Buried filet of limb flaps for the reconstruction of forequarter and hindquarter amputations.

BACKGROUND AND OBJECTIVES: Forequarter and hindquarter amputations have traditionally been closed with local tissues, but the technique is plagued by a high rate of complication such as marginal necrosis, seroma, infection, and dehiscence. Filet of limb flaps have been used when local tissues are insufficient for closure, and despite their use in more extensive and complex wounds, outcomes seem to be better in these cases. Recognizing that filet of limb flaps not only serve to cover the wound, but also eliminate dead space, supplement at-risk and/or radiated tissue, pad underlying hard structures, and facilitate neuroma prevention with target muscle reinnervation, we have change our practice to utilize buried filet of limb flaps even when local tissues are technically "sufficient" to close the wound. The purpose of this article to organize and describe the ways in which buried filet-of-limb flaps can be used to achieve important and discrete surgical objectives in forequarter and hindquarter amputation, and to facilitate increased recognition of collaborative interdisciplinary opportunities for spare-part reconstruction. METHODS: Retrospective data from the medical records of seven patients, collected between 2010 to 2023 at our single tertiary referral center, were reviewed. This included all patients for whom a buried (or partially buried) filet of limb flap was attempted for forequarter or hindquarter amputation reconstruction. RESULTS: Five males and two females ranging 55 to 75 years of age, met the inclusion criteria. Three cases of forequarter amputation and four cases of hindquarter amputation were included. Six flaps were successfully transferred without major flap-related complications. The mean follow-up period was eight and a half months. CONCLUSION: Even when local tissues are technically "sufficient" to close forequarter and hindquarter amputation wounds, we have found buried filet of limb flaps to be useful in several ways. These include occupying dead space, providing double-layer coverage, padding hard structures, preventing neuromas, and reconstructing sacro- and spino-pelvic continuity. Our approach emphasizes interdisciplinary collaboration and highlights the potential advantages of buried filet of limb flaps in optimizing patient outcomes for complex limb amputations.

Clinical Characteristics and Outcomes of Patients Suffering Acute Decompensated Heart Failure Complicated by Cardiogenic Shock.

BACKGROUND: Cardiogenic shock (CS) can stem from multiple causes and portends poor prognosis. Prior studies have focused on acute myocardial infarction-CS; however, acute decompensated heart failure (ADHF)-CS accounts for most cases. We studied patients suffering ADHF-CS to identify clinical factors, early in their trajectory, associated with a higher probability of successful outcomes. METHODS: Consecutive patients with CS were evaluated (N=1162). We studied patients who developed ADHF-CS at our hospital (N=562). Primary end point was native heart survival (NHS), defined as survival to discharge without receiving advanced HF therapies. Secondary end points were adverse events, survival, major cardiac interventions, and hospital readmissions within 1 year following index hospitalization discharge. Association of clinical data with NHS was analyzed using logistic regression. RESULTS: Overall, 357 (63.5%) patients achieved NHS, 165 (29.2%) died, and 41 (7.3%) were discharged post advanced HF therapies. Of 398 discharged patients (70.8%), 303 (53.9%) were alive at 1 year. Patients with NHS less commonly suffered cardiac arrest, underwent intubation or pulmonary artery catheter placement, or received temporary mechanical circulatory support, had better hemodynamic and echocardiographic profiles, and had a lower vasoactive-inotropic score at shock onset. Bleeding, hemorrhagic stroke, hemolysis in patients with mechanical circulatory support, and acute kidney injury requiring renal replacement therapy were less common compared with patients who died or received advanced HF therapies. After multivariable adjustments, clinical variables associated with NHS likelihood included younger age, history of systemic hypertension, absence of cardiac arrest or acute kidney injury requiring renal replacement therapy, lower pulmonary capillary wedge pressure and vasoactive-inotropic score, and higher tricuspid annular plane systolic excursion at shock onset (all P<0.05). CONCLUSIONS: By studying contemporary patients with ADHF-CS, we identified clinical factors that can inform clinical management and provide future research targets. Right ventricular function, renal function, pulmonary artery catheter placement, and type and timing of temporary mechanical circulatory support warrant further investigation to improve outcomes of this devastating condition.

