Sexual Identity Differences in Chronic Pain: Results from the 2019 to 2021 National Health Interview Survey.

INTRODUCTION: Chronic pain has been highlighted as an important public health and clinical health issue. The prevalence of chronic pain has been increasing, with notable disparities for many minoritized populations. However, evidence regarding sexual minoritized populations and chronic pain is lacking. Therefore, the purpose of this study is to compare the prevalence of chronic pain among men and women by sexual identity. METHODS: Data from the 2019 to 2021 National Health Interview Survey (n=78,686), a population-based public health surveillance system were analyzed in 2023-2024. This included 592 lesbian/gay and 952 bisexual women as well as 868 gay and 317 bisexual men. Chronic pain measures included frequency, amount of pain, pain limiting activities, and pain affecting family and others. Covariates included age, race/ethnicity, relationship status, education attainment, income, and employment status. RESULTS: After adjusting for covariates, significantly (p<0.05) more gay/lesbian (26.7%) and bisexual (31.6%) women reported experiencing chronic pain "most days or everyday" than straight women (21.7%). More bisexual women reported chronic pain as well as negative impacts in their life due to chronic pain than straight women. More bisexual men also reported experiencing chronic pain "most days or everyday" compared to straight men (26.1% versus 19.6%), although no differences were found for other aspects of pain. CONCLUSIONS: Sexual minoritized populations have a greater burden of chronic pain that should be considered in moving forward in pain work. Future work in this area is needed to understand why these disparities exist and how best to provide care and treatment to those affected.

Extrapulmonary manifestations of pulmonary arterial hypertension.

INTRODUCTION: Extrapulmonary manifestations of pulmonary arterial hypertension (PAH) may play a critical pathobiological role and a deeper understanding will advance insight into mechanisms and novel therapeutic targets. This manuscript reviews our understanding of extrapulmonary manifestations of PAH. AREAS COVERED: A group of experts was assembled and a complimentary PubMed search performed (October 2023 - March 2024). Inflammation is observed throughout the central nervous system and attempts at manipulation are an encouraging step toward novel therapeutics. Retinal vascular imaging holds promise as a noninvasive method of detecting early disease and monitoring treatment responses. PAH patients have gut flora alterations and dysbiosis likely plays a role in systemic inflammation. Despite inconsistent observations, the roles of obesity, insulin resistance and dysregulated metabolism may be illuminated by deep phenotyping of body composition. Skeletal muscle dysfunction is perpetuated by metabolic dysfunction, inflammation, and hypoperfusion, but exercise training shows benefit. Renal, hepatic, and bone marrow abnormalities are observed in PAH and may represent both end-organ damage and disease modifiers. EXPERT OPINION: Insights into systemic manifestations of PAH will illuminate disease mechanisms and novel therapeutic targets. Additional study is needed to understand whether extrapulmonary manifestations are a cause or effect of PAH and how manipulation may affect outcomes.

Novel Liver Injury Phenotypes and Outcomes in Clinical Trial Participants with Pulmonary Hypertension.

RATIONALE: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) cause right ventricular dysfunction which can impact other solid organs. However, the profiles and consequences of hepatic injury due to PAH and CTEPH have not been well-studied. OBJECTIVES: We aimed to identify underlying patterns of liver injury in a cohort of PAH and CTEPH patients enrolled in 15 randomized clinical trials conducted between 1998 and 2014. METHODS: We used unsupervised machine learning to identify liver injury clusters in 13 trials and validated the findings in two additional trials. We then determined whether these liver injury clusters were associated with clinical outcomes or treatment effect heterogeneity. MEASUREMENTS AND MAIN RESULTS: Our training dataset included 4,219 patients and our validation dataset included 1,756 patients with serum total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and albumin data. Using k-means clustering, we identified phenotypes with no liver injury, hepatocellular injury, cholestatic injury, and combined injury patterns. Patients in the cholestatic injury liver cluster had the shortest time to clinical worsening and the highest risk of mortality. The cholestatic injury group also experienced the greatest placebo-corrected treatment effect on six-minute walk distance. Randomization to the experimental arm transitioned patients to a healthier liver status. CONCLUSIONS: Liver injury was associated with adverse outcomes in patients with PAH and CTEPH. Randomization to active treatment had beneficial effects on liver health compared to placebo. The role of liver disease (often subclinical) in determining outcomes warrants prospective studies.

