Advanced accent/dialect identification and accentedness assessment with multi-embedding models and automatic speech recognition.

The ability to accurately classify accents and assess accentedness in non-native speakers are challenging tasks due primarily to the complexity and diversity of accent and dialect variations. In this study, embeddings from advanced pretrained language identification (LID) and speaker identification (SID) models are leveraged to improve the accuracy of accent classification and non-native accentedness assessment. Findings demonstrate that employing pretrained LID and SID models effectively encodes accent/dialect information in speech. Furthermore, the LID and SID encoded accent information complement an end-to-end (E2E) accent identification (AID) model trained from scratch. By incorporating all three embeddings, the proposed multi-embedding AID system achieves superior accuracy in AID. Next, leveraging automatic speech recognition (ASR) and AID models is investigated to explore accentedness estimation. The ASR model is an E2E connectionist temporal classification model trained exclusively with American English (en-US) utterances. The ASR error rate and en-US output of the AID model are leveraged as objective accentedness scores. Evaluation results demonstrate a strong correlation between scores estimated by the two models. Additionally, a robust correlation between objective accentedness scores and subjective scores based on human perception is demonstrated, providing evidence for the reliability and validity of using AID-based and ASR-based systems for accentedness assessment in non-native speech. Such advanced systems would benefit accent assessment in language learning as well as speech and speaker assessment for intelligibility, quality, and speaker diarization and speech recognition advancements.

Impact of anemia on outcomes and resource utilization in patients with myocardial infarction: A national database analysis.

BACKGROUND: Although anemia is common in patients with myocardial infarction (MI), management remains controversial. We quantified the association of anemia with in-hospital outcomes and resource utilization in patients admitted with MI using a large national database. METHODS: All hospitalizations with a primary diagnosis code for acute MI in the National Inpatient Sample (NIS) between 2014 and 2018 were identified. Among these hospitalizations, patients with anemia were identified using a secondary diagnosis code. Data on demographic and clinical variables were collected. Outcomes of interest included in-hospital adverse events, length of stay (LOS), and total cost. Multivariable logistic regression and generalized linear models were used to evaluate the relationship between anemia and outcomes. RESULTS: Among 1,113,181 MI hospitalizations, 254,816 (22.8%) included concomitant anemia. Anemic patients were older and more likely to be women. After adjustment for demographics and comorbidities, anemia was associated with higher mortality (7.1 vs. 4.3%; odds ratio 1.09; 95% confidence interval [CI] 1.07-1.12, p < 0.001). Anemia was also associated with a mean of 2.71 days longer LOS (average marginal effects [AME] 2.71; 95% CI 2.68-2.73, p < 0.05), and $ 9703 mean higher total costs (AME $9703, 95% CI $9577-$9829, p < 0.05). Anemic patients who received blood transfusions had higher mortality as compared with those who did not (8.2% vs. 7.0, p < 0.001). CONCLUSION: In MI patients, anemia was associated with higher in-hospital mortality, adverse events, total cost, and length of stay. Transfusion was associated with increased mortality, and its role in MI requires further research.

Assessment of respiratory rate monitoring in the emergency department.

Objectives: This study aimed to compare the different respiratory rate (RR) monitoring methods used in the emergency department (ED): manual documentation, telemetry, and capnography. Methods: This is a retrospective study using recorded patient monitoring data. The study population includes patients who presented to a tertiary care ED between January 2020 and December 2022. Inclusion and exclusion criteria were patients with simultaneous recorded RR data from all three methods and less than 10 min of recording, respectively. Linear regression and Bland-Altman analysis were performed between different methods. Results: A total of 351 patient encounters met study criteria. Linear regression yielded an R-value of 0.06 (95% confidence interval [CI] 0.00-0.12) between manual documentation and telemetry, 0.07 (95% CI 0.01-0.13) between manual documentation and capnography, and 0.82 (95% CI 0.79-0.85) between telemetry and capnography. The Bland-Altman analysis yielded a bias of -0.8 (95% limits of agreement [LOA] -12.2 to 10.6) between manual documentation and telemetry, bias of -0.6 (95% LOA -13.5 to 12.3) between manual documentation and capnography, and bias of 0.2 (95% LOA -6.2 to 6.6) between telemetry and capnography. Conclusion: There is a poor correlation between manual documentation and both automated methods, while there is relatively good agreement between the automated methods. This finding highlights the need to further investigate the methodology used by the ED staff in monitoring and documenting RR and ways to improve its reliability given that many important clinical decisions are made based on these assessments.

