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AIM OF STUDY: Chromosomal translocations involving neurotrophic receptor tyrosine kinases (NTRKs) have been identified in 20 % of soft tissue sarcomas. This work focuses on the EML4-NTRK3 translocation identified in cases of Infantile Fibrosarcoma, which contains the coiled-coil multimerization domain of Echinoderm Microtubule-like protein 4 (EML4) fused with the tyrosine kinase domain of Neurotrophic Receptor Tyrosine Kinase 3 (NTRK3). The aim of the study was to test the importance of tyrosine kinase activity and multimerization for the oncogenic activity of EML4-NTRK3. METHODS: These studies examined EML4-NTRK3 proteins containing a kinase-dead or WT kinase domain, together with mutations in specific salt bridge residues within the coiled-coil domain. Biological activity was assayed using focus assays in NIH3T3 cells. The MAPK/ERK, JAK/STAT3 and PI3K/AKT pathways were analyzed for downstream activation of signaling pathways. Localization of EML4-NTRK3 proteins was examined by immunofluorescence microscopy, and the ability of the EML4 coiled-coil domain to drive protein multimerization was examined by biochemical assays. RESULTS: Activation of EML4-NTRK3 relies on both the tyrosine kinase activity of NTRK3 and salt-bridge stabilization within the coiled-coil domain of EML4. The tyrosine kinase activity of NTRK3 is essential for the biological activation of EML4-NTRK3. Furthermore, EML4-NTRK3 activates downstream signaling pathways MAPK/ERK, JAK/STAT3 and PKC/PLCγ. The disruption of three specific salt bridge interactions within the EML4 coiled-coil domain of EML4-NTRK3 blocks downstream activation, biological activity, and the ability to hetero-multimerize with EML4. We also demonstrate that EML4-NTRK3 is localized in the cytoplasm and fails to associate with microtubules. CONCLUDING STATEMENT: These data suggest potential therapeutic strategies for Infantile Fibrosarcoma cases bearing EML4-NTRK3 fusion through inhibition of salt bridge interactions and disruption of multimerization.

When constructed-response items are administered for a second time, it is necessary to evaluate whether the current Time B administration's raters have drifted from the scoring of the original administration at Time A. To study this, Time A papers are sampled and rescored by Time B scorers. Commonly the scores are compared using the proportion of exact agreement across times and/or t-statistics comparing Time A means to Time B means. It is common to treat these rescores with procedures that assume a multinomial sampling model, which is incorrect. The correct, product-multinomial model reflects the stratification of Time A scores. Using direct computation, the research report demonstrates that both proportion of exact agreement and the t-statistic can deviate substantially from expected behavior, providing misleading results. Reweighting the rescore table gives each statistic the correct expected value but does not guarantee that the usual sampling distributions hold. It is also noted that the results apply to a wider class of situations in which a set of papers is scored by one group of raters or scoring engine and then a sample is selected to be evaluated by a different group of raters or scoring engine.

Neurotrophic receptor tyrosine kinases (NTRKs) belong to the receptor tyrosine kinase (RTK) family. NTRKs are responsible for the activation of multiple downstream signaling pathways that regulate cell growth, proliferation, differentiation, and apoptosis. NTRK-associated mutations often result in oncogenesis and lead to aberrant activation of downstream signaling pathways including MAPK, JAK/STAT, and PLCγ1. This study characterizes the NACC2-NTRK2 oncogenic fusion protein that leads to pilocytic astrocytoma and pediatric glioblastoma. This fusion joins the BTB domain (Broad-complex, Tramtrack, and Bric-a-brac) domain of NACC2 (Nucleus Accumbens-associated protein 2) with the transmembrane helix and tyrosine kinase domain of NTRK2. We focus on identifying critical domains for the biological activity of the fusion protein. Mutations were introduced in the charged pocket of the BTB domain or in the monomer core, based on a structural comparison of the NACC2 BTB domain with that of PLZF, another BTB-containing protein. Mutations were also introduced into the NTRK2-derived portion to allow comparison of two different breakpoints that have been clinically reported. We show that activation of the NTRK2 kinase domain relies on multimerization of the BTB domain in NACC2-NTRK2. Mutations which disrupt BTB-mediated multimerization significantly reduce kinase activity and downstream signaling. The ability of these mutations to abrogate biological activity suggests that BTB domain inhibition could be a potential treatment for NACC2-NTRK2-induced cancers. Removal of the transmembrane helix leads to enhanced stability of the fusion protein and increased activity of the NACC2-NTRK2 fusion, suggesting a mechanism for the oncogenicity of a distinct NACC2-NTRK2 isoform observed in pediatric glioblastoma.