Periodic Trends in Intra-ionic Excited State Quenching by Halide.

The preassociation of reactants in a photoinitiated redox reaction through the use of noncovalent interactions can have a significant impact on excited state reactivity. As these noncovalent interactions render some stabilization to the associated species, they impact the kinetics and thermodynamics of photoinitiated electron transfer. Reported herein is a novel iridium(III) photocatalyst, equipped with an anion-sensitive, amide-substituted bipyridine ligand, and its reactivity with the halides (X = I-, Br-, Cl-) in acetonitrile and dichloromethane. A noteworthy periodic trend was observed, where the size and electron affinity dramatically altered the observed photoredox behavior. The binding affinity for the halides increased with decreasing ionic radius (Keq ∼103 to >106) in a polar medium but association was stoichiometric for each halide in a nonpolar medium. Evidence for the static quenching of iodide and bromide is presented while dynamic quenching was observed with all halides. These results highlight how the photophysics of halide adducts and the thermodynamics of intra-ionic photo-oxidation are impacted as a consequence of preassociation of a quencher through hydrogen bonding.

International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024.

The "International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024" updates and replaces the "Listing Criteria for Heart Transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates-2006" and the "2016 International Society for Heart Lung Transplantation Listing Criteria for Heart Transplantation: A 10-year Update." The document aims to provide tools to help integrate the numerous variables involved in evaluating patients for transplantation, emphasizing updating the collaborative treatment while waiting for a transplant. There have been significant practice-changing developments in the care of heart transplant recipients since the publication of the International Society for Heart and Lung Transplantation (ISHLT) guidelines in 2006 and the 10-year update in 2016. The changes pertain to 3 aspects of heart transplantation: (1) patient selection criteria, (2) care of selected patient populations, and (3) durable mechanical support. To address these issues, 3 task forces were assembled. Each task force was cochaired by a pediatric heart transplant physician with the specific mandate to highlight issues unique to the pediatric heart transplant population and ensure their adequate representation. This guideline was harmonized with other ISHLT guidelines published through November 2023. The 2024 ISHLT guidelines for the evaluation and care of cardiac transplant candidates provide recommendations based on contemporary scientific evidence and patient management flow diagrams. The American College of Cardiology and American Heart Association modular knowledge chunk format has been implemented, allowing guideline information to be grouped into discrete packages (or modules) of information on a disease-specific topic or management issue. Aiming to improve the quality of care for heart transplant candidates, the recommendations present an evidence-based approach.

Fibrocartilaginous Mesenchymoma of the Spine: A Case Report.

CASE: A healthy, 19-year-old woman was incidentally found to have a large, destructive tumor of T11 without neurologic symptoms. Biopsy demonstrated fibrocartilaginous mesenchymoma (FCM). The patient was treated with resection including subtotal corpectomy and T8-L1 fusion with use of cage and allograft strut construct. The patient remained without recurrence over 3 years of follow-up. CONCLUSION: FCM arising from the spine is a rare tumor, of which this is the sixth report. FCM affects primarily young adults and is benign but locally aggressive, requiring complete excision to prevent recurrence.

Antiviral activity of the host defense peptide piscidin 1: investigating a membrane-mediated mode of action.

