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To explore the benefits of a brief autism education intervention on peer engagement and inclusion of autistic children at day camps. A convergent, parallel, two-arm (intervention/no intervention), non-randomized, mixed-methods design was used. The individualized, peer-directed, 5--10 min intervention included four components: (1) diagnostic label, (2) description and purpose of unique behaviors, (3) favorite activities and interests, and (4) strategies to engage. A timed-interval behavior-coding system was used to evaluate engagement between each autistic camper and their peers based on videos taken at camp (days 1, 2, 5). Interviews with campers and camp staff explored why changes in targeted outcomes may have occurred. Percent intervals in which the autistic campers were jointly engaged with peers improved in the intervention group (n = 10) and did not change in the control group (n = 5). A large between group intervention effect occurred by day 5 (Z = - 1.942, [eta-squared] = 0.29). Interviews (5 autistic campers, 34 peers, 18 staff) done on the last day of camp in the intervention group garnered three themes: (1) "Changed behavioral attribution," (2) "Knowledge facilitates understanding and engagement," and (3) "(Mis)perceptions of increased inclusion." A brief educational intervention that includes individualized explanatory information and strengths-based strategies might improve peers' understanding of and social engagement with autistic children in community programs such as camps.

Members of a prominent school counseling organization were surveyed to measure their perceived responsibility, self-efficacy, and performance related to increasing students' college knowledge. The purposes of this study were to: (a) understand what level do school counselors believe they bear the responsibility to increase students' college knowledge, (b) determine how efficacious do counselors feel in providing college knowledge to students, and (c) determine the level that school counselors are providing students college knowledge information. There were significant differences across those domains. With the professional expectation that a school counselor's role is to facilitate the increase of college knowledge for students, there are discrepancies between the expectation and the view of the school counselor. Based on the results of our study, we concluded that additional support and guidance for school counselors facilitating college knowledge would be beneficial to staff and students.

Small nucleolar RNAs (snoRNAs) are a class of conserved noncoding RNAs forming complexes with proteins to catalyse site-specific modifications on ribosomal RNA. Besides this canonical role, several snoRNAs are now known to regulate diverse levels of gene expression. While these functions are carried out in trans by mature snoRNAs, evidence has also been emerging of regulatory roles of snoRNAs in cis, either within their genomic locus or as longer transcription intermediates during their maturation. Herein, we review recent findings that snoRNAs can interact in cis with their intron to regulate the expression of their host gene. We also explore the ever-growing diversity of longer host-derived snoRNA extensions and their functional impact across the transcriptome. Finally, we discuss the role of snoRNA duplications into forging these new layers of snoRNA-mediated regulation, as well as their involvement in the genomic imprinting of their host locus.

Abstract Since 2011, holopelagic Sargassum have been massively stranding in the coastal environments of the Caribbean Islands inducing damages to coastal ecosystems, public health and the economy. To limit the risks associated with Sargassum stranding, floating barriers with nets can be placed in front of sensitive areas, to divert Sargassum away from the coast. To evaluate the potential transfer of metallic trace element (MTE) from Sargassum to adjacent marine life, seagrasses (Halophila stipulacea, Thalassia testidinum) and urchin (Lytechinus variegatus) were sampled, both close (0 m) and far (200 m) from barriers installed during 4 years in two bays: Baie Cayol (BC) and Cap Est (CE) in Martinique (FWI). A bay without barriers Baie-Tresor (BT) was also sampled in order to compare the effects of Sargassum accumulated in a natural environment versus an environment with floating barriers. The short-term effects of barriers were evaluated by measuring the evolution of MTE after four days, in the algae (Dictyota spp.), located close to Sargassum accumulations. All sampling was realized during two periods of active (July 2021) and reduced (January 2022) Sargassum stranding. The measured concentrations of 19 metal(loid)s trace elements revealed that the proximity of Sargassum to the barriers did not increase MTE concentration. The absence of increase in MTE was observed all sites (BT, BC and CE) and during periods of limited and important Sargassum stranding. Similarly, translocations of Dictyota close to Sargassum accumulations did not reveal any increase in MTE concentrations in the algae after 4 days. The present study suggests that the use of barriers to manage Sargassum stranding would not constitute an important threat of MTE contamination of marine environments.

