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Indirect Drive Inertial Confinement Fusion Experiments on the National Ignition Facility (NIF) have achieved a burning plasma state with neutron yields exceeding 170 kJ, roughly 3 times the prior record and a necessary stage for igniting plasmas. The results are achieved despite multiple sources of degradations that lead to high variability in performance. Results shown here, for the first time, include an empirical correction factor for mode-2 asymmetry in the burning plasma regime in addition to previously determined corrections for radiative mix and mode-1. Analysis shows that including these three corrections alone accounts for the measured fusion performance variability in the two highest performing experimental campaigns on the NIF to within error. Here we quantify the performance sensitivity to mode-2 symmetry in the burning plasma regime and apply the results, in the form of an empirical correction to a 1D performance model. Furthermore, we find the sensitivity to mode-2 determined through a series of integrated 2D radiation hydrodynamic simulations to be consistent with the experimentally determined sensitivity only when including alpha-heating.

Abstract Background Porcine reproductive and respiratory syndrome virus 2 (PRRSV-2) infection during late gestation substantially lowers fetal viability and survival. In a previous genome-wide association study, a single nucleotide polymorphism on chromosome 7 was significantly associated with probability of fetuses being viable in response to maternal PRRSV-2 infection at 21 days post maternal inoculation. The iodothyronine deiodinase 2 (DIO2) gene, located ~ 14 Kilobase downstream of this SNP, was selected as a priority candidate related to fetal susceptibility following maternal PRRSV-2 infection. Our objectives were to identify mutation(s) within the porcine DIO2 gene and to determine if they were associated with fetal outcomes after PRRSV-2 challenge. Sequencing of the DIO2, genotyping identified variants, and association of DIO2 genotypes with fetal phenotypes including DIO2 mRNA levels, viability, survival, viral loads, cortisol and thyroid hormone levels, and growth measurements were conducted. Results A missense variant (p.Asn91Ser) was identified in the parental populations from two independent PRRSV-2 challenge trials. This variant was further genotyped to determine association with fetal PRRS outcomes. DIO2 mRNA levels in fetal heart and kidney differed by the genotypes of Asn91Ser substitution with significantly greater DIO2 mRNA expression in heterozygotes compared with wild-type homozygotes (P

IntroductionBecause MRGPRX2 is now recognized as the mast cell receptor for basic secretagogues, there is currently a tremendous interest in whether MRGRPX2 could play an important role in various pruritic dermatoses such as chronic spontaneous urticaria. Therefore, we sought to identify new potent and selective antagonists to pharmacologically characterize the biological role of MRGPRX2.MethodsVarious relevant in vitro, ex vivo, and in vivo model systems were used to investigate the role of MRGPRX2. This included the study of freshly isolated human skin mast cells and human basophils as well as an ex vivo human skin microdialysis preparation. The additivity of MRGPRX2 and FcεR1-mediated degranulation was also investigated. Human MRGPRX2 knock-in mice were generated to interrogate pharmacokinetic/pharmacodynamic relationships because both antagonists studied were shown to be human specific.ResultsTwo novel and structurally distinct MRGPRX2 antagonists were identified with one, Compound B, being orally active and demonstrating high potency in blocking Substance P–mediated degranulation using freshly isolated human skin mast cells with half maximal inhibitory concentration (IC50) at 0.42 nM. Compound B also potently blocked Substance P–stimulated histamine release from resident mast cells in a human skin explant setup as well as blocking itch in an established behavioral scratching model using MRGPRX2 knock-in mice. Unlike human mast cells, Substance P failed to elicit a functional response in human basophils.ConclusionThese data fully support the investigation of MRGPRX2 receptor antagonists in mast cell–driven allergic skin disorders such as chronic spontaneous urticaria.