Computed tomography assessment of robotic versus fluoroscopic implant accuracy in sacroiliac joint fusion.

OBJECTIVE: Computed tomography is considered the gold-standard imaging tool to evaluate spinal implant accuracy. However, there are no studies that evaluate the accuracy of robotic sacroiliac joint (SIJ) implant placement using CT to date. The aim of this study was to compare the accuracy of implant placement on CT between robotic and fluoroscopic navigation for SIJ fusion and the subsequent complications and clinical outcomes of suboptimally placed screws. METHODS: A retrospective analysis of SIJ fusions utilizing either robotic or fluoroscopic guidance at a single institution was conducted from 2014 to 2023. Implant placement accuracy was evaluated on intra- or postoperative CT. Primary endpoints were SIJ screw placement accuracy and complications. Secondary endpoints were pain status at the first and second follow-ups and rates of 2-year revision surgery. Statistical analysis was performed using chi-square tests. RESULTS: Sixty-nine patients who underwent 78 SIJ fusions were included, of which 63 were robotic and 15 were fluoroscopic. The mean age of the cohort at the time of surgery was 55.9 ± 14.2 years, and 35 patients (50.7%) were female. There were 135 robotically placed and 34 fluoroscopically placed implants. A significant difference was found in implant placement accuracy between robotic and fluoroscopic fusion (97.8% vs 76.5%, p < 0.001). When comparing optimal versus suboptimal implant placement, no difference was found in the presence of 30-day complications (p = 0.98). No intraoperative complications were present in this cohort. No difference was found in subjective pain status at the first (p = 0.69) and second (p = 0.45) follow-ups between optimal and suboptimal implant placement. No patients underwent 2-year revision surgery. CONCLUSIONS: Use of robotic navigation was significantly more accurate than the use of fluoroscopic navigation for SIJ implant placement. Complications overall were low and not different between optimally and suboptimally placed implants. Suboptimally placed implants did not differ in degree of subjective pain improvement or rates of revision surgery postoperatively.

American College of Lifestyle Medicine Expert Consensus Statement: Lifestyle Medicine for Optimal Outcomes in Primary Care.

OBJECTIVE: Identify areas of consensus on integrating lifestyle medicine (LM) into primary care to achieve optimal outcomes. METHODS: Experts in both LM and primary care followed an a priori protocol for developing consensus statements. Using an iterative, online process, panel members expressed levels of agreement with statements, resulting in classification as consensus, near consensus, or no consensus. RESULTS: The panel identified 124 candidate statements addressing: (1) Integration into Primary Care, (2) Delivery Models, (3) Provider Education, (4) Evidence-base for LM, (5) Vital Signs, (6) Treatment, (7) Resource Referral and Reimbursement, (8) Patient, Family, and Community Involvement; Shared Decision-Making, (9) Social Determinants of Health and Health Equity, and (10) Barriers to LM. After three iterations of an online Delphi survey, statement revisions, and removal of duplicative statements, 65 statements met criteria for consensus, 24 for near consensus, and 35 for no consensus. Consensus was reached on key topics that included LM being recognized as an essential component of primary care in patients of all ages, including LM as a foundational element of health professional education. CONCLUSION: The practice of LM in primary care can be strengthened by applying these statements to improve quality of care, inform policy, and identify areas for future research.

Assessment of Gender Differences in Letters of Recommendation for Physical Therapy Residency Applications.