Abstract Massive stars are a major source of chemical elements in the cosmos, ejecting freshly produced nuclei through winds and core-collapse supernova explosions into the interstellar medium. Among the material ejected, long-lived radioisotopes, such as 60Fe (iron) and 26Al (aluminum), offer unique signs of active nucleosynthesis in our galaxy. There is a long-standing discrepancy between the observed 60Fe/26Al ratio by γ-ray telescopes and predictions from supernova models. This discrepancy has been attributed to uncertainties in the nuclear reaction networks producing 60Fe, and one reaction in particular, the neutron-capture on 59Fe. Here we present experimental results that provide a strong constraint on this reaction. We use these results to show that the production of 60Fe in massive stars is higher than previously thought, further increasing the discrepancy between observed and predicted 60Fe/26Al ratios. The persisting discrepancy can therefore not be attributed to nuclear uncertainties, and points to issues in massive-star models.

Abstract Northern regions are warming faster than the rest of the globe. It is difficult to predict ecosystem responses to warming because the thermal sensitivity of their biophysical components varies. Here, we present an analysis of the authors’ expert judgment regarding the sensitivity of six ecosystem components – permafrost, peatlands, lakes, snowpack, vegetation, and endothermic vertebrates – across northern landscapes ranging from boreal to polar biomes. We identified 28 discontinuous component states across a 3700 km latitudinal gradient in northeastern North America and quantified sensitivity as the transition time from an initial to a contrasting state following a theoretical step change increase in mean annual air temperature of 5 °C. We infer that multiple interconnected state shifts are likely to occur within a narrow subarctic latitudinal band at timescales of 10 to more than 100 years, and response times decrease with latitude. Response times differ between components and across latitudes, which is likely to impair the integrity of ecosystems.

Interventions are strongly recommended for preschoolers experiencing participation difficulties in their daily life, regardless of whether or not they have a diagnosis. Best practices recommend that interventions should include the child's significant adults and be delivered in the child's environments. Occupational Performance Coaching (OPC) has shown promising results in improving children's participation by supporting significant adults of school-aged children either with cerebral palsy or without a definite diagnosis, and of preschoolers with developmental coordination disorder. However, this approach has not yet been studied for preschoolers without a definite diagnosis. A multiple case study design was used to explore the interventions's feasibility for this population. Eight parents and three early childhood educators received OPC to help seven children (cases). Intra- and inter-case analyses were conducted to document the effects of the intervention on the children's participation and the caregivers' goals. All children had difficulties in their daily life, and most presented motor, sensory, behavioral and/or adaptive difficulties. Improvements in children's participation and significant adults' satisfaction as well as goal attainment were observed in most cases. Improvements were generally maintained at a three-month follow-up. These findings support the feasibility of OPC for significant adults of preschoolers with participation difficulties in daily life but no definite diagnosis.

Abstract Alphaviruses, such as chikungunya virus (CHIKV), are mosquito-borne viruses that represent a significant threat to human health due to the current context of global warming. Efficient alphavirus infection relies on the activity of the non-structural protein 3 (nsP3), a puzzling multifunctional molecule whose role in infection remains largely unknown. NsP3 is a component of the plasma membrane-bound viral RNA replication complex (vRC) essential for RNA amplification and is also found in large cytoplasmic aggregates of unknown function. Here, we report the cryo-electron microscopy (cryo-EM) structure of the CHIKV nsP3 at 2.35 Å resolution. We show that nsP3 assembles into tubular structures made by a helical arrangement of its alphavirus unique domain (AUD). The nsP3 helical scaffolds are consistent with crown structures found on tomographic reconstructions of the mature viral RCs. In addition, nsP3 helices assemble into cytoplasmic granules organized in a network of tubular structures that contain viral genomic RNA and capsid as well as host factors required for productive infection. Structure-guided mutagenesis identified residues that prevent or disturb nsP3 assemblies, resulting in impaired viral replication or transcription. Altogether, our results reveal an unexpected nsP3-dependent molecular organization essential for different phases of alphavirus infection.