Fatally impaired glucose digestion by propylene glycol in Aedes aegypti (Diptera: Culicidae) and co-formulation with terpenoids for enhancing attractive toxic sugar baits.

Propylene glycol (PG) demonstrates greater efficacy than other sugar polyols. However, the attributes it confers for toxicity and possible co-formulation with other ingredients are unknown. To evaluate this, α-glucosidase and glucose oxidase reactions were performed in Aedes aegypti (L.) (Diptera: Culicidae) to categorize if PG behaves similarly to prior studied sugar alcohols. A combination of no-choice and choice assays was used to determine effective ratios of PG and sucrose, competitiveness against a control of 10% sucrose, and whether mosquitoes recovered from PG consumption. The final trials included ß-cyclodextrin encapsulated cinnamon leaf oil, clove stem oil, patchouli oil, garlic oil, cedarwood oil, and papaya seed oil formulated with 5% sucrose + 5% PG. PG functioned as a linear competitive inhibitor of α-glucosidase. The efficacy of PG was synergized by co-ingestion with equivalent ratios of sucrose. Unlike the high diuretic response to other sugar alcohols, PG resulted in diminished excretion regardless of being co-formulated with sucrose or terpenoids. PG is not especially competitive against unadulterated sugar meals but is likewise not clearly repellent. Although mosquitoes did not recover from ingestion of the glycol meals, there was no indication that mortality would continue to accumulate once the treatments were removed. Of the terpenoids tested, cinnamon and patchouli caused ~50% or less mortality; garlic, cedarwood, and clove caused 80-90% mortality; and papaya seed caused 100% mortality, exceeding all other test groups and the formulation blank. PG is a useful supporting ingredient in attractive toxic sugar bait formulations with flexibility in formulation.

Inhomogeneous high temperature melting and decoupling of charge density waves in spin-triplet superconductor UTe2.

Charge, spin and Cooper-pair density waves have now been widely detected in exotic superconductors. Understanding how these density waves emerge - and become suppressed by external parameters - is a key research direction in condensed matter physics. Here we study the temperature and magnetic-field evolution of charge density waves in the rare spin-triplet superconductor candidate UTe2 using scanning tunneling microscopy/spectroscopy. We reveal that charge modulations composed of three different wave vectors gradually weaken in a spatially inhomogeneous manner, while persisting to surprisingly high temperatures of 10-12 K. We also reveal an unexpected decoupling of the three-component charge density wave state. Our observations match closely to the temperature scale potentially related to short-range magnetic correlations, providing a possible connection between density waves observed by surface probes and intrinsic bulk features. Importantly, charge density wave modulations become suppressed with magnetic field both below and above superconducting Tc in a comparable manner. Our work points towards an intimate connection between hidden magnetic correlations and the origin of the unusual charge density waves in UTe2.

Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial.

RATIONALE: Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. OBJECTIVES: We aimed to determine whether anastrozole improved six-minute walk distance (6MWD) at six months in pulmonary arterial hypertension (PAH). METHODS: We performed a randomized, double-blind, placebo-controlled Phase II clinical trial of anastrozole in subjects with PAH at seven centers. Eighty-four post-menopausal women and men with PAH were randomized in a 1:1 ratio to receive anastrozole 1 mg or placebo by mouth daily, stratified by sex using permuted blocks of variable sizes. All subjects and study staff were masked. The primary outcome was the change from baseline in 6MWD at six months. Using intent-to-treat analysis, we estimated the treatment effect of anastrozole using linear regression models adjusted for sex and baseline 6MWD. Assuming 10% loss to follow-up, we anticipated having 80% power to detect a difference in the change in 6MWD of 22 meters. MEASUREMENTS AND MAIN RESULTS: Forty-one subjects were randomized to placebo and 43 to anastrozole and all received the allocated treatment. Three subjects in the placebo group and two in the anastrozole group discontinued study drug. There was no significant difference in the change in 6MWD at six months (placebo-corrected treatment effect -7.9 m, 95%CI -32.7 - 16.9, p = 0.53). There was no difference in adverse events between the groups. CONCLUSIONS: Anastrozole did not show a significant effect on 6MWD compared to placebo in post-menopausal women and men with PAH. Anastrozole was safe and did not show adverse effects. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT03229499.

