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AIMS: Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions. METHODS: Data came from n = 999 patients ages 18-75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models. RESULTS: Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31-1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65-2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43-2.87) and bullying (RR = 1.44; 95% CI = 0.99-2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE. CONCLUSIONS: Although individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.

Accurately measuring the translations of objects between images is essential in many fields, including biology, medicine, chemistry, and physics. One important application is tracking one or more particles by measuring their apparent displacements in a series of images. Popular methods, such as the center of mass, often require idealized scenarios to reach the shot noise limit of particle tracking and, therefore, are not generally applicable to multiple image types. More general methods, such as maximum likelihood estimation, reliably approach the shot noise limit, but are too computationally intense for use in real-time applications. These limitations are significant, as real-time, shot-noise-limited particle tracking is of paramount importance for feedback control systems. To fill this gap, we introduce a new cross-correlation-based algorithm that approaches shot-noise-limited displacement detection and a graphics processing unit-based implementation for real-time image analysis of a single particle. [ABSTRACT FROM AUTHOR]

Background: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. Methods: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. Results: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. Conclusions: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories. [ABSTRACT FROM AUTHOR]

Importance: Research on resilience after trauma has often focused on individual-level factors (eg, ability to cope with adversity) and overlooked influential neighborhood-level factors that may help mitigate the development of posttraumatic stress disorder (PTSD)., Objective: To investigate whether an interaction between residential greenspace and self-reported individual resources was associated with a resilient PTSD trajectory (ie, low/no symptoms) and to test if the association between greenspace and PTSD trajectory was mediated by neural reactivity to reward., Design, Setting, and Participants: As part of a longitudinal cohort study, trauma survivors were recruited from emergency departments across the US. Two weeks after trauma, a subset of participants underwent functional magnetic resonance imaging during a monetary reward task. Study data were analyzed from January to November 2023., Exposures: Residential greenspace within a 100-m buffer of each participant's home address was derived from satellite imagery and quantified using the Normalized Difference Vegetation Index and perceived individual resources measured by the Connor-Davidson Resilience Scale (CD-RISC)., Main Outcome and Measures: PTSD symptom severity measured at 2 weeks, 8 weeks, 3 months, and 6 months after trauma. Neural responses to monetary reward in reward-related regions (ie, amygdala, nucleus accumbens, orbitofrontal cortex) was a secondary outcome. Covariates included both geocoded (eg, area deprivation index) and self-reported characteristics (eg, childhood maltreatment, income)., Results: In 2597 trauma survivors (mean [SD] age, 36.5 [13.4] years; 1637 female [63%]; 1304 non-Hispanic Black [50.2%], 289 Hispanic [11.1%], 901 non-Hispanic White [34.7%], 93 non-Hispanic other race [3.6%], and 10 missing/unreported [0.4%]), 6 PTSD trajectories (resilient, nonremitting high, nonremitting moderate, slow recovery, rapid recovery, delayed) were identified through latent-class mixed-effect modeling. Multinominal logistic regressions revealed that for individuals with higher CD-RISC scores, greenspace was associated with a greater likelihood of assignment in a resilient trajectory compared with nonremitting high (Wald z test = -3.92; P < .001), nonremitting moderate (Wald z test = -2.24; P = .03), or slow recovery (Wald z test = -2.27; P = .02) classes. Greenspace was also associated with greater neural reactivity to reward in the amygdala (n = 288; t277 = 2.83; adjusted P value = 0.02); however, reward reactivity did not differ by PTSD trajectory., Conclusions and Relevance: In this cohort study, greenspace and self-reported individual resources were significantly associated with PTSD trajectories. These findings suggest that factors at multiple ecological levels may contribute to the likelihood of resiliency to PTSD after trauma.

Background: Trauma is a risk factor for developing maladaptive alcohol use. Preclinical research has shown that stress alters the processing of midbrain and striatal reward and incentive signals. However, little research has been conducted on alterations in reward-related neurocircuitry post-trauma in humans. Neuroimaging markers may be particularly useful as they can provide insight into the mechanisms that may make an individual vulnerable to developing trauma-related psychopathologies. This study aimed to identify reward-related neural correlates associated with changes in alcohol use after trauma exposure., Methods: Participants were recruited from U.S. emergency departments for the AURORA study (N=286, 178 female). Trauma-related change in alcohol use at 8 weeks post-trauma relative to pre-trauma was quantified as a change in 30-day total drinking per the PhenX Toolkit Alcohol 30-Day Quantity and Frequency Measure. Reward-related neurocircuitry activation and functional connectivity (FC) were assessed 2 weeks post-trauma using fMRI during a monetary reward task using region of interest and whole-brain voxelwise analyses., Results: Greater increase in alcohol use from pre-trauma to 8 weeks post-trauma was predicted by (1) greater ventral tegmental area (VTA) and (2) greater cerebellum activation during Gain>Loss trials measured 2 weeks post-trauma and (3) greater seed-based FC between the VTA and lateral occipital cortex and precuneus., Conclusions: Altered VTA activation and FC early post-trauma may be associated with reward-seeking and processing, contributing to greater alcohol use post-trauma. These data provide novel evidence of neural correlates that underlie increased alcohol use early post-trauma that may be targeted via early interventions to prevent the development of maladaptive alcohol use., (Copyright © 2024. Published by Elsevier Inc.)

A central paradigm of moiré materials relies on the formation of superlattices that yield enlarged effective crystal unit cells. While a critical consequence of this phenomenon is the celebrated flat electronic bands that foster strong interaction effects, the presence of superlattices has further implications. Here we explore the advantages of moiré superlattices in twisted bilayer graphene (TBG) aligned with hexagonal boron nitride (hBN) for passively enhancing optical conductivity in the low-energy regime. To probe the local optical response of TBG/hBN double-moiré lattices, we use infrared (IR) nano-imaging in conjunction with nanocurrent imaging to examine local optical conductivity over a wide range of TBG twist angles. We show that interband transitions associated with the multiple moiré flat and dispersive bands produce tunable transparent IR responses even at finite carrier densities, which is in stark contrast to the previously limited metallic near transparency observed only in undoped pristine graphene.

Therapeutics enhancing apolipoprotein (APOE) positive function are a priority, because APOE4 is the major genetic risk factor for Alzheimer's disease (AD). The function of APOE, the key constituent of lipoprotein particles that transport cholesterol and lipids in the brain, is dependent on lipidation by ABCA1, a cell-membrane cholesterol transporter. ABCA1 transcription is regulated by liver X receptors (LXR): agonists have been shown to increase ABCA1, often accompanied by unwanted lipogenesis and elevated triglycerides (TG). Therefore, nonlipogenic ABCA1-inducers (NLAI) are needed. Two rounds of optimization of an HTS hit, derived from a phenotypic screen, gave lead compound 39 that was validated and tested in E3/4FAD mice that express human APOE3/4 and five mutant APP and PSEN1 human transgenes. Treatment with 39 increased ABCA1 expression, enhanced APOE lipidation, and reversed multiple AD phenotypes, without increasing TG. This NLAI/LXR-agonist study is the first in a human APOE -expressing model with hallmark amyloid-β pathology.

Background: Growing data indicates that thiamine deficiency occurs during acute illness in the absence of alcohol use disorder. Our primary objective was to measure clinical factors associated with thiamine deficiency in patients with sepsis, diabetic ketoacidosis, and oncologic emergencies., Methods: This was an analysis of pooled data from cross-sectional studies that enrolled adult emergency department (ED) patients at a single academic center with suspected sepsis, diabetic ketoacidosis, and oncologic emergencies. We excluded patients who had known alcohol use disorder or who had received ED thiamine treatment prior to enrollment. Investigators collected whole blood thiamine levels in addition to demographics, clinical characteristics, and available biomarkers. We defined thiamine deficiency as a whole blood thiamine level below the normal reference range and modeled the adjusted association between this outcome and age., Results: There were 269 patients, of whom the average age was 57 years; 46% were female, and 80% were Black. Fifty-five (20.5%) patients had thiamine deficiency. In univariate analysis, age >60 years (odds ratio [OR] 2.5, 95% confidence interval [CI], 1.3-4.5), female gender (OR 1.9, 95% CI 1.0-3.4), leukopenia (OR 4.9, 95% CI 2.3-10.3), moderate anemia (OR 2.8, 95% CI 1.5-5.3), and hypoalbuminemia (OR 2.2, 95% CI 1.2-4.1) were associated with thiamine deficiency. In adjusted analysis, thiamine deficiency was significantly higher in females (OR 2.1, 95% CI 1.1-4.1), patients >60 years (OR 2.0, 95% CI 1.0-3.8), and patients with leukopenia (OR 5.1, 95% CI 2.3-11.3)., Conclusion: In this analysis, thiamine deficiency was common and was associated with advanced age, female gender, and leukopenia., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. Funding for the work was through a unrestricted physician scientist award given to Joseph Miller by Henry Ford Health (grant number A20300). There are no other conflicts of interest or sources of funding to declare.

