Search

Objective: Hope is associated with many positive outcomes. However, most research on hope has focused on its cognitive aspect, with few studies examining the affective aspect. To further clarify the nature of hope and its association with well-being, this study examined the relationship between the affective aspect of hope-namely, hopeful feelings-and various aspects of well-being., Method: A daily diary analysis was conducted with 187 Chinese adults (mean age  = 28.17 ± 5.56). Hopeful feelings and affective (positive and negative emotions), eudaimonic (meaning in life), and evaluative (life satisfaction) aspects of well-being were assessed twice per day (morning and night) for 14 consecutive days. A multilevel vector autoregressive model was used to investigate the temporal, contemporaneous, and between-person networks of hopeful feelings with positive emotion and well-being., Results: Hopeful feelings had the strongest outstrength in the temporal networks and were the most central node in the between-person networks. In addition, hopeful feelings exhibited significant cross-lagged predictive roles on all the well-being nodes except negative emotion., Conclusions: These findings revealed a close association between hopeful feelings and well-being, with hopeful feelings predicting various aspects of daily well-being. Future interventions to improve well-being should focus on the enrichment of daily hopeful feelings., (© 2024 Wiley Periodicals LLC.)

Introduction: The Vestibular/Ocular Motor Screening (VOMS) was created as a brief clinical screening tool for identifying vestibular and ocular motor symptoms and impairments post-concussion. It was found to have predictive validity in correctly identifying concussed athletes from healthy controls. In 2018, the Military Acute Concussion Evaluation 2 (MACE2) replaced the original Military Acute Concussion Evaluation (MACE); the most prominent change between the MACE and MACE2 was the addition of the VOMS. Despite its adoption into military medicine, it is not known if the addition of the VOMS to the MACE2 is acutely helpful, and if it provides additional information for diagnosis, prognosis, and/or management. The purposes of this systematic review were: (1) to determine the utility of the VOMS in correctly identifying concussed individuals, particularly as it pertains to military medicine; (2) to explore the extent to which the VOMS can inform concussion prognosis; and (3) to establish the value of the VOMS as a measure for monitoring the evolution of symptoms throughout a service member's course of care., Materials and Methods: A comprehensive search of PubMed was performed from January 1, 2014 through August 16, 2023. Articles were included if they researched concussion or a related health condition or healthy controls and administered the VOMS. Articles were excluded if they discussed health conditions other than concussion; did not administer the VOMS; or were written in languages other than English. The tools used to assess methodological quality and risk of bias varied according to study design. Articles were classified into three primary domains: diagnosis, prognosis, and/or rehabilitation/recovery over time., Results: A total of 231 articles were retrieved and 3 were duplicates, leaving 228 articles for review. Of the 228 articles screened, 100 relevant full-text articles were assessed for eligibility. Fifty-nine articles met our inclusion and exclusion criteria while the other 41 articles were rejected. Thirty-two articles helped to inform diagnosis, 15 prognosis, and 16 rehabilitation/recovery over time., Conclusions: The VOMS had excellent internal consistency and moderate to good test-retest reliability; however, a false-positive rate of 21.9% was found. Most studies indicated that a positive VOMS was associated with a delayed recovery. Several studies indicated that VOMS scores improved with targeted, active interventions and/or a symptom-guided progressive return to activity. The greatest limitation was the paucity of published evidence in the military population. More research is needed on the use of the VOMS in service members., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Vγ9Vδ2 T-cells are antitumor immune effector cells that can detect metabolic dysregulation in cancer cells through phosphoantigen-induced conformational changes in the butyrophilin (BTN) 2A1/3A1 complex. In order to clinically exploit the anticancer properties of Vγ9Vδ2 T-cells, various approaches have been studied including phosphoantigen stimulation, agonistic BTN3A-specific antibodies, adoptive transfer of expanded Vγ9Vδ2 T-cells, and more recently bispecific antibodies. While Vγ9Vδ2 T-cells constitute a sizeable population, typically making up ~1-10% of the total T cell population, lower numbers have been observed with increasing age and in the context of disease., Methods: We evaluated whether bivalent single domain antibodies (VHHs) that link Vδ2-TCR specific VHHs with different affinities could support Vγ9Vδ2 T-cell expansion and could be incorporated in a bispecific engager format when additionally linked to a tumor antigen specific VHH., Results: Bivalent VHHs that link a high and low affinity Vδ2-TCR specific VHH can support Vγ9Vδ2 T-cell expansion. The majority of Vγ9Vδ2 T-cells that expanded following exposure to these bivalent VHHs had an effector or central memory phenotype and expressed relatively low levels of PD-1. Bispecific engagers that incorporated the bivalent Vδ2-TCR specific VHH as well as a tumor antigen specific VHH triggered antitumor effector functions and supported expansion of Vγ9Vδ2 T-cells in vitro and in an in vivo model in NOG-hIL-15 mice., Conclusion: By enhancing the number of Vγ9Vδ2 T-cells available to exert antitumor effector functions, these novel Vδ2-bivalent bispecific T cell engagers may promote the overall efficacy of bispecific Vγ9Vδ2 T-cell engagement, particularly in patients with relatively low levels of Vγ9Vδ2 T-cells., Competing Interests: NV. TG and HV own LAVA Therapeutics NV shares. DH, PY, VI-G, PH and HV are/were employed by LAVA Therapeutics NV. TG is scientific advisor to LAVA Therapeutics NV. The authors declare that this study received funding from Lava Therapeutics NV. LK, MJ and MV were funded by LAVA Therapeutics NV., (Copyright © 2024 King, de Jong, Veth, Lutje Hulsik, Yousefi, Iglesias-Guimarais, van Helden, de Gruijl and van der Vliet.)

Sharpe (2024) draws attention to the role that editors may play in perpetuating bias in the published psychological literature. While Sharpe focuses on perspective-related diversity in reducing such bias, I argue that identity-related diversity is paramount. Editors play an important role in diversifying the scholarly conversation by recruiting diverse reviewers and providing clear and encouraging feedback on submissions. Further, enhancing the identities represented in the scholarly conversation is crucial to ensuring that editorial decisions are well-informed, that published science is of high quality, and that published literature is less biased. In addition to bringing scholarly expertise, editors must embrace a compassionate, humble, and courageous stance in their role as gatekeepers for our science. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Importance: To evaluate and consider how prescribing practices have changed in relation to high-risk overactive bladder (OAB) medications., Objective: The objective of this study was to evaluate trends in the prevalence of OAB and pharmacologic treatment over time in the United States., Study Design: Data from the National Health and Nutrition Examination Survey (NHANES, 2001-2018, n = 30,478) and the National Ambulatory Medical Care Survey (NAMCS, 2003-2019, n = 251,330) were used to identify women with symptomatic incontinence and overactive bladder (OAB) (NHANES) as well as determine the frequency of prescription use for OAB medications (NHANES and NAMCS) using sampling-based weights. Joinpoint regression was used to determine adjusted annual percent change (APC, adjusting for race, age, body mass index, and insurance status). Trends were assessed overall and by race, age, body mass index, and insurance status., Results: The prevalence of OAB was 31.2% in the final survey year of NHANES (2017-2018). Women aged >65 years had the highest prevalence of OAB at 54% compared with other age groups. There was an overall increase in OAB (APC 1.24 [0.64, 1.84], P = 0.002) over time. Overall, only 3.5% of patients with symptoms of OAB reported pharmacologic treatment in NHANES. The NAMCS demonstrated a significant decrease in anticholinergic prescriptions from 2003 until 2019 (APC -6.44 [-9.77, -2.98], P = 0.001). However, in NHANES, there was no significant change in anticholinergic use (APC 0.62 [-20.2, 26.8], P = 0.944). There was a stable prevalence of β3-adrenergic agonist prescriptions since they were introduced to market (APC 0.65 [-2.24, 3.62], P = 0.616)., Conclusion: This study demonstrates an increasing prevalence of OAB and highlights the likely undertreatment of symptomatic patients. The high and increasing prevalence coupled with the relative undertreatment of OAB underscores the importance of screening for this condition., Competing Interests: M.E.F.-R. is a consultant for Boston Scientific. The other authors have declared they have no conflicts of interest., (Copyright © 2024 American Urogynecologic Society. All rights reserved.)

