Measures Of Function Research Articles

Simple Mobility Tests Predict Use of Assistive Devices in Older Adults.

Assistive devices (ADs) for ambulation are commonly provided to improve safety and independence in older adults. Despite the common use of these devices, there are no standard prescribing guidelines, and non-health care providers, including caregivers and family members, often make decisions about the need for ADs. Identifying factors or a single screening test associated with AD use would benefit clinicians and non-health care caregivers in making decisions to adopt an AD for patients, clients, and family members. The purpose of this cross-sectional study was to identify the test that best predicts ADs for ambulation and non-AD use among community-dwelling individuals. Eighty-five older adults (81.6 ± 8.2 years old) who underwent outpatient physical therapy participated in this study. They participated in a series of tests, including the Timed Up and Go, handgrip and quadriceps strength, the 30-second chair-rise test, the 5-m fast gait speed, the Functional Independence Measure, the locomotive syndrome tests (stand-up test, 2-step test [2ST], and the Locomo-5 Checklist), and numeric pain scales. Mann-Whitney U tests were used to identify differences between those who did and did not use an AD for ambulation. Logistic regression analyses were used to examine which test best predicted AD use. 80% of participants (n = 68) used an AD for ambulation. There were significant differences in all test variables between users and nonusers (P = .033 to P < .001), except for quadriceps strength, age, and pain (all P > .05). Only the 2ST was a significant predictor of AD use, with a cutoff distance of the toe-to-toe stride shorter than 93% of body height (sensitivity: 72%, and specificity: 82%, P = .048). Simple functional measures differed between those who did and did not use ADs for ambulation; however, only the 2ST predicted AD status. Individuals who cannot step 93% of their body height may be appropriate for an AD. If comprehensive clinical evaluations are not available to make decisions about AD use, the 2ST can be used to make clinical recommendations for an AD for ambulation.

Aberrant functional connectivity of the salience network in adult patients with tic disorders: a resting-state fMRI study.

Tic disorders (TD) are characterized by the presence of motor and/or vocal tics. Common neurophysiological frameworks suggest dysregulations of the cortico-striatal-thalamo-cortical (CSTC) brain circuit that controls movement execution. Besides the common tics, there are other "non-tic" symptoms that are primarily related to sensory perception, sensorimotor integration, attention, and social cognition. The existence of these symptoms, the sensory tic triggers and the modifying effect of attention and cognitive control mechanisms on tics may indicate the salience network's involvement in the neurophysiology of TD. Resting-state functional MRI measurements were performed in 26 participants with TD and 25 healthy controls. The group differences in resting-state functional connectivity patterns were measured based on seed-to-voxel connectivity analyses. Compared to healthy controls, patients with TD exhibited altered connectivity between the core regions of the salience network (insula, ACC and TPJ) and sensory, associative, and motor-related cortices. Furthermore, connectivity changes were observed in relation to the severity of tics in the TD group. The salience network, particularly the insula, is likely to be an important site of dysregulation in TD. Our results provide evidence for large-scale neural deviations in TD beyond the CSTC pathologies. These findings may be relevant for developing treatment targets.Significance statement Tic disorders (TD) are associated with a variety of symptoms beyond typical motor and vocal tics that affect sensory perception, attention, and social cognition. The presence of such non-tic symptoms suggests the potential involvement of the salience network in the pathophysiology of TD. While previous studies have predominantly focused on the cortico-striato-thalamo-cortical (CSTC) circuitry, which is known to underlie tic generation and expression, we conducted resting-state fMRI to investigate the functional connectivity of the salience network in TD. Notably, we observed impaired connectivity of the salience network with relations to the tic symptom severity. Our research provided important evidence that the pathophysiology of TD involves the salience network, which is highly relevant for developing treatment strategies.

Effects of robot-assisted gait training using the Welwalk on gait independence for individuals with hemiparetic stroke: an assessor-blinded, multicenter randomized controlled trial