Abstract The study of biological soft tissue structures at the micron scale details the function of healthy and pathological tissues, which is vital in the diagnosis and treatment of diseases. Speckle based X-ray phase contrast tomographic scans at a nanometer scale have the potential to thoroughly analyse such tissues in a quantitative and qualitative manner. Diamond light source, the UKs national synchrotron facility developed and refined a 1-D X-ray speckle-based imaging technique, referred to as Fly scan mode. This novel image acquisition technique was used to perform a rapid structural composition scan of rodent lung histology samples. The rodent samples were taken from healthy and Staphylococcus aureus induced acute respiratory distress syndrome models. The analysis and cross comparison of the fly scan method, absorption-based tomography and conventional histopathology H&E staining microscopy are discussed in this paper. This analysis and cross comparison outline the ways the speckle-based technique can be of benefit. These advantages include improved soft tissue contrast, 3-D volumetric rendering, segmentation of specific gross tissue structures, quantitative analysis of gross tissue volume. A further advantage is the analysis of cellular distribution throughout the volumetric rendering of the tissue sample. The study also details the current limitations of this technique and points to ways in which future work on this imaging modality may progress.

Trend scoring constructed response items (i.e. rescoring Time A responses at Time B) gives rise to two-way data that follow a product multinomial distribution rather than the multinomial distribution that is usually assumed. Recent work has shown that the difference in sampling model can have profound negative effects on statistics usually used to monitor rater drift. In this paper, three statistics, termed E-statistics, that account for the product-multinomial sampling by comparing conditional distributions, are introduced. A simulation compares performance with the paired t-test and Stuart's Q in detecting rater drift. Both the paired t-test and Q suffered extreme Type I error inflation for certain rescore study designs. The new E-statistics maintained good Type I error control and had good power to detect rater drift across occasions.

Abstract Background Despite surgical and pharmacological interventions, endometriosis can recur. Reliable information regarding risk of recurrence following a first diagnosis is scant. The aim of this study was to examine clinical and survey data in the setting of disease recurrence to identify predictors of risk of endometriosis recurrence. Methods This observational study reviewed data from 794 patients having surgery for pelvic pain or endometriosis. Patients were stratified into two analytic groups based on self-reported or surgically confirmed recurrent endometriosis. Statistical analyses included univariate, followed by multivariate logistic regression to identify risk factors of recurrence, with least absolute shrinkage and selection operator (Lasso) regularisation. Risk-calibrated Supersparse Linear Integer Models (RiskSLIM) and survival analyses (with Lasso) were undertaken to identify predictive features of recurrence. Results Several significant features were repeatedly identified in association with recurrence, including adhesions, high rASRM score, deep disease, bowel lesions, adenomyosis, emergency room attendance for pelvic pain, younger age at menarche, higher gravidity, high blood pressure and older age. In the surgically confirmed group, with a score of 5, the RiskSLIM method was able to predict the risk of recurrence (compared to a single diagnosis) at 95.3% and included adenomyosis and adhesions in the model. Survival analysis further highlighted bowel lesions, adhesions and adenomyosis. Conclusions Following an initial diagnosis of endometriosis, clinical decision-making regarding disease management should take into consideration the presence of bowel lesions, adhesions and adenomyosis, which increase the risk of endometriosis recurrence.

In recent years, organised and competitive video gaming, esports, has gained enormous popularity in many parts of the world, contributing to the growing professionalisation of this sports branch. To become or remain a professional esports player, individuals practice video gaming for several hours a day while remaining in a sitting posture which may not only lead to a decrease in training quality in the short term (eg, due to cognitive fatigue) but also put them at a higher risk for negative health events in the long-term (eg, overuse injuries). Thus, interrupting periods of prolonged video gaming in a sitting posture with acute physical exercise is strongly recommended for esports players even though the optimal dosage of acute physical exercise breaks remains unclear. To address this gap, we propose in this viewpoint that traditional concepts of exercise prescription and dosage determination using the variables frequency, intensity, time (also referred to as duration) and type of physical exercise (ie, abbreviated with the acronym FITT) should be complemented by the variable density which characterises the timing of consecutive bouts of acute physical exercise during an esports session.