Habitat use of Amazonian birds varies by age and foraging guild along a disturbance gradient.

Patterns of habitat use directly influence a species' fitness, yet for many species an individual's age can influence patterns of habitat use. However, in tropical rainforests, which host the greatest terrestrial species diversity, little is known about how age classes of different species use different adjacent habitats of varying quality. We use long-term mist net data from the Amazon rainforest to assess patterns of habitat use among adult, adolescent (teenage) and young understory birds in forest fragments, primary and secondary forest at the Biological Dynamics of Forest Fragments Project in Brazil. Insectivore adults were most common in primary forest, adolescents were equally likely in primary and secondary forest, and all ages were the least common in forest fragments. In contrast to insectivores, frugivores and omnivores showed no differences among all three habitat types. Our results illustrate potential ideal despotic distributions among breeding populations of some guilds of understory birds where adult insectivores may competitively exclude adolescent individuals from primary forest. Secondary forest recovery appears to hold promise as a breeding habitat for frugivore and omnivore species but only as a pre-breeding habitat for insectivores, but as the forest ages, the demographic structure of bird populations should match that of primary forest.

Orphan high field superconductivity in non-superconducting uranium ditelluride.

Reentrant superconductivity is an uncommon phenomenon in which the destructive effects of magnetic field on superconductivity are mitigated, allowing a zero-resistance state to survive under conditions that would otherwise destroy it. Typically, the reentrant superconducting region derives from a zero-field parent superconducting phase. Here, we show that in UTe2 crystals extreme applied magnetic fields give rise to an unprecedented high-field superconductor that lacks a zero-field antecedent. This high-field orphan superconductivity exists at angles offset between 29o and 42o from the crystallographic b to c axes with applied fields between 37 T and 52 T. The stability of field-induced orphan superconductivity presented in this work defies both empirical precedent and theoretical explanation and demonstrates that high-field superconductivity can exist in an otherwise non-superconducting material.

Skeletal muscle architecture and aging: A comparison of ultrasound techniques and an assessment of intrarater reliability.

OBJECTIVE: To assess intrarater reliability of ultrasound-determined measurements of skeletal muscle characteristics across different measurement outcomes, imaging techniques, and age groups. METHODS: 2D ultrasound images (B-mode) of the quadriceps were obtained from young (26 ± 4 year, n = 8 M, 8 F) and older (70 ± 7 year, n = 7 M, 5 F) adults on two occasions, separated by 6 ± 3 days. With participants in both standing and supine postures, images were collected from five anatomical sites along the anterior (two sites) and lateral (three sites) compartments of the thigh corresponding to 56%, 39%, and 22% (lateral only) of femur length. Images were analysed for muscle thickness, pennation angle, and echogenicity. Intraclass correlation coefficients (ICC) were used to assess reliability. RESULTS: Muscle thickness values were higher (p < 0.05) on images collected in the stand versus supine posture only for muscles of the anterior compartment, independent of age. Echogenicity values were higher (p < 0.05) in the vastus intermedius on images collected in the supine versus stand posture only in older adults. Pennation angle values were not impacted by imaging posture (p > 0.05). ICC values for thickness, echogenicity, and pennation angle were generally higher for analyses conducted on images collected in the supine versus stand posture. Imaging posture generated a greater difference in ICC values in the lateral versus anterior muscles and in older versus younger participants. CONCLUSION: Our findings suggest that participant posture during imaging impacts the absolute values and intrarater reliability of ultrasound-determined muscle characteristics in a muscle-specific fashion, and this effect is greater in older compared to younger individuals.

