Cytoplasmic switch of ARS2 isoforms promotes nonsense-mediated mRNA decay and arsenic sensitivity.

The life of RNA polymerase II (RNAPII) transcripts is shaped by the dynamic formation of mutually exclusive ribonucleoprotein complexes (RNPs) that direct transcript biogenesis and turnover. A key regulator of RNA metabolism in the nucleus is the scaffold protein ARS2 (arsenic resistance protein 2), bound to the cap binding complex (CBC). We report here that alternative splicing of ARS2's intron 5, generates cytoplasmic isoforms that lack 270 amino acids from the N-terminal of the protein and are functionally distinct from nuclear ARS2. Switching of ARS2 isoforms within the CBC in the cytoplasm has dramatic functional consequences, changing ARS2 from a NMD inhibitor to a NMD promoter that enhances the binding of UPF1 to NCBP1 and ERF1, favouring SURF complex formation, SMG7 recruitment and transcript degradation. ARS2 isoform exchange is also relevant during arsenic stress, where cytoplasmic ARS2 promotes a global response to arsenic in a CBC-independent manner. We propose that ARS2 isoform switching promotes the proper recruitment of RNP complexes during NMD and the cellular response to arsenic stress. The existence of non-redundant ARS2 isoforms is relevant for cell homeostasis, and stress response.

Are DEA-waivered buprenorphine prescribers colocated with behavioral health clinicians?

BACKGROUND AND OBJECTIVES: Medication for opioid use disorder (MOUD) in primary care includes a combination of medication, behavioral therapy, and/or other psychosocial services. This study assessed rates of colocation between waivered prescribers and behavioral health clinicians across the United States to understand if rates varied by provider type and geographic indicators. METHODS: Data from the DEA-Drug Addiction Treatment Act of 2000 provider list as of March 2022 and the National Plan and Provider Enumeration System's National Provider Identifier database were gathered, cleaned, and formatted in Stata. Data were geocoded with ESRI StreetMap® database and ArcGIS software. Covariates at individual, county, and state levels were examined and compared. Chi-square statistics and a mixed-effects logistic regression were analyzed. RESULTS: The sample (N = 71, 292 prescribers) included physicians (64%), nurse practitioners (29%), and physician assistants (7%). About 48% of prescribers were colocated with a behavioral health clinician. Physicians were the least likely to be colocated (47%), but differences between provider types were modest. We observed significant geographic differences in provider colocation by provider type. Mixed effects logistic regression identified significant predictors of colocation at individual, county, and state levels. DISCUSSION AND CONCLUSIONS: Optimally distributing the workforce providing MOUD is necessary to broadly ensure the provision of comprehensive MOUD care based on practice guidelines. SCIENTIFIC SIGNIFICANCE: Less than half of all waivered prescribers, outside of hospitals, are colocated with behavioral health clinicians. Findings offer greater clarity on where integrated MOUD is occurring, among which types of providers, and where it needs to be expanded to increase MOUD uptake.

Effectiveness of cognitive behavioral conjoint therapy for posttraumatic stress disorder (PTSD) in a U.S. Veterans Affairs PTSD clinic.

Cognitive behavioral conjoint therapy (CBCT) for posttraumatic stress disorder (PTSD) is a 15-session conjoint treatment for PTSD designed to improve PTSD symptoms and enhance intimate relationship functioning. Numerous studies of CBCT for PTSD document improvements in patient PTSD and comorbid symptoms, partner mental health, and relationship adjustment. However, little is known about its effectiveness in real-world clinical settings. Using an intention-to-treat sample of couples who participated in CBCT for PTSD in an outpatient U.S. Veterans Affairs (VA) PTSD clinic (N = 113), trajectories of session-by-session reports of veterans' PTSD symptoms and both partners' relationship happiness were examined. Across sessions, there were significant reductions in veteran-rated PTSD symptoms, d = -0.69, and significant increases in veteran- and partner-rated relationship happiness, ds = 0.36 and 0.35, respectively. Partner ratings of veterans' PTSD symptoms increased before significantly decreasing, d = -0.24. Secondary outcomes of veteran and partner relationship satisfaction, ds = 0.30 and 0.42, respectively; veteran and partner depressive symptoms, ds = -0.75 and -0.29, respectively; and partner accommodation of PTSD symptoms, d = -0.44, also significantly improved from pre- to posttreatment. The findings suggest that CBCT for PTSD was effective for decreasing PTSD and comorbid symptoms in veterans, as well as for improving relationship functioning and partners' mental health, among a sample of real-world couples seeking treatment in a VA PTSD specialty clinic.

