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Brian E Perron1, Joseph E Glass2, Brian K Ahmedani3, Michael G Vaughn4, Daniel E Roberts1, Li-Tzy Wu51University of Michigan, Ann Arbor, MI, USA; 2Washington University, St Louis, MO, USA; 3Henry Ford Health System, Detroit, MI, USA; 4St Louis University, St Louis, MO, USA; 5Duke University, Durham, NC, USABackground: Inhalants are among the most common and dangerous forms of substance use, but very little research on inhalant use disorders exist. Unlike other substances, the Diagnostic and Statistical Manual, 4th edition (DSM-IV) indicates that inhalants do not have an associated withdrawal syndrome among persons who meet criteria for inhalant dependence.Methods: Using data from the National Epidemiologic Survey on Alcohol and Related Conditions, this study examines the prevalence of withdrawal symptoms among inhalant users. Prevalence of inhalant withdrawal symptoms for inhalants was also compared with the prevalence of cocaine withdrawal symptoms to help determine the presence of an inhalant withdrawal syndrome.Results: Approximately 47.8% of persons who met criteria for inhalant dependence reported experiencing three or more inhalant-related withdrawal symptoms that were clinically significant. Among those with inhalant dependence, almost half of the withdrawal symptoms were as common as the corresponding withdrawal symptoms experienced by persons with cocaine dependence. Furthermore, the percentage of persons with inhalant dependence reporting clinically significant inhalant withdrawal symptoms was almost equal to the percentage of persons with cocaine dependence reporting clinically significant cocaine withdrawal symptoms.Conclusions: These data provide evidence for an inhalant-related withdrawal syndrome among persons with inhalant dependence. Revisions to DSM-IV should consider including inhalant withdrawal as a diagnostic criterion for this disorder.Keywords: Inhalants, volatile solvents, withdrawal, inhalant use disorders

Exercise testing is commonly used in a clinical setting to evaluate the cardiovascular response to medical, surgical, or other therapeutic interventions. Maximal exercise testing is potentially dangerous to the elderly, to persons with cardiovascular health risks, and to persons unaccustomed to high intensity exercise. As an alternative, submaximal exercise tests can be utilized to predict functional capacity and VO2 max. Several submaximal walking tests have recently been developed and validated in a variety of populations. These tests are feasible substitutes to maximal testing in specific populations and environments. Some tests, including the Rockport Fitness Walking Test, the Widrick Test, the Ebbeling Test, and the Treadwalk Test, predict VO2 max from regression equations developed using variables such as heart rate, age, gender, and walk time. Others, such as the Six-Minute Walk Test, predict functional capacity level or prognosis in various populations. This review will describe test characteristics, strengths and weaknesses, and appropriate use of these tests in different populations. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE The Na(+) /Ca(2+) exchanger is a bi-directional transporter that plays an important role in maintaining the concentration of cytosolic Ca(2+) ([Ca(2+) ](i) ) of quiescent platelets and increasing it during activation with some, but not all, agonists. There are two classes of Na(+) /Ca(2+) exchangers: K(+) -independent Na(+) /Ca(2+) exchanger (NCX) and K(+) -dependent Na(+) /Ca(2+) exchanger (NCKX). Platelets have previously been shown to express NCKX1. However, initial studies from our laboratory suggest that NCX may also play a role in platelet activation. The objective of this study was to determine if the human platelet expresses functional NCXs. EXPERIMENTAL APPROACH RT-PCR, DNA sequencing and Western blot analysis were utilized to characterize the human platelet Na(+) /Ca(2+) exchangers. Their function during quiescence and collagen-induced activation was determined by measuring [Ca(2+) ](i) with calcium-green/fura-red in response to: changes in the Na(+) and K(+) gradient, NCX pharmacological inhibitors (CBDMB, KB-R7943 and SEA0400) and antibodies specific to extracellular epitopes of the exchangers. KEY RESULTS Human platelets express NCX1.3, NCX3.2 and NCX3.4. The NCXs operate in the Ca(2+) efflux mode in resting platelets and also during their activation with thrombin but not collagen. Collagen-induced increase in [Ca(2+) ](i) was reduced with the pharmacological inhibitors of NCX (CBDMB, KB-R7943 or SEA0400), anti-NCX1 and anti-NCX3. In contrast, anti-NCKX1 enhanced the collagen-induced increase in [Ca(2+) ](i) . CONCLUSIONS AND IMPLICATIONS Human platelets express K(+) -independent Na(+) /Ca(2+) exchangers NCX1.3, NCX3.2 and NCX3.4. During collagen activation, NCX1 and NCX3 transiently reverse to promote Ca(2+) influx, whereas NCKX1 continues to operate in the Ca(2+) efflux mode to reduce [Ca(2+) ](i) . [ABSTRACT FROM AUTHOR]

