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Rocky asteroids and planets display nucleosynthetic isotope variations that are attributed to the heterogeneous distribution of stardust from different stellar sources in the solar protoplanetary disk. Here we report new high-precision palladium isotope data for six iron meteorite groups. The palladium data display smaller nucleosynthetic isotope variations than the more refractory neighbouring elements. Based on this observation, we present a model in which thermal destruction of interstellar dust in the inner Solar System results in an enrichment of s -process-dominated stardust in regions closer to the Sun. We propose that stardust is depleted in volatile elements due to incomplete condensation of these elements into dust around asymptotic giant branch stars. This led to the smaller nucleosynthetic variations for Pd reported here and the lack of such variations for more volatile elements. The smaller magnitude variations measured in heavier refractory elements suggest that material from high-metallicity asymptotic giant branch stars is the dominant source of stardust in the Solar System. These stars produce fewer heavy s -process elements (proton number Z  ≥ 56) compared with the bulk Solar System composition. Dust in the Solar System originates primarily in two locations: the interstellar medium and stellar outflows. On the basis of measurements of palladium isotopes in iron meteorites, Ek et al. suggest that the interstellar component was destroyed in the inner Solar System, revealing an enhancement of s -process isotopes from stardust.

Rapid cooling of planetesimal cores has been inferred for several iron meteorite parent bodies on the basis of metallographic cooling rates, and linked to the loss of their insulating mantles during impacts. However, the timing of these disruptive events is poorly constrained. Here, we used the short-lived 107 Pd– 107 Ag decay system to date rapid core cooling by determining Pd–Ag ages for iron meteorites. We show that closure times for the iron meteorites equate to cooling in the time frame ~7.8–11.7 Myr after calcium–aluminium-rich inclusion formation, and that they indicate that an energetic inner Solar System persisted at this time. This probably results from the dissipation of gas in the protoplanetary disk, after which the damping effect of gas drag ceases. An early giant planet instability between 5 and 14 Myr after calcium–aluminium-rich inclusion formation could have reinforced this effect. This correlates well with the timing of impacts recorded by the Pd–Ag system for iron meteorites. Impact-related cooling of asteroids happened between 7.8 and 11.7 million years after Solar System formation due to dynamical forcing following the gas disk dissipation, an early giant planet instability, or a combination of the two.

Rapid cooling of planetesimal cores has been inferred for several iron meteorite parent bodies based on metallographic cooling rates, and linked to the loss of their insulating mantles during impacts. However, the timing of these disruptive events is poorly constrained. Here, we used the short-lived 107Pd / 107Ag decay system to date rapid core cooling by determining Pd-Ag ages for iron meteorites. We show closure times for the iron meteorites equate to cooling in the timeframe ~7.8 to 11.7 Myr after CAI, and indicate that an energetic inner Solar System persisted at this time. This likely results from the dissipation of gas in the protoplanetary disk, after which the damping effect of gas drag ceases. An early giant planet instability between 5 and 14 Myr after CAI could have reinforced this effect. This correlates well with the timing of impacts recorded by the Pd Ag system for iron meteorites.

Rocky asteroids and planets display nucleosynthetic isotope variations that are attributed to the heterogeneous distribution of stardust from different stellar sources in the solar protoplanetary disk. Here we report new high precision palladium isotope data for six iron meteorite groups, which display smaller nucleosynthetic isotope variations than the more refractory neighbouring elements. Based on this observation we present a new model in which thermal destruction of interstellar medium dust results in an enrichment of s-process dominated stardust in regions closer to the Sun. We propose that stardust is depleted in volatile elements due to incomplete condensation of these elements into dust around asymptotic giant branch (AGB) stars. This led to the smaller nucleosynthetic variations for Pd reported here and the lack of such variations for more volatile elements. The smaller magnitude variations measured in heavier refractory elements suggest that material from high-metallicity AGB stars dominated stardust in the Solar System. These stars produce less heavy s-process elements compared to the bulk Solar System composition.

