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Evidence-based practices in concussion management (CM) have been codified into legislation. However, legislation is varied, and implementation is narrowly evaluated. School nurses hold a unique position to assess the implementation of health policies. The implementation of concussion management policies across Massachusetts high schools was evaluated by the school nurse. A cross-sectional survey was sent to school nurses (N = 304), and responses (n = 201; 68.1% response rate) were tallied whereby higher scores indicated more practices being implemented. One open-text question was included to encourage nurses to provide context regarding implementation in their school. Descriptive statistics and thematic analysis were used to assess current implementation and nursing perspectives. Findings indicate that the degree of implementation varies, and some nurses reported difficulty with mobilizing clinical uptake of concussion management practices in their schools. Further implementation research is needed, and school nurses are an important stakeholder to include when assessing the clinical uptake of concussion management policies in schools.

Abstract Background During the latter stages of their development, mammalian oocytes under dramatic chromatin reconfiguration, transitioning from a non-surrounded nucleolus (NSN) to a surrounded nucleolus (SN) stage, and concomitant transcriptional silencing. Although the NSN-SN transition is known to be essential for developmental competence of the oocyte, less is known about the accompanying molecular changes. Here we examine the changes in the transcriptome and DNA methylation during the NSN to SN transition in mouse oocytes. Results To study the transcriptome and DNA methylation dynamics during the NSN to SN transition, we used single-cell (sc)M&T-seq to generate scRNA-seq and sc-bisulphite-seq (scBS-seq) data from GV oocytes classified as NSN or SN by Hoechst staining of their nuclei. Transcriptome analysis showed a lower number of detected transcripts in SN compared with NSN oocytes as well as downregulation of 576 genes, which were enriched for processes related to mRNA processing. We used the transcriptome data to generate a classifier that can infer chromatin stage in scRNA-seq datasets. The classifier was successfully tested in multiple published datasets of mouse models with a known skew in NSN: SN ratios. Analysis of the scBS-seq data showed increased DNA methylation in SN compared to NSN oocytes, which was most pronounced in regions with intermediate levels of methylation. Overlap with chromatin immunoprecipitation and sequencing (ChIP-seq) data for the histone modifications H3K36me3, H3K4me3 and H3K27me3 showed that regions gaining methylation in SN oocytes are enriched for overlapping H3K36me3 and H3K27me3, which is an unusual combination, as these marks do not typically coincide. Conclusions We characterise the transcriptome and DNA methylation changes accompanying the NSN-SN transition in mouse oocytes. We develop a classifier that can be used to infer chromatin status in single-cell or bulk RNA-seq data, enabling identification of altered chromatin transition in genetic knock-outs, and a quality control to identify skewed NSN-SN proportions that could otherwise confound differential gene expression analysis. We identify late-methylating regions in SN oocytes that are associated with an unusual combination of chromatin modifications, which may be regions with high chromatin plasticity and transitioning between H3K27me3 and H3K36me3, or reflect heterogeneity on a single-cell level.

Background To minimise the referral gap to pain psychology, the purpose of this study was to describe clinician-perceived patient suitability for pain psychology referral, develop a referral plan and outline essential elements of a referral conversation via a modified Delphi approach with multidisciplinary paediatric pain providers.Methods We employed a three-round modified Delphi approach consulting multidisciplinary paediatric pain providers (n=18) including physicians, psychologists, physical therapists, occupational therapists and nurse practitioners (PT, OT, NP). Based on the responses to an online survey (Round 1), initial statements regarding the pain psychology referral process were developed. These statements were revised in three separate panels (MD panel, PSY panel, PT, OT, NP panel; Round 2). A priori consensus criteria were verified for each statement within and between groups using anonymous responses to a concluding online survey (Round 3).Results Approximately one-third of the statements (35%) reached consensus across all panels. For example, paediatric pain providers agreed that referrals should be communicated verbally, along with written materials, and that pain should be explained early from a biopsychosocial perspective. Paediatric pain providers also suggested minimising barriers through a flexible, stepped-care approach that adapts the delivery of pain psychology beyond traditional models. However, most statements reached consensus in only one or two panels (52%), indicating a lack of consensus across disciplines. The data suggest that it was comparatively easier to reach an overall consensus on statements formulating an ideal referral process to pain psychology (50%) than on statements characterising patient suitability (13%).Conclusions Paediatric pain providers developed an actionable plan for pain psychology referrals. This plan could bridge referral gaps and improve access to pain psychology treatment. Given the low provider consensus on patient suitability, further research is warranted to understand pain psychology referral decision-making, including differing perceptions of patient suitability across disciplines.