The experience of hope predicts a host of positive outcomes. However, to date, the psychology of hope has paid little attention to hope as an emotion, focusing instead on hope as a sense of effective goal pursuit. Seven studies ( N = 3,357) tested various manipulations intended to induce hopeful feelings distinct from general positive mood. Images of infant's faces and tree saplings were found to successfully induce hopeful feelings, even when controlling for happiness, compared with adult faces or full-grown trees, respectively. Infant objects, paintings, or puppies did not produce the same effects. We discuss the necessity of studying the emotion of hope and potential directions with such a hopeful induction. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objectives: In our investigation of an episode of clustered acute epiglottitis occurring in Vendée, western France, between October and December 2022, we described the reported cases and confirmed its unusual character at several geographic levels., Methods: The investigation relied on three data sources: hospitalization and emergency department reports; national reference centre data; and data from the French syndromic surveillance system., Results: The six patients were male, with an average age of 42 years [32-66]; all were hospitalized in an ICU, and one of them died. Documented risk factors for epiglottitis (active smoking, regular alcohol consumption, overweight) were present in the majority of cases. No causal pathogen was identified. Syndromic surveillance data confirmed increased acute epiglottitis at the local, regional and national levels., Conclusion: We not only characterized the episode of serious clustered acute epiglottitis in Vendée, but also observed a nationwide increase in this pathology occurring concomitantly with increased circulation in France of streptococcus A., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Despite considerable advancements in cancer immunotherapy, advanced melanoma still presents a substantial clinical challenge. In an effort to explore treatment options, we examined the immunotherapeutic potential of effector Vγ9Vδ2-T cells in vitro in a three-dimensional (3D) human organotypic melanoma-in-skin (Mel-RhS) model., Materials and Methods: Vγ9Vδ2-T cells were introduced into Mel-RhS via intradermal injection and cultured within the tissue microenvironment for up to 3 days., Results: Vγ9Vδ2-T cells remained viable for up to 3 days and were in close proximity to or within tumor nests. Upon Mel-RhS dissociation, a fraction was shown to be decorated by melanoma-associated chondroitin sulfate proteoglycan (MCSP), demonstrating their ability to actively navigate the tumor microenvironment and trogocytose cancer cells. Investigation into the apparent trogocytosis revealed an enhanced activated state of MCSP-decorated Vγ9Vδ2-T cells, evidenced by increased expression levels of 4-1BB, NKp44, programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1), compared with their MCSP - counterpart. These findings suggest that Vγ9Vδ2-T cells, upon successfully contacting melanoma cells, actively recognize and acquire MCSP from these malignant cells. Evidence of actual tumor cell elimination, although not significant, was only obtained after preincubation of Mel-RhS with pamidronate, a phosphoantigen-inducing agent, indicating the need for additional T cell receptor-mediated signaling for Vγ9Vδ2-T cells to reach their full oncolytic potential., Conclusions: This study highlights the viability and persistence of Vγ9Vδ2-T cells within the 3D microenvironment, their migratory and antitumor functionality, and the suitability of the model for testing T cell-based therapies, contributing both to the understanding of Vγ9Vδ2-T cell biology and their application in cancer immunotherapy., (© 2024 The Author(s).)

Objective Vestibular/ocular deficits occur with mild traumatic brain injury (mTBI). The vestibular/ocular motor screening (VOMS) tool is used to assess individuals post-mTBI, which primarily relies upon subjective self-reported symptoms. Instrumenting the VOMS (iVOMS) with technology may allow for more objective assessment post-mTBI, which reflects actual task performance. This study aimed to validate the iVOMS analytically and clinically in mTBI and controls. Methods Seventy-nine people with sub-acute mTBI (<12 weeks post-injury) and forty-four healthy control participants performed the VOMS whilst wearing a mobile eye-tracking on a one-off visit. People with mTBI were included if they were within 12 weeks of a physician diagnosis. Participants were excluded if they had any musculoskeletal, neurological or sensory deficits which could explain dysfunction. A series of custom-made eye tracking algorithms were used to assess recorded eye-movements. Results The iVOMS was analytically valid compared to the reference (ICC 2,1 0.85-0.99) in mTBI and controls. The iVOMS outcomes were clinically valid as there were significant differences between groups for convergence, vertical saccades, smooth pursuit, vestibular ocular reflex and visual motion sensitivity outcomes. However, there was no significant relationship between iVOMS outcomes and self-reported symptoms. Conclusion The iVOMS is analytically and clinically valid in mTBI and controls, but further work is required to examine the sensitivity of iVOMS outcomes across the mTBI spectrum. Findings also highlighted that symptom and physiological issue resolution post-mTBI may not coincide and relationships need further examination., Competing Interests: Declaration of competing interest The authors confirm there are no competing interests. All authors must disclose any financial and personal relationships with other people or organisations that could inappropriately influence (bias) their work. Examples of potential conflicts of interest include employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is an enveloped DNA virus of the Baculoviridae family. This baculovirus is widely exploited for the biological control of insect pest species and as an expression platform to produce recombinant proteins in insect cells. Extracellular vesicles (EVs) are secreted by all cells and are involved in key roles in many biological processes through their cargo consisting of proteins, RNA or DNA. In viral infections, EVs have been found to transfer both viral and cellular cargo that can elicit either a pro- or antiviral response in recipient cells. Here, small EVs (sEVs) released by Spodoptera frugiperda (Sf) insect cells were characterised for the first time. Using S. frugiperda (SfC1B5) cells stably expressing the baculovirus gp64 , the viral envelope protein GP64 was shown to be incorporated into sEVs. Sf9 cells were also transfected with a bacmid AcMNPV genome lacking p6.9 (AcΔP6.9) to prevent budded virus production. The protein content of sEVs from both mock- and AcΔP6.9-transfected cells were analysed by mass spectrometry. In addition to GP64, viral proteins Ac-F, ME-53 and viral ubiquitin were identified, as well as many host proteins including TSG101-which may be useful as a protein marker for sEVs., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

The design and development of supported catalysts for the oxygen evolution reaction (OER) is a promising pathway to reducing iridium loading in proton exchange membrane water electrolysers. However, supported catalysts often suffer from poor activity and durability, particularly when deployed in membrane electrode assemblies. In this work, we deploy iridium coated hollow titanium dioxide particles as OER catalysts to achieve higher Ir mass activities than the leading commercial catalysts. Critically, we demonstrate state-of-the-art durabilities for supported iridium catalysts when compared against the previously reported values for analogous device architectures, operating conditions and accelerated stress test profiles. Through extensive materials characterisations alongside rotating disk electrode measurements, we investigate the role of conductivity, morphology, oxidation state and crystallinity on the OER electrochemical performance. Our work highlights a new supported catalyst design that unlocks high-performance OER activity and durability in commercially relevant testing configurations., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Although supervised and real-time telerehabilitation by videoconferencing is now becoming common for people with Parkinson's disease (PD), its efficacy for balance and gait is still unclear. This paper uses a scoping approach to review the current evidence on the effects of telerehabilitation by videoconferencing on balance and gait for patients with PD. We also explored whether studies have used wearable technology during telerehabilitation to assess and treat balance and gait via videoconferencing. Literature searches were conducted using PubMed, ISI's Web of Knowledge, Cochrane's Library, and Embase. The data were extracted for study design, treatment, and outcomes. Fourteen studies were included in this review. Of these, seven studies investigated the effects of telerehabilitation (e.g., tele-yoga and adapted physiotherapy exercises) on balance and gait measures (e.g., self-reported balance, balance scale, walking speed, mobility, and motor symptoms) using videoconferencing in both assessment and treatment. The telerehabilitation programs by videoconferencing were feasible and safe for people with PD; however, the efficacy still needs to be determined, as only four studies had a parallel group. In addition, no study used wearable technology. Robust evidence of the effects of telerehabilitation by videoconferencing on balance and gait for patients with PD was not found, suggesting that future powered, prospective, and robust clinical trials are needed.

The quest to identify precious metal free hydrogen evolution reaction catalysts has received unprecedented attention in the past decade. In this Review, we focus our attention to recent developments in precious metal free hydrogen evolution reactions in acidic and alkaline electrolyte owing to their relevance to commercial and near-commercial low-temperature electrolyzers. We provide a detailed review and critical analysis of catalyst activity and stability performance measurements and metrics commonly deployed in the literature, as well as review best practices for experimental measurements (both in half-cell three-electrode configurations and in two-electrode device testing). In particular, we discuss the transition from laboratory-scale hydrogen evolution reaction (HER) catalyst measurements to those in single cells, which is a critical aspect crucial for scaling up from laboratory to industrial settings but often overlooked. Furthermore, we review the numerous catalyst design strategies deployed across the precious metal free HER literature. Subsequently, we showcase some of the most commonly investigated families of precious metal free HER catalysts; molybdenum disulfide-based, transition metal phosphides, and transition metal carbides for acidic electrolyte; nickel molybdenum and transition metal phosphides for alkaline. This includes a comprehensive analysis comparing the HER activity between several families of materials highlighting the recent stagnation with regards to enhancing the intrinsic activity of precious metal free hydrogen evolution reaction catalysts. Finally, we summarize future directions and provide recommendations for the field in this area of electrocatalysis.