Abstract Objective Improving care transitions for older adults can reduce emergency department (ED) revisits, and the strain placed upon caregivers. We analyzed whether caregivers felt a change in burden following a care transition, and what may be improved to reduce it. Methods This mixed-methods observational study nested within LEARNING WISDOM included caregivers of older patients who experienced an ED care transition. Burden was collected with the brief Zarit Burden Interview (ZBI-12), and caregivers also commented on the care transition. A qualitative coding scheme of patient care transitions was created to reflect themes important to caregivers. Comments were randomly analyzed until saturation and themes were extracted from the data. We followed both the SRQR and STROBE checklists. Results Comments from 581 caregivers (mean age (SD) 64.5 (12.3), 68% women) caring for patients (mean age (SD) 77.2 (7.54), 48% women) were analyzed. Caregivers overwhelmingly reported dissatisfaction and unmet service expectations, particularly with home care and domestic help. Communication and follow-up from the ED emerged as an area for improvement. Caregivers who reported an increased level of burden following a patient’s care transition had significantly higher ZBI scores than caregivers who self-reported stable burden levels. Conclusion Caregivers with increasing, stable, and improved levels of subjective burden all reported areas for improvement in the care transition process. Themes centering on the capacity to live at home and inadequate communication were most frequently mentioned and may represent serious challenges to caregivers. Addressing these challenges could improve both caregiver burden and ED care transitions.

Abstract Acute respiratory distress syndrome is a severe lung condition resulting from various causes, with life-threatening consequences that necessitate intensive care. The phenomenon can be modeled in preclinical models, notably through the use of lipopolysaccharide (LPS) instillation in mice. The phenotype induced closely recapitulates the human syndrome, including pulmonary edema, leukocyte infiltration, acute inflammation, impaired pulmonary function, and histological damage. However, the experimental designs using LPS instillations are extremely diverse in the literature. This highly complicates the interpretation of the induced phenotype chronology for future study design and hinders the proper identification of the optimal time frame to assess different readouts. Therefore, the definition of the treatment window in relation to the beginning of the disease onset also presents a significant challenge to address questions or test compound efficacy. In this context, the temporality of the different readouts usually measured in the model was evaluated in both normal and neutrophil-depleted male C57bl/6 mice using LPS-induction to assess the best window for proper readout evaluation with an optimal dynamic response range. Ventilation parameters were evaluated by whole-body plethysmography and neutrophil recruitment were evaluated in bronchoalveolar lavage fluids and in lung tissues directly. Imaging evaluation of myeloperoxidase along with activity in lung lysates and fluids were compared, along with inflammatory cytokines and lung extravasation by enzyme-linked immunoassays. Moreover, dexamethasone, the gold standard positive control in this model, was also administered at different times before and after phenotype induction to assess how kinetics affected each parameter. Overall, our data demonstrate that each readout evaluated in this study has a singular kinetic and highlights the key importance of the timing between ARDS phenotype and treatment administration and/or analysis. These findings also strongly suggest that analyzes, both in-life and post-mortem should be conducted at multiple time points to properly capture the dynamic phenotype of the LPS-ARDS model and response to treatment.

Abstract Background Advanced head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, and new treatment options are needed. Combining immunotherapies with differing mechanisms of action may enhance clinical benefits compared with single-agent immunotherapy. Epacadostat, an indoleamine 2,3 dioxygenase 1 inhibitor, plus pembrolizumab, a PD-1 inhibitor, showed promising activity in advanced HNSCC in the phase 1/2 KEYNOTE-037/ECHO-202 trial. Methods KEYNOTE-669/ECHO-304 is a randomized, open-label, phase 3 study evaluating the efficacy and safety of pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen (cetuximab with a platinum [carboplatin or cisplatin] and 5-fluorouracil) in recurrent/metastatic (R/M) HNSCC. Participants had no prior systemic therapy for R/M HNSCC and were randomly assigned (2:1:2) to pembrolizumab 200 mg intravenously every 3 weeks plus epacadostat 100 mg orally twice daily, pembrolizumab monotherapy, or EXTREME. The primary endpoint was objective response rate (ORR; investigator assessment). Secondary endpoints were safety and tolerability. Change in serum kynurenine was an exploratory endpoint. Study enrollment was discontinued early as a strategic decision on May 2, 2018, and response assessment was discontinued after first on-study imaging assessment at week 9. Data cut-off was January 17, 2019. Results Between December 1, 2017, and May 2, 2018, 89 patients were randomly allocated to pembrolizumab plus epacadostat (n = 35), pembrolizumab monotherapy (n = 19), or EXTREME (n = 35). ORR (95% CI) was 31% (17%–49%) for pembrolizumab plus epacadostat, 21% (6%–46%) for pembrolizumab monotherapy, and 34% (19%–52%) for EXTREME. Treatment-related adverse events (TRAEs) occurred in 82% (n = 28) of patients receiving pembrolizumab plus epacadostat, 63% (n = 12) receiving pembrolizumab monotherapy, and 100% (n = 34) receiving EXTREME. Grade 3–4 TRAEs occurred in 24% (n = 8) of patients receiving pembrolizumab plus epacadostat, 16% (n = 3) receiving pembrolizumab monotherapy, and 82% (n = 28) receiving EXTREME. No deaths occurred due to AEs. Pembrolizumab plus epacadostat treatment reduced kynurenine levels but not to that of healthy subjects. Conclusions Pembrolizumab plus epacadostat and pembrolizumab monotherapy provided a similar response rate to EXTREME and demonstrated a manageable safety profile in patients with R/M HNSCC. Trial registration NCT03358472. Date of trial registration: November 30, 2017.