This article examines the community-level impact of concentrated child welfare agency involvement in African American neighborhoods. Based on interviews of 25 African American women in a Chicago neighborhood, the study found that residents were aware of intense agency involvement in their neighborhood and identified profound effects on social relationships including interference with parental authority, damage to children's ability to form social relationships, and distrust among neighbors. The study also discovered a tension between respondents' identification of adverse consequences of concentrated state supervision for family and community relationships and neighborhood reliance on agency involvement for needed financial support. The author discusses the implications of these findings for a new research paradigm aimed at understanding the community-level effects of racial disproportionality. [ABSTRACT FROM AUTHOR]

This article addresses three questions concerning the legal regulation of the use of race as a category in biomedical research: how does the law currently encourage the use of race in biomedical research?; how might the existing legal framework constrain its use?; and what should be the law's approach to race-based biomedical research? It proposes a social justice approach that aims to promote racial equality by discouraging the use of 'race' as a biological category while encouraging its use as a socio-political category to understand and investigate ways to eliminate disparities in health status, access to health care, and medical treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Nutrition is often a casualty of the busy work day for physicians. We aimed to explore physicians' views of their nutrition in the workplace including their perceptions of the impact of inadequate nutrition upon their personal wellness and their professional performance. Methods This is a qualitative study of a sample of 20 physicians practicing in a large urban teaching hospital. Semi-structured open ended interviews were conducted to explore physicians' views of workplace nutrition. The same physicians had agreed to participate in a related nutrition based wellness intervention study that compared nutritional intake and cognitive function during a day of usual nutrition patterns against another day with scheduled nutrition breaks. A second set of interviews was conducted after the intervention study to explore how participation in the intervention impacted these views. Detailed interview content notes were transcribed and analyzed independently with differences reconciled by discussion. Results At initial interview, participants reported difficulty accessing adequate nutrition at work, linking this deficit with emotional (irritable and frustrated), physical (tired and hungry), and cognitive (difficulty concentrating and poor decision making) symptoms. In addition to identifying practical barriers such as lack of time to stop and eat, inconvenient access to food and poor food choices, the physicians described how their sense of professionalism and work ethic also hinder their work nutrition practices. After participating in the intervention, most physicians reported heightened awareness of their nutrition patterns and intentions to improve their workplace nutrition. Conclusions Physicians report that inadequate workplace nutrition has a significant negative impact on their personal wellness and professional performance. Given this threat to health care delivery, health care organizations and the medical profession need to address both the practical and professional barriers identified.

Abstract Background Physicians are often unable to eat and drink properly during their work day. Nutrition has been linked to cognition. We aimed to examine the effect of a nutrition based intervention, that of scheduled nutrition breaks during the work day, upon physician cognition, glucose, and hypoglycemic symptoms. Methods A volunteer sample of twenty staff physicians from a large urban teaching hospital were recruited from the doctors' lounge. During both the baseline and the intervention day, we measured subjects' cognitive function, capillary blood glucose, "hypoglycemic" nutrition-related symptoms, fluid and nutrient intake, level of physical activity, weight, and urinary output. Results Cognition scores as measured by a composite score of speed and accuracy (Tput statistic) were superior on the intervention day on simple (220 vs. 209, p = 0.01) and complex (92 vs. 85, p < 0.001) reaction time tests. Group mean glucose was 0.3 mmol/L lower (p = 0.03) and less variable (coefficient of variation 12.2% vs. 18.0%) on the intervention day. Although not statistically significant, there was also a trend toward the reporting of fewer hypoglycemic type symptoms. There was higher nutrient intake on intervention versus baseline days as measured by mean caloric intake (1345 vs. 935 kilocalories, p = 0.008), and improved hydration as measured by mean change in body mass (+352 vs. -364 grams, p < 0.001). Conclusions Our study provides evidence in support of adequate workplace nutrition as a contributor to improved physician cognition, adding to the body of research suggesting that physician wellness may ultimately benefit not only the physicians themselves but also their patients and the health care systems in which they work.

The classic psychedelic psilocybin has attracted special interest across clinical and non-clinical settings as a potential tool for mental health. Despite increasing attention to challenging psychedelic experiences, few studies have explored the relevance of shame-related processes with psychedelic use. This prospective, longitudinal study involved sequential, automated, web-based surveys that collected data from 679 adults planning to use psilocybin in naturalistic settings at timepoints before and after psilocybin use. State and trait shame and feelings of guilt were collected using validated measures and assessed alongside other measurements of psychological health. Acute feelings of shame or guilt during psilocybin experiences were commonly reported (68.2% of users) and difficult to predict. Ratings of participant ability to constructively work through these feelings predicted wellbeing 2-4 weeks after psilocybin use. Psilocybin on average produced a small but significant decrease in trait shame that was maintained 2-3 months after use (Cohen's dz = 0.37). Trait shame increased in a notable minority of participants (29.8%). The activation of self-conscious emotions with psychedelics deserves further attention as a challenging experience subcategory that may be relevant to psychological outcomes. Such experiences could pose a unique and context-dependent learning condition for both therapeutic and detrimental forms of shame-related memory reconsolidation.