Summary: Mast cells (MCs) are tissue-resident immune cells known to degranulate in response to FcεRI crosslinking or MRGPRX2 engagement. MCs are found close to nerves, but the mechanisms that regulate this privileged localization remain unclear. Here, we investigated MRGPRX2 expression patterns and specific activities in MCs. We show that MRGPRX2 expression is heterogeneous in human MC (hMC) progenitors and mature MCs. Substance P (SP) is a rapid and specific activator of MRGPRX2, and long-term supplementation of MCs with SP expands MRGPRX2-expressing cells.While high concentrations of SP induce rapid MC degranulation, low concentrations prompt immature MC chemotaxis. Lastly, we demonstrate that in inflammatory skin conditions like psoriasis, the number of MRGPRX2+ MCs is increased, and during in vitro skin reinnervation, MRGPRX2+ MCs preferentially reside in proximity to and migrate toward SP+ nerve fibers (NFs). This indicates that SP-MRGPRX2 signaling defines MC positioning and relocation within tissues and promotes immune cell-NF communication.

IntroductionDecellularized uterine extracellular matrix has emerged as a pivotal focus in the realm of biomaterials, offering a promising source in uterine tissue regeneration, research on disease diagnosis and treatments, and ultimately uterine transplantation. In this study, we examined various protocols for decellularizing porcine uterine tissues, aimed to unravel the intricate dynamics of DNA removal, bioactive molecules preservation, and microstructural alterations.MethodsPorcine uterine tissues were treated with 6 different, yet rigorously selected and designed, protocols with sodium dodecyl sulfate (SDS), Triton® X-100, peracetic acid + ethanol, and DNase I. After decellularization, we examined DNA quantification, histological staining (H&E and DAPI), glycosaminoglycans (GAG) assay, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and Thermogravimetric Analysis (TGA).ResultsA comparative analysis among all 6 protocols was conducted with the results demonstrating that all protocols achieved decellularization; while 0.1% SDS + 1% Triton® X-100, coupled with agitation, demonstrated the highest efficiency in DNA removal. Also, it was found that DNase I played a key role in enhancing the efficiency of the decellularization process by underscoring its significance in digesting cellular contents and eliminating cell debris by 99.79% (19.63 ± 3.92 ng/mg dry weight).ConclusionsOur findings enhance the nuanced understanding of DNA removal, GAG preservation, microstructural alteration, and protein decomposition in decellularized uterine extracellular matrix, while highlighting the importance of decellularization protocols designed for intended applications. This study along with our findings represents meaningful progress for advancing the field of uterine transplantation and related tissue engineering/regenerative medicine.

ABSTRACT Salmonid aquaculture, a major component of the Northern European, North American, and Chilean coastal economies, is under threat from challenges to gill health, many of which originate from plankton communities. A first step toward mitigating losses is to characterize the biological drivers of poor gill health. Numerous planktonic taxa have been implicated, including toxic and siliceous microalgae, hydrozoans, and scyphozoans; however, rigorous longitudinal surveys of plankton diversity and gill health have been lacking. In the current study, we present and assess an exhaustive identification approach combining both morphological and molecular methods together with robust statistical models to identify the planktonic drivers of proliferative gill disease (PGD) and fish mortality. We undertook longitudinal evaluation at two marine aquaculture facilities on the west coast of Scotland using daily data collected during the 2021 growing season (March–October). Examining these two different sites, one sheltered and one exposed to the open sea, we identified potentially new, important, and unexpected planktonic drivers of PGD and mortality (e.g., doliolids and appendicularians) and confirmed the significance of some established threats (e.g., hydrozoans and diatoms). We also explored delayed or “lagged” effects of plankton abundances on gill health and undertook a comparison of environmental DNA (eDNA) metabarcoding and microscopy in their ability to identify and quantify planktonic species. Our data highlight the diversity of planktonic threats to salmonid aquaculture as well as the importance of using both molecular and morphological approaches to detect these. There is now an urgent need to expand systematic longitudinal molecular and morphological approaches across multiple sites and over multiple years. The resultant catalogue of main biological drivers will enable early warning systems, new treatments, and, ultimately, a sustainable platform for future salmonid aquaculture in the marine environment.