Objectives: To investigate the relation between cognitive and motor performance in individuals with mild traumatic brain injury (mTBI) and examine differences in both cognitive and motor performance between adults after mTBI and healthy controls., Design: Multi-center, cross-sectional study., Setting: Three institutional sites (Courage Kenny Research Center, Minneapolis, MN, Oregon Health & Science University, Portland, OR, and University of Utah, Salt Lake City, UT)., Participants: Data were collected from 110 participants (N=110), including those with mTBI and healthy controls, who completed cognitive and physical performance assessments., Interventions: Not applicable., Outcome Measures: Cognitive assessments involved the Automated Neuropsychological Assessment Metrics to evaluate domains of attention, memory, reaction time, processing speed, and executive function. Physical performance was evaluated through clinical performance assessments, such as the 1-min walk test, the modified Illinois Agility Test, the Functional Gait Assessment Tool, the High-Level Mobility Assessment Tool, a complex turning course, and a 4-Item Hybrid Assessment of Mobility for mTBI. Participants also completed additional trials of the 1-min walk test, modified Illinois Agility Test, and complex turning course with a simultaneous cognitive task., Results: Individuals with mTBI performed worse on cognitive assessments, as well as several of the physical performance assessments compared with healthy controls. Complex tasks were more strongly related to cognitive assessments compared with simple walking tasks., Conclusions: Combining complex motor tasks with cognitive demands may better demonstrate functional performance in individuals recovering from mTBI. By understanding the relation between cognitive and physical performance in individuals recovering from mTBI, clinicians may be able to improve clinical care and assist in return to activity decision-making., (Copyright © 2023 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Concussions result in transient symptoms stemming from a cortical metabolic energy crisis. Though this metabolic energy crisis typically resolves in a month, symptoms can persist for years. The symptomatic period is associated with gait dysfunction, the cortical underpinnings of which are poorly understood. Quantifying prefrontal cortex (PFC) activity during gait may provide insight into post-concussion gait dysfunction. The purpose of this study was to explore the effects of persisting concussion symptoms on PFC activity during gait. We hypothesized that adults with persisting concussion symptoms would have greater PFC activity during gait than controls. Within the concussed group, we hypothesized that worse symptoms would relate to increased PFC activity during gait, and that increased PFC activity would relate to worse gait characteristics., Methods: The Neurobehavior Symptom Inventory (NSI) characterized concussion symptoms. Functional near-infrared spectroscopy quantified PFC activity (relative concentration changes of oxygenated hemoglobin [HbO 2 ]) in 14 people with a concussion and 25 controls. Gait was assessed using six inertial sensors in the concussion group., Results: Average NSI total score was 26.4 (13.2). HbO 2 was significantly higher ( P = .007) for the concussed group (0.058 [0.108]) compared to the control group (-0.016 [0.057]). Within the concussion group, HbO 2 correlated with NSI total symptom score (ρ = .62; P = .02), sagittal range of motion ( r = .79; P = .001), and stride time variability ( r = -.54; P = .046)., Conclusion: These data suggest PFC activity relates to symptom severity and some gait characteristics in people with persistent concussion symptoms. Identifying the neurophysiological underpinnings to gait deficits post-concussion expands our knowledge of motor behavior deficits in people with persistent concussion symptoms., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Five experiments (combined N = 4,915) tested the prediction that the moral boost of happiness would persist for social targets with moral failings. In Studies 1 and 2, White and Black participants, respectively, judged happy (versus unhappy) racist targets more morally good. In Study 3, happy (versus unhappy) racist targets were judged more morally good and less (more) likely to engage in racist (good) behavior. Behavioral expectations explained the link between happiness and moral evaluations. Study 4 replicated Studies 1 to 3 in the context of sexism. In Study 5, happy (versus unhappy) targets who engaged in racially biased behavior were evaluated as more morally good, and this effect was explained by behavioral forecasts. Happiness boosts attributions of moral goodness for prejudiced people and does so via expectations for future behavior. Future directions are discussed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Thematically grouped symptom clusters are present during the acute timeline of post-mild traumatic brain injuries (mTBI), representing clinical profiles called subtypes. Exercise intolerance has not been evaluated within the subtype classifications and, because guidelines support early submaximal aerobic exercise, further knowledge is required in regard to the exercise capabilities among the concussion subtypes. This cross-sectional study ( n  = 78) aimed to characterize the presence of exercise intolerance within the clinical subtypes and to explore performance on the Buffalo Concussion Treadmill Test (BCTT) in the adult subacute (2-12 weeks post-injury) mTBI population. All participants were evaluated using the BCTT to determine exercise tolerance. We first used the Neurobehavioral Symptom Inventory (NSI) questionnaire to assign each participant a primary subtype(s). To further explore all five subtypes (headache, cognitive, vestibular, ocular motor, and mood), participants were assessed using a multitude of thematically grouped assessments including self-reported questionnaires, clinical tests of vestibular and ocular motor function, balance function, and computerized cognitive testing. Thirty-seven (47%) subjects were exercise tolerant and 41 (53%) were exercise intolerant. There was no difference in the distribution of primary subtypes between the exercise tolerant and exercise intolerant groups. In addition, no significant differences were found between the exercise tolerant and exercise intolerant groups on other thematically grouped subtype assessments. The exercise intolerant group had a significantly higher resting heart rate (HR), lower percentage of age-predicted maximum HR achieved, lower Borg Rate of Perceived Exertion (RPE), and could walk on the treadmill for less time (lower duration) compared with the exercise tolerant group. The current findings suggest that exercise intolerance is common and pervasive across all five mTBI subtypes. A comprehensive mTBI assessment should include evaluation for exercise intolerance regardless of the primary clustering of symptoms and across patient populations. Therefore, early referral to physical therapists, athletic trainers, or medical clinics that can perform the BCTT may be helpful to initiate appropriate exercise prescriptions for patients with mTBI.

Background: Navigating your environment requires both straight-line gait as well as turning. Gait speed normative values are well established and utilized in determining a person's functional status, however, it has limitations. This study sought to examine whether turning speed declines with age and how it compared to gait speed age-related decline., Methods: A secondary analysis was performed on 275 community dwelling adults between the ages of 18-88 that performed a timed walking test with an inertial measurement unit on their lumbar spine. Turning speed and walking speed were extracted for each participant. A series of mixed models were compared, and Akaike's Information Criterion was used to determine the best fit model between age and turning speed and age and gait speed., Findings: Turning speed and gait speed normative values were reported for each age decade. A linear model with a random intercept of "Condition" was used to assess the relationship between age and turning speed. The results indicated a significant negative relationship between age and turning speed (B = -0.66, p < 0.001). A spline-fit model determined a significant negative relationship between age and gait speed after the age of 65 (B = -0.0097, p = 0.002). The effect of age on gait speed before age 65 was not significant., Interpretation: Turning speed significantly declines with age in a linear fashion while gait speed begins to decline after age 65. Turning speed may be more responsive to age than gait speed. More research is needed to determine if the decline in turning speed with age is associated with a decline in function., Competing Interests: Declaration of competing interest None., (Published by Elsevier Ltd.)

Objective: Unconstrained head motion is necessary to scan for visual cues during navigation, for minimizing threats, and to allow regulation of balance. Following mild traumatic brain injury (mTBI) people may experience alterations in head movement kinematics, which may be pronounced during gait tasks. Gait speed may also be impacted by the need to turn the head while walking in these individuals. The aim of this study was to examine head kinematics during dynamic gait tasks and the interaction between kinematics and gait speed in people with persistent symptoms after mTBI., Setting: A clinical assessment laboratory., Design: A cross-sectional, matched-cohort study., Participants: Forty-five individuals with a history of mTBI and 46 age-matched control individuals., Main Measures: All participants were tested at a single time point and completed the Functional Gait Assessment (FGA) while wearing a suite of body-mounted inertial measurement units (IMUs). Data collected from the IMUs were gait speed, and peak head rotation speed and amplitude in the yaw and pitch planes during the FGA-1, -3, and -4 tasks., Results: Participants with mTBI demonstrated significantly slower head rotations in the yaw ( P = .0008) and pitch ( P = .002) planes. They also demonstrated significantly reduced amplitude of yaw plane head rotations ( P < .0001), but not pitch plane head rotations ( P = .84). Participants with mTBI had significantly slower gait speed during normal gait (FGA-1) ( P < .001) and experienced a significantly greater percent decrease in gait speed than healthy controls when walking with yaw plane head rotations (FGA-3) ( P = .02), but not pitch plane head rotations (FGA-4) ( P = .11)., Conclusions: Participants with mTBI demonstrated smaller amplitudes and slower speeds of yaw plane head rotations and slower speeds of pitch plane head rotations during gait. Additionally, people with mTBI walked slower during normal gait and demonstrated a greater reduction in gait speed while walking with yaw plane head rotations compared with healthy controls., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Purpose: The Functional Gait Assessment (FGA) and High Level Mobility Assessment Tool (HiMAT) are clinical batteries used to assess people with mild traumatic brain injury (mTBI). However, neither assessment was specifically developed for people with mTBI; the FGA was developed to evaluate vestibular deficits, and the HiMAT was developed for individuals with more severe TBI. To maximize the sensitivity and reduce the time burden of these assessments, the purpose of this study was to determine the combination of FGA and HiMAT items that best discriminates persons with persistent symptoms from mTBI from healthy controls., Methods: Fifty-three symptomatic civilians with persistent symptoms from mTBI (21% male, aged 31 (9.5) years, 328 [267] days since concussion) and 57 healthy adults (28% male, aged 32 (9.6) years) participated across 3 sites. The FGA and HiMAT were evaluated sequentially as part of a larger study. To determine the best combination of items, a lasso-based generalized linear model (glm) was fit to all data., Results: The area under the curve (AUC) for FGA and HiMAT total scores was 0.68 and 0.66, respectively. Lasso regression selected 4 items, including FGA Gait with Horizontal Head Turns and with Pivot Turn, and HiMAT Fast Forward and Backward Walk, and yielded an AUC (95% confidence interval) of 0.71 (0.61-0.79) using standard scoring., Discussion and Conclusions: The results provide initial evidence supporting a reduced, 4-Item Hybrid Assessment of Mobility for mTBI (HAM-4-mTBI) for monitoring individuals with mTBI. Future work should validate the HAM-4-mTBI and investigate its utility for tracking progression throughout rehabilitation.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A409 )., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Academy of Neurologic Physical Therapy, APTA.)