Outbreaks of viral diseases are on the rise, fueling the search for antiviral therapeutics that act on a broad range of viruses while remaining safe to human host cells. In this research, we leverage the finding that the plasma membranes of host cells and the lipid bilayers surrounding enveloped viruses differ in lipid composition. We feature Piscidin 1 (P1), a cationic host defense peptide (HDP) that has antimicrobial effects and membrane activity associated with its N-terminal region where a cluster of aromatic residues and copper-binding motif reside. While few HDPs have demonstrated antiviral activity, P1 acts in the micromolar range against several enveloped viruses that vary in envelope lipid composition. Notably, it inhibits HIV-1, a virus that has an envelope enriched in cholesterol, a lipid associated with higher membrane order and stability. Here, we first document through plaque assays that P1 boasts strong activity against SARS-CoV-2, which has an envelope low in cholesterol. Second, we extend previous studies done with homogeneous bilayers and devise cholesterol-containing zwitterionic membranes that contain the liquid disordered (Ld; low in cholesterol) and ordered (Lo, rich in cholesterol) phases. Using dye leakage assays and cryo-electron microscopy on vesicles, we show that P1 has dramatic permeabilizing capability on the Lo/Ld, an effect matched by a strong ability to aggregate, fuse, and thin the membranes. Differential scanning calorimetry and NMR experiments demonstrate that P1 mixes the lipid content of vesicles and alters the stability of the Lo. Structural studies by NMR indicate that P1 interacts with the Lo/Ld by folding into an α-helix that lies parallel to the membrane surface. Altogether, these results show that P1 is more disruptive to phase-separated than homogenous cholesterol-containing bilayers, suggesting an ability to target domain boundaries. Overall, this multi-faceted research highlights how a peptide that interacts strongly with membranes through an aromatic-rich N-terminal motif disrupt viral envelope mimics. This represents an important step towards the development of novel peptides with broad-spectrum antiviral activity.

Human Factors Validation of a Wearable, On-Body Infusor for Subcutaneous Administration of Furosemide.

Purpose: Furoscix® (subcutaneous furosemide) is administered using a wearable On-Body Infusor (OBI) and is approved for the treatment of congestion associated with heart failure (HF). The purpose of this study was to assess the safe and effective use of the OBI and Instructions for Use (IFU) by patients with HF, caregivers, and healthcare practitioners (HCPs). Methods: Sixty participants (patients, n=30; caregivers, n=15; HCPs, n=15) were evaluated on completion of OBI use tasks and IFU knowledge tasks in a simulated use environment. Fifteen of the patients received OBI/IFU training before evaluation. Results: Overall, 893/900 (99.2%) use tasks and 2211/2220 (99.6%) knowledge tasks were completed successfully, without differences due to training. The most common (n=6) use error was failure to wipe skin or cartridge tip with an alcohol wipe. Errors were due to forgetfulness/misinterpretation rather than IFU clarity. Conclusion: The subcutaneous furosemide OBI can be safely and effectively used by patients, caregivers, and HCPs, regardless of training.

Impact of Diabetes and Glycemia on Cardiac Improvement and Adverse Events Following Mechanical Circulatory Support.

BACKGROUND: Type 2 diabetes is prevalent in cardiovascular disease and contributes to excess morbidity and mortality. We sought to investigate the effect of glycemia on functional cardiac improvement, morbidity, and mortality in durable left ventricular assist device (LVAD) recipients. METHODS AND RESULTS: Consecutive patients with an LVAD were prospectively evaluated (n=531). After excluding patients missing pre-LVAD glycated hemoglobin (HbA1c) measurements or having inadequate post-LVAD follow-up, 375 patients were studied. To assess functional cardiac improvement, we used absolute left ventricular ejection fraction change (ΔLVEF: LVEF post-LVAD-LVEF pre-LVAD). We quantified the association of pre-LVAD HbA1c with ΔLVEF as the primary outcome, and all-cause mortality and LVAD-related adverse event rates (ischemic stroke/transient ischemic attack, intracerebral hemorrhage, gastrointestinal bleeding, LVAD-related infection, device thrombosis) as secondary outcomes. Last, we assessed HbA1c differences pre- and post-LVAD. Patients with type 2 diabetes were older, more likely men suffering ischemic cardiomyopathy, and had longer heart failure duration. Pre-LVAD HbA1c was inversely associated with ΔLVEF in patients with nonischemic cardiomyopathy but not in those with ischemic cardiomyopathy, after adjusting for age, sex, heart failure duration, and left ventricular end-diastolic diameter. Pre-LVAD HbA1c was not associated with all-cause mortality, but higher pre-LVAD HbA1c was shown to increase the risk of intracerebral hemorrhage, LVAD-related infection, and device thrombosis by 3 years on LVAD support (P<0.05 for all). HbA1c decreased from 6.68±1.52% pre-LVAD to 6.11±1.33% post-LVAD (P<0.001). CONCLUSIONS: Type 2 diabetes and pre-LVAD glycemia modify the potential for functional cardiac improvement and the risk for adverse events on LVAD support. The degree and duration of pre-LVAD glycemic control optimization to favorably affect these outcomes warrants further investigation.