The neurocardiac circuit is integral to physiological regulation of threat and trauma-related responses. However, few direct investigations of brain-behavior associations with replicable physiological markers of PTSD have been conducted. The current study probed the neurocardiac circuit by examining associations among its core regions in the brain (e.g., insula, hypothalamus) and the periphery (heart rate [HR], high frequency heart rate variability [HF-HRV], and blood pressure [BP]). We sought to characterize these associations and to determine whether there were differences by PTSD status. Participants were N = 315 (64.1 % female) trauma-exposed adults enrolled from emergency departments as part of the prospective AURORA study. Participants completed a deep phenotyping session (e.g., fear conditioning, magnetic resonance imaging) two weeks after emergency department admission. Voxelwise analyses revealed several significant interactions between PTSD severity 8-weeks posttrauma and psychophysiological recordings on hypothalamic connectivity to the prefrontal cortex (PFC), insula, superior temporal sulcus, and temporoparietaloccipital junction. Among those with PTSD, diastolic BP was directly correlated with right insula-hypothalamic connectivity, whereas the reverse was found for those without PTSD. PTSD status moderated the association between systolic BP, HR, and HF-HRV and hypothalamic connectivity in the same direction. While preliminary, our findings may suggest that individuals with higher PTSD severity exhibit compensatory neural mechanisms to down-regulate autonomic imbalance. Additional study is warranted to determine how underlying mechanisms (e.g., inflammation) may disrupt the neurocardiac circuit and increase cardiometabolic disease risk in PTSD., Competing Interests: Declaration of competing interest Dr. Neylan reports consultation for Jazz Pharmaceuticals; Dr. Rauch reports royalties from Oxford University Press, the American Psychiatric Publishing Inc., and Springer Publishing royalties; Dr. McLean reports consultation for Walter Reed Army Institute for Research and for Arbor Medical Innovations; Dr. Kessler reports consultation for Cambridge Health Alliance, Canandaigua VA Medical Center, Holmusk, Partners Healthcare, INC Mirah, PYM, and Roga Sciences; Dr. Koenen reports royalties from Guilford Press and Oxford University Press; Dr. Ressler reports consultation for Bioxcel, Bionomics, Acer, and Jazz Pharma; All other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Females are more likely to develop posttraumatic stress disorder (PTSD) than males. Impaired inhibition has been identified as a mechanism for PTSD development, but studies on potential sex differences in this neurobiological mechanism and how it relates to PTSD severity and progression are relatively rare. Here, we examined sex differences in neural activation during response inhibition and PTSD following recent trauma., Methods: Participants (n = 205, 138 female sex assigned at birth) were recruited from emergency departments within 72 hours of a traumatic event. PTSD symptoms were assessed 2 weeks and 6 months posttrauma. A Go/NoGo task was performed 2 weeks posttrauma in a 3T magnetic resonance imaging scanner to measure neural activity during response inhibition in the ventromedial prefrontal cortex, right inferior frontal gyrus, and bilateral hippocampus. General linear models were used to examine the interaction effect of sex on the relationship between our regions of interest and the whole brain, PTSD symptoms at 6 months, and symptom progression between 2 weeks and 6 months., Results: Lower response inhibition-related ventromedial prefrontal cortex activation 2 weeks posttrauma predicted more PTSD symptoms at 6 months in females but not in males, while greater response inhibition-related right inferior frontal gyrus activation predicted lower PTSD symptom progression in males but not females. Whole-brain interaction effects were observed in the medial temporal gyrus and left precentral gyrus., Conclusions: There are sex differences in the relationship between inhibition-related brain activation and PTSD symptom severity and progression. These findings suggest that sex differences should be assessed in future PTSD studies and reveal potential targets for sex-specific interventions., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

There are significant challenges to identifying which individuals require intervention following exposure to trauma, and a need for strategies to identify and provide individuals at risk for developing PTSD with timely interventions. The present study seeks to identify a minimal set of trauma-related symptoms, assessed during the weeks following traumatic exposure, that can accurately predict PTSD. Participants were 2185 adults (Mean age=36.4 years; 64% women; 50% Black) presenting for emergency care following traumatic exposure. Participants received a 'flash survey' with 6-8 varying symptoms (from a pool of 26 trauma symptoms) several times per week for eight weeks following the trauma exposure (each symptom assessed ∼6 times). Features (mean, sd, last, worst, peak-end scores) from the repeatedly assessed symptoms were included as candidate variables in a CART machine learning analysis to develop a pragmatic predictive algorithm. PTSD (PCL-5 ≥38) was present for 669 (31%) participants at the 8-week follow-up. A classification tree with three splits, based on mean scores of nervousness, rehashing, and fatigue, predicted PTSD with an Area Under the Curve of 0.836. Findings suggest feasibility for a 3-item assessment protocol, delivered once per week, following traumatic exposure to assess and potentially facilitate follow-up care for those at risk., Competing Interests: Declaration of Competing Interest Dr. Neylan has received research support from NIH, VA, and Rainwater Charitable Foundation, and consulting income from Jazz Pharmaceuticals. In the last three years Dr. Clifford has received research funding from the NSF, NIH and LifeBell AI, and unrestricted donations from AliveCor Inc, Amazon Research, the Center for Discovery, the Gates Foundation, Google, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, Nextsense Inc, One Mind Foundation, and the Rett Research Foundation. Dr. Clifford has financial interest in AliveCor Inc and Nextsense Inc. He also is the CTO of MindChild Medical with significant stock. These relationships are unconnected to the current work. Dr. Germine receives funding from the National Institute of Mental Health (R01 MH121617) and is on the board of the Many Brains Project. Her family also has equity in Intelerad Medical Systems, Inc. Dr. Rauch reported serving as secretary of the Society of Biological Psychiatry; serving as a board member of Community Psychiatry and Mindpath Health; serving as a board member of National Association of Behavioral Healthcare; serving as secretary and a board member for the Anxiety and Depression Association of America; serving as a board member of the National Network of Depression Centers; receiving royalties from Oxford University Press, American Psychiatric Publishing Inc, and Springer Publishing; and receiving personal fees from the Society of Biological Psychiatry, Community Psychiatry and Mindpath Health, and National Association of Behavioral Healthcare outside the submitted work. Dr. Jones has no competing interests related to this work, though he has been an investigator on studies funded by AstraZeneca, Vapotherm, Abbott, and Ophirex. Dr. Joormann receives consulting payments from Janssen Pharmaceuticals. Dr. Harte has no competing interest related to this work, though in the last three years he has received research funding from Aptinyx and Arbor Medical Innovations, and consulting payments from Aptinyx. Dr. Koenen’s research has been supported by the Robert Wood Johnson Foundation, the Kaiser Family Foundation, the Harvard Center on the Developing Child, Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, the National Institutes of Health, One Mind, Anonymous Philanthropy, LLC, and Cohen Veterans Bioscience. She has been a paid consultant for the US Department of Justice and Covington Burling, LLP over the last three years. She has been a paid external reviewer for the Chan Zuckerberg Foundation, the University of Cape Town, and Capita Ireland. She has had paid speaking engagements in the last three years with the American Psychological Association, European Central Bank. Sigmund Freud University – Milan, Cambridge Health Alliance, and Coverys. She receives royalties from Guilford Press and Oxford University Press. Dr. McLean has served as a consultant for Walter Reed Army Institute for Research, Arbor Medical Innovations, and BioXcel Therapeutics, Inc., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD., Methods: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men., Results: Women reported higher PTSD severity at 3-months post-trauma. Z -score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects., Conclusions: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Background: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD., Methods: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables., Results: At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated., Conclusion: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata., Competing Interests: KK’s research has been supported by the Robert Wood Johnson Foundation, the Kaiser Family Foundation, the Harvard Center on the Developing Child, Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, the National Institutes of Health, One Mind, the Anonymous Foundation, and Cohen Veterans Bioscience. She has been a paid consultant for Baker Hostetler, Discovery Vitality, and the Department of Justice. She has been a paid external reviewer for the Chan Zuckerberg Foundation, the University of Cape Town, and Capita Ireland. She has had paid speaking engagements in the last three years with the American Psychological Association, European Central Bank. Sigmund Freud University – Milan, Cambridge Health Alliance, and Coverys. She receives royalties from Guilford Press and Oxford University Press. TN has received research support from NIH, VA, and Rainwater Charitable Foundation, and consulting income from Jazz Pharmaceuticals. In the last three years, GDC has received research funding from the NSF, NIH and LifeBell AI, and unrestricted donations from AliveCor Inc, Amazon Research, the Center for Discovery, the Gates Foundation, Google, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, Nextsense Inc, One Mind Foundation, the Rett Research Foundation, and Samsung Research. GDC has financial interest in AliveCor Inc and Nextsense Inc. He also is the CTO of MindChild Medical and CSO of LifeBell AI and has ownership in both companies. These relationships are unconnected to the current work. SR reports grants from NIH during the conduct of the study; personal fees from SOBP Society of Biological Psychiatry paid role as secretary, other from Oxford University Press royalties, other from APP American Psychiatric Publishing Inc. royalties, other from VA Veterans Administration per diem for oversight committee, and other from Community Psychiatry/Mindpath Health paid board service, including equity outside the submitted work; other from National Association of Behavioral Healthcare for paid Board service; other from Springer Publishing royalties; and Leadership roles on Board or Council for SOBP, ADAA Anxiety and Depression Association of America, and NNDC National Network of Depression Centers. SS has received funding from the Florida Medical Malpractice Joint Underwriter’s Association Dr. Alvin E. Smith Safety of Healthcare Services Grant; Allergan Foundation; the NIH/NIA-funded Jacksonville Aging Studies Center JAX-ASCENT; R33AG05654; and the Substance Abuse and Mental Health Services Administration 1H79TI083101-01; and the Florida Blue Foundation. CJ has no competing interests related to this work, though he has been an investigator on studies funded by AstraZeneca, Vapotherm, Abbott, and Ophirex. JJ receives consulting payments from Janssen Pharmaceuticals. SEH has no competing interests related to this work, though in the last three years he has received research funding from Aptinyx and Arbor Medical Innovations, and consulting payments from Aptinyx, Heron Therapeutics, and Eli Lilly. SM served as a consultant for Walter Reed Army Institute for Research and for Arbor Medical Innovations. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor Y-lT declared a shared affiliation with the author(s) GDC., (Copyright © 2024 Garrison-Desany, Meyers, Linnstaedt, House, Beaudoin, An, Zeng, Neylan, Clifford, Jovanovic, Germine, Bollen, Rauch, Haran, Storrow, Lewandowski, Musey, Hendry, Sheikh, Jones, Punches, Swor, Gentile, Hudak, Pascual, Seamon, Harris, Pearson, Peak, Domeier, Rathlev, O’Neil, Sergot, Sanchez, Bruce, Joormann, Harte and McLean, Koenen and Denckla.)

