputs, including impact location, is more predictive of concussion than a single biomechanical measure. This study is the first to the authors' knowledge to quantify improvements in the sensitivity of a biomechanical measure to incidence of concussion when impact location is considered.

Recent research has suggested a possible link between sports-related concussions and neurodegenerative processes, highlighting the importance of developing methods to accurately quantify head impact tolerance. The use of kinematic parameters of the head to predict brain injury has been suggested because they are indicative of the inertial response of the brain. The objective of this study is to characterize the rotational kinematics of the head associated with concussive impacts using a large head acceleration dataset collected from human subjects. The helmets of 335 football players were instrumented with accelerometer arrays that measured head acceleration following head impacts sustained during play, resulting in data for 300,977 sub-concussive and 57 concussive head impacts. The average sub-concussive impact had a rotational acceleration of 1230 rad/s 2 and a rotational velocity of 5.5 rad/s, while the average concussive impact had a rotational acceleration of 5022 rad/s 2 and a rotational velocity of 22.3 rad/s. An injury risk curve was developed and a nominal injury value of 6383 rad/s 2 associated with 28.3 rad/s represents 50% risk of concussion. These data provide an increased understanding of the biomechanics associated with concussion and they provide critical insight into injury mechanisms, human tolerance to mechanical stimuli, and injury prevention techniques.