Search

Expert performance in a domain is often defined as maximal adaptation to stable task constraints. This definition is useful when analysing the vertical transition when novices become experts. However, many workplaces undergo considerable changes and, thus, task constraints change as well. In this paper a complementary conceptualisation of expertise is offered, one that focuses on expert performance as recurring adaptation to dynamic task constraints. This definition is useful when analysing the horizontal transition when experts adapt to dynamically changing work contexts. Using the documentary method, the aim of the present study was to analyze cases of horizontal transitions based on qualitative biographical interview data from five experts reconstructing different types of adaptation to technological change in their domains that they have experienced. Implications for studying horizontal transitions at dynamic worksites are discussed.

This article discusses the opportunities and outcomes provided by the Gregory S. Fehribach Center. The Fehribach Center recruits students with physical disabilities at colleges and universities across Indiana for full-time, eight week, paid internships in positions related to the student's academic major. The Center seeks to place between 50 to 60 students each summer, with a limited number of fall and spring internships also available. Students can apply for the program after completing their first year of college through one year after graduation. Graduate students are also encouraged to apply. Internships can be arranged for students with any academic major. Most internships are onsite in the Indianapolis area, though remote options exist and provisions are made for employers who are outside of Indianapolis. The Fehribach Center also provides weekly professional development opportunities to interns and offers additional career development assistance to current and former interns in the form of disability-informed career assessments and career coaching.

Reflective Learning Journals are used to engage students in the learning process. To motivate students to complete the Reflective Learning Journal it is common practice to allocate marks and it is in this area that problems arise. To address the problems rubrics have been used however, most rubrics are based on assigning marks to very straightforward learning objectives embedded in almost every major assignment, and this is not so easy when evaluating/assessing the writing of a reflective journal. Deriving a rubric to suit a reflective learning journal requires attention to writing analytics rather than traditional learning outcomes. This paper presents a rubric developed from the literature on written self-reflection textual analytics. The approach provides a formula driven method as an objective means to alleviate any perception of subjectivity.

Educators of International Teaching Assistants (ITAs) have been overlooked, erroneously. As teacher educators, their work is exponentially important to North American universities. A multiple case study examined three ITA Educators' ideologies, involving data from two interviews -one being a stimulated recall using classroom observations fieldnotes, syllabi, assignments, and feedback left on students' work. Through qualitative content analysis, two incompatible ideologies were found being implemented in sections of one class: one orienting learners to undergraduate classrooms, and the other towards passing mandatory language testing. Cynicism was found to characterize two instructors' pedagogies. Findings highlight the ethical complexities of language teaching and assessment. ITA training programs must address foundational issues and examine how ITA Educators are supported. This novel study provides a baseline for future work on ITA Educators, and contributes to literature on language teachers' ideologies. Future work should elucidate how ITA Educators' identities and external ideologies impact ITAs' learning trajectories.

In recent years, academic interest in new developments in Artificial Intelligence (AI) and its ethical challenges in higher education has increased. The new emerging technologies that have become popular among the university community in recent times require an exhaustive study to evaluate their impact on academic integrity and plagiarism. The main stakeholders in higher education (SoTL, educational authorities, and policymakers) must understand the new trends and the most relevant studies to have action guides that preserve academic integrity standards in deploying AI in the university. This research analyzes scientific articles published in high-impact journals indexed in the Journal Citation Reports (JCR) (n=254) and carries out a bibliometric study using VOSviewer 1.6.18 and WordStat 2023.1. The Normalized Impact per Document (NID) and per Year (NIY) are studied, and four thematic groups and twelve main themes are identified and discussed, allowing the internal research structure of this field of study to be determined. Based on the findings, a roadmap for implementing AI in higher education is proposed, preserving ethical standards and based on three levels (Micro, Meso, Macro). This study offers practical implications for SoTL, academic authorities, and policymakers. Furthermore, the evidence found allows editors of high-impact journals to advise on unclosed gaps and new research trends and new research trends in the area.