In the ongoing debates about eukaryogenesis-the series of evolutionary events leading to the emergence of the eukaryotic cell from prokaryotic ancestors-members of the Asgard archaea play a key part as the closest archaeal relatives of eukaryotes1. However, the nature and phylogenetic identity of the last common ancestor of Asgard archaea and eukaryotes remain unresolved2-4. Here we analyse distinct phylogenetic marker datasets of an expanded genomic sampling of Asgard archaea and evaluate competing evolutionary scenarios using state-of-the-art phylogenomic approaches. We find that eukaryotes are placed, with high confidence, as a well-nested clade within Asgard archaea and as a sister lineage to Hodarchaeales, a newly proposed order within Heimdallarchaeia. Using sophisticated gene tree and species tree reconciliation approaches, we show that analogous to the evolution of eukaryotic genomes, genome evolution in Asgard archaea involved significantly more gene duplication and fewer gene loss events compared with other archaea. Finally, we infer that the last common ancestor of Asgard archaea was probably a thermophilic chemolithotroph and that the lineage from which eukaryotes evolved adapted to mesophilic conditions and acquired the genetic potential to support a heterotrophic lifestyle. Our work provides key insights into the prokaryote-to-eukaryote transition and a platform for better understanding the emergence of cellular complexity in eukaryotic cells.

Understanding the origin of eukaryotic cells is one of the most difficult problems in all of biology. A key challenge relevant to the question of eukaryogenesis is reconstructing the gene repertoire of the last eukaryotic common ancestor (LECA). As data sets grow, sketching an accurate genomics-informed picture of early eukaryotic cellular complexity requires provision of analytical resources and a commitment to data sharing. Here, we summarise progress towards understanding the biology of LECA and outline a community approach to inferring its wider gene repertoire. Once assembled, a robust LECA gene set will be a useful tool for evaluating alternative hypotheses about the origin of eukaryotes and understanding the evolution of traits in all descendant lineages, with relevance in diverse fields such as cell biology, microbial ecology, biotechnology, agriculture, and medicine. In this Consensus View, we put forth the status quo and an agreed path forward to reconstruct LECA's gene content.

Systems of correlated particles appear in many fields of modern science and represent some of the most intractable computational problems in nature. The computational challenge in these systems arises when interactions become comparable to other energy scales, which makes the state of each particle depend on all other particles1. The lack of general solutions for the three-body problem and acceptable theory for strongly correlated electrons shows that our understanding of correlated systems fades when the particle number or the interaction strength increases. One of the hallmarks of interacting systems is the formation of multiparticle bound states2-9. Here we develop a high-fidelity parameterizable fSim gate and implement the periodic quantum circuit of the spin-½ XXZ model in a ring of 24 superconducting qubits. We study the propagation of these excitations and observe their bound nature for up to five photons. We devise a phase-sensitive method for constructing the few-body spectrum of the bound states and extract their pseudo-charge by introducing a synthetic flux. By introducing interactions between the ring and additional qubits, we observe an unexpected resilience of the bound states to integrability breaking. This finding goes against the idea that bound states in non-integrable systems are unstable when their energies overlap with the continuum spectrum. Our work provides experimental evidence for bound states of interacting photons and discovers their stability beyond the integrability limit.

Rural and northern Indigenous communities across Canada are pursuing new Indigenous-led conservation partnerships with Crown governments as critical alternatives to Western conservation and extractive industries regimes. Colonial conservation policies and industrial development continue to displace Indigenous Peoples from their ancestral territories, with great consequences to land-based economies, food security, and knowledges. Indigenous-led conservation is an umbrella term used to describe a variety of initiatives that includes Indigenous Protected and Conserved Areas. Indigenous communities lead the creation, management, and stewardship of these protected areas, which are guided by localized knowledge and priorities. This creates unique opportunities to build new and bolster existing tourism businesses with sustainable socio-economic, cultural, and environmental outcomes. Our research examines Indigenous-led conservation and tourism in the Dene/Métis community of Fort Providence, Northwest Territories, located adjacent to Canada's first official Indigenous Protected and Conserved Area, Edéhzhíe. Guided by Indigenous methodologies and collaborative approaches, this paper presents the analysis of 23 semi-structured interviews with Elders, knowledgeable land users, and community members. While tourism development in the community is currently limited, our results indicate that participants are hopeful about the contributions of Edéhzhíe and tourism to sustainable economies, cultural resurgence, and environmental stewardship in the surrounding communities. Participants demonstrate that Indigenous-led conservation and tourism have the potential to challenge existing colonial, capitalist land use regimes and foster Indigenous governance, reconciliatory processes, and environmental resiliency. Our findings can be used by other Indigenous communities to inform conservation and sustainable development goals related to regional tourism economies.