ARS2 is required for retinal progenitor cell S-phase progression and Müller glial cell fate specification.

During a developmental period that extends postnatally in the mouse, proliferating multipotent retinal progenitor cells produce one of 7 major cell types (rod, cone, bipolar, horizontal, amacrine, ganglion, and Müller glial cells) as they exit the cell cycle in consecutive waves. Cell production in the retina is tightly regulated by intrinsic, extrinsic, spatial, and temporal cues, and is coupled to the timing of cell cycle exit. Arsenic-resistance protein 2 (ARS2, also known as SRRT) is a component of the nuclear cap-binding complex involved in RNA Polymerase II transcription, and is required for cell cycle progression. We show that postnatal retinal progenitor cells (RPCs) require ARS2 for proper progression through S phase, and ARS2 disruption leads to early exit from the cell cycle. Furthermore, we observe an increase in the proportion of cells expressing a rod photoreceptor marker, and a loss of Müller glia marker expression, indicating a role for ARS2 in regulating cell fate specification or differentiation. Knockdown of Flice Associated Huge protein (FLASH), which interacts with ARS2 and is required for cell cycle progression and 3'-end processing of replication-dependent histone transcripts, phenocopies ARS2 knockdown. These data implicate ARS2-FLASH-mediated histone mRNA processing in regulating RPC cell cycle kinetics and neuroglial cell fate specification during postnatal retinal development.

Simultaneous voltammetric detection of cadmium(II), arsenic(III), and selenium(IV) using gold nanostar-modified screen-printed carbon electrodes and modified Britton-Robinson buffer.

The present work reports a newly developed square wave anodic stripping voltammetry (SWASV) methodology using novel gold nanostar-modified screen-printed carbon electrodes (AuNS/SPCE) and modified Britton-Robinson buffer (mBRB) for simultaneous detection of trace cadmium(II), arsenic(III), and selenium(IV). During individual and simultaneous detection, Cd2+, As3+, and Se4+ exhibited well-separated SWASV peaks at approximately - 0.48, - 0.09, and 0.65 V, respectively (versus Ag/AgCl reference electrode), which enabled a highly selective detection of the three analytes. Electrochemical impedance spectrum tests showed a significant decrease in charge transfer resistance with the AuNS/SPCE (0.8 kΩ) compared with bare SPCE (2.4 kΩ). Cyclic voltammetry experiments showed a significant increase in electroactive surface area with electrode modification. The low charge transfer resistance and high electroactive surface area contributed to the high sensitivity for Cd2+ (0.0767 µA (0.225 µg L-1)-1), As3+ (0.2213 µA (µg L-1)-1), and Se4+ (µA (µg L-1)-1). The three analytes had linear stripping responses over the concentration range of 0 to 100 µg L-1, with the obtained LoD for Cd2+, As3+, and Se4+ of 1.6, 0.8, and 1.6 µg L-1, respectively. In comparison with individual detection, the simultaneous detection of As3+ and Se4+ showed peak height reductions of 40.8% and 42.7%, respectively. This result was associated with the possible formation of electrochemically inactive arsenic triselenide (As2Se3) during the preconcentration step. Surface water analysis resulted in average percent recoveries of 109% for Cd2+, 93% for As3+, and 92% for Se4+, indicating the proposed method is accurate and reliable for the simultaneous detection of Cd2+, As3+, and Se4+ in real water samples. Graphical abstract.

The prolyl isomerase FKBP25 regulates microtubule polymerization impacting cell cycle progression and genomic stability.

FK506 binding proteins (FKBPs) catalyze the interconversion of cis-trans proline conformers in proteins. Importantly, FK506 drugs have anti-cancer and neuroprotective properties, but the effectors and mechanisms underpinning these properties are not well understood because the cellular function(s) of most FKBP proteins are unclear. FKBP25 is a nuclear prolyl isomerase that interacts directly with nucleic acids and is associated with several DNA/RNA binding proteins. Here, we show the catalytic FKBP domain binds microtubules (MTs) directly to promote their polymerization and stabilize the MT network. Furthermore, FKBP25 associates with the mitotic spindle and regulates entry into mitosis. This interaction is important for mitotic spindle dynamics, as we observe increased chromosome instability in FKBP25 knockdown cells. Finally, we provide evidence that FKBP25 association with chromatin is cell-cycle regulated by Protein Kinase C phosphorylation. This disrupts FKBP25-DNA contacts during mitosis while maintaining its interaction with the spindle apparatus. Collectively, these data support a model where FKBP25 association with chromatin and MTs is carefully choreographed to ensure faithful genome duplication. Additionally, they highlight that FKBP25 is a MT-associated FK506 receptor and potential therapeutic target in MT-associated diseases.