This paper presents a review of the literature pertaining to exam anxiety, highlighting findings from empirical studies, theoretical frameworks, and practical strategies. Exam anxiety is a pervasive issue affecting students worldwide, impacting academic performance and psychological well-being. This review explores the causes, manifestations, and consequences of exam anxiety, and evaluates existing interventions. By examining a diverse range of scholarly works, this paper seeks to contribute to a deeper understanding of exam anxiety and offers insights for educators as well as students. The paper also provides a brief list of alternative forms of summative assessment that have the potential to alleviate exam anxiety.

This study connects to an ongoing discussion about the limits and affordances of simulators as realistic and relevant contexts for professional learning, in this case in the development of visual expertise. Earlier studies of simulator-based maritime pilot training conclude that there are risks associated with so-called negative skills transfer due to a lack of photorealism in simulator environments. The aim of this study is to carefully examine how visual expertise develops in and through training in a simulated environment. Through a practice-based approach to the development of visual expertise, and by using qualitative interaction analysis of video recorded training sessions, the analytical focus is directed towards maritime pilot trainees' talk about imperfections and inconsistencies in the virtual environment during exercises in a high-fidelity bridge simulator. Considering the multi-layered nature of the maritime pilot's visual expertise, findings show that the maritime pilots in training noticed and adapted to the specific methodological and technological challenges when manoeuvring a simulated vessel. During such reflection-in-action, they also commented on and explored the differences between, navigating in a simulator, on the one hand, and, on the other hand, navigating on board a ship. Instead of concluding that there is a risk for negative skills transfer that follows from the differences between the two contexts of navigating, we argue that the challenges introduced by representations encountered when training in a virtual environment may add to the expertise of the trainees and lead to enriched conceptual, methodological, and technical knowledge regarding the specificities of visually demanding and ambiguous navigation situations. In this way, this study contributes to advance our understanding of learning in virtual environments to the frontline of learning research.

Transition from high school to higher education poses a significant challenge for students, particularly in chemistry, where students' prior laboratory experience is varied. Traditional laboratory education, focusing on chemical knowledge, scientific methodology, and practical skills, does not focus on the development of translational skills and establishing a proper level of self-efficacy, critical for students' success as future scientists. To address this problem, we developed the Chemical Kitchen, a transdisciplinary simulation utilizing the parallels between professional gastronomy and chemistry laboratory practices. By engaging students in creative food experiments that mimic chemistry experiments, the course aims to enhance practical skills in a less intimidating environment. We evaluated the impact of the Chemical Kitchen on students' self-efficacy through pre- and postcourse surveys. We found a significant adjustment in students' self-efficacy: those with initially lower self-efficacy experienced increases, while those with initially higher self-efficacy saw decreases, showing a "leveling of the playing field" among first-year chemistry students. Qualitative feedback highlighted the course's success in providing a fun, engaging, and meaningful learning experience, underscoring the importance of innovative teaching methods in enhancing practical skills and confidence. This study demonstrates the effectiveness of the Chemical Kitchen in establishing students' self-efficacy and practical and transferable skills, offering a novel approach to laboratory education that could be beneficial across various scientific disciplines. Future research is encouraged to explore the long-term effects of such interventions on students' engagement with science and their overall development as learners.

Transfer pathways are commonly associated with cost savings to students within the policy world. However, few have ventured to empirically examine whether traveling transfer pathways result in savings for students. Through this article, we report on analyses of this topic drawing on a custom linkage between Toronto District School Board, Postsecondary Student Information System, and Canada Student Loans Program administrative data. Such rich data allow us to estimate the relationship between traveling various pathways through Ontario postsecondary education (PSE) and (i) student's propensity to borrow from the CSLP, along with (ii) the total amount they borrowed, while (iii) controlling for a broader range of potential confounders than ever before. Our analyses provide the most conclusive evidence of the cost savings available through transfer pathways in Ontario PSE, and have implications for policy discourse on this topic across comparable jurisdictions.