Interventions for attention-deficit/hyperactivity disorder (ADHD) include positive behavior supports (e.g., parent training, school-based contingency management, behavioral peer interventions), training interventions (e.g., organizational skills training, social skills training, etc.), and other interventions (e.g., academic accommodations/modifications, self-monitoring). There is a need to conduct a comprehensive meta-analysis of psychosocial treatments for ADHD given discrepancies between meta-analyses. The present meta-analysis reports the results of between-group studies that compared a psychosocial treatment to a control condition from 1968 to 2016. In total, 226 studies were identified that met inclusion criteria. Results of the meta-analysis were organized by treatment type, rater, and domain of outcome assessed. Results indicated considerable variability across these parameters, with the strongest effects for proximal outcomes of behavioral parent training (improvements in parenting behaviors yielded a standardized mean difference of 0.70) and improvements in child behavior following implementation of behavioral school intervention (standardized mean difference of 0.66 and 0.72 for teacher ratings of ADHD symptoms and impairment, respectively). Other interventions were not extensively studied as stand-alone approaches. Results are discussed in light of current support for the use of psychosocial interventions for individuals with ADHD.

Abstract In this contribution, we investigate two sparassodonts from the Sarmiento Formation (Colhuehuapian Age; Early Miocene) recovered at the Patagonian locality of Sacanana, Chubut Province, Argentina. The first specimen (MACN-Pv CH1911), identified as Sipalocyon externus, is an almost complete cranium with upper dentition. The second specimen (MACN-Pv CH40), referred to Borhyaena macrodonta, consists of a fragmentary rostral portion of the face with associated m3–m4. The cranium of S. externus was studied through µCT-scanning to investigate its internal anatomy and infer paleoecological aspects of olfaction and hearing. In general, the endocranial anatomy and encephalization quotient are like those of other metatherians. We report the presence of an accessory transverse diploic sinus that has not previously been described in marsupials. Elements of the nasal cavity (e.g., turbinals, ossified nasal septum, cribriform plate) of S. externus exhibit features that are widespread among marsupials. Sense of olfaction, as evaluated from the cribriform plate and the 3D models of the olfactory bulbs, appears to have grossly resembled that of the domestic cat, a well-researched therian proxy. The dimensions of the tympanic membrane, as estimated from the preserved ectotympanic, suggest that the optimal hearing frequency of S. externus would have been similar to that of extant carnivorous marsupials. In sum, our study suggests that S. externus was a typical small-bodied (2–3 kg) hypercarnivorous metatherian that primarily relied on vision to hunt its prey, complemented by other sensory capabilities (olfaction and hearing), in a similar manner to small felids.

Abstract Indirect Drive Inertial Confinement Fusion Experiments on the National Ignition Facility (NIF) have achieved a burning plasma state with neutron yields exceeding 170 kJ, roughly 3 times the prior record and a necessary stage for igniting plasmas. The results are achieved despite multiple sources of degradations that lead to high variability in performance. Results shown here, for the first time, include an empirical correction factor for mode-2 asymmetry in the burning plasma regime in addition to previously determined corrections for radiative mix and mode-1. Analysis shows that including these three corrections alone accounts for the measured fusion performance variability in the two highest performing experimental campaigns on the NIF to within error. Here we quantify the performance sensitivity to mode-2 symmetry in the burning plasma regime and apply the results, in the form of an empirical correction to a 1D performance model. Furthermore, we find the sensitivity to mode-2 determined through a series of integrated 2D radiation hydrodynamic simulations to be consistent with the experimentally determined sensitivity only when including alpha-heating.

Priority question exercises are increasingly used to frame and set future research, innovation and development agendas. They can provide an important bridge between the discoveries, data and outputs generated by researchers, and the information required by policy makers and funders. Microbial biofilms present huge scientific, societal and economic opportunities and challenges. In order to identify key priorities that will help to advance the field, here we review questions from a pool submitted by the international biofilm research community and from practitioners working across industry, the environment and medicine. To avoid bias we used computational approaches to group questions and manage a voting and selection process. The outcome of the exercise is a set of 78 unique questions, categorized in six themes: (i) Biofilm control, disruption, prevention, management, treatment (13 questions); (ii) Resistance, persistence, tolerance, role of aggregation, immune interaction, relevance to infection (10 questions); (iii) Model systems, standards, regulatory, policy education, interdisciplinary approaches (15 questions); (iv) Polymicrobial, interactions, ecology, microbiome, phage (13 questions); (v) Clinical focus, chronic infection, detection, diagnostics (13 questions); and (vi) Matrix, lipids, capsule, metabolism, development, physiology, ecology, evolution environment, microbiome, community engineering (14 questions). The questions presented are intended to highlight opportunities, stimulate discussion and provide focus for researchers, funders and policy makers, informing future research, innovation and development strategy for biofilms and microbial communities.