Investigating the "sex paradox" in pulmonary arterial hypertension: Results from the Pulmonary Hypertension Association Registry (PHAR).

BACKGROUND: Female sex is a significant risk factor for pulmonary arterial hypertension (PAH), yet males with PAH have worse survival - a phenomenon referred to as the "sex paradox" in PAH. METHODS: All adult PAH patients in the Pulmonary Hypertension Association Registry (PHAR) with congruent sex and gender were included. Baseline differences in demographics, hemodynamics, functional parameters, and quality of life were assessed by sex. Kaplan-Meier survival analysis was used to evaluate survival by sex. Mediation analysis was conducted with Cox proportional hazards regression by comparing the unadjusted hazard ratios for sex before and after adjustment for covariates. The plausibility of collider-stratification bias was assessed by modeling how large an unmeasured factor would have to be to generate the observed sex-based mortality differences. Subgroup analysis was performed on idiopathic and incident patients. RESULTS: Among the 1,891 patients included, 75% were female. Compared to men, women had less favorable hemodynamics, lower 6-minute walk distance, more PAH therapies, and worse functional class; however, sex-based differences were less pronounced when accounting for body surface area or expected variability by gender. On multivariate analysis, women had a 48% lower risk of death compared to men (Hazard Ratio 0.52, 95% Confidence interval 0.36 - 0.74, p < 0.001). Modeling found that under reasonable assumptions collider-stratification could account for sex-based differences in mortality. CONCLUSIONS: In this large registry of PAH patients new to a care center, men had worse survival than women despite having more favorable baseline characteristics. Collider-stratification bias could account for the observed greater mortality among men.

Pulmonary arterial hypertension treatment: an individual participant data network meta-analysis.

BACKGROUND AND AIMS: Effective therapies that target three main signalling pathways are approved to treat pulmonary arterial hypertension (PAH). However, there are few large patient-level studies that compare the effectiveness of these pathways. The aim of this analysis was to compare the effectiveness of the treatment pathways in PAH and to assess treatment heterogeneity. METHODS: A network meta-analysis was performed using individual participant data of 6811 PAH patients from 20 Phase III randomized clinical trials of therapy for PAH that were submitted to the US Food and Drug Administration. Individual drugs were grouped by the following treatment pathways: endothelin, nitric oxide, and prostacyclin pathways. RESULTS: The mean (±standard deviation) age of the sample was 49.2 (±15.4) years; 78.4% were female, 59.7% had idiopathic PAH, and 36.5% were on background PAH therapy. After covariate adjustment, targeting the endothelin + nitric oxide pathway {ß: 43.7 m [95% confidence interval (CI): 32.9, 54.4]}, nitric oxide pathway [ß: 29.4 m (95% CI: 22.6, 36.3)], endothelin pathway [ß: 25.3 m (95% CI: 19.8, 30.8)], and prostacyclin pathway [oral/inhaled ß: 19.1 m (95% CI: 14.2, 24.0), intravenous/subcutaneous ß: 24.4 m (95% CI: 15.1, 33.7)] significantly increased 6 min walk distance at 12 or 16 weeks compared with placebo. Treatments also significantly reduced the likelihood of having clinical worsening events. There was significant heterogeneity of treatment effects by age, body mass index, hypertension, diabetes, and coronary artery disease. CONCLUSIONS: Drugs targeting the three traditional treatment pathways significantly improve outcomes in PAH, with significant treatment heterogeneity in patients with some comorbidities. Randomized clinical trials are warranted to identify the most effective treatment strategies in a personalized approach.

Probing delivery of a lipid nanoparticle encapsulated self-amplifying mRNA vaccine using coherent Raman microscopy and multiphoton imaging.

