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Policy, mandating early screening for dyslexia and use of specific interventions, is increasing throughout the United States. The authors designed a descriptive case study to learn what impact policies have on practice and how literacy specialists, trained in both comprehensive and structured literacy approaches, provide support for students. Data collected from focus groups, interviews and observations were analyzed. We found that (1) literacy specialists selected specific instructional practices to address individual reader's profiles, (2) literacy specialists believed that reading intervention support fits best within a balanced, comprehensive, literacy framework, (3) literacy specialists approached their readers with a holistic, humanizing view, (4) literacy specialists capacity for providing reading support has grown over the past fifteen years to meet the varied needs of the students they serve, and (5) literacy specialists deal with misinformation and confusion in their schools about dyslexia that has resulted in lost instructional time with their students. These results highlight the importance of hearing from literacy specialists to understand the complexity of their work and the range of reading behaviors and instructional needs seen in their schools.

Objective The objective of this study was to determine the feasibility and effectiveness of using SUpported Motivational InTerviewing (SUMIT) to increase physical activity in people with knee osteoarthritis (KOA).Design Randomised controlled trial.Setting We recruited people who had completed Good Life with osteoArthritis Denmark (GLA:D) from private, public and community settings in Victoria, Australia.Interventions Participants were randomised to receive SUMIT or usual care. SUMIT comprised five motivational interviewing sessions targeting physical activity over 10 weeks, and access to a multimedia web-based platform.Participants Thirty-two participants were recruited (17 SUMIT, 15 control) including 22 females (69%).Outcome measures Feasibility outcomes included recruitment rate, adherence to motivational interviewing, ActivPAL wear and drop-out rate. Effect sizes (ESs) were calculated for daily steps, stepping time, time with cadence >100 steps per minute, time in bouts >1 min; 6 min walk distance, Knee Osteoarthritis Outcome Score (KOOS) subscales (pain, symptoms, function, sport and recreation, and quality of life (QoL)), Euroqual, systolic blood pressure, body mass index, waist circumference, 30 s chair stand test and walking speed during 40 m walk test.Results All feasibility criteria were achieved, with 32/63 eligible participants recruited over seven months; with all participants adhering to all motivational interviewing calls and achieving sufficient ActivPAL wear time, and only two drop-outs (6%).12/15 outcome measures showed at least a small effect (ES>0.2) favouring the SUMIT group, including daily time with cadence >100 steps per minute (ES=0.43). Two outcomes, walking speed (ES= 0.97) and KOOS QoL (ES=0.81), showed a large effect (ES>0.8).Conclusion SUMIT is feasible in people with knee osteoarthritis. Potential benefits included more time spent walking at moderate intensity, faster walking speeds and better QoL.Trial registration number ACTRN12621000267853.

We present new arcminute-resolution maps of the Cosmic Microwave Background temperature and polarization anisotropy from the Atacama Cosmology Telescope, using data taken from 2013–2016 at 98 and 150 GHz. The maps cover more than 17,000 deg2, the deepest 600 deg2 with noise levels below 10µK-arcmin. We use the power spectrum derived from almost 6,000 deg2 of these maps to constrain cosmology. The ACT data enable a measurement of the angular scale of features in both the divergence-like polarization and the temperature anisotropy, tracing both the velocity and density at last-scattering. From these one can derive the distance to the last-scattering surface and thus infer the local expansion rate, H0. By combining ACT data with large-scale information from WMAP we measure H0 = 67.6±1.1 km/s/Mpc, at 68% confidence, in excellent agreement with the independently-measured Planck satellite estimate (from ACT alone we find H0 = 67.9 ± 1.5 km/s/Mpc). The ΛCDM model provides a good fit to the ACT data, and we find no evidence for deviations: both the spatial curvature, and the departure from the standard lensing signal in the spectrum, are zero to within 1σ; the number of relativistic species, the primordial Helium fraction, and the running of the spectral index are consistent with ΛCDM predictions to within 1.5–2.2σ. We compare ACT, WMAP, and Planck at the parameter level and find good consistency; we investigate how the constraints on the correlated spectral index and baryon density parameters readjust when adding CMB large-scale information that ACT does not measure. The DR4 products presented here will be publicly released on the NASA Legacy Archive for Microwave Background Data Analysis.