BackgroundGait disorder remains a major challenge for individuals with stroke, affecting their quality of life and increasing the risk of secondary complications. Robot-assisted gait training (RAGT) has emerged as a promising approach for improving gait independence in individuals with stroke. This study aimed to evaluate the effect of RAGT in individuals with subacute hemiparetic stroke using a one-leg assisted gait robot called Welwalk WW-1000.MethodsAn assessor-blinded, multicenter randomized controlled trial was conducted in the convalescent rehabilitation wards of eight hospitals in Japan. Participants with first-ever hemiparetic stroke who could not walk at pre-intervention assessment were randomized to either the Welwalk group, which underwent RAGT with conventional physical therapy, or the control group, which underwent conventional physical therapy alone. Both groups received 80 min of physical therapy per day, 7 days per week, while the Welwalk group received 40 min of RAGT per day, 6 days per week, as part of their physical therapy. The primary outcome was gait independence, as assessed using the Functional Independence Measure Walk Score.ResultsA total of 91 participants were enrolled, 85 of whom completed the intervention. As a result, 91 participants, as a full analysis set, and 85, as a per-protocol set, were analyzed. The primary outcome, the cumulative incidence of gait-independent events, was not significantly different between the groups. Subgroup analysis revealed that the interaction between the intervention group and stroke type did not yield significant differences in either the full analysis or per-protocol set. However, although not statistically significant, a discernible trend toward improvement with Welwalk was observed in cases of cerebral infarction for the full analysis and per-protocol sets (HR 4.167 [95%CI 0.914–18.995], p = 0.065, HR 4.443 [95%CI 0.973–20.279], p = 0.054, respectively).ConclusionsThe combination of RAGT using Welwalk and conventional physical therapy was not significantly more effective than conventional physical therapy alone in promoting gait independence in individuals with subacute hemiparetic stroke, although a trend toward earlier gait independence was observed in individuals with cerebral infarction.Trial registrationThis study was registered with the Japan Registry of Clinical Trials (https://jrct.niph.go.jp; jRCT 042180078) on March 3, 2019.

Could self-reported physical performance help predict individuals at the highest risk of mortality and hospital admission events in clinical practice? Findings from the Hertfordshire Cohort Study.

To consider how self-reported physical function measures relate to adverse clinical outcomes measured over 20 years of follow-up in a community-dwelling cohort (aged 59-73 at baseline) as compared with hand grip strength, a well-validated predictor of adverse events. Recent evidence has emphasized the significant association of physical activity, physical performance, and muscle strength with hospital admissions in older people. However, physical performance tests require staff availability, training, specialized equipment, and space to perform them, often not feasible or realistic in the context of a busy clinical setting. In total, 2997 men and women were analyzed. Baseline predictors were measured grip strength (Jamar dynamometer) and the following self-reported measures: physical activity (Dallosso questionnaire); physical function score (SF-36 Health Survey); and walking speed. Participants were followed up from baseline (1998-2004) until December 2018 using UK Hospital Episode Statistics and mortality data, which report clinical outcomes using ICD-10 coding. Predictors in relation to the risk of mortality and hospital admission events were examined using Cox regression with and without adjustment for sociodemographic and lifestyle characteristics. The mean age at baseline was 65.7 and 66.6 years among men and women, respectively. Over follow-up, 36% of men and 26% of women died, while 93% of men and 92% of women were admitted to hospital at least once. Physical activity, grip strength, SF-36 physical function, and walking speed were all strongly associated with adverse health outcomes in both sex- and fully adjusted analyses; poorer values for each of the predictors were related to greater risk of mortality (all-cause, cardiovascular-related) and any, neurological, cardiovascular, respiratory, any fracture, and falls admissions. SF-36 physical function and grip strength were similarly associated with the adverse health outcomes considered.

Cognitive brain activity before and after surgery in meningioma patients.

Neuropsychological studies have demonstrated that meningioma patients frequently exhibit cognitive deficits before surgery and show only limited improvement after surgery. Combining neuropsychological with functional imaging measurements can shed more light on the impact of surgery on cognitive brain function. We aimed to evaluate whether surgery affects cognitive brain activity in such a manner that it may mask possible changes in cognitive functioning measured by neuropsychological tests. Twenty-three meningioma patients participated in a fMRI measurement using a verbal working memory task as well as three neuropsychological tests focused on working memory, just before and 3 months after surgery. A region of interest based fMRI analysis was used to examine cognitive brain activity at these timepoints within the central executive network and default mode network. Neuropsychological assessment showed impaired cognitive functioning before as well as 3 months after surgery. Neuropsychological test scores, in-scanner task performance as well as brain activity within the central executive and default mode network were not significantly different between both timepoints. Our results indicate that surgery does not significantly affect cognitive brain activity in meningioma patients the first few months after surgery. Therefore, the lack of cognitive improvement after surgery is not likely the result of compensatory processes in the brain. Cognitive deficits that are already present before surgery appear to be persistent after surgery and a considerable recovery period. Our study shows potential leads that comprehensive cognitive evaluation can be of added value so that cognitive functioning may become a more prominent factor in clinical decision making.