Intimate partner violence (IPV) impacts more than 40% of people in the U.S. Since the 1980s, the U.S. has maintained a police-centric response to IPV, which relies on arrest-via policies like mandatory arrest laws-as its primary intervention. There is mixed evidence on whether IPV policing decreases subsequent IPV at the individual level, but less is known about IPV policing's broader collateral consequences. This systematic scoping review is the first to synthesize existing evidence for the generalized consequences of IPV policing in the U.S. We searched Web of Science, ProQuest, and EBSCO Host, and identified 36 relevant articles. Survivor criminalization was the most studied generalized consequence of IPV policing and existing studies have documented positive associations between mandatory arrest laws and risk of survivor arrest. We also found numerous methodologically rigorous studies on the effects of mandatory arrest laws on population-level IPV victimization. The review also identifies gaps in the evidence base: there is a need for research on additional potential consequences of IPV policing such as police violence against survivors, involvement of child protective services, and psychosocial and physical health outcomes of survivors., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to declare.

Populations of anadromous brown trout, also known as sea trout, have suffered recent marked declines in abundance due to multiple factors, including climate change and human activities. While much is known about their freshwater phase, less is known about the species' marine feeding migrations. This situation is hindering the effective management and conservation of anadromous trout in the marine environment. Using a panel of 95 single nucleotide polymorphism markers we developed a genetic baseline, which demonstrated strong regional structuring of genetic diversity in trout populations around the English Channel and adjacent waters. Extensive baseline testing showed this structuring allowed high-confidence assignment of known-origin individuals to region of origin. This study presents new data on the movements of anadromous trout in the English Channel and southern North Sea. Assignment of anadromous trout sampled from 12 marine and estuarine localities highlighted contrasting results for these areas. The majority of these fisheries are composed predominately of stocks local to the sampling location. However, there were multiple cases of long-distance movements of anadromous trout, with several individuals originating from rivers in northeast England being caught in the English Channel and southern North Sea, in some cases more than 1000 km from their natal region. These results have implications for the management of sea trout in inshore waters around the English Channel and southern North Sea., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Evolutionary Applications published by John Wiley & Sons Ltd.)

Study Objectives: This study sought to investigate perceptions of sleep disruptions among patients and staff in the inpatient neurology setting. The objectives were to explore the differences between these groups regarding factors that impact sleep, identify the most significant sleep disruptions, and examine the barriers and opportunities suggested to improve inpatient sleep., Methods: A survey-based observational study was conducted on a 25-bed inpatient neurology unit at an academic medical center. Staff and patients completed the Potential Hospital Sleep Disruptions and Noises Questionnaire, and focus groups were held to gather qualitative data. Patient-reported sleep measures were collected for additional assessment. Responses were dichotomized for comparison. Regression models were used to assess associations between disruptors and patient-reported sleep measures. Qualitative thematic analyses were performed., Results: Forty-nine inpatient staff and 247 patients completed sleep surveys. Top primary patient diagnoses included stroke, epilepsy, autoimmune diseases, and psychogenic nonepileptic attacks. Medical interventions, environmental factors, patient-related factors, and unit workflows emerged as key themes related to sleep disruptions. Patient-reported sleep efficiency was significantly reduced when pain, anxiety, stress, temperature, and medication administration disrupted sleep. Staff perspectives highlighted medical interventions as most disruptive to sleep, while patients did not find them as disruptive as expected., Conclusions: Differing perspectives on sleep disruption exist between staff and patients in the inpatient neurology setting. Medical interventions may be overstated in staff perceptions and inpatient sleep research, as pain, anxiety, and stress had the most significant impact on patient-reported sleep efficiency., Citation: Kadura S, Poulakis A, Roberts DE, et al. Sleeping with one cerebrum open: patient and staff perceptions of sleep quality and quantity on an inpatient neurology unit. J Clin Sleep Med . 2024;20(4):619-629., (© 2024 American Academy of Sleep Medicine.)

Hepatocellular carcinoma (HCC) is among the most common cancers worldwide, and tumor recurrence following liver resection or transplantation is one of the highest contributors to mortality in HCC patients after surgery. Using artificial intelligence (AI), we developed an interdisciplinary model to predict HCC recurrence and patient survival following surgery. We collected whole-slide H&E images, clinical variables, and follow-up data from 300 patients with HCC who underwent transplant and 169 patients who underwent resection at the Cleveland Clinic. A deep learning model was trained to predict recurrence-free survival (RFS) and disease-specific survival (DSS) from the H&E-stained slides. Repeated cross-validation splits were used to compute robust C-index estimates, and the results were compared to those obtained by fitting a Cox proportional hazard model using only clinical variables. While the deep learning model alone was predictive of recurrence and survival among patients in both cohorts, integrating the clinical and histologic models significantly increased the C-index in each cohort. In every subgroup analyzed, we found that a combined clinical and deep learning model better predicted post-surgical outcome in HCC patients compared to either approach independently., Competing Interests: The authors do not have any conflicts of interest., (© 2023 The Authors.)