INTRODUCTION: Letters of recommendation (LOR) are an integral component of physical therapy residency applications. Identifying the influence of applicant and writer gender in LOR will help identify whether potential implicit gender bias exists in physical therapy residency application processes. REVIEW OF LITERATURE: Several medical and surgical residency education programs have reported positive, neutral, or negative LOR female gender bias among applicants and writers. Little research exists on gender differences in LOR to physical therapy education programs or physical therapy residency programs. SUBJECTS: Seven hundred sixty-eight LOR were analyzed from 256 applications to 3 physical therapy residency programs (neurologic, orthopaedic, sports) at one institution from 2014 to 2020. METHODS: Thematic categories were developed to identify themes in a sample of LOR. Associations between writer and applicant gender were analyzed using summary statistics, word counts, thematic and psycholinguistic extraction, and rule-based and deep learning Natural Language Processing . RESULTS: No significant difference in LOR word counts were found based on writer or applicant gender. Increased word counts were seen in sports residency LOR compared with the orthopaedic residency. Thematic analysis showed LOR gender differences with male applicants receiving more positive generalized recommendations and female applicants receiving more comments regarding interpersonal relationship skills. No thematic or psycholinguistic gender differences were seen by LOR writer. Male applicants were 1.9 times more likely to select all male LOR writers, whereas female applicants were 2.1 times more likely to choose all female LOR writers. DISCUSSION AND CONCLUSION: Gender differences in LORs for physical therapy residencies were found using a comprehensive Natural Language Processing approach that identified both a positive recommendation male applicant gender bias and a positive interpersonal relationship skill female applicant gender bias. Applicants were not harmed nor helped by selecting LOR writers of the opposite gender. Admissions committees and LOR writers should be mindful of potential implicit gender biases in LOR submitted to physical therapy residency programs.

Influence of socioeconomic status on clinical outcomes of diffuse midline glioma and diffuse intrinsic pontine glioma.

OBJECTIVE: Given the lack of a definitive treatment and the poor prognosis of patients with diffuse midline glioma (DMG) and diffuse intrinsic pontine glioma (DIPG), socioeconomic status (SES) may affect treatment access and therefore survival. Therefore, this study aimed to examine the relationship between SES and treatment modalities, progression-free survival (PFS), and overall survival (OS) in children with DMG/DIPG. METHODS: A retrospective, single-institution review was conducted of medical records of patients ≤ 18 years of age who had DMG or DIPG that was diagnosed between 2000 and 2022. Patient demographics, surgical interventions, chemotherapy, radiation therapy, clinical trial enrollment, and medical care-related travel were extracted. SES variables (education and mean income) for associated patient census tracts were collected and stratified. Statistical analysis using unpaired t-tests, chi-square analysis, and log-rank tests was conducted. RESULTS: Of the 96 patients who met the inclusion criteria, the majority were female (59%) and non-Hispanic White (57%). The median PFS, median OS, and time from diagnosis to treatment did not differ between races/ethnicities or sex. Ninety-one of 96 patients had census tract data available. Patients from higher-income census tracts (> 50% of families with annual household income greater than $50,000) had a longer median OS (480 vs 235 days, p < 0.001) and traveled significantly longer distances for medical care (1550 vs 1114 miles, p = 0.048) than families from lower-income census tracts. Patients from the highest education quartile traveled significantly farther for treatment than the lowest education quartile (mean 2964 vs 478 miles, p = 0.047). Patients who received both oral and intravenous chemotherapy were more likely to be from higher-income census tracts than those who received intravenous or no chemotherapy. Duration of PFS, rates of clinical trial enrollment, biopsy rates, H3K27 mutation status, ventriculoperitoneal shunt placement rates, and radiotherapy rates were not associated with SES variables. CONCLUSIONS: Patients from families from higher-income census tracts experienced longer OS and traveled farther for treatment. Patients from families from higher-education-level census tracts traveled more often for treatment. The authors' findings suggest that SES influences DMG and DIPG OS. More studies should be done to understand the role of SES in the outcomes of children with DMG/DIPG.

Increasing midtarsal joint stiffness reduces triceps surae metabolic costs in walking simulations but has little effect on total stance limb metabolic cost.