Cognition and Functional Capacity: An Initial Comparison of Veteran and Non-Veteran Older Adults.

The U.S. Military Veterans aged 65 and older comprise an estimated 43% of the 22 million living Veterans in the United States. Veterans have high rates of physical, psychiatric, and social challenges, but it is not known whether Veteran status confers additional risk for cognitive or functional impairments in later life. Thus, this investigation specifically compared older Veterans with their non-Veteran peers in cognitive functioning and performance-based functional capacity. Participants (N = 110; 29 Veterans and 81 non-Veterans) were part of a larger longitudinal study on biopsychosocial functioning in independently living older adult residents of a Continuing Care Senior Housing Community. The University of California San Diego Institutional Review Board approved the study and all participants provided written informed consent. Participants provided demographic and mental health information and were administered a comprehensive neuropsychological battery. Functional capacity was assessed using the UCSD Performance-Based Skills Assessment-Brief (UPSA-B), which uses financial and communication role-plays to assess everyday functioning skills. Neuropsychological scores were appropriately normed prior to analysis. Multivariate Analyses of Variances with post hoc t-tests and an Analysis of Covariance were used to examine neuropsychological and functional capacity differences, respectively, between Veterans and non-Veterans. Veterans did not differ from non-Veterans in educational attainment (16.4 years versus 15.5 years, P = 0.110), but they were significantly older (mean age 86.9 years ± 5.7, versus 81.74 years ± 6.53; P < 0.001) and were more likely to be male (X2 [1, N = 110] = 62.39, P < 0.001). Thus, though neuropsychological norms already accounted for demographic differences in our participants, age and sex were controlled in the Analysis of Covariance predicting UPSA-B score from Veteran status. Results suggested that, compared to non-Veterans, Veterans had significantly worse performance in the list learning portion of a test of verbal memory (Hopkins Verbal Learning Test-Revised, Total Recall; t = 2.56, P = 0.012, d = 0.56). Veterans and non-Veterans did not significantly differ in performance on the delayed recall portion of the verbal learning test and did not differ on a cognitive screening test (Montreal Cognitive Assessment) or on measures of premorbid intellectual functioning (Wide Range Achievement Test-4 Reading), language (Boston Naming Test, Verbal Fluency), visual memory (Brief Visuospatial Memory Test-Revised), attention/working memory (WAIS-IV Digit Span), processing speed (WAIS-IV Digit Symbol Coding), executive function (Delis-Kaplan Executive Function System Trails and Color-Word Test), or functional capacity (UPSA-B). Because our examination of multiple outcomes might have inflated Type I error, we performed a post hoc adjustment of P values using Benjamini-Hochberg procedures and the group difference in verbal learning remained significant. Despite largely similar function in most domains, Veterans performed significantly more poorly in verbal list learning than their non-Veteran peers. Additional attention should be given to the understanding, assessment, and possible treatment of learning and memory differences in older Veterans, as this may be an area in which Veteran status confers additional risk or vulnerability to decline. This is the first study to compare objective neuropsychological and functional performance between older (age 65+) US Veterans and non-Veterans.

Utility of intracranial EEG networks depends on re-referencing and connectivity choice