Background: Previous studies identified pre-existing DNR orders as a predictor of mortality after surgery. We sought to evaluate mortality of patients receiving cranial neurosurgery with DNR orders placed at the time of, or within 24 h of admission., Methods: We performed a retrospective cohort study using the California State Inpatient Database, January 2018 to December 2020. We used International Classification of Diseases, 10th Revision (ICD-10) codes to identify emergent hospitalizations with principal diagnosis of brain injury, including traumatic brain injury [TBI], ischemic stroke [IS], intracerebral hemorrhage [ICH], subarachnoid hemorrhage [SAH], or malignant brain tumor [mBT]. We used procedure and Diagnosis Related Group codes to identify cranial neurosurgery. Patients with DNR were one-to-one matched to non-DNR controls based on diagnosis (exact matching), age, sex, Elixhauser comorbidity index, and organ failure (coarsened matching). The primary outcome was inpatient mortality., Results: In California, 30,384 patients underwent cranial neurosurgery, 2018-2020 (n = 3,112, 10% DNR). DNR patients were older, more often female, more often White, with greater comorbidity and organ system dysfunction. There were 2,505 patients with DNR orders 1:1 matched to controls. Patients with DNR had greater inpatient mortality (56% vs. 23%, p < 0.001; Hazard Ratio 3.11, 95% CI 2.50-3.86), received tracheostomy (Odds Ratio [OR] 0.37, 95% CI 0.24-0.57) and gastrostomy less (OR 0.48, 95% CI 0.39-0.58) compared to controls. Multivariable analysis of the unmatched cohort demonstrated similar results., Conclusion: Patients undergoing cranial neurosurgery with early or pre-existing DNR have high inpatient mortality compared to clinically similar non-DNR patients; 1 in 2 died during their hospitalization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging experiences and enhances positive experiences associated with psilocybin/LSD. However, limited research has investigated the acute effects of co-use of MDMA and psilocybin/LSD. In a prospective convenience sample (N = 698) of individuals with plans to use psilocybin/LSD, we examined whether co-use of MDMA with psilocybin/LSD (n = 27) is associated with differences in challenging or positive experiences. Challenging experiences were measured using the Challenging Experiences Questionnaire and positive experiences were measured using the Mystical Experience Questionnaire and single-item measures of self-compassion, compassion, love, and gratitude. Potentially confounding variables were identified and included as covariates. Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium-high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear, as well as increased self-compassion, love and gratitude. Co-use of psilocybin/LSD and MDMA was not associated with differences in mystical-type experiences or compassion. Findings suggest co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences. Limitations include use of a convenience sample, small sample size, and non-experimental design. Additional studies (including controlled dose-response studies) that examine the effects and safety of co-administering MDMA with psilocybin/LSD (in healthy controls and clinical samples) are warranted and may assist the development of personalized treatments., (© 2023. Springer Nature Limited.)

Background: Acute stroke therapy and rehabilitation declined during the COVID-19 pandemic. We characterized changes in acute stroke disposition and readmissions during the pandemic., Methods: We used the California State Inpatient Database in this retrospective observational study of ischemic and hemorrhagic stroke. We compared discharge disposition across a pre-pandemic period (January 2019 to February 2020) to a pandemic period (March to December 2020) using cumulative incidence functions (CIF), and re-admission rates using chi-squared., Results: There were 63,120 and 40,003 stroke hospitalizations in the pre-pandemic and pandemic periods, respectively. Pre-pandemic, the most common disposition was home [46%], followed by skilled nursing facility (SNF) [23%], and acute rehabilitation [13%]. During the pandemic, there were more home discharges [51%, subdistribution hazard ratio 1.17, 95% CI 1.15-1.19], decreased SNF discharges [17%, subdistribution hazard ratio 0.70, 95% CI 0.68-0.72], and acute rehabilitation discharges were unchanged [CIF, p<0.001]. Home discharges increased with increasing age, with an increase of 8.2% for those ≥85 years. SNF discharges decreased in a similar distribution by age. Thirty-day readmission rates were 12.7 per 100 hospitalizations pre-pandemic compared to 11.6 per 100 hospitalizations during the pandemic [p<0.001]. Home discharge readmission rates were unchanged between periods. Readmission rates for discharges to SNF (18.4 vs. 16.7 per 100 hospitalizations, p=0.003) and acute rehabilitation decreased (11.3 vs. 10.1 per 100 hospitalizations, p=0.034)., Conclusions: During the pandemic a greater proportion of patients were discharged home, with no change in readmission rates. Research is needed to evaluate the impact on quality and financing of post-hospital stroke care., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: George P. Albert reports financial support was provided by American Academy of Neurology., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.