The desire to broaden participation and increase campus diversity requires more than simply recruiting students of color. Faculty members' education equity mindset may be useful for determining their motivation to provide students with opportunities to achieve at their highest capacity. The extent to which faculty members think about inclusion and equity and act on those thoughts reflects the strength of their education equity mindset. To begin filling a gap in the literature, we engaged in a cross-section methodology, collecting quantitative and qualitative survey data from 180 faculty members working at four-year institutions to document their education equity mindset and associated teaching practices. We found the faculty members held a moderate education equity mindset, with differences by gender, discipline, years in higher education, number of students taught, age, and level of instruction. Our findings have implications for preparing faculty members and the focus of professional development provided to faculty members.

Arctic and subarctic landscapes have unique hydrological and limnological features and are now experiencing rapid change due to climate warming and permafrost thaw. The highly abundant lakes, ponds, and rivers across these landscapes play an increasingly important role in global biogeochemical cycles and are sentinels of environmental changes. However, studying these remote waters poses challenges for both in situ sampling and remote-sensing analysis. Here we developed a synergistic remote-sensing strategy that combined PlanetScope and Sentinel-2 satellite data to estimate limnicity (water fraction per land surface), limnodensity (density of water bodies), and limnodiversity (optical diversity of water bodies) along a boreal forest-tundra transect, from the non-permafrost to the continuous permafrost zones of western Nunavik (Subarctic Canada). Our analyses show that this region hosts 335,281 water bodies, around 90% in the 0.0001 to 0.01 km2 size range. In bedrock outcrops, large water bodies were mostly associated with glacially carved depressions (higher limnicity). In contrast, small water bodies were predominately found in sedimentary infills along valleys (higher limnodensity). The discontinuous permafrost zone had the highest limnodensity and limnodiversity. This was likely due to permafrost thaw (thermokarst), particularly the collapse, subsidence, and erosion of palsas (organic permafrost mounds), resulting in ponds with black- and brown-colored waters, and lithalsas (mineral permafrost mounds), resulting in ponds with brown, light-brown, and sometimes white-colored waters. Some of these limnodense and limnodiverse landscapes, although covering only 2 to 7% of the total area of the study region, contained over one-third (34%) of the total number of water bodies, 97% of which were