Ultrafast single-shot measurement techniques with high throughput are needed for capturing rare events that occur over short time scales. Such instruments unveil non-repetitive dynamics in complex systems and enable new types of spectrometers, cameras, light scattering, and lidar systems. Photonic time stretch stands out as the most effective method for such applications. However, practical uses have been challenged by the reliance of current time stretch instruments on costly supercontinuum lasers and their fixed spectrum. The challenge is further exacerbated by such a laser’s rigid self-pulsating characteristic, which offers no ability to control the pulse timing. The latter hinders the synchronization of the optical source with the incoming signal—a crucial requirement for the detection of single-shot events. Here, we report the first demonstration of time stretch using electro-optically modulated continuous wave lasers. We do this using diode lasers and modulators commonly used in wavelength-division-multiplexing optical communication systems. This approach offers more cost-effective and compact time stretch instruments and sensors and enables the synchronization of the laser source with the incoming signal. Limitations of this new approach are also discussed, and applications in time stretch microscopy and light scattering are explored.

Abstract Public lands across the United States are managed for multiple uses, resources, and values ranging from energy development to rare plant conservation. Intensified energy development and other land use changes across the Southwestern United States have increased the need for proactive management to mitigate impacts to rare plants. Habitat suitability models can inform decision‐making and lead to more effective conservation of rare plants and their habitats, but high‐quality models that are suited for use at local scales are lacking for many species. Our team of scientists and managers developed ensembles of habitat suitability models for five rare plant species in New Mexico using a coproduced, iterative framework complemented by comprehensive ground truthing and tailoring of products for use in public land decisions. Our process resulted in substantial differences from initial models through changes to environmental predictors, species occurrence and background data, and development of new species‐specific predictors. Involving species experts and end users in model development can strengthen the process and resulting model and build understanding and trust in final products. Both factors can promote use of models to inform public land permitting and planning decisions that may affect rare plants, including by guiding development away from highly suitable habitats.

Despite 40 years of research indicating that parent involvement is important for student achievement, schools have done little to engage parents across Canada. This study and model recommend strategies to enhance the probability of educational involvement for parents who do not speak the school language. The mixed methods research with surveys (N = 86) and interviews (N = 38) identified the successes and challenges of non-francophone parents with children in French minority-language schools. Parents wanted to help but struggled with French schoolwork and school-community involvement. Parents' low French proficiency and low school effort to facilitate parent communication and comprehension were some of the barriers that led to a decreased sense of parent autonomy and competency. Policy and practices by educators and parent-groups can encourage involvement and support parents in a French minority-language population as they overcome language and insecurity barriers at home or school. The findings can be generalized to support parent involvement in other multilingual contexts.

Abstract Microbial biofilms are complex communities of microorganisms that exist in various environments, including natural and human-built systems and have a significant economic impact on a global scale. In addition to their detrimental impacts, biofilms have been extensively studied for their potential benefits. In agriculture, biofilms are considered key organisational structures of microbes, exploited as biofertilisers, biostimulants, and biocontrol agents, with the potential to enhance soil health and plant growth. Despite ongoing research, there are still large knowledge gaps in the understanding of the mechanisms governing interaction between biofilms and plants, and how these can be manipulated to promote sustainable agriculture. The UK’s National Biofilms Innovation Centre [NBIC] and Argentine researchers have established a dialogue aimed at addressing these gaps and improving agricultural productivity through the integration of new technologies that can promote soil health whilst reducing environmental impact. Future research collaborations between the two countries in this area could have significant benefits for global agricultural innovation and the development of sustainable food systems. This publication takes on a ‘white paper’ format, consolidating complex discussions from a workshop between NBIC and Argentine researchers. It offers a comprehensive summary encompassing the insights, perspectives, and outcomes generated during the discussions among the participants, pinpointing three key priority areas for collaborative activities that were identified: (1) Using plant root biofilm composition as a sensor for soil health and to optimise interventions, (2) Biofilms and soil health resilience in a changing environment, (3) Intelligent seeds and innovative / automated large-scale monitoring systems. For the three identified priority areas, the early engagement of end-users [farmers] will be paramount to maximise technology adoption. Commitment from the governments and support from funding bodies in both countries will be essential for the establishment of robust research programmes and long-term successful collaborations between researchers, industry and end users. Graphical Abstract