Materials exhibiting a significant shift current response could potentially outperform conventional solar cell materials. The myriad of factors governing shift-current response, however, poses significant challenges in finding such strong shift-current materials. Here we propose a general design principle that exploits inter-orbital mixing to excite virtual multiband transitions in materials with multiple flat bands to achieve an enhanced shift current response. We further relate this design principle to maximizing Wannier function spread as expressed through the formalism of quantum geometry. We demonstrate the viability of our design using a 1D stacked Rice-Mele model. Furthermore, we consider a concrete material realization - alternating angle twisted multilayer graphene (TMG) - a natural platform to experimentally realize such an effect. We identify a set of twist angles at which the shift current response is maximized via virtual transitions for each multilayer graphene and highlight the importance of TMG as a promising material to achieve an enhanced shift current response at terahertz frequencies. Our proposed mechanism also applies to other 2D systems and can serve as a guiding principle for designing multiband systems that exhibit an enhanced shift current response., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Background: Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians., Methods: In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance., Results: Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12., Conclusions: Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma., (© 2023. The Author(s).)

Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers an avenue to understanding mechanisms as well as possibilities for intervention. Microbiome composition after trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether the gut microbiomes of trauma-exposed emergency department patients who develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms. We performed metagenomic analysis on stool samples (n = 51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumA (AURORA) study. Two-, eight- and twelve-week post-trauma outcomes for post-traumatic stress disorder (PTSD) (PTSD checklist for DSM-5), normalized depression scores (PROMIS Depression Short Form 8b) and somatic symptom counts were collected. Generalized linear models were created for each outcome using microbial abundances and relevant demographics. Mixed-effect random forest machine learning models were used to identify associations between APNS outcomes and microbial features and encoded metabolic pathways from stool metagenomics. Microbial species, including Flavonifractor plautii, Ruminococcus gnavus and, Bifidobacterium species, which are prevalent commensal gut microbes, were found to be important in predicting worse APNS outcomes from microbial abundance data. Notably, through APNS outcome modeling using microbial metabolic pathways, worse APNS outcomes were highly predicted by decreased L-arginine related pathway genes and increased citrulline and ornithine pathways. Common commensal microbial species are enriched in individuals who develop APNS. More notably, we identified a biological mechanism through which the gut microbiome reduces global arginine bioavailability, a metabolic change that has also been demonstrated in the plasma of patients with PTSD., (© 2023. The Author(s).)

Magic-angle twisted trilayer graphene (MATTG) exhibits a range of strongly correlated electronic phases that spontaneously break its underlying symmetries 1,2 . Here we investigate the correlated phases of MATTG using scanning tunnelling microscopy and identify marked signatures of interaction-driven spatial symmetry breaking. In low-strain samples, over a filling range of about two to three electrons or holes per moiré unit cell, we observe atomic-scale reconstruction of the graphene lattice that accompanies a correlated gap in the tunnelling spectrum. This short-scale restructuring appears as a Kekulé supercell-implying spontaneous inter-valley coherence between electrons-and persists in a wide range of magnetic fields and temperatures that coincide with the development of the gap. Large-scale maps covering several moiré unit cells further reveal a slow evolution of the Kekulé pattern, indicating that atomic-scale reconstruction coexists with translation symmetry breaking at a much longer moiré scale. We use auto-correlation and Fourier analyses to extract the intrinsic periodicity of these phases and find that they are consistent with the theoretically proposed incommensurate Kekulé spiral order 3,4 . Moreover, we find that the wavelength characterizing moiré-scale modulations monotonically decreases with hole doping away from half-filling of the bands and depends weakly on the magnetic field. Our results provide essential insights into the nature of the correlated phases of MATTG in the presence of strain and indicate that superconductivity can emerge from an inter-valley coherent parent state., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Importance: Differences in neighborhood socioeconomic characteristics are important considerations in understanding differences in risk vs resilience in mental health. Neighborhood disadvantage is associated with alterations in the function and structure of threat neurocircuitry., Objective: To investigate associations of neighborhood disadvantage with white and gray matter and neural reactivity to positive and negative stimuli in the context of trauma exposure., Design, Setting, and Participants: In this cross-sectional study, survivors of trauma who completed sociodemographic and posttraumatic symptom assessments and neuroimaging were recruited as part of the Advancing Understanding of Recovery After Trauma (AURORA) study between September 2017 and June 2021. Data analysis was performed from October 25, 2022, to February 15, 2023., Exposure: Neighborhood disadvantage was measured with the Area Deprivation Index (ADI) for each participant home address., Main Outcomes and Measures: Participants completed separate threat and reward tasks during functional magnetic resonance imaging. Diffusion-weighted and high-resolution structural images were also collected. Linear models assessed the association of ADI with reactivity, microstructure, and macrostructure of a priori regions of interest after adjusting for income, lifetime trauma, sex at birth, and age. A moderated-mediation model tested whether ADI was associated with neural activity via microstructural changes and if this was modulated by PTSD symptoms., Results: A total of 280 participants (183 females [65.4%]; mean [SD] age, 35.39 [13.29] years) completed the threat task and 244 participants (156 females [63.9%]; mean [SD] age, 35.10 [13.26] years) completed the reward task. Higher ADI (per 1-unit increase) was associated with greater insula (t274 = 3.20; β = 0.20; corrected P = .008) and anterior cingulate cortex (ACC; t274 = 2.56; β = 0.16; corrected P = .04) threat-related activity after considering covariates, but ADI was not associated with reward reactivity. Greater disadvantage was also associated with altered microstructure of the cingulum bundle (t274 = 3.48; β = 0.21; corrected P = .001) and gray matter morphology of the ACC (cortical thickness: t273 = -2.29; β = -0.13; corrected P = .02; surface area: t273 = 2.53; β = 0.13; corrected P = .02). The moderated-mediation model revealed that ADI was associated with ACC threat reactivity via cingulum microstructural changes (index of moderated mediation = -0.02). However, this mediation was only present in individuals with greater PTSD symptom severity (at the mean: β = -0.17; standard error = 0.06, t= -2.28; P = .007; at 1 SD above the mean: β = -0.28; standard error = 0.08; t = -3.35; P < .001)., Conclusions and Relevance: In this study, neighborhood disadvantage was associated with neurobiology that supports threat processing, revealing associations of neighborhood disadvantage with neural susceptibility for PTSD and suggesting how altered structure-function associations may complicate symptoms. Future work should investigate specific components of neighborhood disadvantage that may be associated with these outcomes.