Indigenous Peoples throughout the world have been displaced from their ancestral territories through colonial land use management. Indigenous Peoples have pushed settler-colonial governments to shift their policy frameworks to better support Indigenous rights and leadership across land management, but particularly in conservation. In Canada, this has recently involved the development of Indigenous Protected and Conserved Areas. Combined with pressure from international organizations, Canada’s Federal Government has dedicated substantial funds to support the establishment of these areas and to achieve conservation and reconciliatory goals. In Aotearoa New Zealand, Māori groups have shaped new legislation that recognizes legal personality status for natural features, which contrasts with Western understandings of land ownership. Indigenous-led conservation in Canada faces many interrelated barriers grounded in colonial histories that complicate land jurisdictions, reconciliation, and protected area networks. This research reveals some of this complexity by examining how Indigenous-led conservation can contribute to more equitable and consensus-based decision-making frameworks in land use management. Policy and legal analyses of Canadian, Aotearoa New Zealand, and international conservation and human rights documents inform our results. We affirm that Indigenous-led conservation can foster relationships between Indigenous Nations and Crown governments. They can also provide steps towards reconciling colonial injustices, supporting Indigenous self-determination, and advancing more sustainable land use systems.

Background. Pulmonary embolism (PE) is a rare yet serious postoperative complication for lung transplant recipients (LTRs). The association between timing and severity of PE and the development of chronic allograft lung dysfunction (CLAD) has not been described. Methods. A single-center, retrospective cohort analysis of first LTRs included bilateral or single lung transplants and excluded multiorgan transplants and retransplants. PEs were confirmed by computed tomography angiography or ventilation/perfusion (VQ) scans. Infarctions were confirmed on computed tomography angiography by a trained physician. The PE severity was defined by the Pulmonary Embolism Severity Index (PESI) score, a 30-d post-PE mortality risk calculator, and stratified by low I and II (0–85), intermediate III and IV (85–125), and high V (>125). PE and PESI were analyzed in the outcomes of overall survival, graft failure, and chronic lung allograft dysfunction (CLAD). Results. We identified 57 of 928 patients (6.14%) who had at least 1 PE in the LTR cohort with a median follow-up of 1623 d. In the subset with PE, the median PESI score was 85 (75.8–96.5). Most of the PESI scores (32/56 available) were in the low-risk category. In the CLAD analysis, there were 49 LTRs who had a PE and 16 LTRs (33%) had infarction. When treating PE as time-dependent and adjusting for covariates, PE was significantly associated with death (hazard ratio [HR] 1.8; 95% confidence interval [CI], 1.3-2.5), as well as increased risk of graft failure, defined as retransplant, CLAD, or death (HR 1.8; 95% CI, 1.3-2.5), and CLAD (HR 1.7; 95% CI, 1.2-2.4). Infarction was not associated with CLAD or death. The PESI risk category was not a significant predictor of death or CLAD. Conclusions. PE is associated with decreased survival and increased hazard of developing CLAD. PESI score was not a reliable predictor of CLAD or death in this lung transplant cohort.