Objectives: Patients with severe intracerebral hemorrhage (ICH) often suffer from impaired capacity and rely on surrogates for decision-making. Restrictions on visitors within healthcare facilities during the pandemic may have impacted care and disposition for patient with ICH. We investigated outcomes of ICH patients during the COVID-19 pandemic compared to a pre-pandemic period., Materials and Methods: We conducted a retrospective review of ICH patients from two sources: (1) University of Rochester Get With the Guidelines database and (2) the California State Inpatient Database (SID). Patients were divided into 2019-2020 pre-pandemic and 2020 pandemic groups. We compared mortality, discharge, and comfort care/hospice. Using single-center data, we compared 30-day readmissions and follow-up functional status., Results: The single-center cohort included 230 patients (n = 122 pre-pandemic, n = 108 pandemic group), and the California SID included 17,534 patients (n = 10,537 pre-pandemic, n = 6,997 pandemic group). Inpatient mortality was no different before or during the pandemic in either cohort. Length of stay was unchanged. During the pandemic, more patients were discharged to hospice in the California SID (8.4% vs. 5.9%, p<0.001). Use of comfort care was similar before and during the pandemic in the single center data. Survivors in both datasets were more likely to be discharged home vs. facility during the pandemic. Thirty-day readmissions and follow-up functional status in the single-center cohort were similar between groups., Conclusions: Using a large database, we identified more ICH patients discharged to hospice during the COVID-19 pandemic and, among survivors, more patients were discharged home rather than healthcare facility discharge during the pandemic., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 McHugh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Patients with advanced directives or Medical Orders for Life-Sustaining Treatment (MOLST), including "Do Not Resuscitate" (DNR) and/or "Do Not Intubate" (DNI), may be candidates for procedural interventions when presenting with acute neurologic emergencies. Such interventions may limit morbidity and mortality, but typically they require MOLST reversal. We investigated outcomes of patients with MOLST reversal for treatment of neurologic emergencies., Methods: We conducted a retrospective chart review from July 1, 2019 to April 30, 2021 of patients with MOLST reversal treated in our NeuroMedicine Intensive Care Unit. Variables collected include neurologic disease, MOLST reversal decision maker, procedural interventions, and outcomes., Results: Twenty-seven patients (18 female, median age 78 years (IQR 73-85 years), median baseline modified Rankin score 1 [IQR 0-2.5] were identified with MOLST reversal. The most common pre-procedural MOLST was DNR/DNI (n=22, 81%), and 93% (n=25) pre-procedural MOLSTs were completed by the patient. MOLSTs were reversed by surrogates in n=23 cases (85%). The median time from MOLST completion to MOLST reversal was 603 days (IQR 45 days to 4 years). The most common neurologic emergency was ischemic stroke (n=14, 52%). Most patients died (n=14, 52%), 26% (n=7) were discharged to skilled nursing, and 22% (n=6) returned to home or assisted living., Conclusions: In neurologic emergencies, urgent shared decision making is needed to ensure goal-concordant care, which may result in reversal of existing advanced directives. Outcomes of patients with MOLST reversal were heterogeneous, emphasizing the importance of deliberate patient-centered care weighing the risks and benefits of each intervention., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Borderline personality disorder is a complex psychiatric disorder with limited treatment options that are associated with large heterogeneity in treatment response and high rates of dropout. New or complementary treatments for borderline personality disorder are needed that may be able to bolster treatment outcomes. In this review, the authors comment on the plausibility for research on 3,4-methylenedioxymethamphetamine (MDMA) used in conjunction with psychotherapy for borderline personality disorder (i.e., MDMA-assisted psychotherapy [MDMA-AP]). On the basis of the promise of MDMA-AP in treating disorders overlapping with borderline personality disorder (e.g., posttraumatic stress disorder), the authors speculate on initial treatment targets and hypothesized mechanisms of change that are grounded in prior literature and theory. Initial considerations for designing MDMA-AP clinical trials to investigate the safety, feasibility, and preliminary effects of MDMA-AP for borderline personality disorder are also presented., Competing Interests: Dr. Traynor is a coinvestigator on a Multidisciplinary Association for Psychedelic Studies (MAPS)-funded clinical trial of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy; she has also received compensation as an independent contractor for the role of study therapist on a MAPS-funded clinical trial of MDMA-assisted psychotherapy. Dr. Roberts has received compensation as an independent contractor for his role as an assistant trainer from Fluence. Dr. Ross is a coinvestigator on the MAPS MDMA-assisted psychotherapy for posttraumatic stress disorder phase 3 trials; he also reports research support from Usona and Reset Pharmaceuticals related to psilocybin research, two patents with Reset, and funding from the National Institute on Drug Abuse. Mr. Zeifman has received compensation as an independent contractor for the role of study therapist on a MAPS-funded clinical trial of MDMA-assisted psychotherapy. Dr. Choi-Kain receives book royalties from Springer Publishing and the American Psychiatric Association. None of the aforementioned organizations were involved in the design, execution, interpretation, or communication of findings of this publication., (Copyright © 2022 by the American Psychiatric Association.)