Background: Posttraumatic stress symptoms (PTSS) are common following traumatic stress exposure (TSE). Identification of individuals with PTSS risk in the early aftermath of TSE is important to enable targeted administration of preventive interventions. In this study, we used baseline survey data from two prospective cohort studies to identify the most influential predictors of substantial PTSS., Methods: Self-identifying black and white American women and men ( n = 1546) presenting to one of 16 emergency departments (EDs) within 24 h of motor vehicle collision (MVC) TSE were enrolled. Individuals with substantial PTSS (⩾33, Impact of Events Scale - Revised) 6 months after MVC were identified via follow-up questionnaire. Sociodemographic, pain, general health, event, and psychological/cognitive characteristics were collected in the ED and used in prediction modeling. Ensemble learning methods and Monte Carlo cross-validation were used for feature selection and to determine prediction accuracy. External validation was performed on a hold-out sample (30% of total sample)., Results: Twenty-five percent ( n = 394) of individuals reported PTSS 6 months following MVC. Regularized linear regression was the top performing learning method. The top 30 factors together showed good reliability in predicting PTSS in the external sample (Area under the curve = 0.79 ± 0.002). Top predictors included acute pain severity, recovery expectations, socioeconomic status, self-reported race, and psychological symptoms., Conclusions: These analyses add to a growing literature indicating that influential predictors of PTSS can be identified and risk for future PTSS estimated from characteristics easily available/assessable at the time of ED presentation following TSE.

Floquet moiré materials possess optically-induced flat-electron bands with steady-states sensitive to drive parameters. Within this regime, we show that strong interaction screening and phonon bath coupling can overcome enhanced drive-induced heating. In twisted bilayer graphene (TBG) irradiated by a terahertz-frequency continuous circularly polarized laser, the extremely slow electronic states enable the drive to control the steady state occupation of high-Berry curvature electronic states. In particular, above a critical field amplitude, high-Berry-curvature states exhibit a slow regime where they decouple from acoustic phonons, allowing the drive to control the anomalous Hall response. Our work shows that the laser-induced control of topological and transport physics in Floquet TBG are measurable using experimentally available probes.

Considerable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms., (© 2023. The Author(s).)

Understanding the nature of strongly correlated states in flat-band materials (such as moiré heterostructures) is at the forefront of both experimental and theoretical pursuits. While magnetotransport, scanning probe, and optical techniques are often very successful in investigating the properties of the underlying order, the exact nature of the ground state often remains unknown. Here, we propose to leverage strong light-matter coupling present in the flat-band systems to gain insight through dynamical dielectric response into the structure of the many-body ground state. We argue that because of the enlargement of the effective lattice of the system arising from correlations, conventional long-range plasmon becomes "folded" to yield a multiband plasmon spectrum. We detail several mechanisms through which the structure of the plasmon spectrum and that of the dynamical dielectric response is susceptible to the underlying order, revealing valued insights such as the interaction-driven band gaps, spin-structure, and the order periodicity.

Importance: Adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure are common and have higher incidence among socioeconomically disadvantaged populations. Pain, depression, avoidance of trauma reminders, reexperiencing trauma, anxiety, hyperarousal, sleep disruption, and nightmares have been reported. Wrist-wearable devices with accelerometers capable of assessing 24-hour rest-activity characteristics are prevalent and may have utility in measuring these outcomes., Objective: To evaluate whether wrist-wearable devices can provide useful biomarkers for recovery after traumatic stress exposure., Design, Setting, and Participants: Data were analyzed from a diverse cohort of individuals seen in the emergency department after experiencing a traumatic stress exposure, as part of the Advancing Understanding of Recovery After Trauma (AURORA) study. Participants recruited from 27 emergency departments wore wrist-wearable devices for 8 weeks, beginning in the emergency department, and completed serial assessments of neuropsychiatric symptoms. A total of 19 019 patients were screened. Of these, 3040 patients met study criteria, provided informed consent, and completed baseline assessments. A total of 2021 provided data from wrist-wearable devices, completed the 8-week assessment, and were included in this analysis. The data were randomly divided into 2 equal parts (n = 1010) for biomarker identification and validation. Data were collected from September 2017 to January 2020, and data were analyzed from May 2020 to November 2022., Exposures: Participants were recruited for the study after experiencing a traumatic stress exposure (most commonly motor vehicle collision)., Main Outcomes and Measures: Rest-activity characteristics were derived and validated from wrist-wearable devices associated with specific self-reported symptom domains at a point in time and changes in symptom severity over time., Results: Of 2021 included patients, 1257 (62.2%) were female, and the mean (SD) age was 35.8 (13.0) years. Eight wrist-wearable device biomarkers for symptoms of adverse posttraumatic neuropsychiatric sequelae exceeded significance thresholds in the derivation cohort. One of these, reduced 24-hour activity variance, was associated with greater pain severity (r = -0.14; 95% CI, -0.20 to -0.07). Changes in 6 rest-activity measures were associated with changes in pain over time, and changes in the number of transitions between sleep and wake over time were associated with changes in pain, sleep, and anxiety. Simple cutoffs for these biomarkers identified individuals with good recovery for pain (positive predictive value [PPV], 0.85; 95% CI, 0.82-0.88), sleep (PPV, 0.63; 95% CI, 0.59-0.67, and anxiety (PPV, 0.76; 95% CI, 0.72-0.80) with high predictive value., Conclusions and Relevance: These findings suggest that wrist-wearable device biomarkers may have utility as screening tools for pain, sleep, and anxiety symptom outcomes after trauma exposure in high-risk populations.