The COVID-19 pandemic triggered the resurgence of synthetic RNA vaccine platforms allowing rapid, scalable, low-cost manufacturing, and safe administration of therapeutic vaccines. Self-amplifying mRNA (SAM), which self-replicates upon delivery into the cellular cytoplasm, leads to a strong and sustained immune response. Such mRNAs are encapsulated within lipid nanoparticles (LNPs) that act as a vehicle for delivery to the cell cytoplasm. A better understanding of LNP-mediated SAM uptake and release mechanisms in different types of cells is critical for designing effective vaccines. Here, we investigated the cellular uptake of a SAM-LNP formulation and subsequent intracellular expression of SAM in baby hamster kidney (BHK-21) cells using hyperspectral coherent anti-Stokes Raman scattering (HS-CARS) microscopy and multiphoton-excited fluorescence lifetime imaging microscopy (FLIM). Cell classification pipelines based on HS-CARS and FLIM features were developed to obtain insights on spectral and metabolic changes associated with SAM-LNPs uptake. We observed elevated lipid intensities with the HS-CARS modality in cells treated with LNPs versus PBS-treated cells, and simultaneous fluorescence images revealed SAM expression inside BHK-21 cell nuclei and cytoplasm within 5 h of treatment. In a separate experiment, we observed a strong correlation between the SAM expression and mean fluorescence lifetime of the bound NAD(P)H population. This work demonstrates the ability and significance of multimodal optical imaging techniques to assess the cellular uptake of SAM-LNPs and the subsequent changes occurring in the cellular microenvironment following the vaccine expression.

LSD1 inhibition suppresses ASCL1 and de-represses YAP1 to drive potent activity against neuroendocrine prostate cancer.

Lysine-specific demethylase 1 (LSD1 or KDM1A ) has emerged as a critical mediator of tumor progression in metastatic castration-resistant prostate cancer (mCRPC). Among mCRPC subtypes, neuroendocrine prostate cancer (NEPC) is an exceptionally aggressive variant driven by lineage plasticity, an adaptive resistance mechanism to androgen receptor axis-targeted therapies. Our study shows that LSD1 expression is elevated in NEPC and associated with unfavorable clinical outcomes. Using genetic approaches, we validated the on-target effects of LSD1 inhibition across various models. We investigated the therapeutic potential of bomedemstat, an orally bioavailable, irreversible LSD1 inhibitor with low nanomolar potency. Our findings demonstrate potent antitumor activity against CRPC models, including tumor regressions in NEPC patient-derived xenografts. Mechanistically, our study uncovers that LSD1 inhibition suppresses the neuronal transcriptional program by downregulating ASCL1 through disrupting LSD1:INSM1 interactions and de-repressing YAP1 silencing. Our data support the clinical development of LSD1 inhibitors for treating CRPC - especially the aggressive NE phenotype. Statement of Significance: Neuroendocrine prostate cancer presents a clinical challenge due to the lack of effective treatments. Our research demonstrates that bomedemstat, a potent and selective LSD1 inhibitor, effectively combats neuroendocrine prostate cancer by downregulating the ASCL1- dependent NE transcriptional program and re-expressing YAP1.

Specific and Strong Acceleration of Nitrosation by Nitrosyl Sulfonates Using the Bis-Coordinating Lewis Acid TiCl4 or SnCl4.

Nitrosyl triflate is an excellent donor of NO+ to C═C and very unreactive benzenoids, in contrast to the much less reactive nitrosyl mesylate. However, both of these reagents are strongly activated by the bis-coordinating Lewis acids TiCl4 and SnCl4 and become super reactive NO+ donors. Strong catalysis and activation are even observed with the inherently less electrophilic nitrosyl trifluoroacetate. Monocoordinating strong Lewis acids, e.g., MeAlCl2, are relatively ineffective.

Predicting Acute Brain Injury in Venoarterial Extracorporeal Membrane Oxygenation Patients with Tree-Based Machine Learning: Analysis of the Extracorporeal Life Support Organization Registry.

