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Abstract Deep phenotyping describes the use of standardised terminologies to create comprehensive phenotypic descriptions of biomedical phenomena. These characterisations facilitate secondary analysis, evidence synthesis, and practitioner awareness, thereby guiding patient care. The vast majority of this knowledge is derived from sources that describe an academic understanding of disease, including academic literature and experimental databases. Previous work indicates a gulf between the priorities, perspectives, and perceptions held by different healthcare stakeholders. Using social media data, we develop a phenotype model that represents a public perspective on disease and compare this with a model derived from a combination of existing academic phenotype databases. We identified 52,198 positive disease-phenotype associations from social media across 311 diseases. We further identified 24,618 novel phenotype associations not shared by the biomedical and literature-derived phenotype model across 304 diseases, of which we considered 14,531 significant. Manifestations of disease affecting quality of life, and concerning endocrine, digestive, and reproductive diseases were over-represented in the social media phenotype model. An expert clinical review found that social media-derived associations were considered similarly well-established to those derived from literature, and were seen significantly more in patient clinical encounters. The phenotype model recovered from social media presents a significantly different perspective than existing resources derived from biomedical databases and literature, providing a large number of associations novel to the latter dataset. We propose that the integration and interrogation of these public perspectives on the disease can inform clinical awareness, improve secondary analysis, and bridge understanding and priorities across healthcare stakeholders.

In the century following emancipation, Blackamericans developed robust and effective schools despite limited resources. Unfortunately, their successes and contributions to the education system are often overlooked. This interdisciplinary theoretical paper draws on historiographies of segregated school systems, examining the struggles of Blackamerican educators within segregated education systems through the lenses of coloniality and institutional work. This examination reveals a distinct Blackamerican institutional schema rooted in community, guiding educators in navigating structural and systemic dynamics that shape educational opportunities and successfully challenge dominant white education standards. We discuss the coloniality of schooling, a structural framework, and a mindset that continues to undergird our contemporary education system and then draw attention to an alternative perspective. Our goal is to work toward more inclusive and equitable education systems by recognizing and acknowledging the protest and resistance of Blackamerican educators, their contributions to alternative epistemologies, and the mindsets that guided their actions.

Aims: The management of fractures of the medial epicondyle is one of the greatest controversies in paediatric fracture care, with uncertainty concerning the need for surgery. The British Society of Children’s Orthopaedic Surgery prioritized this as their most important research question in paediatric trauma. This is the protocol for a randomized controlled, multicentre, prospective superiority trial of operative fixation versus nonoperative treatment for displaced medial epicondyle fractures: the Surgery or Cast of the EpicoNdyle in Children’s Elbows (SCIENCE) trial. Methods: Children aged seven to 15 years old inclusive, who have sustained a displaced fracture of the medial epicondyle, are eligible to take part. Baseline function using the Patient-Reported Outcomes Measurement Information System (PROMIS) upper limb score, pain measured using the Wong Baker FACES pain scale, and quality of life (QoL) assessed with the EuroQol five-dimension questionnaire for younger patients (EQ-5D-Y) will be collected. Each patient will be randomly allocated (1:1, stratified using a minimization algorithm by centre and initial elbow dislocation status (i.e. dislocated or not-dislocated at presentation to the emergency department)) to either a regimen of the operative fixation or non-surgical treatment. Outcomes: At six weeks, and three, six, and 12 months, data on function, pain, sports/music participation, QoL, immobilization, and analgesia will be collected. These will also be repeated annually until the child reaches the age of 16 years. Four weeks after injury, the main outcomes plus data on complications, resource use, and school absence will be collected. The primary outcome is the PROMIS upper limb score at 12 months post-randomization. All data will be obtained through electronic questionnaires completed by the participants and/or parents/guardians. The NHS number of participants will be stored to enable future data linkage to sources of routinely collected data (i.e. Hospital Episode Statistics). Cite this article: Bone Jt Open 2024;5(1):69–77.