Introduction: Vestibular/Ocular Motor Screening (VOMS) is often part of a comprehensive evaluation to identify acute mild traumatic brain injury. Most of the reports describe the use of the VOMS in adolescents/young adults and not in older adults or military service members. The purpose of this study was to describe VOMS findings in healthy civilians and active duty military service members up to the age of 50 years., Materials and Methods: Seventy-seven healthy civilians between 18 and 50 years of age (22 males, age 31.8 [9.0] years) participated across three sites in addition to 40 healthy active duty service members (25 males, age 27.5 [4.9] years) from one site. Demographics, Neurobehavioral Symptom Inventory scores, mean near point convergence (NPC) distance, and Total Symptom Change (TSS) scores from the VOMS were evaluated., Results: For civilians, the group mean NPC distance was 4.98 (3.8) cm. For military service members, the group mean NPC distance was 6.17 (4.57) cm. For civilians, the mean TSS was 1.2 (2.3) with 53.2% reporting 0 TSS, 27.3% reporting one TSS, and 19.5% reporting two or more TSS. For military service members, the mean TSS was 0.20 (0.72) with 92.5% reporting 0 TSS, 0% reporting one TSS, and 7.5% reporting two or more TSS. Age did not correlate with the mean NPC distance and TSS in healthy civilians and active duty military service members., Conclusions: Reconsideration of the Military Acute Concussion Evaluation, Version 2 cutoff value for abnormal mean NPC distance may be warranted to improve diagnostic accuracy in both civilian and military adult populations. Similarly, re-evaluating criteria for interpreting the TSS results of the VOMS, specifically in civilians, may be warranted., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

γδ T cells are important components of the immune system due to their ability to elicit a fast and strong response against infected and transformed cells. Because they can specifically and effectively kill target cells in an MHC independent fashion, there is great interest to utilize these cells in anti-tumor therapies where antigen presentation may be hampered. Since only a small fraction of T cells in the blood or tumor tissue are γδ T cells, they require extensive expansion to allow for fundamental, preclinical and ex vivo research. Although expansion protocols can be successful, most are based on depletion of other cell types rather than γδ T cell specific isolation, resulting in unpredictable purity of the isolated fraction. Moreover, the primary focus only lies with expansion of Vδ2 + T cells, while Vδ1 + T cells likewise have anti-tumor potential. Here, we investigated whether γδ T cells directly isolated from blood could be efficiently expanded while maintaining function. γδ T cell subsets were isolated using MACS separation, followed by FACS sorting, yielding >99% pure γδ T cells. Isolated Vδ1 + and Vδ2 + T cells could effectively expand immediately after isolation or upon freeze/thawing and reached expansion ratios between 200 to 2000-fold starting from varying numbers using cytokine supported feeder stimulations. MACS/FACS isolated and PHA stimulated γδ T cells expanded as good as immobilized antibody mediated stimulated cells in PBMCs, but delivered purer cells. After expansion, potential effector functions of γδ T cells were demonstrated by IFN-γ, TNF-α and granzyme B production upon PMA/ionomycin stimulation and effective killing capacity of multiple tumor cell lines was confirmed in killing assays. In conclusion, pure γδ T cells can productively be expanded while maintaining their anti-tumor effector functions against tumor cells. Moreover, γδ T cells could be expanded from low starting numbers suggesting that this protocol may even allow for expansion of cells extracted from tumor biopsies., 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 © 2024 Verkerk, Pappot, Jorritsma, King, Duurland, Spaapen and van Ham.)

Objective: The aim of this study was to establish the test-retest reliability of metrics obtained from wearable inertial sensors that reflect turning performance during tasks designed to imitate various turns in daily activity., Methods: Seventy-one adults who were healthy completed 3 turning tasks: a 1-minute walk along a 6-m walkway, a modified Illinois Agility Test (mIAT), and a complex turning course (CTC). Peak axial turning and rotational velocity (yaw angular velocity) were extracted from wearable inertial sensors on the head, trunk, and lumbar spine. Intraclass correlation coefficients (ICCs) were established to assess the test-retest reliability of average peak turning speed for each task. Lap time was collected for reliability analysis as well., Results: Turning speed across all tasks demonstrated good to excellent reliability, with the highest reliability noted for the CTC (45-degree turns: ICC = 0.73-0.81; 90-degree turns: ICC = 0.71-0.83; and 135-degree turns: ICC = 0.72-0.80). The reliability of turning speed during 180-degree turns from the 1-minute walk was consistent across all body segments (ICC = 0.74-0.76). mIAT reliability ranged from fair to excellent (end turns: ICC = 0.52-0.72; mid turns: ICC = 0.50-0.56; and slalom turns: ICC = 0.66-0.84). The CTC average lap time demonstrated good test-retest reliability (ICC = 0.69), and the mIAT average lap time test-retest reliability was excellent (ICC = 0.91)., Conclusion: Turning speed measured by inertial sensors is a reliable outcome across a variety of ecologically valid turning tasks that can be easily tested in a clinical environment., Impact: Turning performance is a reliable and important measure that should be included in clinical assessments and clinical trials., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

After a mild traumatic brain injury (mTBI), dizziness and balance problems are frequently reported, affecting individuals' daily lives and functioning. Vestibular rehabilitation is a standard treatment approach for addressing these issues, but its efficacy in this population remains inconclusive. A potential reason for suboptimal outcomes is the lack of objective monitoring of exercise performance, which is crucial for therapeutic success. This study utilized wearable inertial measurement units (IMUs) to quantify exercise performance in individuals with mTBI during home-based vestibular rehabilitation exercises. Seventy-three people with mTBI and fifty healthy controls were enrolled. Vestibular exercises were performed, and IMUs measured forehead and sternum velocities and range of motions. The mTBI group demonstrated a slower forehead peak angular velocity in all exercises, which may be a compensatory strategy to manage balance issues or symptom exacerbation. Additionally, the mTBI group exhibited a larger forehead range of motion during specific exercises, potentially linked to proprioceptive deficits. These findings emphasize the usefulness of utilizing IMUs to monitor the quality of home-based vestibular exercises for individuals with mTBI and the potential for IMUs improving rehabilitation outcomes.

Objective: Three studies examined the relationship between adverse childhood experiences and meaning in life, focusing on the facets of meaning-coherence, significance, and purpose., Method: In Study 1 (N = 1804), college students rated adverse childhood experiences, global meaning in life, and its facets. In Study 2 (N = 822), noncollege adults rated childhood trauma, meaning in life facets, attachment style, mood, and neuroticism. In Study 3 (N = 380) college students wrote about a positive and negative childhood memory, rating the facets of meaning immediately after each writing task., Results: In Studies 1-2, at the level of zero-order correlations, adverse childhood experiences related negatively to coherence, significance, and purpose. Controlling for the other facets, adverse childhood experiences remained negatively related to coherence and significance but were unrelated to purpose. Negative relationships between adverse childhood experiences and coherence and significance maintained controlling for covariates (Study 2). In Study 3, the predicted 3-way interaction showed that after recalling a negative childhood memory, adverse childhood experiences predicted lower significance and coherence but higher purpose., Conclusions: Adverse childhood experiences consistently predict lower feelings of coherence and significance but, accounting for these associations, are unrelated to purpose. Purpose may represent a motivational strength emerging out of childhood adversity., (© 2023 Wiley Periodicals LLC.)