Examining the feasibility and utility of heart rate variability on intervention outcomes targeting emotion regulation in autism: a brief report.

Autistic youth experience several behavioral and emotional characteristics that can predispose them to emotion dysregulation (ED). Current literature examining ED in autism spectrum disorder (ASD) is limited to parent- and self-reported measures, indicating a need for biological or physiological methods to better assess emotion regulation in ASD. Utilizing the autonomic nervous system, specifically heart rate variability (HRV), may be a promising method to objectively measure ED in ASD, given it is one of the body's primary means of regulating physiological arousal. Our pilot study is one of the first to examine the feasibility, utility, and construct validity of HRV along with clinical measures within an intervention targeting ED-specific symptoms in ASD. Participants included 30 autistic youth ages 8-17 years who participated in the pilot study of Regulating Together, a group-based intervention targeting emotion regulation. We demonstrate HRV is feasible, demonstrates adequate test-retest reliability, and is complimentary to clinician- and parent-reported measures. Our preliminary findings also point to certain HRV profiles being indicative of long-term outcomes after receiving treatment. HRV may be a useful, objective tool in determining differential needs of long-term follow-up care for treatment maintenance at screening or baseline stages.

Factors that Impact Photochemical Cage Escape Yields.

The utilization of visible light to mediate chemical reactions in fluid solutions has applications that range from solar fuel production to medicine and organic synthesis. These reactions are typically initiated by electron transfer between a photoexcited dye molecule (a photosensitizer) and a redox-active quencher to yield radical pairs that are intimately associated within a solvent cage. Many of these radicals undergo rapid thermodynamically favored "geminate" recombination and do not diffuse out of the solvent cage that surrounds them. Those that do escape the cage are useful reagents that may undergo subsequent reactions important to the above-mentioned applications. The cage escape process and the factors that determine the yields remain poorly understood despite decades of research motivated by their practical and fundamental importance. Herein, state-of-the-art research on light-induced electron transfer and cage escape that has appeared since the seminal 1972 review by J. P. Lorand entitled "The Cage Effect" is reviewed. This review also provides some background for those new to the field and discusses the cage escape process of both homolytic bond photodissociation and bimolecular light induced electron transfer reactions. The review concludes with some key goals and directions for future research that promise to elevate this very vibrant field to even greater heights.

Hospital Readmissions in Patients Supported with Durable Centrifugal-Flow Left Ventricular Assist Devices.