Abstract Objectives We aim to conduct an economic evaluation of the Optilume urethral drug‐coated balloon (DCB) compared with endoscopic management for the treatment of recurrent anterior male urethral stricture in England. Patients and Methods A cohort Markov model was developed to estimate the costs and savings to the NHS over a 5‐year time horizon of adopting Optilume for the treatment of anterior urethral male stricture versus current endoscopic standard of care. A scenario analysis was conducted which compared Optilume to urethroplasty. Probabilistic and deterministic sensitivity analyses were performed to estimate the impact of uncertainties in model parameters. Results When compared with current endoscopic standard of care Optilume resulted in an estimated cost saving of £2502 per patient if introduced in the NHS for the treatment of recurrent anterior male urethral stricture. In the scenario analysis, the use of Optilume compared with urethroplasty resulted in an estimated cost saving of £243. Results were robust to changes in individual input parameters as demonstrated in the deterministic sensitivity analyses, with the monthly probability of symptom recurrence associated with endoscopic management the only exception. Probabilistic sensitivity analysis results demonstrated that Optilume was cost saving in 93.4% of model iterations, when running 1000 iterations. Conclusion Our analysis suggests that the Optilume urethral DCB treatment can be a cost‐saving alternative management option for the treatment of recurrent anterior male urethral stricture within the NHS in England.

IntroductionThe incidence of varicella in Canada has decreased by almost 99% since vaccination was introduced. However, variation in the timing and eligibility of vaccination programs across the country has resulted in some cohorts being under-vaccinated and therefore potentially susceptible to infection.MethodsWe used nationally representative specimens from the Biobank of Statistics Canada's Canadian Health Measures Survey (CHMS) as well as residual specimens from Ontario collected between 2009-2014 to estimate population immunity across age-groups and geography, and identify any groups at increased risk of varicella infection.ResultsThe weighted proportion of specimens with antibody levels above the threshold of protection was 93.6% (95% CI: 92.4, 95.0). Protection was lowest among those aged 3-5 years (54.3%; 95% CI: 47.3, 61.4), but increased with age. Individuals born outside Canada had more than twice the odds of varicella susceptibility than those born in Canada (aOR: 2.7; 95% CI: 1.4, 5.0; p = 0.004). There were no differences by sex or geography within Canada, and there were no statistically significant differences when Ontario CHMS sera were compared to Ontario residual sera, apart from in participants aged 12-19 year age-group, for whom the CHMS estimate (91.2%; 95% CI: 86.7, 95.7) was significantly higher (p = 0.03) than that from residual specimens (85.9%, 95% CI: 81.1, 90.8).DiscussionVaricella immunity in Canada is changing. Children appear to have low population immunity, placing them at greater risk of infection and at increased risk of severe disease as they age. Our results underscore the importance of performing periodic serosurveys to monitor further population immunity changes as the proportion of vaccine-eligible birth-cohorts increases, and to continually assess the risk of outbreaks.

Background: In endurance cycling, both high-intensity interval training (HIIT) and sprint interval training (SIT) have become popular training modalities due to their ability to elicit improvements in performance. Studies have attempted to ascertain which form of interval training might be more beneficial for maximising cycling performance as well as a range of physiological parameters, but an amalgamation of results which explores the influence of different interval training programming variables in trained cyclists has not yet been conducted. Objective: The aims of this study were to: (1) systematically investigate training interventions to determine which training modality, HIIT, SIT or low- to moderate-intensity continuous training (LIT/MICT), leads to greater physiological and performance adaptations in trained cyclists; and (2) determine the moderating effects of interval work-bout duration and intervention length on the overall HIIT/SIT programme. Data Sources: Electronic database searches were conducted using SPORTDiscus and PubMed. Study Selection: Inclusion criteria were: (1) at least recreationally-trained cyclists aged 18–49 years (maximum/peak oxygen uptake [V̇O2max/V̇O2peak] ≥45 mL·kg-1·min-1); (2) training interventions that included a HIIT or SIT group and a control group (or two interval training groups for direct comparisons); (3) minimum intervention length of 2 weeks; (4) interventions that consisted of 2–3 weekly interval training sessions­. Results: Interval training leads to small improvements in all outcome measures combined (overall main effects model, SMD: 0.33 [95%CI = 0.06 to 0.60]) when compared to LIT/MICT in trained cyclists. At the individual level, point estimates favouring HIIT/SIT were negligible (Wingate model: 0.01 [95%CI = -3.56 to 3.57]), trivial (relative V̇O2max/V̇O2peak: 0.10 [95%CI = -0.34 to 0.54]), small (absolute V̇O2max/V̇O2peak: 0.28 [95%CI = 0.15 to 0.40], absolute maximum aerobic power/peak power output: 0.38 [95%CI = 0.15 to 0.61], relative absolute maximum aerobic power/peak power output: 0.43 [95%CI = -0.09 to 0.95], physiological thresholds: 0.46 [95%CI = -0.24 to 1.17]), and large (time-trial/time-to-exhaustion: 0.96 [95%CI = -0.81 to 2.73]) improvements in physiological/performance variables compared to controls, with very imprecise interval estimates for most outcomes. In addition, intervention length did not contribute significantly to the improvements in outcome measures in this population, as the effect estimate was only trivial (βDuration: 0.04 [ 95%CI = -0.07 to 0.15]). Finally, the network meta-analysis did not reveal a clear superior effect of any HIIT/SIT types when directly comparing interval training differing in interval work-bout duration. Conclusion: The results of the meta-analysis indicate that both HIIT and SIT are effective training modalities to elicit physiological adaptations and performance improvements in trained cyclists. Our analyses highlight that the optimisation of interval training prescription in trained cyclists cannot be solely explained by interval type or interval work-bout duration and an individualised approach that takes into account the training/competitive needs of the athlete is warranted.