Introduction: Balance deficits in people with chronic mild traumatic brain injury (mTBI; ≥3 months post-mTBI), thought to relate to central sensory integration deficits, are subtle and often difficult to detect. The purpose of this study was to determine the sensitivity of the instrumented modified clinical test of sensory integration for balance (mCTSIB) in identifying such balance deficits in people with symptomatic, chronic mTBI and to establish the associations between balance and mTBI symptom scores in the chronic mTBI group., Methods: The Institutional Review Board approved these study methods. Forty-one people with chronic mTBI and balance complaints and 53 healthy controls performed the mCTSIB (eyes open/closed on firm/foam surfaces; EoFi, EcFi, EoFo, and EcFo) with a wearable sensor on their waist to quantify sway area (m2/s4). Sensory reweighting variables were calculated for the firm and foam stance conditions. A stopwatch provided the clinical outcome for the mCTSIB (time). Each participant completed the Neurobehavioral Symptom Inventory (NSI), which quantifies mTBI-related symptoms and provides a total score, as well as sub-scores on affective, cognitive, somatic, and vestibular domains., Results: The mTBI group reported significantly higher symptom scores across each NSI sub-score (all Ps < .001). The mTBI group had a significantly larger sway area than the control group across all mCTSIB conditions and the mTBI group had significantly higher sensory reweighting scores compared to the control group on both the firm (P = .01) and foam (P = .04) surfaces. Within the mTBI group, the NSI vestibular score significantly related to the mCTSIB sway area EcFi (r = 0.38; P = .02), sway area EcFo (r = 0.43; P = .006), sensory reweighting firm (r = 0.33; P = .04), and sensory reweighting foam (r = 0.38; P = .02). The average sway area across the 4 mCTSIB conditions was significantly (area under the curve: 0.77; P < .001) better at differentiating groups than the mCTSIB clinical total score. The average sway area across the 4 mCTSIB conditions had a sensitivity of 73% and a specificity of 71%. The clinical mCTSIB outcome scores were not different between groups., Conclusion: People with chronic mTBI appear to have central sensory integration deficits detectable by instrumented measures of postural assessment. These findings suggest that central sensory integration should be targeted in rehabilitation for people with chronic mTBI., (© The Association of Military Surgeons of the United States 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Balance impairments, that lead to falls, are one of the main symptoms of Parkinson's disease (PD). Telerehabilitation is becoming more common for people with PD; however, balance is particularly challenging to assess and treat virtually. The feasibility and efficacy of virtual assessment and virtual treatment of balance in people with PD are unknown. The present study protocol has three aims: I) to determine if a virtual balance and gait assessment (instrumented L-shape mobility test) with wearable sensors can predict a gold-standard, in-person clinical assessment of balance, the Mini Balance Evaluation Systems Test (Mini-BESTest); II) to explore the effects of 12 sessions of balance telerehabilitation and unsupervised home exercises on balance, gait, executive function, and clinical scales; and III) to explore if improvements after balance telerehabilitation transfer to daily-life mobility, as measured by instrumented socks with inertial sensors worn for 7 days., Methods: The TelePD Trial is a prospective, single-center, parallel-group, single-blind, pilot, randomized, controlled trial. This trial will enroll 80 eligible people with PD. Participants will be randomized at a 1:1 ratio into receiving home-based balance exercises in either: 1) balance telerehabilitation (experimental group, n = 40) or 2) unsupervised exercises (control group, n = 40). Both groups will perform 12 sessions of exercise at home that are 60 min long. The primary outcome will be Mini-BESTest. The secondary outcomes will be upper and lower body gait metrics from a prescribed task (instrumented L-shape mobility test); daily-life mobility measures over 7 days with wearable sensors in socks, instrumented executive function tests, and clinical scales. Baseline testing and 7 days of daily-life mobility measurement will occur before and after the intervention period., Conclusion: The TelePD Trial will be the first to explore the usefulness of using wearable sensor-based measures of balance and gait remotely to assess balance, the feasibility and efficacy of balance telerehabilitation in people with PD, and the translation of balance improvements after telerehabilitation to daily-life mobility. These results will help to develop a more effective home-based balance telerehabilitation and virtual assessment that can be used remotely in people with balance impairments., Trial Registration: This trial was prospectively registered on ClinicalTrials.gov (NCT05680597)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: The relationship between mobility and cognition has been studied in the aging population and associations have been also reported in people with Parkinson's disease (PD)., Objective: To compare different aspects of gait and balance between individuals with PD who have normal cognition and those with impaired cognition, using both clinical and instrumented measures., Methods: One-hundred forty-three participants with PD were divided into two groups: 1) normal cognition (n = 71) and 2) impaired cognition (n = 72) based on the Montreal Cognitive Assessment (MoCA) cut-off. Groups were compared using instrumented and clinical measures of gait and balance in the following domains: Sensory Orientation, Anticipatory Postural Adjustments, Automatic Postural Responses and Dynamic Balance for Gait. Instrumented measures were obtained via wearable sensors while performing eight different motor tasks and clinical measures were obtained with the Mini-BESTest., Results: The total Mini-BESTest score was not different between groups. However, the Dynamic Gait domain was worse in individuals with impaired cognition. Among the instrumented measures across domains, all significant group differences were in the Dynamic Gait domain, specifically, dual-task gait speed, dual-task stride length, stance time, and turn velocity., Conclusions: Dynamic balance during gait was more impaired in people with PD who had abnormal cognition than those with normal cognition, for both clinical and instrumented measures. All other balance domains did not differ between groups, for both instrumented and clinical measures., Competing Interests: Declaration of competing interest Natália Mariano Barboza: none. Martina Mancini: none. Suhaila Mahmoud Smaili: none. Fay B. Horak: is employed part-time by APDM, who makes the inertial sensors used to instrument balance and gait in this study. This potential conflict has been reviewed and managed by OHSU. Patricia Carlson-Kuhta: none. Rosie Morris: none. Laurie A. King: none., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Vγ9Vδ2 T cells are effector cells with proven antitumor efficacy against a broad range of cancers. This study aimed to assess the antitumor activity and safety of a bispecific antibody directing Vγ9Vδ2 T cells to EGFR-expressing tumors. An EGFR-Vδ2 bispecific T-cell engager (bsTCE) was generated, and its capacity to activate Vγ9Vδ2 T cells and trigger antitumor activity was tested in multiple in vitro, in vivo, and ex vivo models. Studies to explore safety were conducted using cross-reactive surrogate engagers in nonhuman primates (NHP). We found that Vγ9Vδ2 T cells from peripheral blood and tumor specimens of patients with EGFR+ cancers had a distinct immune checkpoint expression profile characterized by low levels of PD-1, LAG-3, and TIM-3. Vγ9Vδ2 T cells could be activated by EGFR-Vδ2 bsTCEs to mediate lysis of various EGFR+ patient-derived tumor samples, and substantial tumor growth inhibition and improved survival were observed in in vivo xenograft mouse models using peripheral blood mononuclear cells (PBMC) as effector cells. EGFR-Vδ2 bsTCEs exerted preferential activity toward EGFR+ tumor cells and induced downstream activation of CD4+ and CD8+ T cells and natural killer (NK) cells without concomitant activation of suppressive regulatory T cells observed with EGFR-CD3 bsTCEs. Administration of fully cross-reactive and half-life extended surrogate engagers to NHPs did not trigger signals in the safety parameters that were assessed. Considering the effector and immune-activating properties of Vγ9Vδ2 T cells, the preclinical efficacy data and acceptable safety profile reported here provide a solid basis for testing EGFR-Vδ2 bsTCEs in patients with EGFR+ malignancies., (©2023 American Association for Cancer Research.)

