Safety of Infusing Rituximab at a More Rapid Rate in Patients with Rheumatoid Arthritis: Results from the RATE-RA Study

As recommended in the current prescribing information, rituximab infusions in patients with rheumatoid arthritis (RA) take 4.25hours for the first infusion and 3.25hours for subsequent infusions, which is a burden on patients and the health care system. We therefore evaluated the safety of infusing rituximab at a faster rate for an infusion period of 2hours in patients with RA

Head Impact Exposure in Youth and Collegiate American Football

The relationship between head impact and subsequent brain injury for American football players is not well defined, especially for youth. The objective of this study is to quantify and assess Head Impact Exposure (HIE) metrics among youth and collegiate football players. This multiseason study enrolled 639 unique athletes (354 collegiate; 285 youth, ages 9–14), recording 476,209 head impacts (367,337 collegiate; 108,872 youth) over 971 sessions (480 collegiate; 491 youth). Youth players experienced 43 and 65% fewer impacts per competition and practice, respectively, and lower impact magnitudes compared to collegiate players (95th percentile peak linear acceleration (PLA, g) competition: 45.6 vs 61.9; 95th percentile PLA practice: 42.6 vs 58.8; 95th percentile peak rotational acceleration (PRA, rad∙s–2) competition: 2262 vs 4422; 95th percentile PRA practice: 2081 vs 4052; 95th percentile HITsp competition: 25.4 vs 32.8; 95th percentile HITsp practice: 23.9 vs 30.2). Impacts during competition were more frequent and of greater magnitude than during practice at both levels. Quantified comparisons of head impact frequency and magnitude between youth and collegiate athletes reveal HIE differences as a function of age, and expanded insight better informs the development of age-appropriate guidelines for helmet design, prevention measures, standardized testing, brain injury diagnosis, and recovery management

The role of prediction and outcomes in adaptive cognitive control

Humans adaptively perform actions to achieve their goals. This flexible behaviour requires two core abilities: the ability to anticipate the outcomes of candidate actions and the ability to select and implement actions in a goal-directed manner. The ability to predict outcomes has been extensively researched in reinforcement learning paradigms, but this work has often focused on simple actions that are not embedded in hierarchical and sequential structures that are characteristic of goal-directed human behaviour. On the other hand, the ability to select actions in accordance with high-level task goals, particularly in the presence of alternative responses and salient distractors, has been widely researched in cognitive control paradigms. Cognitive control research, however, has often paid less attention to the role of action outcomes. The present review attempts to bridge these accounts by proposing an outcome-guided mechanism for selection of extended actions. Our proposal builds on constructs from the hierarchical reinforcement learning literature, which emphasises the concept of reaching and evaluating informative states, i.e., states that constitute subgoals in complex actions. We develop an account of the neural mechanisms that allow outcome-guided action selection to be achieved in a network that relies on projections from cortical areas to the basal ganglia and back-projections from the basal ganglia to the cortex. These cortico-basal ganglia-thalamo-cortical ‘loops’ allow convergence – and thus integration – of information from non-adjacent cortical areas (for example between sensory and motor representations). This integration is essential in action sequences, for which achieving an anticipated sensory state signals the successful completion of an action. We further describe how projection pathways within the basal ganglia allow selection between representations, which may pertain to movements, actions, or extended action plans. The model lastly envisages a role for hierarchical projections from the striatum to dopaminergic midbrain areas that enable more rostral frontal areas to bias the selection of inputs from more posterior frontal areas via their respective representations in the basal ganglia.This work is supported by the Biotechnology and Biological Sciences Research Council (BBSRC) Grant BB/I019847/1, awarded to NY and FW

Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis:Sixteen-Week Results From a Phase III Randomized, Double-Blind, Placebo-Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors

Objective: To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors (TNFi). Methods: In this phase III randomized, double-blind, placebo-controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNFi and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ASAS] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80-mg subcutaneous ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W), with an 80-mg or 160-mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria (ASAS40) at week 16. Secondary outcomes and safety were also assessed. Results: A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging–evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment-emergent adverse events (AEs) with ixekizumab treatment were more frequent than with placebo. Serious AEs were similar across treatment arms. One death was reported (IXEQ2W group). Conclusion: Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNFi yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo

Gender Gap in Parental Leave Intentions: Evidence from 37 Countries

Despite global commitments and efforts, a gender-based division of paid and unpaid work persists. To identify how psychological factors, national policies, and the broader sociocultural context contribute to this inequality, we assessed parental-leave intentions in young adults (18–30 years old) planning to have children (N = 13,942; 8,880 identified as women; 5,062 identified as men) across 37 countries that varied in parental-leave policies and societal gender equality. In all countries, women intended to take longer leave than men. National parental-leave policies and women’s political representation partially explained cross-national variations in the gender gap. Gender gaps in leave intentions were paradoxically larger in countries with more gender-egalitarian parental-leave policies (i.e., longer leave available to both fathers and mothers). Interestingly, this cross-national variation in the gender gap was driven by cross-national variations in women’s (rather than men’s) leave intentions. Financially generous leave and gender-egalitarian policies (linked to men’s higher uptake in prior research) were not associated with leave intentions in men. Rather, men’s leave intentions were related to their individual gender attitudes. Leave intentions were inversely related to career ambitions. The potential for existing policies to foster gender equality in paid and unpaid work is discussed.Gender Gap in Parental Leave Intentions: Evidence from 37 CountriespublishedVersio