Since 2011, the Ontario provincial government has made significant investments into improving the efficiency of vertical transfer--from community colleges to university--within its post-secondary education system. During this period, local policy analysts have repeatedly emphasized the need to account for geography when developing strategies to facilitate transfer flows and articulation frameworks within the province. However, we still know relatively little about how the demand for transfer pathways varies across the province. Through this study, we assess regional differences in vertical transfer intent across more than 52,000 community college applicants in the province from 2010 to 2017. Our analyses reveal statistically significant and highly robust regional disparities in vertical transfer intent. Notably, community college applicants in the Toronto region are most likely to intend to transfer to university, while those in the southwest area of the province are considerably less likely to do the same. We theorize these patterns by emphasizing the contrasting local forces that might shape student decision-making across Ontario and comparable jurisdictions.

Revisiting his dissertation journal, the author undertook an autoethnographic study of that period in his life. As a full-time student within a U.S. research university, he had funded his studies by teaching international teaching assistants and undergraduates learning French and Arabic. In this study, he used inductive analysis to explore his language teacher identity (De Costa & Norton, 2017) and language teacher emotion (Han et al., 2023). Three identities and two emotions emerged: a challenged time manager (1) and an aspiring professional instructor (2), and the related emotions of pride in observing his former students and efficacy in bridging his teaching undergraduates and grad students. Nonetheless, managing these roles sensitized him to (adjunct) coworkers' cynicism. He started to become a cynic (3), bringing emotion labor (Benesch & Prior, 2023). Findings confirmed language teacher emotion as relational and conjoined to language teacher identity. This study urges the field of Applied Linguistics to rectify its past omissions by acknowledging today's "invisible practitioners": adjuncted language instructors.

Although explicit instruction is effective in helping second language (L2) learners develop intelligible pronunciation, it is necessary to understand why and how L2 teachers implement such explicit pronunciation instruction systematically in class. Because of its key role in enhancing learners' pronunciation skills, understanding the rationale behind the implementation of explicit instruction by teachers in different contexts is necessary. A key aspect of analysis in the implementation of explicit pronunciation instruction is the teacher's metalanguage knowledge, which could showcase a key component of pronunciation teachers' ability to present phonetic-phonological content in an accessible manner to learners during explicit instruction. This case study analyzed an experienced English-as-a-foreign-language (EFL) teacher's metalanguage knowledge in L2 pronunciation instruction. Using qualitative data-collection methods (e.g., semi-structured interviews, classroom observations, and stimulated-recall interviews), and Freeman's (2020) "Knowledge Base of Language Teaching Framework," the results of this study showcase the way an experienced teacher's metalanguage knowledge influenced the implementation of explicit L2 pronunciation instruction, and how the teacher's metalanguage shaped the type of language available to learners in different activities in class. These results are also discussed in terms of their implications for training teachers in L2 pronunciation pedagogy.

Previous research has underscored the negative effects on students of the abrupt shift to online delivery of education due to the COVID-19 pandemic. Positive education applies the principles of positive psychology to education, which highlights the importance of students' well-being and fosters holistic development. This study investigated whether students' well-being at the start of the semester can predict their academic engagement mid-way through the semester. We collected data on students' well-being and academic engagement in two waves; first, at the beginning of the semester (Time 1) and then 3 months in the semester (Time 2). We tested the students' general well-being and the positive emotion, engagement, relationships, meaning, accomplishment (PERMA) elements at Time 1 with their academic engagement in terms of behavioral, emotional, and cognitive facets at Time 2. Our results show that general well-being at Time positively predicts their total academic engagement and all engagement facets. However, among the PERMA elements, the Meaning element is not correlated with students' engagement or any of its facets. We also tested whether there was a significant change in student well-being and engagement from the start of the semester and midway through. We found that there is a significant small increase in well-being and engagement. Our findings suggest the importance of well-being as a potentially positive resource for students where students with better well-being tend to be more academically engaged. Educational institutions may consider fostering student well-being in their goals to improve the academic success of students.