Purpose: Measuring persistent imbalance after mTBI is challenging and may include subjective symptom-reporting as well as clinical scales. Clinical assessments for quantifying balance following mTBI have focused on sensory orientation. It is theorized that balance control goes beyond sensory orientation and also includes subdomains of anticipatory postural adjustments, reactive postural control, and dynamic gait. The Mini Balance Evaluation Systems Test (Mini-BESTest) is a validated balance test that measures balance according to these subdomains for a more comprehensive assessment. The purpose of this study was to compare Mini-BESTest total and subdomain scores after subacute mTBI with healthy controls., Methods: Symptomatic mTBI (n = 90, 20 % male, age=36.0 ± 12.0, 46.3.4 ± 22.1 days since injury) and healthy control (n = 45, 20 % male, age=35.4 ± 12.5) participants completed the Mini-BESTest for balance. Mini-BESTest between-group differences were evaluated using Wilcoxon rank-sum tests., Results: The mTBI group (Median[minimum,maximum]) had a significantly worse Mini-BESTest total score than the healthy controls (24[18,28] vs 27[23-28], p < 0.001). The mTBI group performed significantly worse in 3 of the 4 subdomains compared to the healthy controls: reactive postural control: 5[2-6] vs 6[3-6], p = 0.003; sensory orientation: 6[5,6] vs 6[6], p = 0.005; dynamic gait: 8[5-10] vs 9[8-10], p < 0.001. There was no significance difference between groups in the anticipatory postural adjustments domain (5[3-6] vs 5[3-6], p = 0.12)., Conclusions: The Mini-BESTest identified deficits in people with subacute mTBI in the total score and 3 out of 4 subdomains, suggesting it may be helpful to use in the clinic to identify balance subdomain deficits in the subacute mTBI population. In combination with self-reported assessments, the mini-BESTest may identify balance domain deficits in the subacute mTBI population and help guide treatment for this population., Competing Interests: Conflict of interest The authors have no conflicts of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Humanised antibodies targeting Crimean-Congo Haemorrhagic virus (CCHFV) are needed for the development and standardisation of serological assays. These assays are needed to address a shortfall in available tests that meet regulatory diagnostic standards and to aid surveillance activities to extend knowledge on the distribution of CCHFV. To generate a humanised monoclonal antibody against CCHFV, we have compared two methods: the traditional mouse hybridoma approach with subsequent sequencing and humanisation of antibodies versus a non-animal alternative using a human combinatorial antibody library (HuCAL). Our results demonstrated that the mouse hybridoma followed by humanisation protocol gave higher affinity antibodies. Whilst not yet able to demonstrate the generation of equivalent humanised antibodies without the use of animals, sequencing data enables the subsequent production of recombinant antibodies, thus providing a reduction in future animal usage for this application. Ultimately, our report provides information on development of a humanised standardised control, which can form an important positive control component of serological assays against CCHFV., Competing Interests: Declaration of Competing Interest No potential conflict of interests are declared by any of the authors., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Background: People with Parkinson's disease (PD) have a high fall rate and many falls are associated with turns. Despite this, there is minimal research on effects of rehabilitation on the quality of turns. Further, quantifying turns in the home may have broader implications since rehabilitation of turns would ideally improve turning in real world mobility., Methods: Sixty people with PD and a history of falls will be randomized to receive either a novel TURNing InTervention (TURN-IT) or no intervention (control group). The TURN-IT group will be seen for 6 weeks (18 visits) for an individualized, progressive program that is based on the specific constraints of turning in PD. Wearable sensors will be used to measure 7 days of mobility, including turns, before and after intervention or control period. In addition, blinded assessments of gait, mobility and turns will occur before and after intervention for both groups and falls will be monitored for twelve months post intervention with bimonthly email questionnaires., Discussion: This study has the potential to change how we rehabilitate and assess turning in people with PD and falls. There are several novel aspects to our study including a comprehensive turning-focused intervention that is tailored to the underlying constraints that impair turning in people with PD. Further, our outcome measure of turning quality during 7 days of daily life is novel and has implications for determining real-life changes after rehabilitation. The ultimate goal of this rehabilitation intervention is to improve how patients turn in daily life and to reduce falls., Trials Registration: This protocol is registered at clinicaltrials.gov; #NCT04897256; https://clinicaltrials.gov/ct2/show/NCT04897256?term=Horak&cond=Parkinson+Disease&draw=2&rank=4 ., (© 2022. The Author(s).)

Imbalance is common following mild Traumatic Brain Injury (mTBI) and can persist months after the initial injury. To determine if mTBI subjects with chronic imbalance differed from healthy age- and sex-matched controls (HCs) we used both the Central SensoriMotor Integration (CSMI) test, which evaluates sensory integration, time delay, and motor activation properties and the standard Sensory Organization Test (SOT). Four CSMI conditions evoked center-of-mass sway in response to: surface tilts with eyes closed (SS/EC), surface tilts with eyes open viewing a fixed visual surround (SS/EO), visual surround tilts with eyes open standing on a fixed surface (VS/EO), and combined surface and visual tilts with eyes open (SS+VS/EO). The mTBI participants relied significantly more on visual cues during the VS/EO condition compared to HCs but had similar reliance on combinations of vestibular, visual, and proprioceptive cues for balance during SS/EC, SS/EO, and SS+VS/EO conditions. The mTBI participants had significantly longer time delays across all conditions and significantly decreased motor activation relative to HCs across conditions that included surface-tilt stimuli with a sizeable subgroup having a prominent increase in time delay coupled with reduced motor activation while demonstrating no vestibular sensory weighting deficits. Decreased motor activation compensates for increased time delay to maintain stability of the balance system but has the adverse consequence that sensitivity to both internal (e.g., sensory noise) and external disturbances is increased. Consistent with this increased sensitivity, SOT results for mTBI subjects showed increased sway across all SOT conditions relative to HCs with about 45% of mTBI subjects classified as having an "Aphysiologic" pattern based on published criteria. Thus, CSMI results provided a plausible physiological explanation for the aphysiologic SOT pattern. Overall results suggest that rehabilitation that focuses solely on sensory systems may be incomplete and may benefit from therapy aimed at enhancing rapid and vigorous responses to balance perturbations., 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 © 2022 Campbell, King, Parrington, Fino, Antonellis and Peterka.)

Complaints of non-resolving imbalance are common in individuals with chronic mild traumatic brain injury (mTBI). Vestibular rehabilitation therapy may be beneficial for this population. Additionally, wearable sensors can enable biofeedback, specifically audio biofeedback (ABF), and aid in retraining balance control mechanisms in people with balance impairments. In this study, we described the effectiveness of vestibular rehabilitation therapy with and without ABF to improve balance in people with chronic mTBI. Participants ( n = 31; females = 22; mean age = 40.9 ± 11 y) with chronic (>3 months) mTBI symptoms of self-reported imbalance were randomized into vestibular rehabilitation with ABF ( n = 16) or without ABF ( n = 15). The intervention was a standard vestibular rehabilitation, with or without ABF, for 45 min biweekly for 6 weeks. The ABF intervention involved a smartphone that provided auditory feedback when postural sway was outside of predetermined equilibrium parameters. Participant's completed the Post-Concussion Symptom Scale (PCSS). Balance was assessed with the sensory organization test (SOT) and the Central Sensorimotor Integration test which measured sensory weighting, motor activation, and time delay with sway evoked by surface and/or visual surround tilts. Effect sizes (Hedge's G) were calculated on the change between pre-and post-rehabilitation scores. Both groups demonstrated similar medium effect-sized decreases in PCSS and large increases in SOT composite scores after rehabilitation. Effect sizes were minimal for increasing sensory weighting for both groups. The with ABF group showed a trend of larger effect sizes in increasing motor activation (with ABF = 0.75, without ABF = 0.22) and in decreasing time delay (with ABF = -0.77, without ABF = -0.52) relative to the without ABF group. Current clinical practice focuses primarily on sensory weighting. However, the evaluation and utilization of motor activation factors in vestibular rehabilitation, potentially with ABF, may provide a more complete assessment of recovery and improve outcomes., 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 © 2022 Campbell, Peterka, Fino, Parrington, Wilhelm, Pettigrew and King.)

Background and Purpose: Multimodal physical therapy for mild traumatic brain injury (mTBI) has been shown to improve recovery. Due to the coronavirus disease-2019 (COVID-19) pandemic, a clinical trial assessing the timing of multimodal intervention was adapted for telerehabilitation. This pilot study explored feasibility and adoption of an in-person rehabilitation program for subacute mTBI delivered through telerehabilitation., Methods: Fifty-six in-person participants-9 males; mean (SD) age 34.3 (12.2); 67 (31) days post-injury-and 17 telerehabilitation participants-8 males; age 38.3 (12.7); 61 (37) days post-injury-with subacute mTBI (between 2 and 12 weeks from injury) were enrolled. Intervention included 8, 60-minute visits over 6 weeks and included subcategories that targeted cervical spine, cardiovascular, static balance, and dynamic balance impairments. Telerehabilitation was modified to be safely performed at home with minimal equipment. Outcome measures included feasibility (the number that withdrew from the study, session attendance, home exercise program adherence, adverse events, telerehabilitation satisfaction, and progression of exercises performed), and changes in mTBI symptoms pre- and post-rehabilitation were estimated with Hedges' g effect sizes., Results: In-person and telerehabilitation had a similar study withdrawal rate (13% vs 12%), high session attendance (92% vs 97%), and no adverse events. The telerehabilitation group found the program easy to use (4.2/5), were satisfied with care (4.7/5), and thought it helped recovery (4.7/5). The telerehabilitation intervention was adapted by removing manual therapy and cardiovascular portions and decreasing dynamic balance exercises compared with the in-person group. The in-person group had a large effect size (-0.94) in decreases in symptoms following rehabilitation, while the telerehabilitation group had a moderate effect size (-0.73)., Discussion and Conclusions: Telerehabilitation may be feasible for subacute mTBI. Limited ability to address cervical spine, cardiovascular, and dynamic balance domains along with underdosage of exercise progression may explain group differences in symptom resolution.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A392 )., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Academy of Neurologic Physical Therapy, APTA.)