Objective: To determine if machine learning (ML) can predict acute brain injury (ABI) and identify modifiable risk factors for ABI in venoarterial extracorporeal membrane oxygenation (VA-ECMO) patients. Design: Retrospective cohort study of the Extracorporeal Life Support Organization (ELSO) Registry (2009-2021). Setting: International, multicenter registry study of 676 ECMO centers. Patients: Adults (≥18 years) supported with VA-ECMO or extracorporeal cardiopulmonary resuscitation (ECPR). Interventions: None. Measurements and Main Results: Our primary outcome was ABI: central nervous system (CNS) ischemia, intracranial hemorrhage (ICH), brain death, and seizures. We utilized Random Forest, CatBoost, LightGBM and XGBoost ML algorithms (10-fold leave-one-out cross-validation) to predict and identify features most important for ABI. We extracted 65 total features: demographics, pre-ECMO/on-ECMO laboratory values, and pre-ECMO/on-ECMO settings.Of 35,855 VA-ECMO (non-ECPR) patients (median age=57.8 years, 66% male), 7.7% (n=2,769) experienced ABI. In VA-ECMO (non-ECPR), the area under the receiver-operator characteristics curves (AUC-ROC) to predict ABI, CNS ischemia, and ICH was 0.67, 0.67, and 0.62, respectively. The true positive, true negative, false positive, false negative, positive, and negative predictive values were 33%, 88%, 12%, 67%, 18%, and 94%, respectively for ABI. Longer ECMO duration, higher 24h ECMO pump flow, and higher on-ECMO PaO2 were associated with ABI.Of 10,775 ECPR patients (median age=57.1 years, 68% male), 16.5% (n=1,787) experienced ABI. The AUC-ROC for ABI, CNS ischemia, and ICH was 0.72, 0.73, and 0.69, respectively. The true positive, true negative, false positive, false negative, positive, and negative predictive values were 61%, 70%, 30%, 39%, 29% and 90%, respectively, for ABI. Longer ECMO duration, younger age, and higher 24h ECMO pump flow were associated with ABI. Conclusions: This is the largest study predicting neurological complications on sufficiently powered international ECMO cohorts. Longer ECMO duration and higher 24h pump flow were associated with ABI in both non-ECPR and ECPR VA-ECMO.

Sexual Violence and Mental Health among Young Bi+ and Lesbian Women and Gender Minoritized People.

Introduction: Sexual minoritized people report worse mental health and are at risk of sexual violence compared to their heterosexual peers. Method: We conducted a survey to explore sexual stigma, sexual violence, and mental health among 326 bi+ and lesbian women and gender minoritized people age 18-25. Results: Mental health did not differ by sexual identity; sexual stigma and violence were associated with negative mental health symptoms, as were identifying as BIPOC, as trans or nonbinary, or having less formal education. Conclusion: Sexual stigma and violence are related to mental health among young bi+ and lesbian women and gender minoritized people.

Patient reported outcome measures correlate with step-count in total hip arthroplasty.