The human foot's arch is thought to be beneficial for efficient gait. This study addresses the extent to which arch stiffness changes alter the metabolic energy requirements of human gait. Computational musculoskeletal simulations of steady state walking using direct collocation were performed. Across a range of foot arch stiffnesses, the metabolic cost of transport decreased by less than 1% with increasing foot arch stiffness. Increasing arch stiffness increased the metabolic efficiency of the triceps surae during push-off, but these changes were almost entirely offset by other muscle groups consuming more energy with increasing foot arch stiffness.

Missed opportunities for TB diagnostic testing among people living with HIV in Zimbabwe: Cross-sectional analysis of the Zimbabwe Population-based HIV Impact Assessment (ZIMPHIA) survey 2015-16.

Background: Using data from the Zimbabwe Population-based HIV Impact Assessment survey 2015-2016, we examined the TB care cascade and factors associated with not receiving TB diagnostic testing among adult PLHIV with TB symptoms. Methods: Statistical Analysis was limited to PLHIV aged 15 years and older in HIV care. Weighted logistic regression with not receiving TB testing as outcome was adjusted for covariates with crude odd ratios (ORs) with p < 0.25. All analyses accounted for multistage survey design. Results: Among 3507 adult PLHIV in HIV care, 2288 (59.7 %, 95 % CI:58.1-61.3) were female and 2425 (63.6 %, 95 % CI:61.1-66.1) lived in rural areas. 1197(48.7 %, 95 % CI:46.5-51.0) reported being screened for TB symptoms at their last HIV care visit. In the previous 12 months, 639 (26.0 %, 95 % CI:23.9-28.1) reported having symptoms and of those, 239 (37.8 %, 95 % CI:33.3-42.2) received TB testing. Of PLHIV tested for TB, 36 (49.5 %, 95 % CI:35.0-63.1) were diagnosed with TB; 32 (90.3 %, 95 % CI:78.9-100) of those diagnosed with TB received treatment. Never having used IPT was associated with not receiving TB testing. Conclusion: The results suggest suboptimal utilization of TB screening and diagnostic testing among PLHIV. New approaches are needed to reach opportunities missed in the HIV/TB integrated services.

Contemporary disparities in progression to orchiopexy for cryptorchidism as reported in the Pediatric Health Information System (PHIS) database.

INTRODUCTION: When evaluating the timeliness of orchiopexy for cryptorchidism, health disparities are apparent among Hispanic and African American males and those with public insurance. Since the publication of these data, the COVID-19 pandemic has stressed our healthcare system and significantly affected the provision of pediatric urology care. OBJECTIVE: We sought to assess if certain groups were disproportionately affected in progression to orchiopexy after the diagnosis of cryptorchidism during and after the pandemic in US freestanding children's hospitals. STUDY DESIGN: Using the PHIS database, pediatric patients ≤5 years who underwent orchiopexy between January 2018 and December 2022 were retrospectively analyzed. Exclusion criteria included prematurity, retractile testes, and testicular torsion. Primary outcomes were age at orchiopexy and the proportion of individuals undergoing timely orchiopexy for cryptorchidism. RESULTS: Over the study period 3140 patients ≤5 years old underwent orchiopexy for cryptorchidism. Non-Hispanic Blacks and Hispanics were significantly less likely to have timely orchiopexy and underwent orchiopexy 2.13 and 3.60 months later compared to whites (p < 0.01). As compared to pre-COVID-19, during the pandemic the proportion of patients who had timely surgery was higher and the median age was significantly lower (p = 0.01 and p < 0.01, respectively) in white patients only. Over the study period, patients with public insurance were less likely to have timely orchiopexy and underwent orchiopexy 2.94 months later (p < 0.01) than patients with private insurance. Compared to during the pandemic, post-pandemic a significantly lower proportion of publicly insured patients have since undergone timely orchiopexy (p = 0.04). Patients in the West were less likely to have timely orchiopexy and had a higher age at time of orchiopexy (p < 0.01) than other regions. However, in the West during the pandemic, the proportion of children who had timely surgery was higher compared to pre-and post-COVID-19 (p < 0.01). DISCUSSION: Overall, regardless of insurance status, race, or location, a significant proportion of patients did not undergo timely orchiopexy. During the pandemic white patients had a lower median age and an increased proportion underwent timely orchiopexy, despite the number of orchiopexies remaining constant. Disparities in the post-COVID-19 era have been further exacerbated for publicly insured patients, who a significantly lower proportion of have since undergone timely orchiopexy. Specific efforts are required across the United States to increase timely orchiopexy for all boys. CONCLUSIONS: Progression to timely orchiopexy remains low for all boys in the era surrounding COVID-19; certain groups appear to be more adversely affected.