Objective: The purpose of this study was to (1) explore differences in vestibular ocular motor screening (VOMS) symptoms between healthy adults and adults with persistent symptoms after mild traumatic brain injury (mTBI), and (2) explore the relationships between VOMS symptoms and other measures (self-reported vestibular symptoms, clinical measures of balance and gait, and higher-level motor ability tasks)., Setting: Research laboratory setting., Participants: Fifty-three persons with persistent symptoms (>3 weeks) following mTBI and 57 healthy controls were recruited. Eligibility for participation included being 18 to 50 years of age and free of medical conditions that may affect balance, with the exception of recent mTBI for the mTBI group., Design: Cross-sectional., Main Measures: The primary outcomes were the VOMS symptom scores and near point of convergence (NPC) distance. Secondary outcomes included the Dizziness Handicap Inventory (DHI) total and subdomain scores, sway area, Functional Gait Analysis total score, gait speed, and modified Illinois Agility Task completion time, and Revised High-Level Mobility Assessment Tool total score., Results: The mTBI group reported more VOMS symptoms ( z range, -7.28 to -7.89) and a further NPC ( t = -4.16) than healthy controls (all P s < .001). DHI self-reported symptoms (total and all subdomain scores) were strongly associated with the VOMS symptom scores (rho range, 0.53-0.68; all P s < .001). No significant relationships existed between VOMS symptoms and other measures., Conclusion: Significant group differences support the relevance of the VOMS for mTBI in an age-diverse sample with persistent symptoms. Furthermore, strong association with DHI symptoms supports the ability of the VOMS to capture vestibular complaints in this population., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

Background and Aim: Individuals with Parkinson's disease (PD) with and without freezing of Gait (FoG) may respond differently to exercise interventions for several reasons, including disease duration. This study aimed to determine whether both people with and without FoG benefit from the Agility Boot Camp with Cognitive Challenges (ABC-C) program., Methods: This secondary analysis of our ABC-C trial included 86 PD subjects: 44 without FoG (PD-FoG) and 42 with FoG (PD + FoG). We collected measures of standing sway balance, anticipatory postural adjustments, postural responses, and a 2-minute walk with and without a cognitive task. Two-way repeated analysis of variance, with disease duration as covariate, was used to investigate the effects of ABC-C program. Effect sizes were calculated using standardized response mean (SRM) for PD-FoG and PD + FoG, separately., Results: The ABC-C program was effective in improving gait performance in both PD-FoG and PD + FoG, even after controlling for disease duration. Specifically, dual-task gait speed ( P  < .0001), dual-cost stride length ( P  = .012), and these single-task measures: arm range of motion ( P  < .0001), toe-off angle ( P  = .005), gait cycle duration variability ( P  = .019), trunk coronal range of motion ( P  = .042), and stance time ( P  = .046) improved in both PD-FoG and PD + FoG. There was no interaction effect between time (before and after exercise) and group (PD-FoG/PD + FoG) in all 24 objective measures of balance and gait. Dual-task gait speed improved the most in PD + FoG (SRM = 1.01), whereas single-task arm range of motion improved the most in PD-FoG (SRM = 1.01)., Conclusion: The ABC-C program was similarly effective in improving gait (and not balance) performance in both PD-FoG and PD + FoG.

Background: Up to 40% of mild traumatic brain injuries (mTBI) can result in chronic unresolved symptoms, such as balance impairment, that persist beyond three months. Sensorimotor control, the collective coordination and regulation of both sensory and motor components of the postural control system, may underlie balance deficits in chronic mTBI. The aim of this study was to determine if the relationship between severity of impairment in chronic (> 3 months) mTBI and poorer balance performance was mediated by sensorimotor integration measures., Methods: Data were collected from 61 healthy controls and 58 mTBI participants suffering persistent balance problems. Participants completed questionnaires (Dizziness Handicap Inventory (DHI), Neurobehavioral Symptom Inventory (NSI), and Sports Concussion Assessment Tool Symptom Questionnaire (SCAT2)) and performed instrumented postural sway assessments and a test of Central Sensory Motor Integration (CSMI). Exploratory Factor Analysis was used to reduce the variables used within the mediation models to constructs of impairment (Impairment Severity - based on questionnaires), balance (Sway Dispersion - based on instrumented postural sway measures), and sensorimotor control (Sensory Weighting, Motor Activation and Time Delay - based on parameters from CSMI tests). Mediation analyses used path analysis to estimate the direct effect (between impairment and balance) and indirect (mediating) effects (from sensorimotor control)., Results: Two out of three sensorimotor integration factors (Motor Activation and Time Delay) mediated the relationship between Impairment Severity and Sway Dispersion, however, there was no mediating effect of Sensory Weighting., Significance: These findings have clinical implications since rehabilitation of balance commonly focuses on sensory cues. Our findings indicate the importance of Motor Activation and Time Delay, and thus a focus on strategies to improve factors related to these constructs throughout the rehabilitative process (i.e., level of muscular contractions to control joint torques; response time to stimuli/perturbations) may improve a patient's balance control., (Copyright © 2022 Elsevier B.V. All rights reserved.)

γδ T-cells directly recognize and kill transformed cells independently of HLA-antigen presentation, which makes them a highly promising effector cell compartment for cancer immunotherapy. Novel γδ T-cell-based immunotherapies, primarily focusing on the two major γδ T-cell subtypes that infiltrate tumors ( i.e. Vδ1 and Vδ2), are being developed. The Vδ1 T-cell subset is enriched in tissues and contains both effector T-cells as well as regulatory T-cells with tumor-promoting potential. Vδ2 T-cells, in contrast, are enriched in circulation and consist of a large, relatively homogeneous, pro-inflammatory effector T-cell subset. Healthy individuals typically harbor in the order of 50-500 million Vγ9Vδ2 T-cells in the peripheral blood alone (1-10% of the total CD3 + T-cell population), which can rapidly expand upon stimulation. The Vγ9Vδ2 T-cell receptor senses intracellular phosphorylated metabolites, which accumulate in cancer cells as a result of mevalonate pathway dysregulation or upon pharmaceutical intervention. Early clinical studies investigating the therapeutic potential of Vγ9Vδ2 T-cells were based on either ex vivo expansion and adoptive transfer or their systemic activation with aminobisphosphonates or synthetic phosphoantigens, either alone or combined with low dose IL-2. Immune-related adverse events (irAE) were generally \mild, but the clinical efficacy of these approaches provided overall limited benefit. In recent years, critical advances have renewed the excitement for the potential of Vγ9Vδ2 T-cells in cancer immunotherapy. Here, we review γδ T-cell-based therapeutic strategies and discuss the prospects of those currently evaluated in clinical studies in cancer patients as well as future therapies that might arise from current promising pre-clinical results., Competing Interests: JS-E, MJ and LK are funded by Lava therapeutics. HV, PP, EE, BW are employed by and hold stock of LAVA Therapeutics. TG holds stock of LAVA Therapeutics., (Copyright © 2022 Saura-Esteller, de Jong, King, Ensing, Winograd, de Gruijl, Parren and van der Vliet.)

Background: Each year, approximately one million older adults die in American intensive care units (ICUs) or survive with significant functional impairment. Inadequate symptom management, surrogates' psychological distress and inappropriate healthcare use are major concerns. Pioneering work by Dr. J. Randall Curtis paved the way for integrating palliative care (PC) specialists to address these needs, but convincing proof of efficacy has not yet been demonstrated., Design: We will conduct a multicenter patient-randomized efficacy trial of integrated specialty PC (SPC) vs. usual care for 500 high-risk ICU patients over age 60 and their surrogate decision-makers from five hospitals in Pennsylvania., Intervention: The intervention will follow recommended best practices for inpatient PC consultation. Patients will receive care from a multidisciplinary SPC team within 24 hours of enrollment that continues until hospital discharge or death. SPC clinicians will meet with patients, families, and the ICU team every weekday. SPC and ICU clinicians will jointly participate in proactive family meetings according to a predefined schedule. Patients in the control arm will receive routine ICU care., Outcomes: Our primary outcome is patient-centeredness of care, measured using the modified Patient Perceived Patient-Centeredness of Care scale. Secondary outcomes include surrogates' psychological symptom burden and health resource utilization. Other outcomes include patient survival, as well as interprofessional collaboration. We will also conduct prespecified subgroup analyses using variables such as PC needs, measured by the Needs of Social Nature, Existential Concerns, Symptoms, and Therapeutic Interaction scale., Conclusions: This trial will provide robust evidence about the impact of integrating SPC with critical care on patient, family, and health system outcomes., Competing Interests: Conflicts of Interests See relevant ICMJE forms., (Copyright © 2022 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Physical function remains a crucial component of mild traumatic brain injury (mTBI) assessment and recovery. Traditional approaches to assess mTBI lack sensitivity to detect subtle deficits post-injury, which can impact a patient's quality of life, daily function and can lead to chronic issues. Inertial measurement units (IMU) provide an opportunity for objective assessment of physical function and can be used in any environment. A single waist worn IMU has the potential to provide broad/macro quantity characteristics to estimate gait mobility, as well as more high-resolution micro spatial or temporal gait characteristics (herein, we refer to these as measures of quality). Our recent work showed that quantity measures of mobility were less sensitive than measures of turning quality when comparing the free-living physical function of chronic mTBI patients and healthy controls. However, no studies have examined whether measures of gait quality in free-living conditions can differentiate chronic mTBI patients and healthy controls. This study aimed to determine whether measures of free-living gait quality can differentiate chronic mTBI patients from controls., Methods: Thirty-two patients with chronic self-reported balance symptoms after mTBI (age: 40.88 ± 11.78 years, median days post-injury: 440.68 days) and 23 healthy controls (age: 48.56 ± 22.56 years) were assessed for ~ 7 days using a single IMU at the waist on a belt. Free-living gait quality metrics were evaluated for chronic mTBI patients and controls using multi-variate analysis. Receiver operating characteristics (ROC) and Area Under the Curve (AUC) analysis were used to determine outcome sensitivity to chronic mTBI., Results: Free-living gait quality metrics were not different between chronic mTBI patients and controls (all p > 0.05) whilst controlling for age and sex. ROC and AUC analysis showed stride length (0.63) was the most sensitive measure for differentiating chronic mTBI patients from controls., Conclusions: Our results show that gait quality metrics determined through a free-living assessment were not significantly different between chronic mTBI patients and controls. These results suggest that measures of free-living gait quality were not impaired in our chronic mTBI patients, and/or, that the metrics chosen were not sensitive enough to detect subtle impairments in our sample., (© 2022. The Author(s).)