BACKGROUND: Passive smartphone-based apps are becoming more common for measuring patient progress after total hip arthroplasty (THA). Optimum activity levels during early THA recovery have not been well documented. OBJECTIVES: Correlations between step-count and patient reported outcome measures (PROMs) during early recovery were explored. This study also investigated how demographics impact step-count during early post-operative recovery. METHODS: Smartphone captured step-count data from 666 THA patients was retrospectively reviewed. Mean age was 64 ± 11 years. 55% were female. Mean BMI was 29 ± 8kg/m2. Mean daily step-count was calculated for each patient over four time-windows: 60 days prior to surgery (preop), 42-49 days postop (6 weeks), 91-98 days postop (3 months), and 183-197 days postop (6 months). Spearman correlation coefficients and linear regression were used to assess the association between PROMs (HOOS-12, HOOS-Jr, and UCLA) were performed. Patients were separated into three step-count levels: low (< 2500 steps/day), medium (2500-5500 steps/day), and high (> 5500 steps/day). Age > 65 years, BMI > 35 kg/m2, and sex were used for demographic comparisons. Post hoc analyses were performed using Welch's unequal variances t-tests, or Wilcoxon rank-sum tests, both with Bonferroni corrections, where appropriate when comparing between groups. Chi-squared analyses were also used when comparing categorical variables. RESULTS: UCLA correlated with step-count at all time-windows (p< 0.001). HOOS12-Function correlated with step-count preoperatively, at 6 weeks, and at 3 months (p< 0.001). High step-count individuals had improved UCLA scores compared to low step-count individuals preoperatively (Δ1.5, p< 0.001), at 6 weeks (Δ0.9, p< 0.001), at 3 months (Δ1.4, p< 0.001), and at 6 months (Δ1.4, p< 0.001). High step-count individuals had improved HOOS12-Function scores compared to low step-count individuals preoperatively (Δ9.6, p< 0.001), at 6 weeks (Δ5.3, p< 0.001), and at 3 months (Δ6.1, p< 0.001). Males had greater step-count at all time points (p< 0.001). Younger patients and low BMI patients had greater step-count across all time points (p< 0.001). CONCLUSION: High step-count improved PROMs scores compared to low step-count. Early post-operative step-count was significantly impacted by age, sex, and BMI. Generic recovery profiles may not be appropriate across diverse populations.

Interpretable machine learning-based predictive modeling of patient outcomes following cardiac surgery.

BACKGROUND: The clinical applicability of machine learning predictions of patient outcomes following cardiac surgery remains unclear. We applied machine learning to predict patient outcomes associated with high morbidity and mortality after cardiac surgery and identified the importance of variables to the derived model's performance. METHODS: We applied machine learning to the Society of Thoracic Surgeons Adult Cardiac Surgery Database to predict postoperative hemorrhage requiring reoperation, venous thromboembolism (VTE), and stroke. We used permutation feature importance to identify variables important to model performance and a misclassification analysis to study the limitations of the model. RESULTS: The study dataset included 662,772 subjects who underwent cardiac surgery between 2015 and 2017 and 240 variables. Hemorrhage requiring reoperation, VTE, and stroke occurred in 2.9%, 1.2%, and 2.0% of subjects, respectively. The model performed remarkably well at predicting all 3 complications (area under the receiver operating characteristic curve, 0.92-0.97). Preoperative and intraoperative variables were not important to model performance; instead, performance for the prediction of all 3 outcomes was driven primarily by several postoperative variables, including known risk factors for the complications, such as mechanical ventilation and new onset of postoperative arrhythmias. Many of the postoperative variables important to model performance also increased the risk of subject misclassification, indicating internal validity. CONCLUSIONS: A machine learning model accurately and reliably predicts patient outcomes following cardiac surgery. Postoperative, as opposed to preoperative or intraoperative variables, are important to model performance. Interventions targeting this period, including minimizing the duration of mechanical ventilation and early treatment of new-onset postoperative arrhythmias, may help lower the risk of these complications.

Resolving problems with the skill retention literature: An empirical demonstration and recommendations for researchers.

Questions about the degree of retention and decay for procedural skills, once acquired but not used for a period of time, have been raised repeatedly in basic and applied research. Despite widespread interest and numerous empirical investigations, definitive answers to the question "How much skill is retained after a period of disuse?" remain elusive. Shortcomings with the literature were identified that limit the ability of researchers to develop models of skill decay for various tasks, including medical/health care, military, sports, and other applications. Problems with design, measurement, analysis, and interpretation aspects of research are reviewed. An empirical study of acquisition and retention after a 1-month delay for four tasks is presented: (1) A mid fidelity air traffic control simulation, (2) a low-fidelity air traffic control task, and (3, 4) two versions of a perceptual/memory search task, with data from 150 participants. The results illustrate how different approaches to measurement and analysis lead to biased interpretations of decay, especially in the context of relearning. Recommendations are provided for research that can clarify decay functions for procedural tasks and may generate improved understanding and actionable models for refresher training programs to optimize skill retention over extended time periods. (PsycInfo Database Record (c) 2023 APA, all rights reserved).