Background: Centrifugal-flow left ventricular assist devices (CF-LVADs) have improved morbidity and mortality for their recipients. Hospital readmissions remain common, negatively impacting quality of life and survival. We sought to identify risk factors associated with hospital readmissions among patients with CF-LVADs. Methods: Consecutive patients receiving a CF-LVAD between February 2011 and March 2021 were retrospectively evaluated using prospectively maintained institutional databases. Hospital readmissions within three years post-LVAD implantation were dichotomized into heart failure (HF)/LVAD-related or non-HF/LVAD-related readmissions. Multivariable Cox regression models augmented using a machine learning algorithm, the least absolute shrinkage and selection operator (LASSO) method, for variable selection were used to estimate associations between HF/LVAD-related readmissions and pre-, intra- and post-operative clinical variables. Results: A total of 204 CF-LVAD recipients were included, of which 138 (67.7%) had at least one HF/LVAD-related readmission. HF/LVAD-related readmissions accounted for 74.4% (436/586) of total readmissions. The main reasons for HF/LVAD-related readmissions were major bleeding, major infection, HF exacerbation, and neurological dysfunction. Using pre-LVAD variables, HF/LVAD-related readmissions were associated with substance use, previous cardiac surgery, HF duration, pre-LVAD inotrope dependence, percutaneous LVAD/VA-ECMO support, LVAD type, and the left ventricular ejection fraction in multivariable analysis (Harrell's concordance c-statistic; 0.629). After adding intra- and post-operative variables in the multivariable model, LVAD implant hospitalization length of stay was an additional predictor of readmission. Conclusions: Using machine learning-based techniques, we generated models identifying pre-, intra-, and post-operative variables associated with a higher likelihood of rehospitalizations among patients on CF-LVAD support. These models could provide guidance in identifying patients with increased readmission risk for whom clinical strategies to mitigate this risk may further improve LVAD recipient outcomes.

Bridge-to-transplant temporary mechanical circulatory support and risk of allosensitization.

INTRODUCTION: Since the 2018 change in the US adult heart allocation policy, more patients are bridged-to-transplant on temporary mechanical circulatory support (tMCS). Previous studies indicate that durable left ventricular assist devices (LVAD) may lead to allosensitization. The goal of this study was to assess whether tMCS implantation is associated with changes in sensitization. METHODS: We included patients evaluated for heart transplants between 2015 and 2022 who had alloantibody measured before and after MCS implantation. Allosensitization was defined as development of new alloantibodies after tMCS implant. RESULTS: A total of 41 patients received tMCS before transplant. Nine (22.0%) patients developed alloantibodies following tMCS implantation: 3 (12.0%) in the intra-aortic balloon pump group (n = 25), 2 (28.6%) in the microaxial percutaneous LVAD group (n = 7), and 4 (44.4%) in the veno-arterial extra-corporeal membrane oxygenation group (n = 9)-p = .039. Sensitized patients were younger (44.7 ± 11.6 years vs. 54.3 ± 12.5 years, p = .044), were more likely to be sensitized at baseline - 3 of 9 (33.3%) compared to 2 out of 32 (6.3%) (p = .028) and received more transfusions with red blood cells (6 (66.6%) vs. 8 (25%), p = .02) and platelets (6 (66.6%) vs. 5 (15.6%), p = .002). There was no significant difference in tMCS median duration of support (4 [3,15] days vs. 8.5 [5,14.5] days, p = .57). Importantly, out of the 11 patients who received a durable LVAD after tMCS, 5 (45.5%) became sensitized, compared to 4 out of 30 patients (13.3%) who only had tMCS-p = .028. CONCLUSIONS: Our findings suggest that patients bridged-to-transplant with tMCS, without significant blood product transfusions and a subsequent durable LVAD implant, have a low risk of allosensitization. Further studies are needed to confirm our findings and determine whether risk of sensitization varies by type of tMCS and duration of support.

Impact of Diimine Ligand on Singlet-to-Triplet Charge Transfer Electroabsorption in Iron and Ruthenium Complexes.