Background The sea spiders (Pycnogonida Latreille, 1810) of the Hunsrück Slate (Lower Devonian, ~400 million years ago) are iconic in their abundance, exquisite pyritic preservation, and in their distinctive body plan compared to extant sea spiders (Pantopoda Gerstäcker, 1863). Consequently, the Hunsrück sea spiders are important in understanding the deep evolutionary history of Pycnogonida, yet they remain poorly characterised, impacting upon attempts to establish a time-calibrated phylogeny of sea spiders. Methods Here, we investigated previously described and new material representing four of the five Hunsrück pycnogonids: Flagellopantopus blocki Poschmann & Dunlop, 2006; Palaeoisopus problematicus Broili, 1928; Palaeopantopus maucheri Broili, 1929; and Pentapantopus vogteli Kühl, Poschmann & Rust, 2013; as well as a few unidentified specimens. Using X-ray microtomography and Reflectance Transformation Imaging, we describe new fossils, provide evidence for newly revealed anatomical features, and interpret these data in comparison to extant species. We also reinterpret the previously published illustration of the (probably lost) holotype of Palaeothea devonica Bergström, Stürmer & Winter, 1980. Results We provide the first detailed description of the cephalic appendages of Palaeoisopus problematicus and revise the interpretation of the organisation of its ocular tubercle. Furthermore, we provide new insights into the structure of the legs and the proboscis of Palaeopantopus maucheri, the first description of the body of Flagellopantopus blocki and describe a new specimen of Pentapantopus vogteli, demonstrating that it had eight legs, in contrast to previous interpretations. We argue that, contrary to previous suggestions, Palaeothea devonica probably had a different body plan from extant pantopods. We discuss the ecological traits of the Hunsrück pycnogonids based on their morphological adaptations, and conclude that there is no compelling evidence of Pantopoda in the Devonian. Through comparative interpretation of the legs as well as general morphology, we can divide the Hunsrück pycnogonids into two morphological groups, while Pantopoda constitutes a third morphological group.

Summary: Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury. Methods: Exposure–response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates. Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13–15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13–15 and positive CT (1.21–2.81), GCS 9–12 (1.16–2.02), GCS 3–8 (1.09–1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51–1.80) percentages of unfavourable outcome were 37–51% in the lowest quintiles of biomarker levels and reached 90–94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83–3.79), the percentages were 2–4% and 19–28% in the lowest and highest biomarker quintiles, respectively. Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity. Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.

The effective containment of fission products (FPs) within tri-structural isotropic (TRISO) fuel particles is crucial for the safety and efficiency of High Temperature Gas-cooled Reactors (HTGRs). Combining multi-scale (µm to nm) and multi-dimensional (2D and 3D) analysis, this study focuses on the migration mechanisms of silver (Ag), for which the Ag-110 m FP isotope is radiotoxic, facilitated by reactions with palladium (Pd) alloys and the silicon carbide (SiC) layer at elevated temperatures (1300–1500 °C). Three primary pathways for Ag migration are identified: (1) diffusion in solid palladium silicide to form (Pd,Ag)2Si, (2) infiltration through cracks and pores in the carbon phase, and (3) liquid phase migration along SiC grain boundaries. Especially at temperatures above the melting point of Pd2Si (1404 °C), a ‘dissolution-recrystallisation’ mechanism is proposed of the Ag-Pd-Si liquid phase migrating along SiC grain boundaries. The study employs state-of-the-art in-situ heating transmission electron microscopy (TEM) techniques to directly observe the dynamic migration processes of Pd silicide within SiC, providing unprecedented insights into the liquid behaviour in TRISO fuel. These findings highlight the significant role of liquid phases in determining the transport of FPs through the TRISO-SiC which is vital for developing strategies that enhance the safety and efficacy of HTGRs.