Cesario misrepresents or ignores data on real-world racist and sexist patterns and processes in an attempt to discredit the assumptions of implicit bias experimentation. His position stands in stark contradiction to substantive research across the social sciences recognizing the widespread, systematic, and structuring processes of racism and sexism. We argue for centering the relationship between structural racism and individual bias.

We respond to recent comments on our proposal to improve justice in ventilator triage, in which we used as an example New Jersey's (NJ) publicly available and legally binding Directive Number 2020-03. We agree with Bernard Lo and Doug White that equity implications of triage frameworks should be continually reassessed, which is why we offered six concrete options for improvement, and called for monitoring the consequences of adopted triage models. We disagree with their assessment that we mis-characterised their Model Guidance, as included in the NJ Directive, in ways that undermine our conclusions. They suggest we erroneously described their model as a two-criterion allocation framework; that recognising other operant criterion reveals it 'likely mitigate[s] rather than exacerbate[s] racial disparities during triage', and allege that concerns about inequitable outcomes are 'without evidence'. We highlight two major studies robustly demonstrating why concerns about disparate outcomes are justified. We also show that White and Lo seek to retrospectively-and counterfactually-correct the version of the Model Guideline included in the NJ Directive. However, as our facsimile reproductions show, neither the alleged four-criteria form, nor other key changes, such as dropping the Sequential Organ Failure Assessment score, are found in the Directive. These points matter because (1) our conclusions hence stand, (2) because the public version of the Model Guidance had not been updated to reduce the risk of inequitable outcomes until June 2021 and (3) NJ's Directive still does not reflect these revisions, and, hence, represents a less equitable version, as acknowledged by its authors. We comment on broader policy implications and call for ways of ensuring accurate, transparent and timely updates for users of high-stakes guidelines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Withholding or withdrawing life-saving ventilators can become necessary when resources are insufficient. In the USA, such rationing has unique social justice dimensions. Structural elements of dominant allocation frameworks simultaneously advantage white communities, and disadvantage Black communities-who already experience a disproportionate burden of COVID-19-related job losses, hospitalisations and mortality. Using the example of New Jersey's Crisis Standard of Care policy, we describe how dominant rationing guidance compounds for many Black patients prior unfair structural disadvantage, chiefly due to the way creatinine and life expectancy are typically considered.We outline six possible policy options towards a more just approach: improving diversity in decision processes, adjusting creatinine scores, replacing creatinine, dropping creatinine, finding alternative measures, adding equity weights and rejecting the dominant model altogether. We also contrast these options with making no changes, which is not a neutral default, but in separate need of justification, despite a prominent claim that it is simply based on 'objective medical knowledge'. In the regrettable absence of fair federal guidance, hospital and state-level policymakers should reflect on which of these, or further options, seem feasible and justifiable.Irrespective of which approach is taken, all guidance should be supplemented with a monitoring and reporting requirement on possible disparate impacts. The hope that we will be able to continue to avoid rationing ventilators must not stand in the way of revising guidance in a way that better promotes health equity and racial justice, both to be prepared, and given the significant expressive value of ventilator guidance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Previous comparative kinetic isotope effects have inferred an allosteric site for fatty acids and their derivatives that modulates substrate selectivity in 15-lipoxygenases. Hydrogen-deuterium exchange also previously revealed regionally defined enhanced protein flexibility, centred at helix α2 - a gate to the substrate entrance. Direct evidence for allosteric binding and a complete understanding of its mechanism remains elusive. In this study, we examine the binding thermodynamics of the fatty acid mimic, oleyl sulfate (OS), with the monomeric model plant 15-LOX, soybean lipoxygenase (SLO), using isothermal titration calorimetry. Dynamic light scattering and differential scanning calorimetry rule out OS-induced oligomerization or structural changes. These data provide evidence that the fatty acid allosteric regulation of SLO is controlled by the dynamics of helix α2., (© 2022 Federation of European Biochemical Societies.)

Previous work suggests that juvenile salmon recruitment in rain-fed rivers is negatively influenced by warm and wet winters and cool springs. We tested whether this is generally applicable to a southern England chalk stream characterized by comparatively stable discharges and temperatures. We found that warm spawning and cool emergence temperatures negatively influenced juvenile recruitment between 2015 and 2020. Together these findings suggest an ability to predict juvenile productivity from water temperature records around spawning and fry emergence, thereby allowing time for management interventions in years of unfavourable temperatures., (© 2021 Fisheries Society of the British Isles.)