We present the temperature and polarization angular power spectra of the CMB measured by the Atacama Cosmology Telescope (ACT) from 5400 deg2 of the 2013–2016 survey, which covers >15000 deg2 at 98 and 150 GHz. For this analysis we adopt a blinding strategy to help avoid confirmation bias and, related to this, show numerous checks for systematic error done before unblinding. Using the likelihood for the cosmological analysis we constrain secondary sources of anisotropy and foreground emission, and derive a “CMB-only” spectrum that extends to ` = 4000. At large angular scales, foreground emission at 150 GHz is ∼1% of TT and EE within our selected regions and consistent with that found by Planck. Using the same likelihood, we obtain the cosmological parameters for ΛCDM for the ACT data alone with a prior on the optical depth of τ = 0.065 ± 0.015. ΛCDM is a good fit. The best-fit model has a reduced χ2 of 1.07 (PTE = 0.07) with H0 = 67.9 ± 1.5 km/s/Mpc. We show that the lensing BB signal is consistent with ΛCDM and limit the celestial EB polarization angle to ψP = −0.07◦ ±0.09◦. We directly cross correlate ACT with Planck and observe generally good agreement but with some discrepancies in TE. All data on which this analysis is based will be publicly released.

BackgroundAlthough several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.MethodsWe conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.ResultsA total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P

In a complex and dynamic environment, the brain flexibly adjusts its circuits to preferentially process behaviorally relevant information. Here, we investigated how the olfactory bulb copes with this demand by examining the plasticity of adult-born granule cells (abGCs). We found that learning of olfactory discrimination elevates odor responses of young abGCs and increases their apical dendritic spines. This plasticity did not occur in abGCs during passive odor experience nor in resident granule cells (rGCs) during learning. Furthermore, we found that feedback projections from the piriform cortex show elevated activity during learning, and activating piriform feedback elicited stronger excitatory postsynaptic currents in abGCs than rGCs. Inactivation of piriform feedback blocked abGC plasticity during learning, and activation of piriform feedback during passive experience induced learning-like plasticity of abGCs. Our work describes a neural circuit mechanism that uses adult neurogenesis to update a sensory circuit to flexibly adapt to new behavioral demands.

Methods for one-photon fluorescent imaging of calcium dynamics can capture the activity of hundreds of neurons across large fields of view at a low equipment complexity and cost. In contrast to two-photon methods, however, one-photon methods suffer from higher levels of crosstalk from neuropil, resulting in a decreased signal-to-noise ratio and artifactual correlations of neural activity. We address this problem by engineering cell-body-targeted variants of the fluorescent calcium indicators GCaMP6f and GCaMP7f. We screened fusions of GCaMP to natural, as well as artificial, peptides and identified fusions that localized GCaMP to within 50 μm of the cell body of neurons in mice and larval zebrafish. One-photon imaging of soma-targeted GCaMP in dense neural circuits reported fewer artifactual spikes from neuropil, an increased signal-to-noise ratio, and decreased artifactual correlation across neurons. Thus, soma-targeting of fluorescent calcium indicators facilitates usage of simple, powerful, one-photon methods for imaging neural calcium dynamics.

ObjectiveTo determine the association of self-selected walking step rate with worsening of cartilage damage in the patellofemoral (PF) joint and tibiofemoral (TF) joint compartments at a 2-year follow-up visit.MethodsThe Multicenter Osteoarthritis Study (MOST) is a prospective cohort of men and women with or at risk of knee osteoarthritis. Self-selected step rate was measured using an instrumented GAITRite walkway (CIR Systems) at the 60-month visit. Cartilage damage was semiquantitatively graded on magnetic resonance images at the 60- and 84-month visits in the medial and lateral PF and TF compartments. Step rate was divided into quartiles, and logistic regression was used to determine the association of step rate with the risk of worsening cartilage damage in men and women separately. Analyses were adjusted for age, body mass index, and knee injury/surgery.ResultsA total of 1,089 participants were included. Mean ± SD age was 66.9 ± 7.5 years, mean ± SD body mass index was 29.6 ± 4.7 kg/m2 , and 62.3% of the participants were women. Women with the lowest step rate had increased risk of lateral PF (risk ratio [RR] 2.1 [95% confidence interval (95% CI) 1.1-3.8]) and TF (RR 1.8 [95% CI 1.1-2.9]) cartilage damage worsening 2 years later compared to those with the highest step rate. Men with the lowest step rate had increased risk of medial TF cartilage damage worsening 2 years later (RR 2.1 [95% CI 1.1-3.9]).ConclusionLower step rate was associated with increased risk of cartilage damage worsening in the lateral PF and TF compartments in women and worsening medial TF joint damage in men. Future research is necessary to understand the influence of step rate manipulation on joint biomechanics in women and men.