GaInP 2 has shown promise as the wide bandgap top junction in tandem absorber photoelectrochemical (PEC) water splitting devices. Among previously reported dual-junction PEC devices with a GaInP 2 top cell, those with the highest performance incorporate an AlInP 2 window layer (WL) to reduce surface recombination and a thin GaInP 2 capping layer (CL) to protect the WL from corrosion in electrolytes. However, the stability of these III-V systems is limited, and durability continues to be a major challenge broadly in the field of PEC water splitting. This work provides a systematic investigation into the durability of GaInP 2 systems, examining the impacts of the window layer and capping layer among single junction pn-GaInP 2 photocathodes coated with an MoS 2 catalytic and protective layer. The photocathode with both a CL and WL demonstrates the highest PEC performance and longest lifetime, producing a significant current for >125 h. In situ optical imaging and post-test characterization illustrate the progression of macroscopic degradation and chemical state. The surface architecture combining an MoS 2 catalyst, CL, and WL can be translated to dual-junction PEC devices with GaInP 2 or other III-V top junctions to enable more efficient and stable PEC systems.

Clonal expansion is a core aspect of T cell immunity. However, little is known with respect to the relationship between replicative history and the formation of distinct CD8 + memory T cell subgroups. To address this issue, we developed a genetic-tracing approach, termed the DivisionRecorder, that reports the extent of past proliferation of cell pools in vivo. Using this system to genetically 'record' the replicative history of different CD8 + T cell populations throughout a pathogen-specific immune response, we demonstrate that the central memory T (T CM ) cell pool is marked by a higher number of prior divisions than the effector memory T cell pool, owing to the combination of strong proliferative activity during the acute immune response and selective proliferative activity after pathogen clearance. Furthermore, by combining DivisionRecorder analysis with single-cell transcriptomics and functional experiments, we show that replicative history identifies distinct cell pools within the T CM compartment. Specifically, we demonstrate that lowly divided T CM cells display enriched expression of stem-cell-associated genes, exist in a relatively quiescent state, and are superior in eliciting a proliferative recall response upon activation. These data provide the first evidence that a stem-cell-like memory T cell pool that reconstitutes the CD8 + T cell effector pool upon reinfection is marked by prior quiescence., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Associations between benign gynecologic pathologies and circulating inflammatory markers are unknown. Our goal was to evaluate self-reported history of benign gynecologic pathology and subsequent alterations in systemic inflammation., Methods: Using nested case-control studies from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, study-specific associations between self-reported history of benign ovarian cysts, uterine fibroids, and endometriosis with inflammatory marker concentrations were evaluated using logistic regression and combined using meta-analysis. Inflammatory markers associated with individual benign pathologies were mutually adjusted for one another to evaluate independent associations., Results: Compared to women without a self-reported history of the pathology evaluated, benign ovarian cysts were associated with increased PAI-1 (OR [95% CI] 6.24 [2.53-15.39], P <.001) and TGF-β1 (3.79 [1.62-8.86], P =.002) and decreased BCA-1 (0.38 [0.19-0.73], P =.004). Uterine fibroids were associated with decreased CXCL11 (0.37 [0.22-0.63], P <.001) and VEGFR3 (0.40 [0.24-0.65], P <.001). Endometriosis was associated with increased SIL-4R (4.75 [1.84-12.26], P =.001)., Conclusions: Self-reported history of benign gynecologic pathologies were associated with alterations in inflammatory markers that have been previously linked to cancer risk. Understanding interactions between benign gynecologic pathologies and the systemic immune system may help inform disease risk later in life., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Two studies examined the relationship between right-wing authoritarianism (RWA) and religious fundamentalism (RF), and tested their unique contributions to meaning in life (MIL)., Method: We recruited Amazon Mechanical Turk Participants located in the United States. Studies 1 (N = 827) included measures of RWA, RF, and global MIL. Study 2 (N = 809) additionally included measures of the facets of global MIL (existential significance, purpose, and coherence), and intrinsic religiosity., Results: In both studies, RWA, RF, and MIL were positively correlated. Partial correlations and structural equation modeling showed that, when modeled together, RF significantly contributes to MIL and RWA facets were either unrelated or negatively related. Study 2 extended these results to show that RF primarily contributed positively to global MIL through existential significance, rather than purpose or coherence. When modeled jointly with intrinsic religiosity, religious fundamentalism no longer contributed to MIL., Conclusions: These studies demonstrate that RF positively contributes to the experience of MIL, and that the link between RWA and MIL arises from their mutual overlap with RF. The link between RF and MIL is about religiosity, rather than fundamentalism. Implications are discussed., (© 2021 Wiley Periodicals, Inc.)

Objective: To explore patterns of postconcussion care at a level 1 trauma center., Design: Retrospective cohort study., Setting: U.S. level 1 trauma center and local satellite units., Participants: Patients of any age with a concussion diagnosis that reported to level 1 trauma center and local satellite units between 2016 and 2018 (N=2417)., Intervention: Not applicable., Main Outcome Measures: Age, sex, point of entry, rehabilitation referrals, and pre-existing comorbidity diagnosis., Results: Patient age (mean [SD]) significantly differed among points of entry, from youngest to oldest: 26.0 (14.0) years in sports medicine, 29.3 (23.0) years in the emergency department, 34.6 (23.6) years at primary care providers, and 46.0 (19.7) years at specialty care departments. Sex also significantly differed among points of entry; emergency departments reported more men (55.6%), whereas the other points of entry reported more women (59.3%-65.6%). Patients were more likely to receive a referral from sports medicine (odds ratio [OR] unadjusted =75.05, P <.001), primary care providers (OR unadjusted =7.98, P <.001), and specialty care departments (OR unadjusted =7.62, P <.001) than from the emergency department. Women were more likely to receive a referral (OR unadjusted =1.92, P <.0001), regardless of point of entry. Lastly, patients with a preexisting comorbidity were more likely (OR adjusted =2.12, P <.001) to get a rehabilitation referral than patients without a comorbidity., Conclusions: Point of entry, age, sex, and preexisting comorbidities are associated with postconcussion care rehabilitation referral patterns. Improving concussion education dissemination across all entry points of a level 1 trauma center may standardize the postconcussion rehabilitation referral patterns, potentially improving the time to recovery from a concussion., (© 2022 The Authors.)

The ability to kill tumor cells while maintaining an acceptable safety profile makes Natural Killer (NK) cells promising assets for cancer therapy. Strategies to enhance the preferential accumulation and activation of NK cells in the tumor microenvironment can be expected to increase the efficacy of NK cell-based therapies. In this study, we show binding of a novel bispecific single domain antibody (VHH) to both CD16 (FcRγIII) on NK cells and the epidermal growth factor receptor (EGFR) on tumor cells of epithelial origin. The bispecific VHH triggered CD16- and EGFR-dependent activation of NK cells and subsequent lysis of tumor cells, regardless of the KRAS mutational status of the tumor. Enhancement of NK cell activation by the bispecific VHH was also observed when NK cells of colorectal cancer (CRC) patients were co-cultured with EGFR expressing tumor cells. Finally, higher levels of cytotoxicity were found against patient-derived metastatic CRC cells in the presence of the bispecific VHH and autologous peripheral blood mononuclear cells or allogeneic CD16 expressing NK cells. The anticancer activity of CD16-EGFR bispecific VHHs reported here merits further exploration to assess its potential therapeutic activity either alone or in combination with adoptive NK cell-based therapeutic approaches.