Objectives: To compare the effectiveness of cognitive aid use during resuscitation with no use of cognitive aids on cardiopulmonary resuscitation quality and performance. Methods: This systematic review followed the PICOST format. All randomised controlled trials and non-randomised studies evaluating cognitive aid use during (simulated) resuscitation were included in any setting. Unpublished studies were excluded. We did not include studies that reported cognitive aid use during training for resuscitation alone. Medline, Embase and Cochrane databases were searched from inception until July 2019 (updated August 2022, November 2023, and 23 April 2024). We did not search trial registries. Title and abstract screening, full-text screening, data extraction, risk of bias assessment (using RoB2 and ROBINS-I), and certainty of evidence (using GRADE) were performed by two researchers. PRISMA reporting standards were followed, and registration (PROSPERO CRD42020159162, version 19 July 2022) was performed. No funding has been obtained. Results: The literature search identified 5029 citations. After removing 512 duplicates, reviewing the titles and abstracts of the remaining articles yielded 103 articles for full-text review. Hand-searching identified 3 more studies for full-text review. Of these, 29 studies were included in the final analysis. No clinical studies involving patients were identified. The review was limited to indirect evidence from simulation studies only. The results are presented in five different populations: healthcare professionals managing simulated resuscitations in neonates, children, adult advanced life support, and other emergencies; as well as lay providers managing resuscitations. Main outcomes were adherence to protocol or process, adherence to protocol or process assessed by performance score, CPR performance and retention, and feasibility of chatbot guidance. The risk of bias assessment ranged from low to high. Studies in neonatal, paediatric and adult life support delivered by healthcare professionals showed benefits of using cognitive aids, however, some studies evaluating resuscitations by lay providers reported undesirable effects. The performance of a meta-analysis was not possible due to significant methodological heterogeneity. The certainty of evidence was rated as moderate to very low due to serious indirectness, (very) serious risk of bias, serious inconsistency and (very) serious imprecision. Conclusion: Because of the very low certainty evidence from simulation studies, we suggest that cognitive aids should be used by healthcare professionals during resuscitation. In contrast, we do not suggest use of cognitive aids for lay providers, based on low certainty evidence.

Lentinula is a broadly distributed group of fungi that contains the cultivated shiitake mushroom, L. edodes. We sequenced 24 genomes representing eight described species and several unnamed lineages of Lentinula from 15 countries on four continents. Lentinula comprises four major clades that arose in the Oligocene, three in the Americas and one in Asia-Australasia. To expand sampling of shiitake mushrooms, we assembled 60 genomes of L. edodes from China that were previously published as raw Illumina reads and added them to our dataset. Lentinula edodes sensu lato (s. lat.) contains three lineages that may warrant recognition as species, one including a single isolate from Nepal that is the sister group to the rest of L. edodes s. lat., a second with 20 cultivars and 12 wild isolates from China, Japan, Korea, and the Russian Far East, and a third with 28 wild isolates from China, Thailand, and Vietnam. Two additional lineages in China have arisen by hybridization among the second and third groups. Genes encoding cysteine sulfoxide lyase (lecsl) and γ-glutamyl transpeptidase (leggt), which are implicated in biosynthesis of the organosulfur flavor compound lenthionine, have diversified in Lentinula. Paralogs of both genes that are unique to Lentinula (lecsl 3 and leggt 5b) are coordinately up-regulated in fruiting bodies of L. edodes. The pangenome of L. edodes s. lat. contains 20,308 groups of orthologous genes, but only 6,438 orthogroups (32%) are shared among all strains, whereas 3,444 orthogroups (17%) are found only in wild populations, which should be targeted for conservation.

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.

FGFR3-TACC3 represents an oncogenic fusion protein frequently identified in glioblastoma, lung cancer, bladder cancer, oral cancer, head and neck squamous cell carcinoma, gallbladder cancer, and cervical cancer. Various exon breakpoints of FGFR3-TACC3 have been identified in cancers; these were analyzed to determine the minimum contribution of TACC3 for activation of the FGFR3-TACC3 fusion protein. While TACC3 exons 11 and 12 are dispensable for activity, our results show that FGFR3-TACC3 requires exons 13-16 for biological activity. A detailed analysis of exon 13, which consists of 8 heptads forming a coiled coil, further defined the minimal region for biological activity as consisting of 5 heptads from exon 13, in addition to exons 14-16. These conclusions were supported by transformation assays of biological activity, examination of MAPK pathway activation, analysis of disulfide-bonded FGFR3-TACC3, and by examination of the Endoglycosidase H-resistant portion of FGFR3-TACC3. These results demonstrate that clinically identified FGFR3-TACC3 fusion proteins differ in their biological activity, depending upon the specific breakpoint. This study further suggests the TACC3 dimerization domain of FGFR3-TACC3 as a novel target in treating FGFR translocation driven cancers.