Study Objective: To derive and initially validate a brief bedside clinical decision support tool that identifies emergency department (ED) patients at high risk of substantial, persistent posttraumatic stress symptoms after a motor vehicle collision., Methods: Derivation (n=1,282, 19 ED sites) and validation (n=282, 11 separate ED sites) data were obtained from adults prospectively enrolled in the Advancing Understanding of RecOvery afteR traumA study who were discharged from the ED after motor vehicle collision-related trauma. The primary outcome was substantial posttraumatic stress symptoms at 3 months (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders-5 ≥38). Logistic regression derivation models were evaluated for discriminative ability using the area under the curve and the accuracy of predicted risk probabilities (Brier score). Candidate posttraumatic stress predictors assessed in these models (n=265) spanned a range of sociodemographic, baseline health, peritraumatic, and mechanistic domains. The final model selection was based on performance and ease of administration., Results: Significant 3-month posttraumatic stress symptoms were common in the derivation (27%) and validation (26%) cohort. The area under the curve and Brier score of the final 8-question tool were 0.82 and 0.14 in the derivation cohort and 0.76 and 0.17 in the validation cohort., Conclusion: This simple 8-question tool demonstrates promise to risk-stratify individuals with substantial posttraumatic stress symptoms who are discharged to home after a motor vehicle collision. Both external validation of this instrument, and work to further develop more accurate tools, are needed. Such tools might benefit public health by enabling the conduct of preventive intervention trials and assisting the growing number of EDs that provide services to trauma survivors aimed at promoting psychological recovery., (Copyright © 2022 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Prior sexual trauma (ST) is associated with greater risk for posttraumatic stress disorder after a subsequent traumatic event; however, the underlying neurobiological mechanisms remain opaque. We investigated longitudinal posttraumatic dysfunction and amygdala functional dynamics following admission to an emergency department for new primarily nonsexual trauma in participants with and without previous ST., Methods: Participants ( N  = 2178) were recruited following acute trauma exposure (primarily motor vehicle collision). A subset ( n  = 242) completed magnetic resonance imaging that included a fearful faces task and a resting-state scan 2 weeks after the trauma. We investigated associations between prior ST and several dimensions of posttraumatic symptoms over 6 months. We further assessed amygdala activation and connectivity differences between groups with or without prior ST., Results: Prior ST was associated with greater posttraumatic depression ( F 1,1120  = 28.35, p  = 1.22 × 10 -7 , η p 2  = 0.06), anxiety ( F 1,1113  = 17.43, p  = 3.21 × 10 -5 , η p 2  = 0.05), and posttraumatic stress disorder ( F 1,1027  = 11.34, p  = 7.85 × 10 -4 , η p 2  = 0.04) severity and more maladaptive beliefs about pain ( F 1,1113  = 8.51, p  = .004, η p 2  = 0.02) but was not related to amygdala reactivity to fearful versus neutral faces (all p s > .05). A secondary analysis revealed an interaction between ST and lifetime trauma load on the left amygdala to visual cortex connectivity (peak Z value: -4.41, corrected p < .02)., Conclusions: Findings suggest that prior ST is associated with heightened posttraumatic dysfunction following a new trauma exposure but not increased amygdala activity. In addition, ST may interact with lifetime trauma load to alter neural circuitry in visual processing regions following acute trauma exposure. Further research should probe the relationship between trauma type and visual circuitry in the acute aftermath of trauma., (© 2023 The Authors.)

The authors sought to characterize adverse posttraumatic neuropsychiatric sequelae (APNS) symptom trajectories across ten symptom domains (pain, depression, sleep, nightmares, avoidance, re-experiencing, anxiety, hyperarousal, somatic, and mental/fatigue symptoms) in a large, diverse, understudied sample of motor vehicle collision (MVC) survivors. More than two thousand MVC survivors were enrolled in the emergency department (ED) and completed a rotating battery of brief smartphone-based surveys over a 2-month period. Measurement models developed from survey item responses were used in latent growth curve/mixture modeling to characterize homogeneous symptom trajectories. Associations between individual trajectories and pre-trauma and peritraumatic characteristics and traditional outcomes were compared, along with associations within and between trajectories. APNS across all ten symptom domains were common in the first two months after trauma. Many risk factors and associations with high symptom burden trajectories were shared across domains. Both across and within traditional diagnostic boundaries, APNS trajectory intercepts, and slopes were substantially correlated. Across all domains, symptom severity in the immediate aftermath of trauma (trajectory intercepts) had the greatest influence on the outcome. An interactive data visualization tool was developed to allow readers to explore relationships of interest between individual characteristics, symptom trajectories, and traditional outcomes ( http://itr.med.unc.edu/aurora/parcoord/ ). Individuals presenting to the ED after MVC commonly experience a broad constellation of adverse posttraumatic symptoms. Many risk factors for diverse APNS are shared. Individuals diagnosed with a single traditional outcome should be screened for others. The utility of multidimensional categorizations that characterize individuals across traditional diagnostic domains should be explored., (© 2023. The Author(s).)

In the presence of a large perpendicular electric field, Bernal-stacked bilayer graphene (BLG) features several broken-symmetry metallic phases 1-3 as well as magnetic-field-induced superconductivity 1 . The superconducting state is quite fragile, however, appearing only in a narrow window of density and with a maximum critical temperature T c  ≈ 30 mK. Here we show that placing monolayer tungsten diselenide (WSe 2 ) on BLG promotes Cooper pairing to an extraordinary degree: superconductivity appears at zero magnetic field, exhibits an order of magnitude enhancement in T c and occurs over a density range that is wider by a factor of eight. By mapping quantum oscillations in BLG-WSe 2 as a function of electric field and doping, we establish that superconductivity emerges throughout a region for which the normal state is polarized, with two out of four spin-valley flavours predominantly populated. In-plane magnetic field measurements further reveal that superconductivity in BLG-WSe 2 can exhibit striking dependence of the critical field on doping, with the Chandrasekhar-Clogston (Pauli) limit roughly obeyed on one end of the superconducting dome, yet sharply violated on the other. Moreover, the superconductivity arises only for perpendicular electric fields that push BLG hole wavefunctions towards WSe 2 , indicating that proximity-induced (Ising) spin-orbit coupling plays a key role in stabilizing the pairing. Our results pave the way for engineering robust, highly tunable and ultra-clean graphene-based superconductors., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Anxiety sensitivity, or fear of anxious arousal, is cross-sectionally associated with a wide array of adverse posttraumatic neuropsychiatric sequelae, including symptoms of posttraumatic stress disorder, depression, anxiety, sleep disturbance, pain, and somatization. The current study utilizes a large-scale, multi-site, prospective study of trauma survivors presenting to emergency departments. Hypotheses tested whether elevated anxiety sensitivity in the immediate posttrauma period is associated with more severe and persistent trajectories of common adverse posttraumatic neuropsychiatric sequelae in the eight weeks posttrauma. Participants from the AURORA study (n = 2,269 recruited from 23 emergency departments) completed self-report assessments over eight weeks posttrauma. Associations between heightened anxiety sensitivity and more severe and/or persistent trajectories of trauma-related symptoms identified by growth mixture modeling were analyzed. Anxiety sensitivity assessed two weeks posttrauma was associated with severe and/or persistent posttraumatic stress, depression, anxiety, sleep disturbance, pain, and somatic symptoms in the eight weeks posttrauma. Effect sizes were in the small to medium range in multivariate models accounting for various demographic, trauma-related, pre-trauma mental health-related, and personality-related factors. Anxiety sensitivity may be a useful transdiagnostic risk factor in the immediate posttraumatic period identifying individuals at risk for the development of adverse posttraumatic neuropsychiatric sequelae. Further, considering anxiety sensitivity is malleable via brief intervention, it could be a useful secondary prevention target. Future research should continue to evaluate associations between anxiety sensitivity and trauma-related pathology., Competing Interests: Declaration of competing interest Dr. Neylan has received research support from NIH, VA, and Rainwater Charitable Foundation, and consulting income from Jazz Pharmaceuticals. In the last three years Dr. Clifford has received research funding from the NSF, NIH and LifeBell AI, and unrestricted donations from AliveCor, Amazon Research, the Center for Discovery, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, the Gates Foundation, Google, One Mind Foundation, and Samsung Research. Dr. Clifford has financial interest in AliveCor, and receives unrestricted funding from the company. He also is the CTO of MindChild Medical and CSO of LifeBell AI and has ownership in both companies. These relationships are unconnected to the current work. Dr. Rauch reports grants from NIH during the conduct of the study; personal fees from SOBP (Society of Biological Psychiatry) paid role as secretary, other from Oxford University Press royalties, other from APP (American Psychiatric Publishing Inc.) royalties, other from VA (Veterans Administration) per diem for oversight committee, and other from Community Psychiatry/Mindpath Health paid board service, including equity outside the submitted work; other from National Association of Behavioral Healthcare for paid Board service; and Leadership roles on Board or Council for SOBP, ADAA (Anxiety and Depression Association of America), and NNDC (National Network of Depression Centers). Dr. Sophia Sheikh has received funding from the Florida Medical Malpractice Joint Underwriter's Association Dr. Alvin E. Smith Safety of Healthcare Services Grant; Allergan Foundation; the NIH/NIA-funded Jacksonville Aging Studies Center (JAX-ASCENT; R33AG05654); and the Substance Abuse and Mental Health Services Administration (1H79TI083101-01); and the Florida Blue Foundation. Dr. Jones has no competing interests related to this work, though he has been an investigator on studies funded by AstraZeneca, Janssen, Holigic, Inc, and Ophirex. Dr. Datner serves as Medical Advisor for Cayaba Care. Dr. Joormann receives consulting payments from Janssen Pharmaceuticals. Dr. Barch has received function from the NIMH, NIDA, and the American Foundation for Suicide Prevention, and consults for Boehringer-Ingelheim. Over the past 3 years, Dr. Pizzagalli has received consulting fees from Albright Stonebridge Group, Boehringer Ingelheim, Compass Pathways, Concert Pharmaceuticals, Engrail Therapeutics, Neumora Therapeutics (former BlackThorn Therapeutics), Neurocrine Biosciences, Neuroscience Software, Otsuka Pharmaceuticals, and Takeda Pharmaceuticals; honoraria from the Psychonomic Society (for editorial work) and Alkermes, and research funding from NIMH, Dana Foundation, Brain and Behavior Research Foundation, and Millennium Pharmaceuticals. In addition, he has received stock options from Neumora Therapeutics (former BlackThorn Therapeutics), Compass Pathways, Engrail Therapeutics, and Neuroscience Software. Dr. Harte has no competing interests related to this work, though in the last three years he has received research funding from Aptinyx and Arbor Medical Innovations, and consulting payments from Aptinyx, Heron Therapeutics, and Eli Lilly. Dr. Elliott reports support from the National Institutes of Health (NIH) through Grant Numbers R01HD079076 & R03HD094577: Eunice Kennedy Shriver National Institute of Child Health & Human Development; National Center for Medical Rehabilitation Research. He also reports funding from New South Wales Health, Spinal Cord Injury Award (2020–2025) and consulting fees (<$15,000 per annum) from Orofacial Therapeutics, LLC. In the past 3 years, Dr. Kessler was a consultant for Datastat, Inc., Holmusk, RallyPoint Networks, Inc., and Sage Pharmaceuticals. He has stock options in Mirah, PYM, and Roga Sciences. PTSD = posttraumatic stress disorder. Clinical outcomes were calculated using the following cut-offs: Clinically significant new or worsening pain = increased pain from pre-to posttrauma by ≥ 2 points on the pain numeric rating scale (Bijur et al., 2003); PTSD ≥31 on the Posttraumatic Stress Disorder Checklist (PCL; Weathers et al., 2013); Depression ≥60 on the Patient-Reported Outcome Measurement Information System (PROMIS; Cella et al., 2010); Insomnia = Insomnia Severity Index scores of at least 15 (Morin et al., 2011). Of note, a brief PROMIS anxiety scale was administered, precluding the ability to assess clinically significant symptoms based on typical cut-off scores. Thus, means for anxiety are reported (range = 0–16)., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Graphene moiré superlattices show an abundance of correlated insulating, topological, and superconducting phases. Whereas the origins of strong correlations and nontrivial topology can be directly linked to flat bands, the nature of superconductivity remains enigmatic. We demonstrate that magic-angle devices made of twisted tri-, quadri-, and pentalayer graphene placed on monolayer tungsten diselenide exhibit flavor polarization and superconductivity. We also observe insulating states in the tril- and quadrilayer arising at finite electric displacement fields. As the number of layers increases, superconductivity emerges over an enhanced filling-factor range, and in the pentalayer it extends well beyond the filling of four electrons per moiré unit cell. Our results highlight the role of the interplay between flat and more dispersive bands in extending superconducting regions in graphene moiré superlattices.