CUG-BP, Elav-like family member 1 (CELF1) is required for normal myofibrillogenesis, morphogenesis, and contractile function in the embryonic heart.

BACKGROUND: CUG-BP, Elav-like family member 1 (CELF1) is a multifunctional RNA binding protein found in a variety of adult and embryonic tissues. In the heart, CELF1 is found exclusively in the myocardium. However, the roles of CELF1 during cardiac development have not been completely elucidated. RESULTS: Myofibrillar organization is disrupted and proliferation is reduced following knockdown of CELF1 in cultured chicken primary embryonic cardiomyocytes. In vivo knockdown of Celf1 in developing Xenopus laevis embryos resulted in myofibrillar disorganization and a trend toward reduced proliferation in heart muscle, indicating conserved roles for CELF1 orthologs in embryonic cardiomyocytes. Loss of Celf1 also resulted in morphogenetic abnormalities in the developing heart and gut. Using optical coherence tomography, we showed that cardiac contraction was impaired following depletion of Celf1, while heart rhythm remained unperturbed. In contrast to cardiac muscle, loss of Celf1 did not disrupt myofibril organization in skeletal muscle cells, although it did lead to fragmentation of skeletal muscle bundles. CONCLUSIONS: CELF1 is required for normal myofibril organization, proliferation, morphogenesis, and contractile performance in the developing myocardium. Developmental Dynamics 245:854-873, 2016. © 2016 Wiley Periodicals, Inc.

Do Negative Changes in Worldview Mediate Links Between Mass Trauma and Reckless Behavior? A Longitudinal Exploratory Study.

Trauma exposure heightens the risk of reckless behavior and is now included in DSM-5 posttraumatic stress disorder symptomatology. Individuals exposed to trauma may be likely to engage in reckless behavior because of negative changes in their worldview (referred to as disrupted worldview). The current study investigates the relationship between DSM-IV posttraumatic stress symptoms, disrupted worldview, and increased reckless behavior among 1145 students exposed to mass violence. Total posttraumatic stress symptomatology was associated with increased and persistent reckless behavior, supporting DSM-5 diagnostic inclusion. Although posttraumatic stress symptomatology predicted reckless behavior among those with varying levels of posttraumatic symptomatology, individuals with high symptomatology reported significantly higher recklessness. Disrupted worldview mediated the relationship between posttraumatic symptomatology and reckless behavior among individuals with high symptomatology, while only partially mediating the relationship among those with low symptomatology. These findings provide support for worldview disruptions as a mechanism by which prolonged reckless behavior may be manifested.

Longitudinal Predictors of Criminal Arrest After Traumatic Brain Injury: Results From the Traumatic Brain Injury Model System National Database.

OBJECTIVE: To examine how pre-traumatic brain injury (TBI) variables and TBI-related characteristics predict post-TBI criminal arrest, using longitudinal data from the Traumatic Brain Injury Model System National Database. SETTINGS: Medical hospitals; rehabilitation facilities. PARTICIPANTS: Participants with documented TBI and nonmissing Traumatic Brain Injury Model System data, resulting in N = 6315 at 1 year post-TBI, N = 4982 at 2 years post-TBI, and N = 2690 at 5 years post-TBI. DESIGN: Prospective cohort study with secondary data analysis of the relationship between pre-TBI/TBI factors and post-TBI criminal arrest as measured at 3 time points. MAIN MEASURES: Self-report of post-TBI criminal arrest. RESULTS: Post-TBI criminal arrest was associated with gender, age, marital status, educational attainment, pre-TBI felony, pre-TBI drug abuse, pre-TBI alcohol abuse, and violent cause of TBI. Frontal, temporal, parietal, or occipital lobe lesions from computed tomographic scans did not predict post-TBI criminal arrests. Higher numbers of post-TBI arrests were predicted by loss of consciousness (≥24 hours), combined with retention of motor function. CONCLUSION: Premorbid variables, especially pre-TBI felonies, were strongly linked to post-TBI criminal arrests. The relationship between TBI and arrest was complex, and different brain functions (eg, physical mobility) should be considered when understanding this association. Findings highlight that for post-TBI criminal behavior, many risk factors mirror those of the non-TBI general population.