Glioblastoma (GBM) is characterized by a particularly invasive phenotype, supported by oncogenic signals from the fibroblast growth factor (FGF)/ FGF receptor (FGFR) network. However, a possible role of FGFR4 remained elusive so far. Several transcriptomic glioma datasets were analyzed. An extended panel of primary surgical specimen-derived and immortalized GBM (stem)cell models and original tumor tissues were screened for FGFR4 expression. GBM models engineered for wild-type and dominant-negative FGFR4 overexpression were investigated regarding aggressiveness and xenograft formation. Gene set enrichment analyses of FGFR4-modulated GBM models were compared to patient-derived datasets. Despite widely absent in adult brain, FGFR4 mRNA was distinctly expressed in embryonic neural stem cells and significantly upregulated in glioblastoma. Pronounced FGFR4 overexpression defined a distinct GBM patient subgroup with dismal prognosis. Expression levels of FGFR4 and its specific ligands FGF19/FGF23 correlated both in vitro and in vivo and were progressively upregulated in the vast majority of recurrent tumors. Based on overexpression/blockade experiments in respective GBM models, a central pro-oncogenic function of FGFR4 concerning viability, adhesion, migration, and clonogenicity was identified. Expression of dominant-negative FGFR4 resulted in diminished (subcutaneous) or blocked (orthotopic) GBM xenograft formation in the mouse and reduced invasiveness in zebrafish xenotransplantation models. In vitro and in vivo data consistently revealed distinct FGFR4 and integrin/extracellular matrix interactions. Accordingly, FGFR4 blockade profoundly sensitized FGFR4-overexpressing GBM models towards integrin/focal adhesion kinase inhibitors. Collectively, FGFR4 overexpression contributes to the malignant phenotype of a highly aggressive GBM subgroup and is associated with integrin-related therapeutic vulnerabilities.

Key Clinical Message It is important to consider all potential pain management modalities including alternative treatment on managing complex pain presentations. Acupuncture is a treatment modality that may result in reduction of pain in patients with significant medical comorbidities due to MPS IVA.

Aim of study: Chromosomal translocations involving neurotrophic receptor tyrosine kinases (NTRKs) have been identified in 20 % of soft tissue sarcomas. This work focuses on the EML4-NTRK3 translocation identified in cases of Infantile Fibrosarcoma, which contains the coiled-coil multimerization domain of Echinoderm Microtubule-like protein 4 (EML4) fused with the tyrosine kinase domain of Neurotrophic Receptor Tyrosine Kinase 3 (NTRK3). The aim of the study was to test the importance of tyrosine kinase activity and multimerization for the oncogenic activity of EML4-NTRK3. Methods: These studies examined EML4-NTRK3 proteins containing a kinase-dead or WT kinase domain, together with mutations in specific salt bridge residues within the coiled-coil domain. Biological activity was assayed using focus assays in NIH3T3 cells. The MAPK/ERK, JAK/STAT3 and PI3K/AKT pathways were analyzed for downstream activation of signaling pathways. Localization of EML4-NTRK3 proteins was examined by immunofluorescence microscopy, and the ability of the EML4 coiled-coil domain to drive protein multimerization was examined by biochemical assays. Results: Activation of EML4-NTRK3 relies on both the tyrosine kinase activity of NTRK3 and salt-bridge stabilization within the coiled-coil domain of EML4. The tyrosine kinase activity of NTRK3 is essential for the biological activation of EML4-NTRK3. Furthermore, EML4-NTRK3 activates downstream signaling pathways MAPK/ERK, JAK/STAT3 and PKC/PLCγ. The disruption of three specific salt bridge interactions within the EML4 coiled-coil domain of EML4-NTRK3 blocks downstream activation, biological activity, and the ability to hetero-multimerize with EML4. We also demonstrate that EML4-NTRK3 is localized in the cytoplasm and fails to associate with microtubules. Concluding statement: These data suggest potential therapeutic strategies for Infantile Fibrosarcoma cases bearing EML4-NTRK3 fusion through inhibition of salt bridge interactions and disruption of multimerization.