Background: Developing context-specific, evidence-informed, and implementable injury-prevention programs is challenging. Women playing in the elite Australian Football League for Women are at high risk of serious knee injuries, and no specific injury-prevention program exists. The objective of the study was to describe the collaborative process used to create a context-specific injury-prevention program. Methods: A previously used intervention-development process was modified to incorporate a partnership with the sport's governing organization and focus on engaging program implementers. The Reach Effectiveness Adoption Implementation and Maintenance (RE-AIM) Sports Setting Matrix guided program development and implementation strategies. Results: The 7-step process, aligned with the RE-AIM Sports Setting Matrix, was applied to develop the injury-prevention program and was titled Prep to Play PRO. The steps were: (Step 1) gaining organizational support and establishing a project partnership; (Step 2) using research evidence and clinical experience; (Step 3) consulting content and context experts; (Step 4) engaging the organization, experts, program implementers, and end-users to concreate the intervention and develop implementation strategies; (Step 5) testing the intervention acceptability and feasibility; (Step 6) evaluating the intervention and implementation strategies against theory; and (Step 7) obtaining feedback from early implementers and end-users. Conclusion: Engaging critical stakeholders at multiple ecological levels (organization, team, and athlete) throughout program development and implementation planning support real-world use. The processes and activities described can guide future sports injury-prevention program development and implementation.

Zika virus (ZIKV) is a flavivirus primarily transmitted by Aedes species mosquitoes, first discovered in Africa in 1947, that disseminated through Southeast Asia and the Pacific Islands in the 2000s. The first ZIKV infections in the Americas were identified in 2014, and infections exploded through populations in Brazil and other countries in 2015/16. ZIKV infection during pregnancy can cause severe brain and eye defects in offspring, and infection in adults has been associated with higher risks of Guillain-Barré syndrome. We initiated a study to describe the natural history of Zika (the disease) and the immune response to infection, for which some results have been reported. In this paper, we identify ZIKV-specific CD4+ and CD8+ T cell epitopes that induce responses during infection. Two screening approaches were utilized: an untargeted approach with overlapping peptide arrays spanning the entire viral genome, and a targeted approach utilizing peptides predicted to bind human MHC molecules. Immunoinformatic tools were used to identify conserved MHC class I supertype binders and promiscuous class II binding peptide clusters predicted to bind 9 common class II alleles. T cell responses were evaluated in overnight IFN-γ ELISPOT assays. We found that MHC supertype binding predictions outperformed the bulk overlapping peptide approach. Diverse CD4+ T cell responses were observed in most ZIKV-infected participants, while responses to CD8+ T cell epitopes were more limited. Most individuals developed a robust T cell response against epitopes restricted to a single MHC class I supertype and only a single or few CD8+ T cell epitopes overall, suggesting a strong immunodominance phenomenon. Noteworthy is that many epitopes were commonly immunodominant across persons expressing the same class I supertype. Nearly all of the identified epitopes are unique to ZIKV and are not present in Dengue viruses. Collectively, we identified 31 immunogenic peptides restricted by the 6 major class I supertypes and 27 promiscuous class II epitopes. These sequences are highly relevant for design of T cell-targeted ZIKV vaccines and monitoring T cell responses to Zika virus infection and vaccination.

There is disagreement on how best to define and investigate fear. Nature Neuroscience asked Dean Mobbs to lead experts from the fields of human and animal affective neuroscience to discuss their viewpoints on how to define fear and how to move forward with the study of fear.