Violent behaviour and post-traumatic stress disorder in US Iraq and Afghanistan veterans.

BACKGROUND: Violence towards others in the community has been identified as a significant problem for a subset of Iraq and Afghanistan veterans. AIMS: To investigate the extent to which post-traumatic stress disorder (PTSD) and other risk factors predict future violent behaviour in military veterans. METHOD: A national, multiwave survey enrolling a random sample of all US veterans who served in the military after 11 September 2001 was conducted. A total of 1090 veterans from 50 US states and all military branches completed two survey waves mailed 1 year apart (retention rate = 79%). RESULTS: Overall, 9% endorsed engaging in severe violence and 26% in other physical aggression in the previous year, as measured at Wave 2. Younger age, financial instability, history of violence before military service, higher combat exposure, PTSD, and alcohol misuse at Wave 1 were significantly associated with higher severe violence and other physical aggression in the past year at Wave 2. When combinations of these risk factors were present, predicted probability of violence in veterans rose sharply. Veterans with both PTSD and alcohol misuse had a substantially higher rate of subsequent severe violence (35.9%) compared with veterans with alcohol misuse without PTSD (10.6%), PTSD without alcohol misuse (10.0%) or neither PTSD nor alcohol misuse (5.3%). Using multiple regression, we found that veterans with PTSD and without alcohol misuse were not at significantly higher risk of severe violence than veterans with neither PTSD nor alcohol misuse. There was a trend for other physical aggression to be higher in veterans with PTSD without alcohol misuse. CONCLUSIONS: Co-occurring PTSD and alcohol misuse was associated with a marked increase in violence and aggression in veterans. Compared with veterans with neither PTSD nor alcohol misuse, veterans with PTSD and no alcohol misuse were not significantly more likely to be severely violent and were only marginally more likely to engage in other physical aggression. Attention to cumulative effects of multiple risk factors beyond diagnosis--including demographics, violence history, combat exposure, and veterans' having money to cover basic needs like food, shelter, transportation, and medical care--is crucial for optimising violence risk management.

PTSD symptoms and family versus stranger violence in Iraq and Afghanistan veterans.

As a diagnosis, posttraumatic stress disorder (PTSD) has been associated with violence committed by veterans in many studies; however, a potential link to specific PTSD symptoms has received relatively less attention. This paper examines the relationship between PTSD symptoms and different types of violent behavior in Iraq and Afghanistan veterans. Participants were randomly sampled from a roster of all separated U.S. military service members or national guard/reservists who served after September 11, 2001. Data were collected at baseline and 1-year follow-up from a national sample of N = 1,090 veterans, from 50 states and all military branches. Of these veterans, 13% reported aggression toward a family member and 9% toward a stranger during the 1-year study period. Anger symptoms at baseline predicted higher odds of family violence at follow-up, both severe (OR = 1.30, CI [1.13, 1.48], p < .0001) and any (OR = 1.28, CI [1.19, 1.37], p < .0001). PTSD flashback symptoms at baseline predicted higher odds of stranger violence at follow-up, both severe (OR = 1.26, CI [1.11, 1.42], p < .0001) and any (OR = 1.16, CI [1.05, 1.28], p = .0029). Analyses revealed that males were more likely to engage in stranger violence, whereas females were more likely to endorse aggression in the family context. The results provide limited support to the hypothesis that PTSD "flashbacks" in veterans are linked to violence. The differing multivariate models illustrate distinct veteran characteristics associated with specific types of violence.

An examination of the potential core symptoms of posttraumatic stress disorder: What is integral after removing general psychopathology & distress?

Many confirmatory factor analyses (CFA) have examined the structure of posttraumatic stress disorder (PTSD) with some suggesting increased complexity (i.e., 6+ factors), while others suggesting a more refined structure (i.e., 2-factors). These competing PTSD structures may be due to conflation of non-trauma specific symptoms that have been added overtime. However, none of these studies examined if all symptoms being examined are specific to PTSD or potentially more related to general distress and psychopathology. The current study re-evaluated the structure of PTSD using bifactor exploratory factor analysis (EFA) to identify the construct's core symptoms. Data for EFA models were taken from a sample of Veterans (N = 694) attending outpatient therapy for PTSD and were cross-validated using CFA in a sample of 297 Veterans attending residential treatment. Clinician Administered PTSD Scale for DSM-5 (CAPS-5) at pre-treatment was used across sample. Factor analyses resulted in a 2-factor, bifactor model comprised of eight total items. Model fit was robust, RMSEA = 0 [0.000, 0.036]; robust CFI = 1; robust TLI = 1.017. The bifactor analytic approach captured what might be the core structure of PTSD, which were pathognomonic symptoms of PTSD (Factor one). A distinct second factor related to depression was also found. In identifying this structure, the model eliminates redundancies and lesser performing items and differentiates depressive reactions as potentially distinct and separate. Overall, these findings may assist in future research of PTSD by determining the unique elements of the construct within a veteran sample versus associated features, general psychological distress, and comorbid psychopathology.