Abstract Background Cancers of the head and neck region are often characterized by locally advanced, non-metastatic disease. Standard treatments for advanced cervico-facial cancers of the skin or primary head and neck squamous cell carcinoma (HNSCC) include combinations of surgery, radiation and chemotherapy, which are associated with high rates of acute toxicity and complications. Stereotactic body radiotherapy (SBRT) has been shown to be a promising modality of treatment for this patient population in retrospective studies; to our knowledge, there are no prospective clinical studies evaluating the safety and efficacy of SBRT in these patients. Methods This phase 2, single institution, single arm study aims to evaluate response rates to SBRT in older age patients with locally advanced HNSCC for whom primary surgery is not recommended or performed. The intervention is SBRT 45 Gy in 5 fractions given every 3–4 days. Toxicity, quality of life and patient outcomes will be recorded regularly up to 24 months after completion of SBRT. Discussion For this patient population, SBRT may offer a shorter and more effective treatment than the current standard of care palliative regimens. If the study demonstrates that SBRT is safe and effective, then this may lead to randomized studies comparing conventional radiotherapy to SBRT for selected head and neck cancer patients. Trial registration ClinicalTrials.gov Identifier: NCT04435938 . Date registered: June 17, 2020.

Purpose: The natural history of microinvasive (T1mi) breast cancer is uncertain. The objective was to evaluate long-term local and distant recurrence rates following breast conserving surgery (BCS) in a prospective cohort of patients with T1mi compared to T1a-2 disease who received whole breast irradiation (WBI) in the context of a randomized trial of hypofractionation. Methods: 1234 patients with T1-2 N0 breast cancer were randomized to receive adjuvant WBI of 42.5Gy in 16 daily fractions, or 50Gy in 25 daily fractions after BCS. An analysis of patients with T1mi tumors compared with T1a-2 disease was performed. Kaplan-Meier estimates of local recurrence (LR), distant recurrence, and overall survival (OS) were compared using the log-rank test. Results: Median follow-up was 12 years. T1mi was found in 3% (n = 38) of patients. The 10-year LR rate was 22.6% in T1mi vs. 6.9% in T1a-2 breast cancer [hazard ratio (HR) = 3.73; 95% confidence interval (CI): 1.93, 7.19; p

A theoretical account of development in mesocortical anatomy is derived from the free energy principle, operating in a neural field with both Hebbian and anti-Hebbian neural plasticity. An elementary structural unit is proposed, in which synaptic connections at mesoscale are arranged in paired patterns with mirror symmetry. Exchanges of synaptic flux in each pattern form coupled spatial eigenmodes, and the line of mirror reflection between the paired patterns operates as a Markov blanket, so that prediction errors in exchanges between the pairs are minimized. The theoretical analysis is then compared to the outcomes from a biological model of neocortical development, in which neuron precursors are selected by apoptosis for cell body and synaptic connections maximizing synchrony and also minimizing axonal length. It is shown that this model results in patterns of connection with the anticipated mirror symmetries, at micro-, meso- and inter-arial scales, among lateral connections, and in cortical depth. This explains the spatial organization and functional significance of neuron response preferences, and is compatible with the structural form of both columnar and noncolumnar cortex. Multi-way interactions of mirrored representations can provide a preliminary anatomically realistic model of cortical information processing.