Book review of Burns, Rachel A., and Rafael J. Pascual, eds. 2022. Tradition and Innovation in Old English Metre. Leeds: Arc Humanities Press. Pp. xii + 281. ISBN 1802700250.

Aim: To systematically review published literature to evaluate the impact of gamified learning on educational and clinical outcomes during life support education. Methods: This systematic review was conducted as part of the continuous evidence evaluation process of the International Liaison Committee on Resuscitation (ILCOR). A search of PubMed, Embase, and Cochrane was conducted from inception until February 12, 2024. Studies examining incorporation of gamified learning were eligible for inclusion. Reviewers independently extracted data on study design and outcomes; appropriate risk of bias assessment tools were used across all outcomes. Results: 2261 articles were identified and screened, yielding sixteen articles (seven randomized trials, nine observational studies) which comprised the final review. No meta-analyses were conducted due to significant heterogeneity of intervention, population, and outcome. Only one study was found to have a low risk of bias; the remaining studies were found to have moderate to high risk. Fourteen studies were in healthcare providers and two were in laypersons. Most studies (11 of 16) examined the impact of a digital platform (computer or smartphone). Most (15 of 16) studies found a positive effect on at least one educational domain; one study found no effect. No included study found a negative effect on any educational domain. Conclusion: This systematic review found a very heterogeneous group of studies with low certainty evidence, all but one of which demonstrated a positive effect on one or more educational domains. Future studies should examine the underlying causes of improved learning with gamification and assess the resource requirements with implementation and dissemination of gamified learning.

Aim: To evaluate the effectiveness of Rapid Cycle Deliberate Practice (RCDP) compared to traditional instruction or other forms of learning on resuscitation training outcomes and on clinical and/or patient-related outcomes. Methods: As part of the continuous evidence evaluation process of the International Liaison Committee on Resuscitation it was conducted this review and searched Medline, Embase and Cochrane from inception to Feb 12th, 2024. Risk of bias assessment was performed with the Risk of Bias in Non-randomized Studies of Interventions assessment tool and the Revised Cochrane risk-of-bias tool for randomized trials. The GRADE approach was used to evaluate the overall certainty of evidence for each outcome. Results: 4420 abstracts were retrieved by the initial search and 10 additional studies were identified through other resources. Sixty-five studies were selected for eligibility and nine simulated studies met the inclusion criteria. A meta-analysis was performed on three outcomes: time to chest compressions, time to defibrillation and time to first epinephrine given, which showed that RCDP had significantly shorter time to defibrillation and time to administration of epinephrine than controls. The overall certainty of evidence was very low across all outcomes due to risk of bias, inconsistency, indirectness, and imprecision. Conclusion: It may be reasonable to include RCDP as an instructional design feature of basic and advanced life support training. However, substantial variations of delivering RCDP exist and there is no uniform use of RCDP. Further research is necessary on medium/long-term effects of RCDP training, and on the effects on different target groups of training.

Much of the student-staff partnership literature calls for increased collaboration and power sharing among staff and students. Less common are accounts by student partners themselves that take up the challenge of what partnership and power feel like as universities embrace their neoliberal trajectory - and - purport to do so on behalf of students themselves. Especially acute is the conundrum of how partnership initiatives can, and do, reproduce the very power dynamics they set out to transform. We are a group of students and staff working in curriculum partnership together at Western Sydney University. The context of our work together is the 21C project, a university-wide strategy to transform curriculum, teaching, and learning, drawing on 'partnership pedagogy'. In this paper, we engage in a process of reflexive inquiry to interrogate a new elective unit that many of us are involved in as advocates, co-creators, as students and staff learning together, and as evaluators, called "We are the university: Students co-creating change" (WATU). To highlight partnership's intricate power plays, we offer a fictionalised account to reflect our multi-voiced experiences of being involved in WATU. We have come to understand power's simultaneity in partnership as forms of power "over," as "permission-giving," as "sharing (or partnership)," and as the power "to act (agency)." The account is our story of partnership's inevitable contradictions - a collaboration that teaches us about the challenges of working together while being cautious of partnership's transformatory claims. [The page range (258-274) cited in the .pdf is incorrect. The correct page range is p258-272.]