Brief Report: Self-Reported HIV-Positive Status but Subsequent HIV-Negative Test Results in Population-Based HIV Impact Assessment Survey Participants-11 Sub-Saharan African Countries, 2015-2018.

BACKGROUND: HIV testing is a critical step to accessing antiretroviral therapy (ART) because early diagnosis can facilitate earlier initiation of ART. This study presents aggregated data of individuals who self-reported being HIV-positive but subsequently tested HIV-negative during nationally representative Population-Based HIV Impact Assessment surveys conducted in 11 countries from 2015 to 2018. METHOD: Survey participants aged 15 years or older were interviewed by trained personnel using a standard questionnaire to determine HIV testing history and self-reported HIV status. Home-based HIV testing and counseling using rapid diagnostic tests with return of results were performed by survey staff according to the respective national HIV testing services algorithms on venous blood samples. Laboratory-based confirmatory HIV testing for all participants identified as HIV-positives and self-reported positives, irrespective of HIV testing results, was conducted and included Geenius HIV-1/2 and DNA polymerase chain reaction if Geenius was negative or indeterminate. RESULTS: Of the 16,630 participants who self-reported as HIV-positive, 16,432 (98.6%) were confirmed as HIV-positive and 198 (1.4%) were HIV-negative by subsequent laboratory-based testing. Participants who self-reported as HIV-positive but tested HIV-negative were significantly younger than 30 years, less likely to have received ART, and less likely to have received a CD4 test compared with participants who self-reported as HIV-positive with laboratory-confirmed infection. CONCLUSIONS: A small proportion of self-reported HIV-positive individuals could not be confirmed as positive, which could be due to initial misdiagnosis, deliberate wrong self-report, or misunderstanding of the questionnaire. As universal ART access is expanding, it is increasingly important to ensure quality of HIV testing and confirmation of HIV diagnosis before ART initiation.

Survival disparities in non-Hispanic Black and White cervical cancer patients vary by histology and are largely explained by modifiable factors.

PURPOSE: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities. METHODS: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). RESULTS: This study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p < 0.0001). After balancing the selected demographic, socioeconomic and clinical factors, survival in Black vs. White patients was no longer different in those with SCC (AHR = 1.01, 95% CI 0.97-1.06) or AC (AHR = 1.09, 95% CI = 0.96-1.24). In SCC, the largest contributors to survival disparities were neighborhood income and insurance. In AC, age was the most significant contributor followed by neighborhood income, insurance, and stage. Diagnosis of AC (but not SCC) at ≥65 years old was more common in Black vs. White patients (26% vs. 13%, respectively). CONCLUSIONS: Histology matters in survival disparities and diagnosis at ≥65 years old between Black and White cervical cancer patients. These disparities were largely explained by modifiable factors.

Applications of waste polyethylene terephthalate (PET) based nanostructured materials: A review.

While polyethylene terephthalate (PET) has enjoyed widespread use, a large volume of plastic waste has also been produced as a result, which is detrimental to the environment. Traditional treatment of plastic waste, such as landfilling and incinerating waste, causes environmental pollution and poses risks to public health. Recycling PET waste into useful chemicals or upcycling the waste into high value-added materials can be remedies. This review first provides a brief introduction of the synthesis, structure, properties, and applications of virgin PET. Then the conversion process of waste PET into high value-added materials for different applications are introduced. The conversion mechanisms (including degradation, recycling and upcycling) are detailed. The advanced applications of these upgraded materials in energy storage devices (supercapacitors, lithium-ion batteries, and microbial fuel cells), and for water treatment (to remove dyes, heavy metals, and antibiotics), environmental remediation (for air filtration, CO2 adsorption, and oil removal) and catalysis (to produce H2, photoreduce CO2, and remove toxic chemicals) are discussed at length. In general, this review details the exploration of advanced technologies for the transformation of waste PET into nanostructured materials for various applications, and provides insights into the role of high value-added waste products in sustainability and economic development.