Universal pH electrocatalytic hydrogen evolution with Au-based high entropy alloys.

The creation of electrocatalysts with reduced concentrations of platinum-group metals remains a critical challenge for electrochemical hydrogen production. High-entropy alloys (HEAs) offer a distinct type of catalyst with tunable compositions and engineered surface activity, significantly enhancing the hydrogen evolution reaction (HER). We present the synthesis of AuPdFeNiCo HEA nanoparticles (NPs) using a wet impregnation method. The composition and structure of the AuPdFeNiCo HEA NPs are characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and high-resolution transmission electron microscopy (HR-TEM). These nanoparticles exhibit robust HER performance quantified over a broad pH range, with higher activity than any of the unary metal counterparts in all pHs. In comparison to a commercial 10%Pt/C electrocatalyst, AuPdFeNiCo HEA NPs exhibit enhanced electrochemical activity in both acidic and alkaline electrolytes at a current density of 10 mA cm-2. Additionally, these nanoparticles achieve a current density of 100 mA cm-2 at a voltage of 540 mV in neutral electrolytes, outperforming Pt/C which requires 570 mV. These findings help enable broad use of reduced precious metal electrocatalysts for water electrolysis in a variety of water and pH conditions.

The Effect of Social Deprivation on Hospital Utilization Following Distal Radius Fracture Treatment.

Purpose: Social determinants of health disparities have been shown to adversely impact outcomes following distal radius fracture (DRF) treatment. Identifying risk factors for increased hospital use following DRF has been historically difficult; however, it is of utmost concern to orthopedic surgeons to improve outcomes and decrease the total cost of care. The effect of social deprivation following DRF has yet to be fully investigated. Methods: This is a retrospective cohort analysis of a single institution's experience in treating DRF with either an operative or nonsurgical modality between 2005 and 2020. Patient demographic information and health care utilization (hospital readmission, emergency department [ED] visitation, office visits, and telephone use) were collected from within 90 days of treatment. Area Deprivation Index (ADI) national percentiles were recorded. Patients were stratified into terciles based on their relative level of deprivation, and their outcomes were compared. Secondary analyses included stratifying patients based on treatment modality, race, and legal sex. Results: In total, 2,149 patients were included. The least, intermediate, and most deprived groups consisted of 552, 1,067, and 530 patients, respectively. Risk factors for hospital readmission included higher levels of relative deprivation. Identifying as Black or African American and nonsurgical management were risk factors for increased ED visitation. No differences in rate of hospital readmission, ED visitation, office visitation, or telephone use were seen based on deprivation level. Conclusions: High levels of social deprivation, treatment modality, race, and legal sex disparities may influence the amount of hospital resource utilization following DRF treatment. Understanding and identifying risk factors for greater resource utilization can help to mitigate inappropriate use and decrease health care costs. We hope to use these findings to guide clinical decision making, educate patient populations, and optimize outcomes following DRF treatment. Type of Study/Level of Evidence: Therapeutic III.

Homelessness and money mismanagement in Iraq and Afghanistan veterans.

OBJECTIVES: We examined the empirical link between money mismanagement and subsequent homelessness among veterans. METHODS: We used a random sample of Iraq and Afghanistan War era veterans from the National Post-Deployment Adjustment Survey in 2009-2011. RESULTS: Veterans were randomly selected from a roster of all US military service members in Operation Iraqi Freedom or Operation Enduring Freedom who were separated from active duty or in the Reserves/National Guard. Veterans (n = 1090) from 50 states and all military branches completed 2 waves of data collection 1 year apart (79% retention rate). Thirty percent reported money mismanagement (e.g., bouncing or forging a check, going over one's credit limit, falling victim to a money scam in the past year). Multivariate analysis revealed money mismanagement (odds ratio [OR] = 4.09, 95% CI = 1.87, 8.94) was associated with homelessness in the next year, as were arrest history (OR = 2.65, 95% CI = 1.33, 5.29), mental health diagnosis (OR = 2.59, 95% CI = 1.26, 5.33), and income (OR = 0.30, 95% CI = 0.13, 0.71). CONCLUSIONS: Money mismanagement, reported by a substantial number of veterans, was related to a higher rate of subsequent homelessness. The findings have implications for policymakers and clinicians, suggesting that financial education programs offered by the US Departments of Defense and Veterans Affairs may be targeted to effectively address veteran homelessness.