Maura MacPhee,1 Farinaz Havaei,1 Sue Bookey-Bassett,2 W Patrick Neumann,3 Sadeem Munawar Qureshi,3 Michael A Greig,3 David Keselman1 1School of Nursing, University of British Columbia, Vancouver, British Columbia, Canada; 2Daphne Cockwell School of Nursing, Toronto Metropolitan University, Toronto, Ontario, Canada; 3Department of Mechanical and Industrial Engineering, Toronto Metropolitan University, Toronto, Ontario, CanadaCorrespondence: Maura MacPhee, School of Nursing, University of British Columbia, T201 2211 Wesbrook Mall, Vancouver, BC, V6T2B5, Canada, Tel +1 778-926-4068, Email maura.macphee@ubc.caAbstract: The aim of this paper is to enhance readers’ understanding of research design strategies, past and present, for studying nursing workloads. Future research directions are also discussed. Nursing workloads are associated with nurse burnout and turnover. During our current global nursing shortage, researchers must identify ways to mitigate nurses’ heavy workloads. Relevant, prior nursing workload research is presented with brief descriptions of designs, methods and findings. To illustrate the current complexity of nurses’ work environments and the myriad factors that influence nurses’ workloads, this paper features the ongoing nursing workload research of two Canadian research teams with different methodological approaches. These two teams are employing current research innovations, such as human factors multi-systems frameworks, design thinking, simulation modeling and integrated knowledge translation. With respect to future research implications, the teams are melding methods and tools to promote a more sophisticated way of understanding the complex linkages between patient needs, systems design and the management of nurses’ workloads.Keywords: nursing workloads, nurses’ work environments, synergy tool, patient needs assessment, human factors, simulation modeling

Background: Youth with ADHD are at risk of academic impairments, dropping out of high school, and dysfunction in young adulthood. Interventions delivered early in high school could prevent these harmful outcomes, yet few high school students with ADHD receive treatment due to limited access to intervention providers. This study will test a peer-delivered intervention (STRIPES) for general education 9th grade students with impairing ADHD symptoms. Methods: A type 1 hybrid effectiveness-implementation design will be used to evaluate the effectiveness of STRIPES and explore the intervention's implementability. Analyses will test the impact of STRIPES vs. enhanced school services control on target mechanisms and determine whether differences in basic cognitive profiles moderate intervention response. The acceptability and feasibility of STRIPES and treatment moderators will also be examined. Discussion: This study will generate knowledge about the effectiveness and implementability of STRIPES, which will inform dissemination efforts in the future. A peer-delivered high school intervention for organization, time management, and planning skills can provide accessible and feasible treatment targeting declines in academic motivation, grades, and attendance during the ninth-grade year.

Integrating community-based learning (CBL) into graduate education has gained attention in higher education during the past decade because CBL allows students to inculcate professional values and ethics, situate academic knowledge and understanding in contexts, and practice academic citizenship through serving communities with disciplinary knowledge and skills. In a North American higher education context, about half of the graduate student population are international students, who have needs in several areas. However, their experiences in CBL are under-investigated and scarcely documented in existing literature and scholarship in either community-based learning or international education. Drawing on international students' experiences in a graduate program infused with CBL components in Canadian higher education, this mixed methods case study examined the impact of CBL on international students' developments in five areas: academic, sociocultural, personal, professional, and global citizenship. Through discussions on the benefit, barriers, and implications of providing CBL to international graduate students, this article offers recommendations for improved higher education policy, programs, and praxis to make CBL more inclusive and responsive to international graduate students.