In this qualitative study, preservice early childhood education teachers created block-based code to control robots and used the robots in field experience at local preschools. The study is grounded in a conceptual framework that weaves together playful programing and resilience, interlocking concepts that can explain sustained engagement during times of challenge. We investigated how and why preservice early childhood teachers exhibit resilience during collaborative programing. We analyzed their debugging processes, reflections, and interviews using a phenomenological lens. We conducted open and axial coding and analysis of discourse and actions during debugging episodes. Results suggest that teachers exhibited resilience due to the following three reasons: through playful coding, preservice early childhood teachers (a) learned that computer science is approachable and fun, (b) engaged in adaptive attribution, and (c) engaged in joint celebration when they observed each other's successes during collaborative tinkering. These findings provide potential insights for teacher learning of computing but also for novices learning to program.

Playing three-dimensional (3D) video games enhances stereo acuity (i.e., the precision of stereopsis) in young adults with normal vision Here we asked whether the improvement in stereoacuity was the result of a reduced disparity pedestal, as indicated by a decreased subjective depth bias (i.e., the accuracy of stereopsis). Twenty-one healthy young participants with normal vision and limited previous video game experience, none had played 3D video games, played first-person-shooter action stereoscopic 3D video games for a total of 40 h. Depth detection performance was measured using random dot stereograms before and after the video game intervention. We found that playing stereoscopic 3D video games boosts the precision, but not the accuracy of depth perception, suggesting that the enhanced stereoacuity did not result from reducing the effects of a disparity pedestal. These types of video games have potential therapeutic applications for improving stereo vision in patients with binocular vision anomalies.

BACKGROUND: Upper limb impairment post-stroke often leads to a predominant use of the less affected arm and consequent learned disuse of the affected side, hindering upper limb outcome. Wearable sensors such as accelerometers, combined with smart reminders (i.e., based on the amount of arm activity), offer a potential approach to promote increased use of the affected arm to improve upper limb use during daily life. This study aimed to evaluate the efficacy of wrist vibratory reminders during a six-week home-based intervention in chronic stroke survivors. METHODS: We evaluated the impact of the home-based intervention on the primary outcome, the Motor Activity Log-14 Item Version scores Amount of Use (MAL-14 AOU), and the secondary outcomes MAL-14 Quality of Movement (QOM) and sensor-derived activity metrics from the affected arm. A randomized controlled trial design was used for the study: the intervention group received personalized reminders based on individualized arm activity goals, while the control group did not receive any feedback. Mixed linear models assessed the influence of the group, week of the intervention period, and initial impairment level on MAL-14 and arm activity metrics. RESULTS: Forty-two participants were enrolled in the study. Overall, participants exhibited modest but not clinically relevant increases in MAL-14 AOU (+ 0.2 points) and QOM (+ 0.2 points) after the intervention period, with no statistically significant differences between the intervention and control group. Feasibility challenges were noted, such as adherence to wearing the trackers and sensor data quality. However, in participants with sufficiently available sensor data (n = 23), the affected arm use extracted from the sensor data was significantly higher in the intervention group (p

We report an experiment eliciting ordering preferences for binomial expressions (e.g. bread and butter vs. butter and bread) in order to investigate the respective influences of productive and item-specific knowledge in language processing. Binomial ordering preferences reflect both (i) productive constraints involving phonological, semantic, and lexical properties, and (ii) item-specific relative frequencies. Bayesian and exemplar-based computational models of acquisition and use predict influences of both productive and item-specific knowledge on ordering preferences, with item-specific knowledge playing a smaller role the lower the expression’s overall frequency. Our results confirm this prediction, but also reveal a role of item-specific knowledge even for binomials with overall frequency less than one in ten million. These findings bring a quantitative perspective to the debate over the roles of productive and item-specific knowledge in language.*.

X-linked lymphoproliferative disease (XLP1) results from SH2D1A gene mutations affecting the SLAM-associated protein (SAP). A regulated lentiviral vector (LV), XLP-SMART LV, designed to express SAP at therapeutic levels in T, NK, and NKT cells, is crucial for effective gene therapy. We experimentally identified 34 genomic regulatory elements of the SH2D1A gene and designed XLP-SMART LVs to emulate the lineage and stage-specific control of SAP. We screened them for their on-target enhancer activity in T, NK, and NKT cells and their off-target enhancer activity in B cell and myeloid populations. In combination, three enhancer elements increased SAP promoter expression up to 4-fold in on-target populations in vitro. NSG-Tg(Hu-IL15) xenograft studies with XLP-SMART LVs demonstrated up to 7-fold greater expression in on-target cells over a control EFS-LV, with no off-target expression. The XLP-SMART LVs exhibited stage-specific T and NK cell expression in peripheral blood, bone marrow, spleen, and thymic tissues (mimicking expression patterns of SAP). Transduction of XLP1 patient CD8+ T cells or BM CD34+ cells with XLP-SMART LVs restored restimulation-induced cell death and NK cytotoxicity to wild-type levels, respectively. These data demonstrate that it is feasible to create a lineage and stage-specific LV to restore the XLP1 phenotype by gene therapy.