Prevalence and nature of prior developmental and medical concerns in toddlers who screen positive for autism in primary care.

LAY ABSTRACT: The American Academy of Pediatrics recommends that all children be screened for autism at their 18- and 24-month well-child visit. For children who screen positive for autism, it is unknown whether this usually represents the first time a developmental concern has been raised or if other developmental concerns typically precede a positive autism screen. Such knowledge could help guide providers in how to appropriately convey feedback regarding autism screening. This study found that, for close to 80% of children with a positive autism screen, caregivers or providers had a prior autism, language, motor, or other developmental concern documented in the electronic health record. Many also had other prior concerns frequently linked to autism, such as sleep and gastrointestinal problems, and received physical or speech therapy. On average, prior to screening children who received a positive Modified-Checklist for Autism in Toddlers had two documented concerns by at 1 year of age and three concerns by 2 years of age. These findings imply that screening for autism as a part of routine pediatric care likely takes place in the context of larger conversations regarding existing developmental concerns, allowing for a less stigmatizing discussion of autism. Framing the presence of prior concerns in the setting of a positive screen in this context may create a reaffirming space for existing caregiver concerns and a lessened emotional burden on caregivers.

Current landscape of research ethics consultation services: National survey results.

Introduction: The goal of a research ethics consultation service (RECS) is to assist relevant parties in navigating the ethical issues they encounter in conduct of research. The goal of this survey was to describe the current landscape of research ethics consultation and document if and how it has changed over the last decade. Methods: The survey instrument was based on the survey previously circulated. We included a number of survey domains from the previous survey with the goal of direct comparison of outcomes. The survey was sent to 57 RECS in the USA and Canada. Results: Forty-nine surveys were completed for an overall response rate of 86%. With the passing of 10 years, the volume of consults received by RECS surveyed has increased. The number of consults received by a subset of RECS remains low. RECS continues to receive requests for consults from a wide range of stakeholders. About a quarter of RECS surveyed actively evaluate their services, primarily through satisfaction surveys routinely shared with requestors. The number of RECS evaluating their services has increased. We identified a group of eight key competencies respondents find as key to providing RECS. Conclusions: The findings from our survey demonstrate that there have been growth and development of RECS since 2010. Further developing evaluation and competency guidelines will help existing RECS continue to grow and facilitate newly established RECS maturation. Both will allow RECS personnel to better serve their institutions and add value to the research conducted.

Predictive Value of Early Autism Detection Models Based on Electronic Health Record Data Collected Before Age 1 Year.

Importance: Autism detection early in childhood is critical to ensure that autistic children and their families have access to early behavioral support. Early correlates of autism documented in electronic health records (EHRs) during routine care could allow passive, predictive model-based monitoring to improve the accuracy of early detection. Objective: To quantify the predictive value of early autism detection models based on EHR data collected before age 1 year. Design, Setting, and Participants: This retrospective diagnostic study used EHR data from children seen within the Duke University Health System before age 30 days between January 2006 and December 2020. These data were used to train and evaluate L2-regularized Cox proportional hazards models predicting later autism diagnosis based on data collected from birth up to the time of prediction (ages 30-360 days). Statistical analyses were performed between August 1, 2020, and April 1, 2022. Main Outcomes and Measures: Prediction performance was quantified in terms of sensitivity, specificity, and positive predictive value (PPV) at clinically relevant model operating thresholds. Results: Data from 45 080 children, including 924 (1.5%) meeting autism criteria, were included in this study. Model-based autism detection at age 30 days achieved 45.5% sensitivity and 23.0% PPV at 90.0% specificity. Detection by age 360 days achieved 59.8% sensitivity and 17.6% PPV at 81.5% specificity and 38.8% sensitivity and 31.0% PPV at 94.3% specificity. Conclusions and Relevance: In this diagnostic study of an autism screening test, EHR-based autism detection achieved clinically meaningful accuracy by age 30 days, improving by age 1 year. This automated approach could be integrated with caregiver surveys to improve the accuracy of early autism screening.