Abstract Studies of intracranial EEG (iEEG) networks have been used to reveal seizure generators in patients with drug-resistant epilepsy. iEEG is implanted to capture the epileptic network, the collection of brain tissue that forms a substrate for seizures to start and spread. Interictal iEEG measures brain activity at baseline and networks computed during this state can reveal aberrant brain tissue without requiring seizure recordings. iEEG network analyses require choosing a reference and applying statistical measures of functional connectivity. Approaches to these technical choices vary widely across studies, and the impact of these technical choices on downstream analyses is poorly understood. Our objective was to examine the effects of different re-referencing and connectivity approaches on connectivity results and on the ability to lateralize the seizure onset zone in patients with drug-resistant epilepsy. We applied 48 pre-processing pipelines to a cohort of 125 patients with drug-resistant epilepsy recorded with interictal iEEG across two epilepsy centers to generate iEEG functional connectivity networks. 24 functional connectivity measures across time and frequency domains were applied in combination with common average re-referencing (CAR) or bipolar re-referencing (BR). We applied an unsupervised clustering algorithm to identify groups of pre-processing pipelines. We subjected each pre-processing approach to three quality tests: 1) the introduction of spurious correlations, 2) robustness to incomplete spatial sampling, and 3) the ability to lateralize the clinician-defined seizure onset zone. Three groups of similar pre-processing pipelines emerged: CAR pipelines, BR pipelines, and relative entropy-based connectivity pipelines. Relative entropy and CAR networks were more robust to incomplete electrode sampling than BR and other connectivity methods (Friedman test, Dunn-Sˇidák test p &amp;lt; 0.0001). BR reduced spurious correlations at non-adjacent channels better than CAR (Δ mean from machine ref = -0.36 vs -0.22), and worse in adjacent channels (Δ mean from machine ref = -0.14 vs -0.40). Relative entropy-based network measures lateralized the seizure onset hemisphere better than other measures in patients with temporal lobe epilepsy (BH-corrected p &amp;lt; 0.05, Cohen’s d: 0.60 - 0.76). Finally, we present an interface where users can rapidly evaluate iEEG pre-processing choices to select the optimal preprocessing methods tailored to specific research questions. The choice of preprocessing methods affects downstream network analyses. Choosing a single method among highly correlated approaches can reduce redundancy in processing. Relative entropy outperforms other connectivity methods in multiple quality tests. We present a method and interface for researchers to optimize their preprocessing methods for deriving iEEG brain networks.

Improving measurement of functional status among older adults in primary care: A pilot study.

Despite its importance for clinical care and outcomes among older adults, functional status-the ability to perform basic activities of daily living (ADLs) and instrumental ADLs (IADLs)-is seldom routinely measured in primary care settings. The objective of this study was to pilot test a person-centered, interprofessional intervention to improve identification and management of functional impairment among older adults in Veterans Affairs (VA) primary care practices. The four-component intervention included (1) an interprofessional educational session; (2) routine, standardized functional status measurement among patients aged ≥75; (3) annual screening by nurses using a standardized instrument and follow-up assessment by primary care providers; and (4) electronic tools and templates to facilitate increased identification and improved management of functional impairment. Surveys, semi-structured interviews, and electronic health record data were used to measure implementation outcomes (appropriateness, acceptability and satisfaction, feasibility, fidelity, adoption/reach, sustainability). We analyzed qualitative interviews using rapid qualitative analysis. During the study period, all 959 eligible patients were screened (100% reach), of whom 7.3% (n = 58) reported difficulty or needing help with ≥1 ADL and 11.8% (n = 113) reported difficulty or needing help with ≥1 IADL. In a chart review among a subset of 50 patients with functional impairment, 78% percent of clinician notes for the visit when screening was completed had content related to function, and 48% of patients had referrals ordered to address impairments (e.g., physical therapy) within 1 week. Clinicians highly rated the quality of the educational session and reported increased ability to measure and communicate about function. Clinicians and patients reported that the intervention was appropriate, acceptable, and feasible to complete, even during the COVID pandemic. These findings suggest that this intervention is a promising approach to improve identification and management of functional impairment for older patients in primary care. Broader implementation and evaluation of this intervention is currently underway.

Resistance exercise training to improve post‐operative rehabilitation in knee arthroplasty patients: A narrative review

AbstractKnee osteoarthritis is associated with deficits in muscle strength, muscle mass, and physical functioning. These muscle‐related deficits are acutely exacerbated following total knee arthroplasty (TKA) and persist long after surgery, despite the application of standardized rehabilitation programs that include physical/functional training. Resistance exercise training (RET) has been shown to be a highly effective strategy to improve muscle‐related outcomes in healthy as well as clinical populations. However, the use of RET in traditional rehabilitation programs after TKA is limited. In this narrative review, we provide an updated view on whether adding RET to the standard rehabilitation (SR) in the recovery period (up to 1 year) after TKA leads to greater improvements in muscle‐related outcomes when compared to SR alone. Overall, research findings clearly indicate that both muscle strength and muscle mass can be improved to a greater extent with RET‐based rehabilitation compared to SR. Additionally, measures of physical functioning that rely on quadriceps strength and balance (e.g., stair climbing, chair standing, etc.) also appear to benefit more from a RET‐based program compared to SR, especially in patients with low levels of physical functioning. Importantly though, for RET to be optimally effective, it should be performed at 70%–80% of the one‐repetition maximum, with 3–4 sets per exercise, with a minimum of 3 times per week for 8 weeks. Based upon this narrative review, we recommend that such high‐intensity progressive RET should be incorporated into standard programs during rehabilitation after TKA.