The applicability of interprofessional education for collaborative people-centered practice and care to health plans and workforce issues: A thematic global case review.

Background: This article focuses on a growing, global recognition of the importance of the field of interprofessional education for person-centered collaborative practice (IPECP) expressed through high-level policy and accreditation decisions/actions taking place in 5 countries. Policy decisions are used to motivate strategies related to IPECP that align with national health plans, and workforce issues. Methods: Using a collective of representative stories from around the globe, a grouping of case studies were developed to illustrate different approaches and challenges to IPECP implementation. Results: Institutions from countries of various income levels face many similar challenges in the execution, delivery, and sustainability of IPECP. All programs face issues of financing, of preparing faculty, of developing and organizing curricula, and of bridging between campus and community. Discussion: Policies are being developed that promote a global approach to the inclusion of IPECP in the accreditation and regulation of postsecondary institutions and health service organizations, in keeping with WHO National Health Workforce Accounts. Policies developed promote and demonstrate the benefits of IPECP through remote emergency learning methods. The policies also build national systems for IPECP as an integral part of continuing professional development and lifelong learning. The organization of interprofessional research programs and the increasing publication of their results of such programs will lead to a clearer understanding of the efficacy of the field of IPECP. To ensure sustainability, stakeholders and policymakers should continue to foster policies that facilitate IPECP.

Hamstring spasticity assessment: does the hip flexion angle impact outcomes?

PURPOSE: Hamstring spasticity is prevalent following neurological injury. The standardized assessment involves passive knee extension, in a position of 90° hip flexion. This creates passive insufficiency of the muscle and lacks ecological validity for walking, whereby the hip typically flexes to a maximum of 40° during swing phase, while the knee extends. This study compared assessment outcomes when completed in 40° and 90° hip flexion. METHODS: The Modified Ashworth Scale and Modified Tardieu Scale, were performed on 35 adults with a neurological condition. Each participant was assessed by three assessors, resulting in 105 trials at 40° and 90°. RESULTS: There was a significant increase in the proportion of trials rated as spastic using the Modified Ashworth Scale (p=.012, phi=.27), and Modified Tardieu Scale (p<.001, phi=.36), and the severity of spasticity using the Modified Ashworth Scale (p<.001, effect size (ES)=.50), and Modified Tardieu Scale (p<.001 ES=.47), at 90° hip flexion. The angle of reaction occurred 32° earlier at 90° hip flexion (p<.001, ES = 1.61). CONCLUSIONS: Completing hamstring assessments in 40° hip flexion may reduce the passive insufficiency and improve the ecological validity of assessment, for walking. This may assist in the selection of patients requiring intervention, when their goal relates to walking.

The position of the hip joint impacts hamstring spasticity assessment outcomes, regardless of the clinical outcome measure chosenThe application of bedside assessment methods in a manner reflective of functional tasks may assist in selecting individuals who require active spasticity interventionAs per international guidelines, the use of validated outcome measures in a goal directed and patient centered manner is required to maximize patient care.

A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials.