Consumption of herbal supplements has been linked to multiorgan toxicities. Kratom is an herbal extract that has gained popularity for its analgesic and psychotropic properties. Several cases of kratom-induced liver injury have been reported, but data on multiorgan involvement remain scarce. We present the case of a 37-year-old woman who developed a mixed hepatocellular and cholestatic pattern of acute liver injury, acute kidney injury, and pancolitis after prolonged use of kratom-containing herbal supplements., (© 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Purpose: The study purpose was to compare suicide risk between lesbian, gay, bisexual, transgender, queer, and/or questioning (LGBTQ) and non-LGBTQ adolescents in a psychiatric hospital. Methods: Data were obtained from self-report measures completed by patients 12-17 years of age ( n  = 334) in a Midwestern psychiatric hospital from 2016 to 2017. Factors analyzed included sexual orientation, gender identity, suicidality, depression, nonsuicidal self-injury, abuse, substance use, bullying, perceived discrimination, and adult support. Results: Nearly one-third of patients identified as LGBTQ. A lifetime suicide attempt was reported by 69.6% of LGBTQ patients compared with 43.6% of non-LGBTQ patients. However, the prevalence of suicide attempts among LGBTQ patients with high adult support did not differ from that of non-LGBTQ patients. In the full logistic regression model adjusting for 13 factors, the adjusted odds ratio of a suicide attempt was 5.25 among transgender/questioning patients and 2.41 among nontransgender lesbian, gay, bisexual, queer, or questioning patients. All risk factors, apart from substance use, were more prevalent among LGBTQ than non-LGBTQ patients ( p  < 0.005). Among LGBTQ patients of color (Black/Latinx/Other), 91.3% had a lifetime suicide attempt versus 62.3% of White LGBTQ patients ( p  = 0.009). Conclusion: LGBTQ patients overall, and LGBTQ patients of color in particular, had higher rates of suicide attempts than non-LGBTQ patients. LGBTQ patients also had a higher prevalence of risk factors for suicide; however, the study variables did not fully explain the higher prevalence of suicide attempts. Future research should further examine possible risk factors for suicide among LGBTQ youth, such as stigma and discrimination.

Objective: Mechanical ventilation (MV) has a complex interplay with the pathophysiology of aneurysmal subarachnoid hemorrhage (aSAH). We aim to provide a review of the physiology of MV in patients with aSAH, give recommendations based on a systematic review of the literature, and highlight areas that still need investigation., Data Sources: PubMed was queried for publications with the Medical Subject Headings (MeSH) terms "mechanical ventilation" and "aneurysmal subarachnoid hemorrhage" published between January 1, 1990, and March 1, 2020. Bibliographies of returned articles were reviewed for additional publications of interest., Study Selection: Study inclusion criteria included English language manuscripts with the study population being aSAH patients and the exposure being MV. Eligible studies included randomized controlled trials, observational trials, retrospective trials, case-control studies, case reports, or physiologic studies. Topics and articles excluded included review articles, pediatric populations, non-aneurysmal etiologies of subarachnoid hemorrhage, mycotic and traumatic subarachnoid hemorrhage, and articles regarding tracheostomies., Data Extraction: Articles were reviewed by one team member, and interpretation was verified by a second team member., Data Synthesis: Thirty-one articles met the inclusion criteria for this review., Conclusions: We make recommendations on oxygenation, hypercapnia, PEEP, APRV, ARDS, and intracranial pressure monitoring.

Patients undergoing surgical resection of a brain tumor have the potential risk for beingintubated post-operatively, which may be associated with significant morbidity and/or mortality after surgery. This study was analyzed various preoperative patient characteristics, postoperative outcomes, and complications to identify risk factors for unplanned intubation (UI) in adult patients undergoing craniotomy for a brain tumor and created a risk score framework for that cohort. Patients undergoing surgery for a brain tumor were identified according to primary Current Procedural Terminology codes, and information found in The American College of Surgeons (ACS) National Surgical Quality Improvement Project (NSQIP) database from 2012 to 2015 was reviewed. A total of 18,642 adult brain tumor patients were included in the ACS-NSQIP. The rate of unplanned intubation in this cohort was 2.30% (4 2 8). The mortality rate of patients who underwent UI after surgical resection of brain tumor was 24.78% compared to an overall mortality of 2.46%. During the first 30 days after surgery, 33% of patients who underwent UI had an unplanned reoperation, compared to 4.76% of patients who did not undergo unplanned intubation. Bivariate and multivariate analyses identified several predictors and computed a risk score for UI. A risk score based on patient factors for those undergoing a craniotomy for a brain tumor predicts the postoperative UI rate. This could aid in surgical decision-making by identify patients at a higher risk of UI, while modifying perioperative management may help prevent UI., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: To examine the diagnoses, demographics, and prevalence of psychotherapy use among children and adolescents prescribed antipsychotics by psychiatric providers in a community setting., Methods: Medical records from 1127 children aged 0 to 17 years who were prescribed antipsychotics in 2014-2015 at Pine Rest Christian Mental Health Services (PRCMHS) outpatient network were analyzed. Antipsychotics, diagnosis codes, demographics, and number of psychotherapy sessions during this time frame were analyzed using χ and logistic regression analyses., Results: During this year, 50.8% of the patients attended psychotherapy, and 35.6% attended 5 or more sessions of psychotherapy. The most prevalent primary diagnosis was bipolar disorder (37.1%), followed by attention-deficit/hyperactivity disorder (19.7%). Females being treated with antipsychotics were significantly more likely to attend psychotherapy than their male peers (55.7% vs. 47.9%, P=0.01). In the fully adjusted models, patients with diagnoses of bipolar disorder or disorders first diagnosed in infancy, childhood, or adolescence were less than half as likely to attend psychotherapy as patients with depressive disorders, with adjusted odds ratios of 0.41 and 0.42, respectively., Conclusions: Approximately half of the child and adolescent patients prescribed antipsychotics in this community sample did not attend psychotherapy, and 39% of the patients did not have a diagnosis of bipolar disorder, psychotic disorder, or autistic disorder.