Summary: Background: Adopted in 2015, the sustainable development goals (SDGs) have set specific targets (SDG 3.2) for countries to reduce their neonatal mortality rate (NMR) to below 12 deaths per 1000 live births and under 5 mortality rate (U5MR) to below 25 deaths per 1000 live births by 2030. For Pakistan to achieve these targets, there is a need to measure these rates and understand the predictors of child mortality at sub-national level. Launched in 2016, the Umeed-e-Nau (UeN) or New Hope project is based on scaling up proven and effective Maternal and Newborn Child Health (MNCH) interventions in 8 of the highest burden districts of the country, using existing public sector platforms in Pakistan at both the community and facility level. The primary aim of the project is to reduce perinatal mortality in these districts by 20% from baseline. Methods: We report overall neonatal and post neonatal mortality rates for the two years preceding the UeN baseline household survey. Rates were calculated using the synthetic cohort probability method and predictors of neonatal and post neonatal mortality examined using Cox regression. To investigate spatial variations in the mortality rates, we calculated Moran's I at the district level using predicted probabilities of mortality. Finally, we create district level maps of predicted under 5 child mortality using a stochastic partial differentiation approach. Findings: A total of 26,258 children contributed to the analysis of mortality with 838 deaths in the neonatal period and 2236 under-5 deaths during the observation period from March 1, 2015 to March 17, 2017. Overall, we estimated the NMR to be 29.2 per 1000 live births (95% CI: 26.9–31.4) and the U5MR to be 86.1 per 1000 live births (95% CI: 85.5–86.8). We found evidence of within-district geospatial clustering of under 5 mortality (P

Objective The FOURIER trial showed a benefit of the PCSK9 inhibitor evolocumab over placebo with respect to cardiovascular outcomes in patients with cardiovascular disease. However, we observed some inconsistencies between the information in the Clinical Study Report (CSR) and that in the 2017 primary trial results publication. We aimed to restore the mortality data in the FOURIER trial based on the information contained in the death narratives in the CSR.Methods Mortality data in the primary results publication were compared with that in the CSR. In cases of discrepancy between the sources, an independent committee blindly readjudicated and restored the cause of death according to the information in the CSR narratives.Results For 360/870 deaths (41.4%), the cause of death adjudicated by the FOURIER clinical events committee differed from that declared by the local clinical investigator. When comparing the CSR information with the 2017 primary results publication, we found 11 more deaths from myocardial infarction in the evolocumab group (36 vs 25) and 3 less deaths in the placebo group (27 vs 30, respectively). In the CSR, the number of deaths due to cardiac failure in the evolocumab group was almost double those in the placebo group (31 vs 16). While cardiac and vascular deaths were not assessed as separate outcomes in the original trial analysis, after readjudication, we noted that cardiac deaths were numerically, but non-significantly, higher in the evolocumab group (113) than in the placebo group (88; relative risk (RR) 1.28, 95% CI 0.97 to 1.69, p=0.078), whereas non-cardiac vascular deaths were similar between groups (37 in each; RR 1.00, 95% CI 0.63 to 1.58, p=0.999). The reported HR for cardiovascular mortality in the original trial analysis was 1.05 (95% CI 0.88 to 1.25); after readjudication, we found a greater (although still non-significant) relative increase in cardiovascular mortality in the evolocumab treatment group (RR 1.20, 95% CI 0.95 to 1.51, p=0.13).Conclusion After readjudication, deaths of cardiac origin were numerically higher in the evolocumab group than in the placebo group in the FOURIER trial, suggesting possible cardiac harm. At the time the trial was terminated early, a non-significantly higher risk of cardiovascular mortality was observed with evolocumab, which was numerically greater in our readjudication. A complete restoration of the FOURIER trial data is required. In the meantime, clinicians should be sceptical about prescribing evolocumab for patients with established atherosclerotic cardiovascular disease.Trial registration numbers NCT01764633.

Background: Given that K-12 schools necessitate leaders who can advance equity and justice, preparation programs in higher education institutions have prioritized the development of equity-oriented school leaders. However, there has been relatively limited exploration of pedagogical approaches that equip educational leaders to navigate adverse emotional responses and utilize their discomforting emotions as a source of transformation toward equity-oriented principles. When negative emotions are suppressed and/or unexplored within leadership development programs, adult learners will likely miss crucial opportunities for personal growth and transformative change. Purpose: This theoretical article aims to enhance and expand existing scholarship on the pedagogies of emotional discomfort by developing a conceptual-pedagogical framework for preparing equity-driven school leaders. Conceptual Model: We explore the role of emotions in/as learning, drawing insights from the learning science literature, and analyze empirical studies in leadership education to unravel how and why discomforting emotions are triggered and operationalized when learning about racism and inequities. We present a framework, the pedagogy of discomfort toward critical hope, drawing on scholarly work bridging emotional discomfort and critical pedagogy, and exemplified by various examples of pedagogies of discomfort. Building on this foundation, we introduce an emotional scaffolding design centered around three concepts: generating discomfort to make oppression and privilege visible, guided emotion participation for engaging critical reflection and dialogue, and appraising emotions with metacognitive and meta-affect tools. Discussion and Implications: This article extends the scholarship on teaching and learning for developing equity leaders by bridging insights from learning science and critical pedagogy.