Human prenatal skin is populated by innate immune cells, including macrophages, but whether they act solely in immunity or have additional functions in morphogenesis is unclear. Here we assembled a comprehensive multi-omics reference atlas of prenatal human skin (7-17 post-conception weeks), combining single-cell and spatial transcriptomics data, to characterize the microanatomical tissue niches of the skin. This atlas revealed that crosstalk between non-immune and immune cells underpins the formation of hair follicles, is implicated in scarless wound healing and is crucial for skin angiogenesis. We systematically compared a hair-bearing skin organoid (SkO) model derived from human embryonic stem cells and induced pluripotent stem cells to prenatal and adult skin1. The SkO model closely recapitulated in vivo skin epidermal and dermal cell types during hair follicle development and expression of genes implicated in the pathogenesis of genetic hair and skin disorders. However, the SkO model lacked immune cells and had markedly reduced endothelial cell heterogeneity and quantity. Our in vivo prenatal skin cell atlas indicated that macrophages and macrophage-derived growth factors have a role in driving endothelial development. Indeed, vascular network remodelling was enhanced following transfer of autologous macrophages derived from induced pluripotent stem cells into SkO cultures. Innate immune cells are therefore key players in skin morphogenesis beyond their conventional role in immunity, a function they achieve through crosstalk with non-immune cells.

Human embryonic bone and joint formation is determined by coordinated differentiation of progenitors in the nascent skeleton. The cell states, epigenetic processes and key regulatory factors that underlie lineage commitment of these cells remain elusive. Here we applied paired transcriptional and epigenetic profiling of approximately 336,000 nucleus droplets and spatial transcriptomics to establish a multi-omic atlas of human embryonic joint and cranium development between 5 and 11 weeks after conception. Using combined modelling of transcriptional and epigenetic data, we characterized regionally distinct limb and cranial osteoprogenitor trajectories across the embryonic skeleton and further described regulatory networks that govern intramembranous and endochondral ossification. Spatial localization of cell clusters in our in situ sequencing data using a new tool, ISS-Patcher, revealed mechanisms of progenitor zonation during bone and joint formation. Through trajectory analysis, we predicted potential non-canonical cellular origins for human chondrocytes from Schwann cells. We also introduce SNP2Cell, a tool to link cell-type-specific regulatory networks to polygenic traits such as osteoarthritis. Using osteolineage trajectories characterized here, we simulated in silico perturbations of genes that cause monogenic craniosynostosis and implicate potential cell states and disease mechanisms. This work forms a detailed and dynamic regulatory atlas of bone and cartilage maturation and advances our fundamental understanding of cell-fate determination in human skeletal development.

The ab initio theoretical treatment of one-photon double photoionization processes has been limited to atoms and diatomic molecules by the challenges posed by large grid-based representations of the double ionized continuum wave function. To provide a path for extensions to polyatomics, an energy-adapted orbital basis approach is demonstrated that reduces the dimensions of such representations and simultaneously allows larger time steps in time-dependent computational descriptions of double ionization. Additionally, an algorithm that exploits the diagonal nature of the two-electron integrals in the grid basis and dramatically accelerates the transformation between grid and orbital representations is presented. Excellent agreement between the present results and benchmark theoretical calculations is found for H- and Be atoms, as well as the hydrogen molecule, including for the triply differential cross sections that relate the angular distribution and energy sharing of all of the particles in the molecular frame.