Objective: Whether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use., Methods: Participants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed for euphoria) in the 30 days before enrollment, and missing or incomplete data regarding opioid exposure or pain. We used multivariable logistic regression to assess the relationship between ED opioid exposure and at-risk opioid use, defined as any self-reported non-medical opioid use after initial ED encounter or prescription opioid use at 3-months., Results: Of 1441 subjects completing 3-month follow-up, 872 participants were included for analysis. At-risk opioid use occurred within 3 months in 33/620 (5.3%, CI: 3.7,7.4) participants without ED opioid analgesic exposure; 4/16 (25.0%, CI: 8.3, 52.6) with ED opioid prescription only; 17/146 (11.6%, CI: 7.1, 18.3) with ED opioid administration only; 12/90 (13.3%, CI: 7.4, 22.5) with both. Controlling for clinical factors, adjusted odds ratios (aORs) for at-risk opioid use after ED opioid exposure were: ED prescription only: 4.9 (95% CI 1.4, 17.4); ED administration for analgesia only: 2.0 (CI 1.0, 3.8); both: 2.8 (CI 1.2, 6.5)., Conclusions: ED opioids were associated with subsequent at-risk opioid use within three months in a geographically diverse cohort of adult trauma patients. This supports need for prospective studies focused on the long-term consequences of ED opioid analgesic exposure to estimate individual risk and guide therapeutic decision-making., Competing Interests: Conflict of Interest: In the last three years Dr. Clifford has received research funding from the NSF, NIH and LifeBell AI, and unrestricted donations from AliveCor, Amazon Research, the Center for Discovery, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, the Gates Foundation, Google, One Mind Foundation, and Samsung Research. Dr Clifford has financial interest in AliveCor, and receives unrestricted funding from the company. He also is the CTO of MindChild Medical and CSO of LifeBell AI and has ownership in both companies. These relationships are unconnected to the current work. In the past three years, Dr. Germine has served on the Scientific Advisory Board of Sage Bionetworks, for which she received a small honorarium. She also receives grant support from NIH. Dr. Rauch reports grants from NIH during the conduct of the study; personal fees from SOBP (Society of Biological Psychiatry) paid role as secretary, other from Oxford University Press royalties, other from APP (American Psychiatric Publishing Inc.) royalties, other from VA (Veterans Administration) per diem for oversight committee, and other from Community Psychiatry paid board service, including equity outside the submitted work; and Leadership roles on Board or Council for SOBP, ADAA (Anxiety and Depression Association of America), and NNDC (National Network of Depression Centers). Sophia Sheikh has received funding from the Florida Medical Malpractice Joint Underwriter’s Association Dr. Alvin E. Smith Safety of Healthcare Services Grant; Allergan Foundation; the NIH/NIA-funded Jacksonville Aging Studies Center (JAX-ASCENT; R33AG05654); and the Substance Abuse and Mental Health Services Administration (1H79TI083101-01); and the Florida Blue Foundation. Christopher Jones has been an investigator on studies funded by Roche Diagnostics, AstraZeneca, Janssen, and Hologic Inc, for which my department has received research funding. No direct conflicts related to this paper, and no ongoing conflicts. Dr. Joormann receives consulting payments from Janssen Pharmaceuticals. Over the past 3 years, Dr. Pizzagalli has received consulting fees from Albright Stonebridge Group, BlackThorn Therapeutics, Boehringer Ingelheim, Compass Pathway, Concert Pharmaceuticals, Engrail Therapeutics, Neurocrine Biosciences, Otsuka Pharmaceuticals, and Takeda Pharmaceuticals; one honorarium from Alkermes, and research funding from NIMH, Dana Foundation, Brain and Behavior Research Foundation, and Millennium Pharmaceuticals. In addition, he has received stock options from BlackThorn Therapeutics. J Elliott reports support from the National Institutes of Health (NIH) through Grant Numbers R01HD079076 & R03HD094577: Eunice Kennedy Shriver National Institute of Child Health & Human Development; National Center for Medical Rehabilitation Research. He also reports funding from New South Wales Health, Spinal Cord Injury Award (2020-2025) and consulting fees (< $15,000 per annum) from Orofacial Therapeutics, LLC. In the past 3 years, Dr. Kessler was a consultant for Datastat, Inc., Holmusk, RallyPoint Networks, Inc., and Sage Pharmaceuticals. He has stock options in Mirah, PYM, and Roga Sciences. Dr. Ressler has received consulting income from Alkermes and Takeda, research support from NIH, Alkermes, Genomind and Brainsway, and he has served on advisory boards for Takeda, Resilience Therapeutics, Janssen and Verily/Google.