Implementation of the International Classification of Diseases 11th revision behavioural indicators for disorders of intellectual development with co-occurring autism spectrum disorder.

The classification of mental, behavioural and neurodevelopmental disorders in the World Health Organization's International Classification of Diseases 11th revision (ICD-11) includes a comprehensive set of behavioural indicators (BIs) within the neurodevelopmental disorders grouping. BIs can be used to assess the severity of disorders of intellectual development in situations in which standardised measures of intellectual functioning and adaptive behaviours are not available or feasible. This international study examines the implementation characteristics of the BIs and compares them to standardised measures for assessing the severity of intellectual impairment and adaptive behaviours in disorders of intellectual development and autism spectrum disorder (ASD). The clinical utility of the ICD-11 and the fidelity of its application in international clinical settings were also assessed. A total of 116 children and adolescents (5-18years old) with a suspected or established diagnosis of disorders of intellectual development were included across four sites [Italy (n=18), Sri Lanka (n=19) and two sites in India (n=79)]. A principal component analysis was conducted to evaluate the application of the ICD-11 guidance for combining severity levels. Assessment using the BIs showed a higher proportion of individuals classified with mild severity, whereas the standardised measures indicated a higher proportion of severe ratings. Additionally, individuals with co-occurring ASD tended to have more severe impairments compared with those without ASD, as indicated by both BIs and standardised measures. Overall, the BIs were considered clinically useful, although more time and consideration were required when applying the guidelines for individuals with a co-occurring disorder of intellectual development and ASD. The principal component analysis revealed one principal component representing overall disorders of intellectual development severity levels. The ICD-11 BIs can be implemented as intended in international clinical settings for a broad range of presentations of individuals with neurodevelopmental disorders. Use of the BIs results in similar severity diagnoses to those made using standardised measures. The BIs are expected to improve the reliability of severity assessments in settings where appropriate standardised measures for intellectual and adaptive behaviours are not available or feasible.

JEWELFISH: 24-month results from an open-label study in non-treatment-naïve patients with SMA receiving treatment with risdiplam.

Risdiplam is a once-daily oral, survival of motor neuron 2 (SMN2) splicing modifier approved for the treatment of spinal muscular atrophy (SMA). JEWELFISH (NCT03032172) investigated the safety, tolerability, pharmacokinetics (PK), and PK/pharmacodynamic (PD) relationship of risdiplam in non-treatment-naïve patients with SMA. JEWELFISH enrolled adult and pediatric patients (N = 174) with confirmed diagnosis of 5q-autosomal recessive SMA who had previously received treatment with nusinersen (n = 76), onasemnogene abeparvovec (n = 14), olesoxime (n = 71), or were enrolled in the MOONFISH study (NCT02240355) of the splicing modifier RG7800 (n = 13). JEWELFISH was an open-label study with all participants scheduled to receive risdiplam. The most common adverse event (AE) was pyrexia (42 patients, 24%) and the most common serious AE (SAE) was pneumonia (5 patients, 3%). The rate of AEs and SAEs decreased by > 50% from the first to the second year of treatment, and there were no treatment-related AEs that led to withdrawal from treatment. An increase in SMN protein in blood was observed following risdiplam treatment and sustained over 24months of treatment irrespective of previous treatment. Exploratory efficacy assessments of motor function showed an overall stabilization in mean total scores as assessed by the 32-item Motor Function Measure, Hammersmith Functional Motor Scale-Expanded, and Revised Upper Limb Module. The safety profile of risdiplam in JEWELFISH was consistent with previous clinical trials of risdiplam in treatment-naïve patients. Exploratory efficacy outcomes are reported but it should be noted that the main aim of JEWELFISH was to assess safety and PK/PD, and the study was not designed for efficacy analysis. TRIAL REGISTRATION: The study was registered (NCT03032172) on ClinicalTrials.gov on January 24, 2017; First patient enrolled: March 3, 2017.

Effect of Incorporating 1 Avocado per Day Versus Habitual Diet on Vascular Function in Adults With Abdominal Obesity: An Ancillary Study of HAT, a Randomized Controlled Trial.