The electroabsorption and absorption spectra of eight homoleptic complexes of the general form [M(LL)3]2+ where M = Ru, Fe, and LL = 1,10-phenanthroline (phen), 2,2'-bipyridine (bpy), and 4,4',-(R)2-bpy where R = -OCH3, -CF3, were quantified at 77 K in a butyronitrile glass. Intense metal-to-ligand charge transfer (MLCT) absorption bands were evident in the visible region. Electroabsorption spectra measured with applied electric fields >0.2 MV/cm were analyzed by the two-state Liptay model. Significant light-induced dipole moment changes of Δµâ‡€ = 4-13 D were found consistent with a metal-to-ligand charge transfer (MLCT) excited state comprised an electron localized on a single diimine ligand, [MIII(LL-)(LL)2]*2+, in the initially formed Franck-Condon excited state. A low energy feature evident in the electroabsorption spectra was assigned to a direct singlet-to-triplet MLCT excited state. The identity of the diimine ligand had an unexpected and large impact on these transitions. Analysis relative to the higher energy absorption provides a comparison of spin-allowed and disallowed transitions for first- and second-row transition metal complexes. With the notable exception of [Fe(CF3bpy)3]2+, the change in dipole moment for the 3MLCT excited states was less than or equal to that of the 1MLCT excited states. The charge transfer distances for the iron complexes were generally larger than those for the Ru complexes, a behavior attributed to a smaller degree of iron-diimine coupling in the ground state. A striking result was the sensitivity of the extinction coefficient and spectral profile of the low energy electroabsorption assigned to the identity of the diimine ligand; data that suggests electronic coupling with ligand localized triplet states and high spin metal centered states must be considered when modeling the Franck-Condon excited state.

Gamma-spectrometry measurements of filtration media from an Advanced Gas-cooled Reactor.

Filtration media used to quantify particulate and gaseous releases have been collected from Hartlepool Power Station in the United Kingdom and measured using high-sensitivity gamma-spectrometry systems. Radionuclides that are relevant to the monitoring regime of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) have been detected. Results are reported and compared to detections recorded on the International Monitoring System (IMS). Time series activity plots have been produced and results interpreted with respect to known plant activities. The reported results improve the understanding of trace-level radionuclide emissions from Advanced Gas-cooled Reactors (AGRs) and aid interpretation of IMS measurements. This work is being performed as part of the Xenon Environmental Nuclide Analysis at Hartlepool (XENAH) collaboration between the Atomic Weapons Establishment (AWE, UK), EDF Energy (UK), Pacific Northwest National Laboratory (PNNL, US) and the Swedish Defence Agency (FOI, Sweden).

Assessing the Accessibility, Engagement, and Value of the Virtual Global Spine Conference as an Educational Platform for Spine: A Three-Year Review.

INTRODUCTION: The Coronavirus disease 2019 pandemic ushered a paradigm shift in medical education, accelerating the transition to virtual learning in select cases. The Virtual Global Spine Conference (VGSC), launched at the height of the pandemic, is a testament to this evolution, providing an independent educational series for spine care professionals worldwide. This study assesses VGSC's 3-year performance, focusing on accessibility, engagement, and educational value. METHODOLOGY: Through retrospective data analysis from April 2020 to August 2023, we examined our social media metrics to measure VGSC's reach and impact. RESULTS: Over the study period, VGSC's webinars successfully attracted 2337 unique participants, maintaining an average attendance of 47 individuals per session. The YouTube channel demonstrated significant growth, amassing over 2693 subscribers and releasing 168 videos. These videos collectively garnered 112,208 views and 15,823.3 hours of watch time. Viewer demographics reveal a predominant age group of 35-44 years, representing 56.81% of the audience, closely followed by the 25-34 age group at 40.2%. Male participants constituted 78.95% of the subscriber base. Geographically, the viewership primarily originates from the United States, with India, Canada, South Korea, and the United Kingdom also contributing substantial audience numbers. The VGSC's presence on the "X account" has grown to 2882 followers, significantly enlarging the digital community and fostering increased engagement. CONCLUSIONS: The VGSC has demonstrated significant value as a virtual educational tool in spine education. Its diverse content and ease of access will likely enable it to drive value well into the post-pandemic years. Maintaining and expanding engagement, beyond North America in particular, remains a priority.

Minimally Invasive Direct Aortic Implantation of Impella 5.5 As Bridge to Transplant: A Case Report.