Abstract. Introduction:. Neuropathic pain (NP) arises from nerve damage or disease, and when not defined, it can impair function and quality of life. Early detection allows for interventions that can enhance outcomes. Diagnosis of NP can be difficult if not properly evaluated. PainDETECT is a NP screening tool developed and successfully used in adults. Objectives:. We evaluated the validity of painDETECT in a pediatric population. Methods:. Adolescents and young adults (10–19 years old) completed painDETECT and quantitative sensory testing (QST), which assessed mechanical allodynia and hyperalgesia, common symptoms of NP. Pain diagnoses, including neuropathic pain (n = 10), were collected through documentation in the medical chart. Descriptive statistics were used to examine age, gender, pain diagnoses, and painDETECT scores. Kruskal–Wallis H tests were conducted to examine differences in QST results across painDETECT categorizations. Results:. Youth with chronic pain (N = 110, Mage = 15.08 ± 2.4 years, Nfemale = 88) and peers without pain (N = 55, Mage = 15.84 ± 3.9 years, Nfemale = 39) completed the painDETECT. The painDETECT scores for youth with pain (M = 12.7 ± 6.76) were significantly higher than those for peers without pain (M = 2.05 ± 2.41). PainDETECT demonstrated 80% sensitivity and 33% specificity in a pediatric population. Individuals who screened positively on the PainDETECT had significantly higher mechanical allodynia (M = 0.640 ± 0.994) compared with those who screened negatively (M = 0.186 ± 0.499; P = 0.016). Conclusion:. PainDETECT demonstrated the ability to screen for NP, and QST mechanical allodynia results were consistent with a positive NP screen. Results of the study offer preliminary support for the ongoing assessment of the painDETECT as a brief, inexpensive, and simple-to-use screening tool for pediatric patients with primary pain complaints.

Colon mucus segregates the intestinal microbiota from host tissues, but how it organizes to function throughout the colon is unclear. In mice, we found that colon mucus consists of two distinct O-glycosylated entities of Muc2: a major form produced by the proximal colon, which encapsulates the fecal material including the microbiota, and a minor form derived from the distal colon, which adheres to the major form. The microbiota directs its own encapsulation by inducing Muc2 production from proximal colon goblet cells. In turn, O-glycans on proximal colon-derived Muc2 modulate the structure and function of the microbiota as well as transcription in the colon mucosa. Our work shows how proximal colon control of mucin production is an important element in the regulation of host-microbiota symbiosis.

Mitochondrial metabolism is entirely dependent on the biosynthesis of the [4Fe-4S] clusters, which are part of the subunits of the respiratory chain. The mitochondrial late ISC pathway mediates the formation of these clusters from simpler [2Fe-2S] molecules and transfers them to client proteins. Here, we characterized the late ISC pathway in one of the simplest mitochondria, mitosomes, of the anaerobic protist Giardia intestinalis that lost the respiratory chain and other hallmarks of mitochondria. In addition to IscA2, Nfu1 and Grx5 we identified a novel BolA1 homologue in G. intestinalis mitosomes. It specifically interacts with Grx5 and according to the high-affinity pulldown also with other core mitosomal components. Using CRISPR/Cas9 we were able to establish full bolA1 knock out, the first cell line lacking a mitosomal protein. Despite the ISC pathway being the only metabolic role of the mitosome no significant changes in the mitosome biology could be observed as neither the number of the mitosomes or their capability to form [2Fe-2S] clusters in vitro was affected. We failed to identify natural client proteins that would require the [2Fe-2S] or [4Fe-4S] cluster within the mitosomes, with the exception of [2Fe-2S] ferredoxin, which is itself part of the ISC pathway. The overall uptake of iron into the cellular proteins remained unchanged as also observed for the grx5 knock out cell line. The pull-downs of all late ISC components were used to build the interactome of the pathway showing specific position of IscA2 due to its interaction with the outer mitosomal membrane proteins. Finally, the comparative analysis across Metamonada species suggested that the adaptation of the late ISC pathway identified in G. intestinalis occurred early in the evolution of this supergroup of eukaryotes.

Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers1-10 and strategies to augment clinical response have largely focused on the T cell compartment. However, other immune subsets may also contribute to anti-tumour immunity11-15, although these have been less well-studied in ICB treatment16. A previously conducted neoadjuvant ICB trial in patients with melanoma showed via targeted expression profiling17 that B cell signatures were enriched in the tumours of patients who respond to treatment versus non-responding patients. To build on this, here we performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumours of responders versus non-responders. Our findings were corroborated using a computational method (MCP-counter18) to estimate the immune and stromal composition in this and two other ICB-treated cohorts (patients with melanoma and renal cell carcinoma). Histological evaluation highlighted the localization of B cells within tertiary lymphoid structures. We assessed the potential functional contributions of B cells via bulk and single-cell RNA sequencing, which demonstrate clonal expansion and unique functional states of B cells in responders. Mass cytometry showed that switched memory B cells were enriched in the tumours of responders. Together, these data provide insights into the potential role of B cells and tertiary lymphoid structures in the response to ICB treatment, with implications for the development of biomarkers and therapeutic targets.