The short-lived \\(^{182}\\)Hf-\\(^{182}\\)W decay system is a powerful chronometer for constraining the timing of metal-silicate separation and core formation in planetesimals and planets. Neutron capture effects on W isotopes, however, significantly hamper the application of this tool. In order to correct for neutron capture effects, Pt isotopes have emerged as a reliable in-situ neutron dosimeter. This study applies this method to IAB iron meteorites, in order to constrain the timing of metal segregation on the IAB parent body. The \\(\\epsilon^{182}\\)W values obtained for the IAB iron meteorites range from -3.61 \\(\\pm\\) 0.10 to -2.73 \\(\\pm\\) 0.09. Correlating \\(\\epsilon^{\\mathrm{i}}\\)Pt with \\(^{182}\\)W data yields a pre-neutron capture \\(^{182}\\)W of -2.90 \\(\\pm\\) 0.06. This corresponds to a metal-silicate separation age of 6.0 \\(\\pm\\) 0.8 Ma after CAI for the IAB parent body, and is interpreted to represent a body-wide melting event. Later, between 10 and 14 Ma after CAI, an impact led to a catastrophic break-up and subsequent reassembly of the parent body. Thermal models of the interior evolution that are consistent with these estimates suggest that the IAB parent body underwent metal-silicate separation as a result of internal heating by short-lived radionuclides and accreted at around 1.4 \\(\\pm\\) 0.1 Ma after CAIs with a radius of greater than 60 km.

In a trial in the United Kingdom, patients with depression who were being treated in primary care practices and who felt well enough to discontinue antidepressant therapy were randomly assigned to maintain their current antidepressant therapy or to discontinue such therapy. By 1 year, relapse had occurred in 39% of patients in the maintenance group and in 56% in the discontinuation group.

Background Knee trauma permanently elevates one’s risk for knee osteoarthritis. Despite this, people at-risk of post-traumatic knee osteoarthritis rarely seek or receive care, and accessible and efficacious interventions to promote knee health after injury are lacking. Exercise can ameliorate some mechanisms and independent risk factors for osteoarthritis and, education and action-planning improve adherence to exercise and promote healthy behaviours. Methods To assess the efficacy of a virtually-delivered, physiotherapist-guided exercise-based program (SOAR) to improve knee health in persons discharged from care after an activity-related knee injury, 70 people (16–35 years of age, 12–48 months post-injury) in Vancouver Canada will be recruited for a two-arm step-wedged assessor-blinded delayed-control randomized trial. Participants will be randomly allocated to receive the intervention immediately or after a 10-week delay. The program consists of 1) one-time Knee Camp (group education, 1:1 individualized exercise and activity goal-setting); 2) weekly individualized home-based exercise and activity program with tracking, and; 3) weekly 1:1 physiotherapy-guided action-planning with optional group exercise class. Outcomes will be measured at baseline, 9- (primary endpoint), and 18-weeks. The primary outcome is 9-week change in knee extension strength (normalized peak concentric torque; isokinetic dynamometer). Secondary outcomes include 9-week change in moderate-to-vigorous physical activity (accelerometer) and self-reported knee-related quality-of-life (Knee injury and OA Outcome Score subscale) and self-efficacy (Knee Self Efficacy Scale). Exploratory outcomes include 18-week change in primary and secondary outcomes, and 9- and 18- week change in other components of knee extensor and flexor muscle function, hop function, and self-reported symptoms, function, physical activity, social support, perceived self-care and kinesiophobia. Secondary study objectives will assess the feasibility of a future hybrid effectiveness-implementation trial protocol, determine the optimal intervention length, and explore stakeholder experiences. Discussion This study will assess the efficacy of a novel, virtually-delivered, physiotherapist-guided exercise-based program to optimize knee health in persons at increased risk of osteoarthritis due to a past knee injury. Findings will provide valuable information to inform the management of osteoarthritis risk after knee trauma and the conduct of a future effectiveness-implementation trial. Trial registration Clinicaltrials.gov reference: NTC04956393. Registered August 5, 2021, https://clinicaltrials.gov/ct2/show/NCT04956393?term=SOAR&cond=osteoarthritis&cntry=CA&city=Vancouver&draw=2&rank=1