The use of temporary mechanical circulatory support in cardiogenic shock (CS) is increasing. The Impella (Abiomed) is a percutaneous, microaxial ventricular assist device approved for short-term use in CS that can be implanted peripherally. Direct aortic placement is an alternative commonly performed when the sternum is open, for example, in post-cardiotomy shock or when the peripheral vasculature is of insufficient size or quality for implantation. Herein, we describe direct aortic implantation of the Impella 5.5 via right mini-thoracotomy for a patient in CS secondary to decompensated heart failure as a bridge to candidacy and, ultimately, transplantation.

Radionuclide measurements of the international monitoring system.

The International Monitoring System (IMS) is a unique global network of sensors, tuned to measure various phenomenology, with the common goal of detecting a nuclear explosion anywhere in the world. One component of this network collects measurements of radioactive particulates and gases (collectively known as radionuclides) present in the atmosphere; through this, compliance with the Comprehensive Nuclear-Test-Ban Treaty (CTBT) can be verified. The radionuclide sub-network consists of 120 sensors across 80 locations, supported by 16 measurement laboratories. All radionuclide stations make use of a form of γ-ray spectroscopy to measure radionuclides from samples; this remains largely unchanged since the network was first established 25 years ago. Advances in sampling and spectroscopy systems can yield improvements to the sensitivity of the network to detect a nuclear explosion. This paper summarises the status of the IMS radionuclide network, the current suite of technology used and reviews new technology that could enhance future iterations, potentially improving the verification power of the IMS.

Adaptive thresholding increases sensitivity to detect changes in the rate of skin conductance responses to psychologically arousing stimuli in both laboratory and ambulatory settings.

Psychophysiologists recording electrodermal activity (EDA) often derive measures of slow, tonic activity-skin conductance level (SCL)-and faster, more punctate changes-skin conductance responses (SCRs). A SCR is conventionally considered to have occurred when the local amplitude of the EDA signal exceeds a researcher-determined threshold (e.g., 0.05 µS), typically fixed across study participants and conditions. However, fixed SCR thresholds can preferentially exclude data from individuals with low SCL because their SCRs are smaller on average, thereby reducing statistical power for group-level analyses. Thus, we developed a fixed plus adaptive (FA) thresholding method that adjusts identification of SCRs based on an individual's SC at the onset of the SCR to increase statistical power and include data from more participants. We assess the utility of applying FA thresholding across two independent samples and explore age and race-related associations with EDA outcomes. Study 1 uses wired EDA measurements from 254 healthy adults responding to evocative images and sounds in a laboratory setting. Study 2 uses wireless EDA measurements from 20 children with autism in a clinical environment while they completed behavioral tasks. Compared to a 0.01, 0.03, and 0.05 µS fixed threshold, FA thresholding at 1.9% modestly increases statistical power to detect a difference in SCR rate between tasks with higher vs. lower subjective arousal and reduces exclusion of participants by up to 5% across both samples. This novel method expands the EDA analytical toolbox and may be useful in populations with highly variable basal SCL or when comparing groups with different basal SCL. Future research should test for reproducibility and generalizability in other tasks, samples, and contexts. IMPACT STATEMENTS: This article is important because it introduces a novel method to enhance sensitivity and statistical power in analyses of skin conductance responses from electrodermal data.

Can peripheral psychophysiological markers predict response to exposure-based cognitive behavioral therapy in youth with severely impairing irritability? A study protocol.