Background In Canada, the Public Health Agency surveillance of new HIV cases has demonstrated annual increasing rates since 2020. The rates of new HIV cases are highest in the province of Saskatchewan.Objectives The aim of the project was to conduct a resident-oriented realist evaluation of an innovative supportive housing programme, Sanctum, for people living with HIV/AIDS who also face social care issues, such as homelessness. This project took place in Saskatchewan, a province that is seeking innovative approaches to improve quality of life and HIV/AIDS management for its citizens. Our evaluation addressed how and why participants were successful (or not) within the Sanctum programme.Design and setting Sanctum is a housing programme located in an inner-city location within the province of Saskatchewan. A unique component of this evaluation was the inclusion of an individual with lived experience, a resident partner, as a member of the research team.Participants 11 recent Sanctum graduates, seven men and four women, were recruited for client partner-led in-depth, semistructured interviews.Interventions Prior to the evaluation, we developed a realist programme theory with potential causal explanations, known as context-mechanism-outcomes (CMO) configurations. Interview data from the evaluation and ongoing discussions with Sanctum board members and our resident partner were used to test, refine and validate the final programme theory and CMO configurations.Results CMO configurations at the micro (individual), meso (interpersonal) and macro (community) levels complement the over-arching programme theory. Key findings were the importance of Sanctum’s harm reduction philosophy, accompanied by a non-judgmental and patient-oriented approach. Participants were supported to reduce risky behaviour, improve self-care management and develop healthier relationships within a ‘safe’ home-like setting. Underlying mechanisms that contributed to participants’ success in the programme included: intrinsic motivation, self-worth, belongingness, empowerment and self-efficacy. Evidence-informed recommendations are offered to support Sanctum-like programme development for individuals with holistic health needs related to HIV/AIDS diagnoses and lack of access to necessary social determinants of health.Conclusions Stigma associated with HIV/AIDS and living circumstances, such as homelessness, were successfully addressed using harm reduction principles and judgement-free approaches within a family-like environment.

Implementing and sustaining technological innovations in healthcare is a complex process. Commonly, innovations are abandoned due to unsuccessful attempts to sustain and scale-up post implementation. Limited information is available on what characterizes successful e-health innovations and the enabling factors that can lead to their sustainability in complex hospital environments. We present a successful implementation, sustainability and scale-up of a virtual care program consisting of three e-health applications (telemedicine, telehome monitoring, and interactive voice response) in a major cardiac care hospital in Canada. We describe their evolution and adaptation over time, present the innovative approach for their “business case” and funding that supported their implementation, and identify key factors that enabled their sustainability and success, which may inform future research and serve as a benchmark for other health care organizations. Despite resource constraints, e-health innovations can be deployed and successfully sustained in complex healthcare settings contingent key considerations: simplifying technology to make it intuitive for patients; providing significant value proposition that is research supported to influence policy changes; involving early supporters of adoption from administrative and clinical staff; engaging patients throughout the innovation cycle; and partnering with industry/technology providers.

ObjectiveEvaluate whether stimulant medication improves acquisition of academic material in children with attention deficit hyperactivity disorder (ADHD) receiving small-group, content-area instruction in a classroom setting.MethodParticipants were 173 children between the ages of 7 and 12 years old (77% male, 86% Hispanic) who met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for ADHD and were participating in a therapeutic summer camp. The design was a triple-masked, within-subject, AB/BA crossover trial. Children completed two consecutive phases of daily, 25-min instruction in both (a) subject-area content (science, social studies) and (b) vocabulary. Each phase was a standard instructional unit lasting for 3 weeks. Teachers and aides taught the material to small groups in a summer classroom setting. Each child was randomized to be medicated with daily osmotic-release oral system methylphenidate (OROS-MPH) during either the first or second of the instructional phases, receiving placebo during the other.ResultsMedication had large, salutary, statistically significant effects on children's academic seatwork productivity and classroom behavior on every single day of the instructional period. However, there was no detectable effect of medication on learning the material taught during instruction: Children learned the same amount of subject-area and vocabulary content whether they were taking OROS-MPH or placebo during the instructional period.ConclusionsAcute effects of OROS-MPH on daily academic seatwork productivity and classroom behavior did not translate into improved learning of new academic material taught via small-group, evidence-based instruction. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Nous avons effectué cette revue exploratoirepour connaître les interventions de soutien offertes actuellement aux membres de la famille d’un enfant subissant une greffe de cellules souches hématopoïétiques (GCSH). Nous avons consulté trois bases de données (CINAHL, Embase et Medline) pour répondre à la question suivante : Quelles sont les interventions de soutien offertes aux membres de la famille d’un enfant subissant une greffe de cellules souches hématopoïétiques, et sont-elles fondées sur une approche de soins axés sur la famille? Parmi les 665 articles présélectionnés, nous en avons retenu neuf à lire au complet. Nos résultats montrent qu’il existe deux principaux types d’interventions de soutien axées sur la famille : les interventions psychologiques en personne et les interventions pratiquées à l’aide de la technologie. La plupart de ces interventions ont contribué à améliorer le bien-être psychologique des membres de la famille et s’appuyaient sur certains principes du modèle de soins de l’Institute for Patient- and Family-Centered Care. La présente revue exploratoire nous permet d’affirmer que les interventions qui s’appuient sur les principes des soins axés sur la famille peuvent améliorer le bien-être psychologique et la qualité de vie des membres de la famille d’un enfant subissant une GCSH.