Objectives Our primary objective was to assess the association between symptoms at the time of surgery and postoperative pulmonary complications and mortality in patients with COVID-19. Our secondary objective was to compare postoperative outcomes between patients who had recovered from COVID-19 and asymptomatic patients and explore the effect of the time elapsed between infection and surgery in the former. Our hypotheses were that symptomatic patients had a higher risk of pulmonary complications, whereas patients who had recovered from the infection would exhibit outcomes similar to those of asymptomatic patients.Background Managing COVID-19-positive patients requiring surgery is complex due to perceived heightened perioperative risks. However, Canadian data in this context remains scarce.Design To address this gap, we conducted a multicentre observational cohort study.Setting Across seven hospitals in the province of Québec, the Canadian province was most affected during the initial waves of the pandemic.Participants We included adult surgical patients with either active COVID-19 at the time of surgery or those who had recovered from the disease, from March 22, 2020 to April 30, 2021.Outcomes We evaluated the association between symptoms or recovery time and postoperative pulmonary complications and hospital mortality using multivariable logistic regression and Cox models. The primary outcome was a composite of any postoperative pulmonary complication (atelectasis, pneumonia, acute respiratory distress syndrome and pneumothorax). Our secondary outcome was hospital mortality, assessed from the date of surgery up to hospital discharge.Results We included 105 patients with an active infection (47 were symptomatic and 58 were asymptomatic) at the time of surgery and 206 who had recovered from COVID-19 prior to surgery in seven hospitals. Among patients with an active infection, those who were symptomatic had a higher risk of pulmonary complications (OR 3.19, 95% CI 1.12 to 9.68, p=0.03) and hospital mortality (HR 3.67, 95% CI 1.19 to 11.32, p=0.02). We did not observe any significant effect of the duration of recovery prior to surgery on patients who had recovered from their infection. Their postoperative outcomes were also similar to those observed in asymptomatic patients.Interpretation Symptomatic status should be considered in the decision to proceed with surgery in COVID-19-positive patients. Our results may help optimise surgical care in this patient population.Study registration ClinicalTrials.gov Identifier: NCT04458337 registration date: 7 July 2020.

This article contextualizes contemporary forms of digital ghosting by examining how two of its historical precursors—Victorian calling culture and answering machines—have been represented in North American women’s magazines. To do so, we develop mediated avoidance as an analytical heuristic. This concept captures the material, relational and social dimensions of a set of understudied media practices that seek to strategically engage with the gaps that are inherent in all communication, to defer, deflect, or disrupt mediated connections. Representations of mediated avoidance from respective eras were found to reflect different anxieties over the management of the public/private divide. Calling culture relied on unpaid labor to facilitate the transmission of printed messages between bourgeoise women and was constrained by an array of social protocols that regulated interactions along conceptions of propriety. The disconnective features of answering machines, meanwhile, were represented as giving women the upper hand in courtship, as well as providing means for increased productivity and self-care, foreshadowing contemporary justifications of digital disconnection. Concerns over contemporary ghosting are discussed as produced by a spillage of media practices. Ghosting is considered acceptable in feminine-coded spheres like courtship. But it is viewed as inappropriate—sometimes even as signaling a broader social crisis—when it bleeds into other contexts, like when an employee ghosts their employer.

Introduction Home-based, virtually-supported care models may represent the most efficient and scalable approach to delivering prehabilitation services. However, virtual approaches to prehabilitation are understudied. This manuscript describes the protocol for an internal pilot randomised controlled trial of a virtually-delivered, multimodal prehabilitation intervention.Methods and analysis We will conduct a pragmatic, individual patient, internal pilot randomised controlled trial of home-based, virtually supported, multimodal prehabilitation compared with standard perioperative care in adults undergoing elective, inpatient thoracic, abdominal, pelvic and vascular surgery at five Canadian hospitals. Participants will be partially blinded; clinicians and outcome assessors will be fully blinded. The intervention consists of 3–12 weeks of a home-based, multimodal (exercise, nutrition and psychosocial support) prehabilitation programme supported through an online platform. The primary feasibility outcomes and their progression targets are (1) monthly recruitment of>6 participants at each centre, (2) intervention adherence of>75%, (3) retention of>90% of participants at the patient-reported primary outcome point of 30-days after surgery and (4) elicitation of patient, clinician and researcher-identified barriers to our pragmatic trial. A sample size of 144 participants will be adequate to estimate recruitment, adherence and retention rates with acceptable precision. All participants will be followed to either death or up to 1 year. As an internal pilot, if no substantive changes to the trial or intervention design are required, pilot participant outcome data will migrate, unanalysed by allocation, to the future full-scale trial.Ethics and dissemination Ethical approval has been granted by Clinical Trials Ontario (Project ID: 4479) and our ethics review board (Protocol Approval #20230399–01T). Results will be disseminated through presentations at scientific conferences, peer-reviewed publications, partner organisations and engagement of social and traditional media.Trial registration number ClinicalTrials.gov identifier NCT06042491. Protocol, V.1.2, dated 6 June 2024.