BACKGROUND: Irritability, an increased proneness to anger, is a primary reason youth present for psychiatric care. While initial evidence supports the efficacy of exposure-based cognitive behavioral therapy (CBT) for youth with clinically impairing irritability, treatment mechanisms remain unclear. Here, we propose to measure peripheral psychophysiological indicators of arousal-heart rate (HR)/electrodermal activity (EDA)-and regulation-heart rate variability (HRV)-during exposures to anger-inducing stimuli as potential predictors of treatment efficacy. The objective of this study is to evaluate whether in-situ biosensing data provides peripheral physiological indicators of in-session response to exposures. METHODS: Blood volume pulse (BVP; from which HR and HRV canl be derived) and EDA will be collected ambulatorily using the Empatica EmbracePlus from 40 youth (all genders; ages 8-17) undergoing six in-person exposure treatment sessions, as part of a multiple-baseline trial of exposure-based CBT for clinically impairing irritability. Clinical ratings of irritability will be conducted at baseline, weekly throughout treatment, and at 3-month and 6-month follow-ups via the Clinical Global Impressions Scale (CGI) and the Affective Reactivity Index (ARI; clinician-, parent-, and child-report). Multilevel modeling will be used to assess within- and between-person changes in physiological arousal and regulation throughout exposure-based CBT and to determine whether individual differences are predictive of treatment response. DISCUSSION: This study protocol leverages a wearable biosensor (Empatica) to continuously record HR/HRV (derived from BVP) and EDA during in-person exposure sessions for youth with clinically impairing irritability. Here, the goal is to identify changes in physiological arousal (EDA, HR) and regulation (HRV) over the course of treatment in tandem with changes in clinical symptoms. TRIAL REGISTRATION: The participants in this study come from an overarching clinical trial (trial registration numbers: NCT02531893 first registered on 8/25/2015; last updated on 8/25/2023). The research project and all related materials were submitted and approved by the appropriate Institutional Review Board of the National Institute of Mental Health (NIMH).

Wearable Biosensing to Predict Imminent Aggressive Behavior in Psychiatric Inpatient Youths With Autism.

Importance: Aggressive behavior is a prevalent and challenging issue in individuals with autism. Objective: To investigate whether changes in peripheral physiology recorded by a wearable biosensor and machine learning can be used to predict imminent aggressive behavior before it occurs in inpatient youths with autism. Design, Setting, and Participants: This noninterventional prognostic study used data collected from March 2019 to March 2020 from 4 primary care psychiatric inpatient hospitals. Enrolled participants were 86 psychiatric inpatients with confirmed diagnoses of autism exhibiting operationally defined self-injurious behavior, emotion dysregulation, or aggression toward others; 16 individuals were not included (18.6%) because they would not wear the biosensor (8 individuals) or were discharged before an observation could be made (8 individuals). Data were analyzed from March 2020 through October 2023. Main Outcomes and Measures: Research staff performed live behavioral coding of aggressive behavior while inpatient study participants wore a commercially available biosensor that recorded peripheral physiological signals (cardiovascular activity, electrodermal activity, and motion). Logistic regression, support vector machines, neural networks, and domain adaptation were used to analyze time-series features extracted from biosensor data. Area under the receiver operating characteristic curve (AUROC) values were used to evaluate the performance of population- and person-dependent models. Results: There were 70 study participants (mean [range; SD] age, 11.9 [5-19; 3.5] years; 62 males [88.6%]; 1 Asian [1.4%], 5 Black [7.1%], 1 Native Hawaiian or Other Pacific Islander [1.4%], and 63 White [90.0%]; 5 Hispanic [7.5%] and 62 non-Hispanic [92.5%] among 67 individuals with ethnicity data). Nearly half of the population (32 individuals [45.7%]) was minimally verbal, and 30 individuals (42.8%) had an intellectual disability. Participant length of inpatient hospital stay ranged from 8 to 201 days, and the mean (SD) length was 37.28 (33.95) days. A total of 429 naturalistic observational coding sessions were recorded, totaling 497 hours, wherein 6665 aggressive behaviors were documented, including self-injury (3983 behaviors [59.8%]), emotion dysregulation (2063 behaviors [31.0%]), and aggression toward others (619 behaviors [9.3%]). Logistic regression was the best-performing overall classifier across all experiments; for example, it predicted aggressive behavior 3 minutes before onset with a mean AUROC of 0.80 (95% CI, 0.79-0.81). Conclusions and Relevance: This study replicated and extended previous findings suggesting that machine learning analyses of preceding changes in peripheral physiology may be used to predict imminent aggressive behaviors before they occur in inpatient youths with autism. Further research will explore clinical implications and the potential for personalized interventions.