Gender Gap in Parental Leave Intentions: Evidence from 37 Countries

Despite global commitments and efforts, a gender-based division of paid and unpaid work persists. To identify how psychological factors, national policies, and the broader sociocultural context contribute to this inequality, we assessed parental-leave intentions in young adults (18–30 years old) planning to have children (N = 13,942; 8,880 identified as women; 5,062 identified as men) across 37 countries that varied in parental-leave policies and societal gender equality. In all countries, women intended to take longer leave than men. National parental-leave policies and women’s political representation partially explained cross-national variations in the gender gap. Gender gaps in leave intentions were paradoxically larger in countries with more gender-egalitarian parental-leave policies (i.e., longer leave available to both fathers and mothers). Interestingly, this cross-national variation in the gender gap was driven by cross-national variations in women’s (rather than men’s) leave intentions. Financially generous leave and gender-egalitarian policies (linked to men’s higher uptake in prior research) were not associated with leave intentions in men. Rather, men’s leave intentions were related to their individual gender attitudes. Leave intentions were inversely related to career ambitions. The potential for existing policies to foster gender equality in paid and unpaid work is discussed

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Psychometric properties of the standardized assessment of concussion in youth football: Validity, reliability, and demographic factors

The objective of this study was to determine the psychometrics (reliability, validity) of the original Standardized Assessment of Concussion (SAC) in a youth sample (ages 11 to 13). Demographic factors of race, level of vocabulary knowledge, mother’s level of education were also considered. Over 150 youth football athletes completed the SAC and a brief battery of NIH Toolbox cognitive tests as part of a larger study on biomechanical factors in youth sport concussion. This was a within-subjects design (pre-season, post-season assessments), and correlational analysis of convergent and discriminant validity. Between groups analysis based on demographic differences was also employed. The pre-season SAC scores were not different by age; however, SAC scores were statistically different by race: t(155) = 3.162, p = .002, d = .519. Maternal level of education and participant vocabulary scores were related to racial group membership. Convergent and discriminant validity were established compared to NIH Toolbox tests of memory and speed. Pre–post-season tests for 108 participants established marginally acceptable test–retest reliability (ICC = .692). These data support the use of the original SAC in youth football although clinicians must be aware of racial differences in scores

Strategies for Environmental Protection: Governmental, Legal and Private

This panel looked at strategies to protect the environment from three different perspectives: those of private citizens, public interest groups, and government. Peter Greenwald is senior policy advisor for the South Coast Air Quality Management District, the air pollution control agency for Orange County and urban portions of Los Angeles, Riverside and San Bernardino counties. Greenwald has more than 20 years experience in air quality law and policy and is involved in improving air quality for the Los Angeles Basin.Duncan McFetridge is president and founder of Save Our Forests and Ranchlands. SOFAR is committed to defending the San Diego backcountry against urban sprawl and working toward the adoption and implementation of a plan to preserve rural resources.Jonathan Parfrey is executive director of Physicians for Social Responsibility in Los Angeles. PSR-LA brings together health professionals and the diverse communities of Southern California to reduce threats to public health related to war, environmental toxins, and gun violence.Joel Reynolds joined the National Resources Defense Council’s Los Angeles office as a senior attorney in 1990. He is director of the Marine Mammal Protection and Southern California Ecosystem projects and co-director of NRDC’s Urban Program. NRDC uses law, science and the support of 1.2 million members to protect the planet’s wildlife and wild places and to insure a safe and healthy environment for all living things

Comparative Histological Studies of the Tunable Dye (at 577 nm) Laser and Argon Laser: The Specific Vascular Effects of the Dye Laser

This study compares the histological changes occurring after argon laser and dye laser (operating at 577nm) treatment of normal human skin. The initial effect of the argon laser is a diffuse nonspecific epidermal and upper dermal necrosis with subsequent cell death and a neutrophilic response at 48hr. These changes occur at 15 joules/cm2 and their extent closely correlates with the energy applied. In sharp contrast, the immediate effect of the dye laser is erythrocyte aggregation, vessel rupture, and hemorrhage. At 48hr, there is a pattern of acute vasculitis in the upper dermis and a prominent perivascular neutrophilic response in the mid-dermis. Focal epidermal necrosis does occur but is relatively minimal, while skin appendages and collagen are preserved. The energy to produce these alterations is relatively small, approximately 3 J/cm2. Thus, the dye laser at 577nm can selectively damage the cutaneous vascular plexus and may provide a basis for treatment of cutaneous vascular lesions