Objective: Dissociation, a disruption or discontinuity in psychological functioning, is often linked with worse psychiatric symptoms; however, the prognostic value of dissociation after trauma is inconsistent. Determining whether trauma-related dissociation is uniquely predictive of later outcomes would enable early identification of at-risk trauma populations. The authors conducted the largest prospective longitudinal biomarker study of persistent dissociation to date to determine its predictive capacity for adverse psychiatric outcomes following acute trauma., Methods: All data were part of the Freeze 2 data release from the Advancing Understanding of Recovery After Trauma (AURORA) study. Study participants provided self-report data about persistent derealization (N=1,464), a severe type of dissociation, and completed a functional MRI emotion reactivity task and resting-state scan 2 weeks posttrauma (N=145). Three-month follow-up reports were collected of posttraumatic stress, depression, pain, anxiety symptoms, and functional impairment., Results: Derealization was associated with increased ventromedial prefrontal cortex (vmPFC) activation in the emotion reactivity task and decreased resting-state vmPFC connectivity with the cerebellum and orbitofrontal cortex. In separate analyses, brain-based and self-report measures of persistent derealization at 2 weeks predicted worse 3-month posttraumatic stress symptoms, distinct from the effects of childhood maltreatment history and current posttraumatic stress symptoms., Conclusions: The findings suggest that persistent derealization is both an early psychological and biological marker of worse later psychiatric outcomes. The neural correlates of trauma-related dissociation may serve as potential targets for treatment engagement to prevent posttraumatic stress disorder. These results underscore dissociation assessment as crucial following trauma exposure to identify at-risk individuals, and they highlight an unmet clinical need for tailored early interventions.

Hippo campal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma ( N = 116, 76 female), we found that PTSD symptoms at 2 weeks were associated with decreased hippocampal responses to threat as assessed with fMRI. Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of fear potentiated startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function because of increases in fear-potentiated arousal. SIGNIFICANCE STATEMENT Alterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on nontrauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk., (Copyright © 2022 the authors.)

Visual components of trauma memories are often vividly re-experienced by survivors with deleterious consequences for normal function. Neuroimaging research on trauma has primarily focused on threat-processing circuitry as core to trauma-related dysfunction. Conversely, limited attention has been given to visual circuitry which may be particularly relevant to posttraumatic stress disorder (PTSD). Prior work suggests that the ventral visual stream is directly related to the cognitive and affective disturbances observed in PTSD and may be predictive of later symptom expression. The present study used multimodal magnetic resonance imaging data (n = 278) collected two weeks after trauma exposure from the AURORA study, a longitudinal, multisite investigation of adverse posttraumatic neuropsychiatric sequelae. Indices of gray and white matter were combined using data fusion to identify a structural covariance network (SCN) of the ventral visual stream 2 weeks after trauma. Participant's loadings on the SCN were positively associated with both intrusion symptoms and intensity of nightmares. Further, SCN loadings moderated connectivity between a previously observed amygdala-hippocampal functional covariance network and the inferior temporal gyrus. Follow-up MRI data at 6 months showed an inverse relationship between SCN loadings and negative alterations in cognition in mood. Further, individuals who showed decreased strength of the SCN between 2 weeks and 6 months had generally higher PTSD symptom severity over time. The present findings highlight a role for structural integrity of the ventral visual stream in the development of PTSD. The ventral visual stream may be particularly important for the consolidation or retrieval of trauma memories and may contribute to efficient reactivation of visual components of the trauma memory, thereby exacerbating PTSD symptoms. Potentially chronic engagement of the network may lead to reduced structural integrity which becomes a risk factor for lasting PTSD symptoms., (© 2022. The Author(s).)

Magic-angle twisted trilayer graphene (MATTG) has emerged as a moiré material that exhibits strong electronic correlations and unconventional superconductivity 1,2 . However, local spectroscopic studies of this system are still lacking. Here we perform high-resolution scanning tunnelling microscopy and spectroscopy of MATTG that reveal extensive regions of atomic reconstruction favouring mirror-symmetric stacking. In these regions, we observe symmetry-breaking electronic transitions and doping-dependent band-structure deformations similar to those in magic-angle bilayers, as expected theoretically given the commonality of flat bands 3,4 . Most notably in a density window spanning two to three holes per moiré unit cell, the spectroscopic signatures of superconductivity are manifest as pronounced dips in the tunnelling conductance at the Fermi level accompanied by coherence peaks that become gradually suppressed at elevated temperatures and magnetic fields. The observed evolution of the conductance with doping is consistent with a gate-tunable transition from a gapped superconductor to a nodal superconductor, which is theoretically compatible with a sharp transition from a Bardeen-Cooper-Schrieffer superconductor to a Bose-Einstein-condensation superconductor with a nodal order parameter. Within this doping window, we also detect peak-dip-hump structures that suggest that superconductivity is driven by strong coupling to bosonic modes of MATTG. Our results will enable further understanding of superconductivity and correlated states in graphene-based moiré structures beyond twisted bilayers 5 ., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Importance: SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates lung injury in preclinical models, although data in humans with COVID-19 remain mixed., Objective: To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19., Design, Setting, and Participants: This blinded, placebo-controlled randomized clinical trial was conducted in 13 hospitals in the United States from April 2020 to February 2021. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already using a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible for participation. Data were analyzed from April 19 to August 24, 2021., Interventions: Losartan 50 mg orally twice daily vs equivalent placebo for 10 days or until hospital discharge., Main Outcomes and Measures: The primary outcome was the imputed arterial partial pressure of oxygen to fraction of inspired oxygen (Pao2:Fio2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity; days without supplemental o2, ventilation, or vasopressors; and mortality. Losartan pharmacokinetics and RAAS components (AII, angiotensin-[1-7] and angiotensin-converting enzymes 1 and 2)] were measured in a subgroup of participants., Results: A total of 205 participants (mean [SD] age, 55.2 [15.7] years; 123 [60.0%] men) were randomized, with 101 participants assigned to losartan and 104 participants assigned to placebo. Compared with placebo, losartan did not significantly affect Pao2:Fio2 ratio at 7 days (difference, -24.8 [95%, -55.6 to 6.1]; P = .12). Compared with placebo, losartan did not improve any secondary clinical outcomes and led to fewer vasopressor-free days than placebo (median [IQR], 9.4 [9.1-9.8] vasopressor-free days vs 8.7 [8.2-9.3] vasopressor-free days)., Conclusions and Relevance: This randomized clinical trial found that initiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury did not improve Pao2:Fio2 ratio at 7 days. These data may have implications for ongoing clinical trials., Trial Registration: ClinicalTrials.gov Identifier: NCT04312009.

Background: Previous work has indicated that differences in neurocognitive functioning may predict the development of adverse post-traumatic neuropsychiatric sequelae (APNS). Such differences may be vulnerability factors or simply correlates of APNS-related symptoms. Longitudinal studies that measure neurocognitive functioning at the time of trauma are needed to determine whether such differences precede the development of APNS., Methods: Here, we present findings from a subsample of 666 ambulatory patients from the AURORA (Advancing Understanding of RecOvery afteR trumA) study. All patients presented to EDs after a motor vehicle collision (MVC). We examined associations of neurocognitive test performance shortly after MVC with peritraumatic symptoms in the ED and APNS (depression, post-traumatic stress, post-concussive symptoms, and pain) 2 weeks and 8 weeks later. Neurocognitive tests assessed processing speed, attention, verbal reasoning, memory, and social perception., Results: Distress in the ED was associated with poorer processing speed and short-term memory. Poorer short-term memory was also associated with depression at 2 weeks post-MVC, even after controlling for peritraumatic distress. Finally, higher vocabulary scores were associated with pain 2 weeks post-MVC., Limitations: Self-selection biases among those who present to the ED and enroll in the study limit generalizability. Also, it is not clear whether observed neurocognitive differences predate MVC exposure or arise in the immediate aftermath of MVC exposure., Conclusions: Our results suggest that processing speed and short-term memory may be useful predictors of trauma-related characteristics and the development of some APNS, making such measures clinically-relevant for identifying at-risk individuals., (Copyright © 2021. Published by Elsevier B.V.)