A scoping review was conducted to explore support interventions for family members of a child treated with a hematopoietic stem cell transplant (HSCT). Three databases (CINAHL, Embase, and Medline) were searched to answer the review question: What are the support interventions offered to family members of a child treated with HSCT, and are they based on a family-centered care approach? Out of 665 screened articles, nine were selected for a full review. Findings revealed two main types of family-centered support interventions: psychological face-to-face and technology-based interventions. The majority of interventions assisted in improving family members' psychological well-being and none included all four principles of the Institute for Patient and Family-Centered Care Model. Based on the review findings, to improve both the family members and the child’s psychological well-being and quality of life, all four family-centered care principles should be incorporated within family support interventions.

Abstract Pharmacological challenge models are deployed to evaluate drug effects during clinical development. Intradermal injection of Substance P (SP) neuropeptide, a potential challenge agent for investigating local mediators, is associated with wheal and flare response mediated by the MRGPRX2 receptor. Although dose‐dependent data on SP effects exist, full characterization and information on potential carryover effect after repeated challenge are lacking. This open‐label, two‐part, prospective enabling study of SP intradermal challenge in healthy participants aimed to understand and distinguish between wheal and flare responses following various SP doses. Part 1 included one challenge visit to determine optimum SP dose range for evaluation in part 2, which determined variability in 20 participants and used intradermal microdialysis (IDM) for SP‐challenged skin sampling. At 5, 15, 50, and 150 pmol doses, respectively, posterior median area under the curve (AUC; AUC0–2h) was 4090.4, 5881.2, 8846.8, and 9212.8 mm2/min, for wheal response, and 12020.9, 38154.3, 65470.6, and 67404.4 mm2/min for flare response (SP‐challenge visit 2). When the challenge was repeated ~2 weeks later, no carryover effect was observed. IDM histamine levels were relatively low, resulting in low confidence in the data to define temporal characteristics for histamine release following SP challenge. No safety concerns were identified using SP. Wheal and flare responses following intradermal SP challenge were dose‐dependent and different. The results indicate that this challenge model is fit‐for‐purpose in future first‐in‐human studies and further assessment of novel drugs targeting dermal inflammatory disease responses, such as chronic spontaneous urticaria, chronic inducible urticaria, and pseudo‐allergic reactions.

Abstract Background Within the Learning Health System (LHS) model, learning routines, including evaluation, allow for continuous incremental change to take place. Within these learning routines, evaluation assists in problem identification, data collection, and data transformation into contextualized information, which is then re-applied to the LHS environment. Evaluation that catalyzes learning and improvement may also contribute to health innovation sustainability. However, there is little consensus as to why certain evaluations seem to support learning and sustainability, while others impede it. This realist synthesis seeks to understand the contextual factors and underlying mechanisms or drivers that best support health systems learning and sustainable innovation. Methods This synthesis will be guided by Pawson and colleagues’ 2005 and Emmel and colleagues’ 2018 guidelines for conducting realist syntheses. The review process will encompass five steps: (1) scoping the review, (2) building theories, (3) identifying the evidence, (4) evidence selection and appraisal, and (5) data extraction and synthesis. An Expert Committee comprised of leaders in evaluation, innovation, sustainability, and realist methodology will guide this synthesis. Review findings will be reported using the RAMESES guidelines. Discussion The use of a realist review will allow for exploration and theorizing about the contextual factors and underlying mechanisms that make evaluations ‘work’ (or ‘not work’) to support learning and sustainability. Depending on results, we will attempt to synthesize findings into a series of recommendations for evaluations with the intention to support health systems learning and sustainability. Finalized results will be presented at national and international conferences, as well as disseminated via a peer-reviewed publication. Systematic review registration This realist synthesis protocol has been registered with PROSPERO ( https://www.crd.york.ac.uk/prospero/ ID 382690).