Monkeypox virus has recently infected more than 88 000 people, raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side-effects than previous smallpox vaccines and has shown immunogenicity against monkeypox in animal models. This study aims to elucidate human immune responses to JYNNEOS vaccination compared with mpox-induced immunity. Peripheral blood mononuclear cells and sera were obtained from ten individuals vaccinated with one or two doses of JYNNEOS and six individuals diagnosed with monkeypox virus infection. Samples were obtained from seven individuals before vaccination to serve as a baseline. We examined the polyclonal serum (ELISA) and single B-cell (heavy chain gene and transcriptome data) antibody repertoires and T-cell responses (activation-induced marker and intracellular cytokine staining assays) induced by the JYNNEOS vaccine versus monkeypox virus infection. All participants were men between the ages of 21 and 60 years, except for one woman in the group of mpox-convalescent individuals, and none had previous orthopoxvirus exposure. All mpox cases were mild. Vaccinee samples were collected 6–33 days after the first dose and 5–40 days after the second dose. Mpox-convalescent samples were collected 20–102 days after infection. In vaccine recipients, gene-level plasmablast and antibody responses were negligible and sera displayed moderate binding to recombinant orthopoxviral proteins (A29L, A35R, E8L, A30L, A27L, A33R, B18R, and L1R) and native proteins from the 2022 monkeypox outbreak strain. By contrast, recent monkeypox virus infection (within 20–102 days) induced robust serum antibody responses to monkeypox virus proteins and to native monkeypox virus proteins from a viral isolate obtained during the 2022 outbreak. JYNNEOS vaccine recipients presented robust orthopoxviral CD4+ and CD8+ T-cell responses. Infection with monkeypox virus resulted in robust B-cell and T-cell responses, whereas immunisation with JYNNEOS elicited more robust T-cell responses. These data can help to inform vaccine design and policies for preventing mpox in humans. National Cancer Institute (National Institutes of Health), National Institute of Allergy and Infectious Diseases (National Institutes of Health), and Icahn School of Medicine.

Background People who tear their anterior cruciate ligament and have reconstruction surgery (ACLR) are at elevated risk of inactivity, obesity, and early-onset knee osteoarthritis. Consensus recommendations to prevent post-traumatic knee osteoarthritis include person-centered education and exercise-based treatments. The effectiveness of these recommendations is unknown. This study will assess if a digital education and exercise therapy intervention is superior to minimal intervention for improving knee-related symptoms, function, and quality of life in young people after ACLR. Methods The Stop OsteoARthritis (SOAR) study is a parallel, two-arm, assessor-blinded, superiority, hybrid effectiveness-implementation type 1 randomized controlled trial. After baseline testing, 166 participants aged 16–35 years, 9–36 months past, a first-time ACLR with ongoing symptoms will be randomly allocated to one of two treatment groups (1:1 ratio, stratified by sex). Ongoing symptoms will be defined as not meeting a Patient Acceptable Symptom State (PASS) on the averaged Knee injury and Osteoarthritis Outcome Score pain, symptoms function in sport and recreation, and quality-of-life subscales (KOOS 4  < 79). Participants randomized to the experimental intervention will receive a digital (remote videoconferencing) 6-month program of group-based learning, individualized weekly home-based exercise therapy and physical activity program with tracking, and 1:1 physiotherapist-guided counseling. Participants randomized to the minimal intervention control group will receive an educational recording, best-practice guide for ACLR rehabilitation, one videoconferencing session, and tracking. The primary effectiveness outcome is the between-group difference in KOOS 4 change from baseline to 6-months, with secondary endpoints at 12- and 24months. Secondary effectiveness outcomes include differences in the change of individual KOOS subscale scores, proportions of participants achieving KOOS subscale PASS scores, perceived self-management, and MRI features of knee OA. We will also assess secondary implementation (perceived barriers and facilitators of SOAR delivery), secondary efficiency (incremental cost-utility ratio), and exploratory outcomes. Missing data will be imputed and blinded intention-to-treat analyses performed. Discussion By assessing the effect, implementation, and efficiency of a digital education and exercise-based intervention designed to improve the knee health of young people at increased risk of knee osteoarthritis, this study will provide a basis for future scale-up to help curb the mounting burden of osteoarthritis. Trial registration ClinicalTrials.gov NCT06195423. Registered on December 22, 2023.

The genetics of multiple sclerosis Multiple sclerosis is a disease of the central nervous system that involves interplay between inflammation and neurodegeneration. Despite intensive study, much of the genetic architecture underlying susceptibility to the disease remains to be defined. A large, international, collaborative genome-wide association study involving almost 10,000 cases, all of European descent, has confirmed about 20 previously reported multiple-sclerosis-linked regions of DNA, and identified an additional 29 novel susceptibility loci. Further analysis implicates the differentiation of T-helper cells as particularly relevant to the pathogenesis of this disease. Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability 1 . Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals 2 , 3 , and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk 4 . Modestly powered genome-wide association studies (GWAS) 5 , 6 , 7 , 8 , 9 , 10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility 11 . Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.