Colorectal cancer harbors tremendous heterogeneity, with temporal and spatial differences in genetic mutations, epigenetic regulation, and tumor microenvironment. Analyzing the distribution and frequency of genetic, epigenetic, and microenvironment differences within a given tumor and between different sites of a metastatic tumor has been used as a powerful tool to investigate tumorigenesis, tumor progression, and to yield insight into various models of tumor development. A better understanding of tumor heterogeneity would have tremendous clinical relevance, which may manifest most clearly when genetic analyses to inform treatment decisions are performed on a very limited sample of a large tumor. This review summarizes the current concepts of tumor heterogeneity, with a focus on primary colorectal cancers and their corresponding metastases as well as potential clinical implications.

Background: Hospital stays for patients discharged to post-acute care are longer and more costly than routine discharges. Issues disrupting patient flow from hospital to post-acute care facilities are an underrecognized strain on hospital resources. We sought to quantify the burden of medically unnecessary hospital days for inpatients with neurologic illness and planned discharge to post-acute care facilities., Methods: We conducted a retrospective evaluation of hospital discharge delays for patients with neurologic disease and plans for discharge to post-acute care. We identified 100 sequential hospital admissions to an academic neurology inpatient service that were medically ready for discharge from December 4, 2017, to January 25, 2018. For each patient, we quantified the number of medically unnecessary hospital days, or all days in the hospital following the determination of medical discharge readiness., Results: Among 100 patients medically ready for discharge with plans for post-acute care disposition (47 female, mean age 72.5 years, mean length of stay 12.3 days), 50 patients were planned for discharge to skilled nursing, 37 to acute rehabilitation, 10 to hospice/palliative care, and 3 to other facilities. There was a total of 1,226 patient-days, and 480 patient-days (39%) occurred following medical readiness for discharge. Medically unnecessary days ranged from 0 to 80 days per patient (mean 4.8, median 2.5, interquartile range 1-5 days)., Conclusion: Unnecessary hospital days represent a large burden for patients with neurologic illness requiring post-acute care on discharge. These discharge delays present an opportunity to improve hospital-wide patient flow.

Eligibility for liver transplant is most commonly decided by measuring tumor size and number on radiographic imaging. However, this method often underestimates the extent of disease. Evaluation of tumor histology has been shown to improve risk stratification when compared with imaging-based transplant criteria, but the World Health Organization (WHO) guidelines for grading hepatocellular carcinoma (HCC) are imprecise and require subjective interpretation by the pathologist. We performed a retrospective analysis of 190 explanted livers containing HCC and correlated histologic features with posttransplant recurrence to formulate a three-tiered, point-based scoring system that categorizes tumors as having a low, intermediate, or high risk of recurrence. Our Recurrence Risk Assessment Score (RRAS) evaluates tumor architecture and specific cytologic features-nuclear pleomorphism, cytoplasmic amphophilia, and nuclear-to-cytoplasmic ratio-showing superior stratification of HCC recurrence risk compared with imaging criteria and grade assigned by WHO methodology. Stratifying tumors using RRAS criteria, the rate of recurrence after transplant was 0% among low-risk tumors (compared with 3% of well-differentiated tumors), 12% among intermediate-risk tumors (compared with 15% of moderately differentiated tumors), and 54% among high-risk tumors (compared with 29% of poorly differentiated tumors). Receiver operating characteristic analysis shows significantly improved performance of RRAS criteria in predicting HCC recurrence compared with WHO grade (area under curve of 0.841 and 0.671, respectively; P=0.0061). Our results indicate that evaluation of tumor histology offers superior prediction of recurrence risk following liver transplantation compared with radiographic criteria, and that the RRAS system better stratifies recurrence risk compared with HCC grading by WHO methodology.

Parallel sorting of orbital and spin angular momentum components of structured optical beams is demonstrated. Both spin channels are multiplexed within the novel orbital angular momentum (OAM) sorter, reducing the size, weight, and number of elements. The sorted states are linearly spaced over 70 topological charge values. We experimentally and theoretically evaluate the operational range and crosstalk between neighboring channels and find that 30 orbital angular momentum states are available per spin channel for quantum communication or cryptography. This is achieved using an angular momentum sorter that we developed based on geometric phase optical elements. We present two devices consisting of liquid crystal polymer films photoaligned with complex two-dimensional patterns.