Background: Interventional trials that evaluate treatment effects using surrogate endpoints have become increasingly common. This paper describes four linked empirical studies and the development of a framework for defining, interpreting and reporting surrogate endpoints in trials. Methods: As part of developing the CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) extensions for randomised trials reporting surrogate endpoints, we undertook a scoping review, e-Delphi study, consensus meeting, and a web survey to examine current definitions and stakeholder (including clinicians, trial investigators, patients and public partners, journal editors, and health technology experts) interpretations of surrogate endpoints as primary outcome measures in trials. Findings: Current surrogate endpoint definitional frameworks are inconsistent and unclear. Surrogate endpoints are used in trials as a substitute of the treatment effects of an intervention on the target outcome(s) of ultimate interest, events measuring how patients feel, function, or survive. Traditionally the consideration of surrogate endpoints in trials has focused on biomarkers (e.g., HDL cholesterol, blood pressure, tumour response), especially in the medical product regulatory setting. Nevertheless, the concept of surrogacy in trials is potentially broader. Intermediate outcomes that include a measure of function or symptoms (e.g., angina frequency, exercise tolerance) can also be used as substitute for target outcomes (e.g., all-cause mortality)-thereby acting as surrogate endpoints. However, we found a lack of consensus among stakeholders on accepting and interpreting intermediate outcomes in trials as surrogate endpoints or target outcomes. In our assessment, patients and health technology assessment experts appeared more likely to consider intermediate outcomes to be surrogate endpoints than clinicians and regulators. Interpretation: There is an urgent need for better understanding and reporting on the use of surrogate endpoints, especially in the setting of interventional trials. We provide a framework for the definition of surrogate endpoints (biomarkers and intermediate outcomes) and target outcomes in trials to improve future reporting and aid stakeholders' interpretation and use of trial surrogate endpoint evidence. Funding: SPIRIT-SURROGATE/CONSORT-SURROGATE project is Medical Research Council Better Research Better Health (MR/V038400/1) funded.

Biofidelity assessment of the GHBMC M50-O in a rear-facing seat configuration during high-speed frontal impact.

The objective of this study was to assess the biofidelity of the Global Human Body Models Consortium (GHBMC) 50th male (M50-O) v6.0 seated in an upright (25-degree recline) all-belts-to-seat (ABTS) in a 56 km/h rear-facing frontal impact. The experimental boundary conditions from the post-mortem human subjects (PMHS) tests were replicated in the computational finite element (FE) environment. The performance of the rigidized FE ABTS model obtained from the original equipment manufacturer was validated via simulations using a Hybrid III FE model and comparison with experiments. Biofidelity of the GHBMC M50-O was evaluated using the most updated NHTSA Biofidelity Ranking System (BRS) method, where a biofidelity score under 2 indicates that the GHBMC response varies from the mean PMHS response by less than two standard deviations, suggesting good biofidelity. The GHBMC M50-O received an occupant response score and a seat loading score of 1.71 and 1.44, respectively. Head (BRS = 0.93) and pelvis (BRS = 1.29) resultant accelerations, and T-spine (avg. BRS = 1.55) and pelvis (BRS = 1.66) y-angular velocities were similar to the PMHS. The T-spine resultant accelerations (avg. BRS = 1.93) and head (BRS = 2.82), T1 (BRS = 2.10) and pelvis (BRS = 2.10) Z-displacements were underestimated in the GHBMC. Peak chest deflection in the anterior-posterior deflection in the GHBMC matched with the PMHS mean, however, the relative upward motion of abdominal contents and subsequent chest expansion were not observed in the GHBMC. Updates to the GHBMC M50-O towards improved thorax kinematics and mobility of abdominal organs should be considered to replicate PMHS characteristics more closely.

Disentangling age, gender, and racial/ethnic disparities in multiple myeloma burden: a modeling study.

Multiple myeloma (MM) is a hematological malignancy that is consistently preceded by an asymptomatic condition, monoclonal gammopathy of undetermined significance (MGUS). Disparities by age, gender, and race/ethnicity in both MGUS and MM are well-established. However, it remains unclear whether these disparities can be explained by increased incidence of MGUS and/or accelerated progression from MGUS to MM. Here, we fit a mathematical model to nationally representative data from the United States and showed that the difference in MM incidence can be explained by an increased incidence of MGUS among male and non-Hispanic Black populations. We did not find evidence showing differences in the rate of progression from MGUS to MM by either gender or race/ethnicity. Our results suggest that screening for MGUS among high-risk groups (e.g., non-Hispanic Black men) may hold promise as a strategy to reduce the burden and MM health disparities.