Immunisation is a high priority for improving health outcomes. Yet, in many low-income and middle-income countries, achieving coverage targets independently is hindered by lack of domestic resources and reliance on partners support. Both the 2001 Abuja Declaration and 2016 Addis Declaration were key political commitments to improving immunisation coverage; however, many signatories have yet to meet international targets. Despite signing the Global Vaccine Action Plan and Addis Declaration, the Democratic Republic of the Congo (DRC) was unable to fully disburse its portion of allocated funds to cover vaccines without support from Gavi, the Vaccine Alliance and the World Bank between 2017 and 2019. Additionally, during the same time, vaccine coverage outcomes indicated negative trends, with over 750 000 children considered zero-dose in 2018. In 2019, a primary focus of the then newly elected Presidents agenda was universal healthcare. In collaboration with development partners and stakeholders, the first Presidential Forum was held as a public commitment to increasing childhood immunisation and ensuring the country remains polio-free. This article seeks to highlight the key outcomes of the Forum such as the signing of the Kinshasa Declaration, which formally set targets and specified national, provincial and community-level commitments to vaccination and polio eradication. As of 2023, three Forums have been conducted to reiterate political commitment to routine immunisation in the DRC. This type of high-level commitment could serve as a template for other countries struggling to have high engagement as targets for polio eradication and strengthened routine immunisation are set for 2025-2030.

OBJECTIVES: To characterise the long-term success rate of ventral onlay buccal mucosa graft urethroplasty (vBMG) in the management of bulbar urethral stricture disease (USD), assess patient-reported postoperative satisfaction and decision regret, and delineate clinical factors impacting patient-reported metrics. SUBJECTS AND METHODS: Patients with prior vBMG for bulbar USD, performed at Cleveland Clinic between 2003 and 2022, were contacted and brief structured interviews were performed. Stricture recurrence and need for secondary procedures, baseline demographics, and patient-reported outcome surveys were collected. The surveys included the Decision Regret Scale (DRS), the Urethral Stricture Symptom Impact Measure (USSIM) and the 10-item Patient-Reported Outcomes Measurement Information System Short Form, version 1.2 (PROMIS-10). Descriptive, univariate and multivariable analyses were performed for clinical outcomes and survey responses. RESULTS: A total of 104 patients recorded responses. The median patient age was 49 years and the median follow-up was 7.4 years at time of survey. The median graft length was 5 cm and 38% of patients underwent partial thickness augmented anastomotic urethroplasty. At time of follow-up, 10 patients underwent a secondary procedure. Moderate to severe regret on the DRS was found in 12% of patients, and greater regret was associated with recurrence. The mean physical and mental health PROMIS-10 Global Health T-scores were 52 and 53. The mean total USSIM score was 56. A significant correlation was found between USSIM and DRS scores, with higher DRS score and recurrence negatively impacting USSIM score. USSIM scoring across all domains was significantly worse in the moderate to severe DRS group. CONCLUSION: This study showed that vBMG for bulbar USD confers both high success rates and patient-reported satisfaction at extended follow-up, based on emerging and validated patient-reported outcome measures.

PurposeThis study reports on a prospective, multicenter, single-arm, clinical trial utilizing the SonoMotion (San Mateo, California) Break Wave lithotripsy (BWL) device to fragment urinary stones.Materials and methodsPatients with a urinary stone underwent a single treatment of 30 minutes and peak negative pressure of 4.5 to 8 MPa. Subjects were contacted and outcomes assessed at 7, 14, and 35 days after treatment, with clinical follow-up and CT imaging 70 ± 14 days postprocedure. The primary objectives were to assess the safety (hematomas, complications, etc) and effectiveness of BWL (any fragmentation, residual fragments ≤4 mm or ≤2 mm, and completely stone-free rate) as assessed via noncontrast CT-kidneys, ureters, and bladder.ResultsForty-four patients with a ureteral (43%) or renal (57%) stone were treated across 5 centers. Stone fragmentation occurred in 88% of cases; 70% had fragments ≤ 4 and 51% ≤ 2 mm, while 49% were completely stone free on CT; no serious adverse events were reported. Eighty-six percent of patients received either no analgesic medication at all (50%) or minor analgesia (36%). After determining optimal therapy settings, 36 patients were treated and the effectiveness improved exhibiting fragmentation in 92% (33/36), residual fragments ≤ 4 mm in 75% and 58% with fragments ≤ 2 mm with 58% completely stone free. Effectiveness was less in subjects with lower pole stones with 81% fragmentation, 71% having fragments ≤ 4 mm, 29% with fragments ≤ 2 mm, and 29% completely stone free; of distal ureteral stone patients, 89% were completely stone free.ConclusionsBWL offered safe and effective noninvasive stone therapy requiring little to no anesthesia and was carried out successfully in nonoperative environments.Trial registrationClinicalTrials.gov identifier: NCT03811171.