Human cytomegalovirus is being recognized as a potential oncovirus beside its oncomodulation role. We previously isolated two clinical isolates, HCMV-DB (KT959235) and HCMV-BL (MW980585), which in primary human mammary epithelial cells promoted oncogenic molecular pathways, established anchorage-independent growth in vitro , and produced tumorigenicity in mice models, therefore named high-risk oncogenic strains. In contrast, other clinical HCMV strains such as HCMV-FS, KM, and SC did not trigger such traits, therefore named low-risk oncogenic strains. In this study, we compared high-risk oncogenic HCMV-DB and BL strains (high-risk) with low-risk oncogenic strains HCMV-FS, KM, and SC (low-risk) additionally to the prototypic HCMV-TB40/E, knowing that all strains infect HMECs in vitro . Numerous pro-oncogenic features including enhanced expression of oncogenes, cell survival, proliferation, and epithelial-mesenchymal transition genes were observed with HCMV-BL. In vitro , mammosphere formation was observed only in high-risk strains. HCMV-TB40/E showed an intermediate transcriptome landscape with limited mammosphere formation. Since we observed that Ki67 gene expression allows us to discriminate between high and low-risk HCMV strains in vitro , we further tested its expression in vivo . Among HCMV-positive breast cancer biopsies, we only detected high expression of the Ki67 gene in basal tumors which may correspond to the presence of high-risk HCMV strains within tumors. Altogether, the transcriptome of HMECs infected with HCMV clinical isolates displays an "oncogenic gradient" where high-risk strains specifically induce a prooncogenic environment which might participate in breast cancer development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Haidar Ahmad, Pasquereau, El Baba, Nehme, Lewandowski and Herbein.)

Early neurological improvement as assessed with the NIH stroke scale (NIHSS) at 24 h has been associated with improved long-term functional outcomes following acute ischemic stroke (AIS). Cardiac dysfunction is often present in AIS, but its association with outcomes is incompletely defined. We performed a pilot study to evaluate the association between non-invasively measured cardiac parameters and 24-h neurological improvement in prospectively enrolled patients with suspected AIS who presented within 12 h of symptom-onset and had an initial systolic blood pressure>140 mm Hg. Patients receiving thrombolytic therapy or mechanical thrombectomy were excluded. Non-invasive pulse contour analysis was used to measure mean arterial blood pressure (MAP), cardiac stroke volume index (cSVI), cardiac output (CO) and cardiac index (CI). Transcranial Doppler recorded mean middle cerebral artery flow velocity (MFV). We defined a decrease of 4 NIHSS points or NIHSS ≤ 1 at 24-h as neurological improvement. Of 75 suspected, 38 had confirmed AIS and did not receive reperfusion therapy. Of these, 7/38 (18.4%) had neurological improvement over 24 h. MAP was greater in those without improvement (108, IQR 96-123 mm Hg) vs. those with (89, IQR 73-104 mm Hg). cSVI, CO, and MFV were similar between those without and with improvement: 37.4 (IQR 30.9-47.7) vs. 44.7 (IQR 42.3-55.3) ml/m 2 ; 5.2 (IQR 4.2-6.6) vs. 5.3 (IQR 4.7-6.7) mL/min; and 39.9 (IQR 32.1-45.7) vs. 34.4 (IQR 27.1-49.2) cm/s, respectively. Multivariate analysis found MAP and cSVI as predictors for improvement (OR 0.93, 95%CI 0.85-0.98 and 1.14, 95%CI 1.03-1.31). In this pilot study, cSVI and MAP were associated with 24-h neurological improvement in AIS., Competing Interests: JM discloses that Edwards Lifesciences provided the Nexfin device at no cost but provided no other financial support. The Henry Ford Health System funded the study through an investigator initiated grant. PL discloses the receipt of unrelated research funding from Edwards Lifesciences. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Miller, Chaudhry, Tirgari, Calo, Walker, Thompson, Nahab, Lewandowski and Levy.)

Objective: Major negative life events, such as trauma exposure, can play a key role in igniting or exacerbating psychopathology. However, few disorders are diagnosed with respect to precipitating events, and the role of these events in the unfolding of new psychopathology is not well understood. The authors conducted a multisite transdiagnostic longitudinal study of trauma exposure and related mental health outcomes to identify neurobiological predictors of risk, resilience, and different symptom presentations., Methods: A total of 146 participants (discovery cohort: N=69; internal replication cohort: N=77) were recruited from emergency departments within 72 hours of a trauma and followed for the next 6 months with a survey, MRI, and physiological assessments., Results: Task-based functional MRI 2 weeks after a motor vehicle collision identified four clusters of individuals based on profiles of neural activity reflecting threat reactivity, reward reactivity, and inhibitory engagement. Three clusters were replicated in an independent sample with a variety of trauma types. The clusters showed different longitudinal patterns of posttrauma symptoms., Conclusions: These findings provide a novel characterization of heterogeneous stress responses shortly after trauma exposure, identifying potential neuroimaging-based biotypes of trauma resilience and psychopathology.

Importance: A substantial proportion of the 40 million people in the US who present to emergency departments (EDs) each year after traumatic events develop posttraumatic stress disorder (PTSD) or major depressive episode (MDE). Accurately identifying patients at high risk in the ED would facilitate the targeting of preventive interventions., Objectives: To develop and validate a prediction tool based on ED reports after a motor vehicle collision to predict PTSD or MDE 3 months later., Design, Setting, and Participants: The Advancing Understanding of Recovery After Trauma (AURORA) study is a longitudinal study that examined adverse posttraumatic neuropsychiatric sequalae among patients who presented to 28 US urban EDs in the immediate aftermath of a traumatic experience. Enrollment began on September 25, 2017. The 1003 patients considered in this diagnostic/prognostic report completed 3-month assessments by January 31, 2020. Each patient received a baseline ED assessment along with follow-up self-report surveys 2 weeks, 8 weeks, and 3 months later. An ensemble machine learning method was used to predict 3-month PTSD or MDE from baseline information. Data analysis was performed from November 1, 2020, to May 31, 2021., Main Outcomes and Measures: The PTSD Checklist for DSM-5 was used to assess PTSD and the Patient Reported Outcomes Measurement Information System Depression Short-Form 8b to assess MDE., Results: A total of 1003 patients (median [interquartile range] age, 34.5 [24-43] years; 715 [weighted 67.9%] female; 100 [weighted 10.7%] Hispanic, 537 [weighted 52.7%] non-Hispanic Black, 324 [weighted 32.2%] non-Hispanic White, and 42 [weighted 4.4%] of non-Hispanic other race or ethnicity were included in this study. A total of 274 patients (weighted 26.6%) met criteria for 3-month PTSD or MDE. An ensemble machine learning model restricted to 30 predictors estimated in a training sample (patients from the Northeast or Midwest) had good prediction accuracy (mean [SE] area under the curve [AUC], 0.815 [0.031]) and calibration (mean [SE] integrated calibration index, 0.040 [0.002]; mean [SE] expected calibration error, 0.039 [0.002]) in an independent test sample (patients from the South). Patients in the top 30% of predicted risk accounted for 65% of all 3-month PTSD or MDE, with a mean (SE) positive predictive value of 58.2% (6.4%) among these patients at high risk. The model had good consistency across regions of the country in terms of both AUC (mean [SE], 0.789 [0.025] using the Northeast as the test sample and 0.809 [0.023] using the Midwest as the test sample) and calibration (mean [SE] integrated calibration index, 0.048 [0.003] using the Northeast as the test sample and 0.024 [0.001] using the Midwest as the test sample; mean [SE] expected calibration error, 0.034 [0.003] using the Northeast as the test sample and 0.025 [0.001] using the Midwest as the test sample). The most important predictors in terms of Shapley Additive Explanations values were symptoms of anxiety sensitivity and depressive disposition, psychological distress in the 30 days before motor vehicle collision, and peritraumatic psychosomatic symptoms., Conclusions and Relevance: The results of this study suggest that a short set of questions feasible to administer in an ED can predict 3-month PTSD or MDE with good AUC, calibration, and geographic consistency. Patients at high risk can be identified in the ED for targeting if cost-effective preventive interventions are developed.