Context: Hip and groin injuries are common in field sports such as football, with measurement of hip strength and range of motion (ROM) recommended for assessment of these conditions. We aimed to report hip strength, hip ROM, and functional task performance in young elite Australian football athletes. Design: Cross-sectional study. Methods: Fifty-eight newly drafted Australian Football League athletes completed hip abduction, adduction, internal rotation, external rotation, and flexion strength testing with an adjustable stabilized or hand-held dynamometer. Hip internal rotation and external rotation, bent knee fall out, and ankle dorsiflexion ROM were also measured. Players completed hop for distance, side bridge, and star excursion balance functional tests. We compared findings between the dominant and nondominant limbs. Results: We found small deficits unlikely to be clinically meaningful in the dominant limb for hip abduction and adduction strength, and a small deficit in the nondominant limb for external rotation strength and side bridge time. Athletes had lower hip internal rotation (mean difference 2.56°; 95% confidence interval, 0.87 to 4.26) and total rotation ROM (2.03°; 95% confidence interval, 0.06 to 4.01) on the dominant limb. Conclusions: There were no meaningful differences between dominant and nondominant limbs for hip strength, ROM, or functional tests. Our results may be used for benchmarking young male Australian football athletes when targeting optimal strength and returning from injury. [ABSTRACT FROM AUTHOR]

Computer vision has emerged as a powerful tool to elevate behavioral research. This protocol describes a computer vision machine learning pipeline called AlphaTracker, which has minimal hardware requirements and produces reliable tracking of multiple unmarked animals, as well as behavioral clustering. AlphaTracker pairs a top-down pose-estimation software combined with unsupervised clustering to facilitate behavioral motif discovery that will accelerate behavioral research. All steps of the protocol are provided as open-source software with graphic user interfaces or implementable with command-line prompts. Users with a graphical processing unit (GPU) can model and analyze animal behaviors of interest in less than a day. AlphaTracker greatly facilitates the analysis of the mechanism of individual/social behavior and group dynamics.

Child-led research is gaining increasing attention. Such research involves children leading throughout the research process, from research design to dissemination. Child-led research has tested adult-centric research assumptions, with debates in the literature about researchers’ expertise and responsibilities. If these debates are testing for child-led research undertaken with older children and young people, they are even more so for young children below school-starting age. This article examines child-led research undertaken in a Froebelian early years setting, over 11 months, with 36 children aged between 2 and 5 years, from the adult facilitators’ perspectives. The article utilises the research’s documentation, including mind maps, photographs and story books, songs and video recordings, and an interview undertaken with the facilitating early years practitioner and supporting academic. Learning from this, the article challenges the assumption, in much of the literature on child-led research, that adults need to transmit their knowledge of research methods to children. Instead, a ‘slow pedagogy’ can build on children’s own knowledge, collectively, with time to come to research understandings. The article concludes that child-led research is feasible with young children, but the research process can include or exclude certain forms of children’s communication, making some children more ‘competent’ to undertake research than others.

Objective The study objective was to determine the relationship of magnetic resonance imaging (MRI)‐detected features of patellofemoral joint osteoarthritis to pain and functional outcomes. Methods We sampled 1,099 participants from the 60‐month visit of the Multicenter Osteoarthritis Study (mean ± SD age: 66.8 ± 7.5 years; body mass index: 29.6 ± 4.8; 65% female). We determined the prevalence of MRI‐detected features of patellofemoral joint osteoarthritis (eg, cartilage damage, bone marrow lesions, and osteophytes) and assessed the relationship between these features and knee pain severity, knee pain on stairs, chair stand time, and walking less than 6,000 steps per day. We evaluated the relationship of MRI features to each outcome using logistic and linear regression, adjusting for potential covariates. Results Participants with cartilage damage in 3‐4 subregions had the highest mean pain severity (22.0/100; 95% confidence interval [CI]: 17.6‐26.4 mm). They also showed higher odds of having at least mild pain on stairs (odds ratio [OR]: 3.3; 95% CI: 1.7‐6.5) and of walking less than 6,000 steps per day (OR: 2.3; 95% CI: 1.1‐4.4) compared with those without cartilage damage. Participants with bone marrow lesions in 3‐4 subregions had higher odds of at least mild pain on stairs than those without (OR: 3.3; 95% CI: 2.2‐5.2). Participants with osteophytes in 3‐4 subregions also had higher odds of walking less than 6,000 steps/day (OR 2.1, 95% CI: 1.3‐3.5, respectively). Conclusion MRI‐detected features of osteoarthritis of the patellofemoral joint are related to pain and functional performance. This knowledge highlights the need to develop treatments for those with patellofemoral joint osteoarthritis to improve pain and maximize function.