Introduction: Health care system transformations that align with the principles of integrated care require the collaborative efforts of various macro-, meso- and micro-level stakeholders. Understanding the roles of various system actors can improve collaboration in ways that support purposeful health system change. Professional associations (PAs) have considerable influence, but little is known about the strategies they use to influence health system transformation. Methods: Using a qualitative descriptive approach, eight interviews with 11 senior level leaders from local PAs were conducted to learn about the strategies used to influence the province-wide reorganization of health care into Ontario Health Teams. Results: During times of health system transformation, PAs balance: (1) supporting members, (2) negotiating with government, (3) collaborating with stakeholders, and (4) reflecting on their role. The enactment of these various functions demonstrates the strategic nature of PAs, and showcases their ability to evolve in ways that align with the dynamic nature of healthcare. Discussion: PAs are highly connected groups, deeply engaged with their members and regularly engaged with other key stakeholders and decision-makers. PAs play a critical role in influencing health system transformations, by bringing forward practical solutions to government that reflect the needs of their members, often frontline clinicians. PAs strategically seek opportunities for collaboration with stakeholders that can amplify their message. Conclusion: Insights from this work could support health system leaders, policymakers, and researchers in leveraging the role of PAs in health system transformations via strategic collaboration.

BackgroundA correlate of protection (CoP) is an immunological marker associated with protection against infection. Despite an urgent need, a CoP for SARS-CoV-2 is currently undefined.ObjectivesOur objective was to review the evidence for a humoral correlate of protection for SARS-CoV-2, including variants of concern.MethodsWe searched OVID MEDLINE, EMBASE, Global Health, Biosis Previews and Scopus to January 4, 2022 and pre-prints (using NIH iSearch COVID-19 portfolio) to December 31, 2021, for studies describing SARS-CoV-2 re-infection or breakthrough infection with associated antibody measures. Two reviewers independently extracted study data and performed quality assessment.ResultsTwenty-five studies were included in our systematic review. Two studies examined the correlation of antibody levels to VE, and reported values from 48.5% to 94.2%. Similarly, several studies found an inverse relationship between antibody levels and infection incidence, risk, or viral load, suggesting that both humoral immunity and other immune components contribute to protection. However, individual level data suggest infection can still occur in the presence of high levels of antibodies. Two studies estimated a quantitative CoP: for Ancestral SARS-CoV-2, these included 154 (95% confidence interval (CI) 42, 559) anti-S binding antibody units/mL (BAU/mL), and 28.6% (95% CI 19.2, 29.2%) of the mean convalescent antibody level following infection. One study reported a CoP for the Alpha (B.1.1.7) variant of concern of 171 (95% CI 57, 519) BAU/mL. No studies have yet reported an Omicron-specific CoP.ConclusionsOur review suggests that a SARS-CoV-2 CoP is likely relative, where higher antibody levels decrease the risk of infection, but do not eliminate it completely. More work is urgently needed in this area to establish a SARS-CoV-2 CoP and guide policy as the pandemic continues.

This article analyzes links between the origins of higher education institutions and the university "faculty development" movements. University faculty development programs surged during the peak of Cold War geopolitics. Thus, we trace the genealogy of higher education institutions to the surge in faculty development programs, specifically relative to histories and ideologies informing and shaping higher education institutions and faculty development programs. Subsequently, the contemporary issues BIPOC faculty members face relative to faculty development programs deriving from developmental psychology and non-academic faculty, clinicians, and university administrators are analyzed. This critical examination of the origins of faculty development concludes with a few suggested opportunities for repurposing faculty development toward decoloniality in higher education.

This article contextualises the crisis in Black education and the death of a 100-year-old Black educational system resulting from an unintended consequence of Brown: the excavation of thousands of highly educated and skilled Black educators. This theoretical article advances the literature on Brown using two critical race theory (CRT) tenets, the permanence of racism and interest convergence, to discursively trace the regression of Black education. This article illustrates the myriad ways interest convergence and the permanence of racism contribute to crises in Black educational systems and the death of a 100-year-old Black educational system. A limitation of CRT in education is the homogenous treatment of Black people despite their variations and conditions. Additionally, analysing connections between Brown, ESEA, and NCLB needs further examination. Finally, I advance that Black resistance to the permanence of racism in the US had global interest convergence implications and aligned with decolonial and independence movements.