Converging lines of preclinical and clinical research indicate that females, in stark contrast to males, display an increased prevalence of chronic pain. Females also demonstrate weaker analgesic efficacy in response to opioid therapies when compared with males. These sex-specific differences may be driven by dimorphic endogenous opioidergic responses. In rodent models, analgesia exhibited in males but not females was reversed by inhibiting endogenous opioidergic reception. In humans, the sex-specific endogenous system(s) supporting the direct attenuation of evoked pain has not been identified. To determine whether opioidergic blockade reverses self-regulated analgesia in males as compared to females, the present study combined two operationally analogous clinical trials (n = 98; 51 females and 47 males). In a double-blinded, counterbalanced study involving healthy (n = 39) and chronic low back pain (n = 59) populations, a high-dose naloxone (μ-, κ-, δ-opioid antagonist) vs. placebo-saline cross-over design (15 mg/kg bolus +0.1 mg/kg/h) tested the hypothesis that endogenous opioids mediate analgesia in males but not females. An 11-point visual analog scale (VAS) (0 = no pain; 10 = worst pain imaginable) evaluated pain ratings in response to noxious heat stimulation (49 °C; calf). After baseline pain testing, participants were randomized to a validated four-session mindfulness meditation or sham mindfulness meditation training intervention. Participants practiced their respective meditation during noxious heat, intravenous high-dose naloxone, and placebo saline, respectively. In males and females, meditation significantly lowered evoked pain during saline infusion. Intravenous naloxone inhibited analgesia in males, but pain relief was well preserved in females. The present findings indicate that endogenous opioids mediate self-regulated analgesia in males but not females and underscore the need to establish sex-specific pain therapeutics.

BackgroundCompared to normal high-density lipoprotein (HDL) cholesterol values, very high HDL cholesterol is associated with a higher incidence of mortality and atherosclerotic cardiovascular disease (ASCVD). As such, clinical risk stratification among persons with very high HDL cholesterol is challenging.ObjectivesAmong persons with very high HDL cholesterol, the purpose was to determine the prevalence of coronary artery calcium (CAC) and compare the association between traditional risk factors vs CAC for all-cause mortality and ASCVD.MethodsThe primary analysis was completed among 446 participants from the Cedars-Sinai Medical Center of the CAC Consortium with very high HDL cholesterol (≥77 mg/dL in men, ≥97 mg/dL in women). Cox proportional hazards regression assessed the association of CAC and traditional risk factors with all-cause mortality during a median follow-up of 10.7 years. Replication and validation analyses were performed for all-cause mortality among 119 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with very high HDL cholesterol, who also had information on incident ASCVD.ResultsThe mean age was 57.9 years old, 49% were women, and the median HDL cholesterol was 98 mg/dL. One-half of participants (50%) had prevalent CAC, in whom the median CAC score was 118. Prevalent CAC conferred a 3.6-fold higher risk of all-cause mortality (HR: 3.64; 95% CI: 1.21-11.01), which appeared to be a more robust predictor than individual traditional risk factors beyond age. In the validation sample, prevalent CAC but not individual traditional risk factors were associated with all-cause mortality (HR: 2.39; 95% CI: 1.07-5.34) and a 4.0-fold higher risk of ASCVD (HR: 4.06; 95% CI: 1.11-14.84).ConclusionsMeasurement of CAC may facilitate clinical risk assessment among individuals with very high HDL cholesterol.