Objective Describe the co-design process and learnings related to developing the web-based Translating Research Evidence and Knowledge (TREK) ‘My Knee’ education and self-management toolkit for people with knee osteoarthritis. Co-design process Stage (i): Understand and define; systematically reviewed education interventions in published trials; appraised web-based information about knee osteoarthritis; and used concept mapping to identify education priorities of people with knee osteoarthritis and physiotherapists. Stage (ii): Prototype; created a theory-, guideline- and evidence-informed toolkit. Stage (iii): Test and iterate; completed three co-design workshops with end-users (i.e., people with knee osteoarthritis and health professionals); plus an expert review. Results The toolkit is available at myknee.trekeducation.org. Stage (i) identified the need for more accurate and co-designed resources to address broad education needs generated during concept mapping, including guidance on surgery, dispelling common misconceptions and facilitating engagement with exercise therapy and weight management. A theory- and research-informed prototype was created in Stage (ii) to address broad learning and education needs. Stage (iii) co-design workshops ( n = 15 people with osteoarthritis and n = 9 health professionals) informed further content creation and refinement, alongside improvements to optimise usability. Expert opinion review ( n = 8) further refined accuracy and usability. Conclusions The novel co-design methodology employed to create the TREK ‘My Knee’ toolkit facilitated the alignment of the content and usability to meet the broad education needs of people with knee osteoarthritis and health professionals. This toolkit aims to improve and facilitate engagement with guideline-recommended first-line care for people with knee osteoarthritis. Future work will determine its effectiveness in improving clinical outcomes in this population.

Introduction Running is one of the most popular recreational activities worldwide, due to its low cost and accessibility. However, little is known about the impact of running on knee joint health in runners with and without a history of knee surgery. The primary aim of this longitudinal cohort study is to compare knee joint structural features on MRI and knee symptoms at baseline and 4-year follow-up in runners with and without a history of knee surgery. Secondary aims are to explore the relationships between training load exposures (volume and/or intensity) and changes in knee joint structure and symptoms over 4 years; explore the relationship between baseline running biomechanics, and changes in knee joint structure and symptoms over 4 years. In addition, we will explore whether additional variables confound, modify or mediate these associations, including sex, baseline lower-limb functional performance, knee muscle strength, psychological and sociodemographic factors.Methods and analysis A convenience sample of at least 200 runners (sex/gender balanced) with (n=100) and without (n=100) a history of knee surgery will be recruited. Primary outcomes will be knee joint health (MRI) and knee symptoms (baseline; 4 years). Exposure variables for secondary outcomes include training load exposure, obtained daily throughout the study from wearable devices and three-dimensional running biomechanics (baseline). Additional variables include lower limb functional performance, knee extensor and flexor muscle strength, biomarkers, psychological and sociodemographic factors (baseline). Knowledge and beliefs about osteoarthritis will be obtained through predefined questions and semi-structured interviews with a subset of participants. Multivariable logistic and linear regression models, adjusting for potential confounding factors, will explore changes in knee joint structural features and symptoms, and the influence of potential modifiers and mediators.Ethics and dissemination Approved by the La Trobe University Ethics Committee (HEC-19524). Findings will be disseminated to stakeholders, peer-review journals and conferences.

Introduction Anterior cruciate ligament injury and reconstruction (ACLR) is often associated with pain, functional loss, poor quality of life and accelerated knee osteoarthritis development. The effectiveness of interventions to enhance outcomes for those at high risk of early-onset osteoarthritis is unknown. This study will investigate if SUpervised exercise-therapy and Patient Education Rehabilitation (SUPER) is superior to a minimal intervention control for improving pain, function and quality of life in young adults with ongoing symptoms following ACLR.Methods and analysis The SUPER-Knee Study is a parallel-group, assessor-blinded, randomised controlled trial. Following baseline assessment, 184 participants aged 18–40 years and 9–36 months post-ACLR with ongoing symptoms will be randomly allocated to one of two treatment groups (1:1 ratio). Ongoing symptoms will be defined as a mean score of