Abstract SARS-CoV-2 variants and seasonal coronaviruses continue to cause disease and coronaviruses in the animal reservoir pose a constant spillover threat. Importantly, understanding of how previous infection may influence future exposures, especially in the context of seasonal coronaviruses and SARS-CoV-2 variants, is still limited. Here we adopted a step-wise experimental approach to examine the primary immune response and subsequent immune recall toward antigenically distinct coronaviruses using male Syrian hamsters. Hamsters were initially inoculated with seasonal coronaviruses (HCoV-NL63, HCoV-229E, or HCoV-OC43), or SARS-CoV-2 pango B lineage virus, then challenged with SARS-CoV-2 pango B lineage virus, or SARS-CoV-2 variants Beta or Omicron. Although infection with seasonal coronaviruses offered little protection against SARS-CoV-2 challenge, HCoV-NL63-infected animals had an increase of the previously elicited HCoV-NL63-specific neutralizing antibodies during challenge with SARS-CoV-2. On the other hand, primary infection with HCoV-OC43 induced distinct T cell gene signatures. Gene expression profiling indicated interferon responses and germinal center reactions to be induced during more similar primary infection-challenge combinations while signatures of increased inflammation as well as suppression of the antiviral response were observed following antigenically distant viral challenges. This work characterizes and analyzes seasonal coronaviruses effect on SARS-CoV-2 secondary infection and the findings are important for pan-coronavirus vaccine design.

Obesity is a chronic, prevalent, and complex health condition that adversely impairs physical and mental health. The World Health Organization calls for integrating obesity care into existing chronic disease management programs within primary healthcare services. This scoping review aimed to examine registered nurses’ roles in the primary healthcare management of individuals with obesity. A scoping review was conducted using the Johanna Briggs Institute methodology framework. Thematic analysis was used to identify and categorize nurses’ roles in primary healthcare obesity management of adults. Of 1142 documents included in this review, 15 papers met the inclusion criteria. Thematic analysis yielded the following six themes representing nurses’ major roles: patient-centred care, patient assessments, therapeutic interventions, care management, patient education, and professional development. This review identified that the literature on nurses’ roles primarily described their focus on lifestyle interventions (mainly nutrition and physical activity), anthropometric measurements, health planning, goal setting, supportive care, monitoring progress, and arranging follow-up. The Discussion highlights the importance of determining RN knowledge gaps and biases. More research is required to determine the need for additional RN pre-and or post-education related to obesity as a complex chronic disease.

This study examined the ways in which PDS participants use language to co-construct knowledge about literacy teaching and learning during debriefing conversations following shared instructional experiences in K-3 classrooms. The debriefing conversations were part of a collaboratively developed pedagogical model situated in a literacy methods course. The primary data sources for the study were transcriptions from one collaborative planning conversation and six debriefing conversations. Both qualitative and quantitative methods were employed (1) to understand how participants used language during debriefing conversations and (2) to identify the focus of the debriefing conversations as they related to Bransford, Darling-Hammond, and LePage's (2005) Framework for Understanding Teaching and Learning. The study was conducted during year four of a five-year design-based project. The goal of the project was to engage in continuous improvement to enhance, for all stakeholders in the PDS, the potential for professional growth. Findings reveal that, despite varied uses of language to explore literacy teaching and learning, participant interactions largely reflected institutionalized discourses of pre-service teacher education. Additionally, findings provide insight about the focus of debriefing conversations as they related to research on relevant knowledge in pre-service teacher preparation. Most importantly, the study demonstrates that pedagogical innovations in PDS settings can be continuously improved through collaborative design-based processes.