Abdominal obesity is associated with endothelial dysfunction and poorer vascular health. Avocado consumption improves postprandial endothelial function; however, the longer-term effects remain unclear. It was hypothesized that the daily addition of 1 avocado to a habitual diet for 6 months would improve flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity in individuals with abdominal obesity (waist circumference ≥35 in for women, ≥40 in for men), compared with a habitual diet low in avocados. HAT (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled, parallel-arm study that investigated the health effects of adding 1 avocado per day to a habitual diet in individuals with abdominal obesity. At the Pennsylvania State University, University Park study center (n=134; age, 50 ± 13 years; women, 78%; body mass index, 32.6 ± 4.8 kg/m2), markers of vascular function were measured, including endothelial function, assessed via brachial artery flow-mediated dilation, and arterial stiffness, assessed via carotid-femoral pulse wave velocity. Between-group differences in 6-month change in flow-mediated dilation and carotid-femoral pulse wave velocity were assessed using independent t tests. Prespecified subgroup analyses were conducted using linear regression. No significant between-group differences in flow-mediated dilation (mean difference=-0.62% [95% CI, -1.70 to 0.46]) or carotid-femoral pulse wave velocity (0.25 m/s [95% CI, -0.13 to 0.63]) were observed. Results of the subgroup analyses were consistent with the primary analyses. Longer-term consumption of 1 avocado per day as part of a habitual diet did not improve measures of vascular function compared with a habitual diet low in avocados in individuals with abdominal obesity. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03528031.

Identifying factors associated with physical therapy use versus non‐use among injured workers with back pain in Washington State

AbstractBackgroundThere is little information about predictors of physical therapy (PT) use among injured workers with back pain. The primary objective of this study is to investigate the associations between PT use and baseline factors not routinely captured in workers’ compensation (WC) data.MethodsWe conducted a secondary analysis using the Washington State Workers’ Compensation Disability Risk Identification Study Cohort, which combines self‐reported surveys with claims data from the Washington State Department of Labor and Industries State Fund. Workers with an accepted or provisional WC claim for back injury between June 2002 and April 2004 were eligible. Baseline factors for PT use were selected from six domains (socio‐demographic, pain and function, psychosocial, clinical, health behaviors, and employment‐related). The outcome was a binary measure for PT use within 1 year of injury. Bivariate and multivariable logistic regression models were conducted to evaluate the associations between PT use and baseline factors.ResultsAmong the 1370 eligible study participants, we identified 673 (49%) who received at least one PT service. Baseline factors from five of the six domains (all but health behaviors) were associated with PT use, including gender, income, pain and function measures, injury severity rating, catastrophizing, recovery expectations, fear avoidance, mental health score, body mass index, first provider seen for injury, previous injury, and several work‐related factors.ConclusionWe identify baseline factors that are associated with PT use, which may be useful in addressing disparities in access to care for injured workers with back pain in a WC system.

Electroencephalographic Correlates of Clinical Severity in the Natural history study of RTT and Related Disorders.

This study was undertaken to characterize quantitative electroencephalographic (EEG) features in participants from the Natural history study of RTT and Related Disorders and to assess the potential for these features to act as objective measures of cortical function for Rett syndrome (RTT). EEG amplitude and power features were derived from the resting EEG of 60 females with RTT (median age = 10.7 years) and 26 neurotypical females (median age = 10.6 years). Analyses focus on group differences and within the RTT group, associations between the EEG parameters and clinical severity. For a subset of participants (n = 20), follow-up data were available for assessing the reproducibility of the results and the stability in the parameters over 1 year. Compared to neurotypical participants, participants with RTT had greater amplitude variability and greater low-frequency activity as reflected by greater delta power, more negative 1/f slope, and lower theta/delta, alpha/delta, beta/delta, alpha/theta, and beta/theta ratios. Greater delta power, more negative 1/f slope, and lower power ratios were associated with greater severity. Analyses of year 1 data replicated the associations between 1/f slope and power ratios and clinical severity and demonstrated good within-subject consistency in these measures. Overall, group comparisons reflected a greater predominance of lower versus higher frequency activity in participants with RTT, which is consistent with prior clinical interpretations of resting EEG in this population. The observed associations between the EEG power measures and clinical assessments and the repeatability of these measures underscore the potential for EEG to provide an objective measure of cortical function and clinical severity for RTT. ANN NEUROL 2024.

Validity of the brief executive-function assessment tool in an outpatient substance use disorder setting

The Brief Executive-function Assessment Tool (BEAT) was developed and validated for use in residential substance use disorder treatment settings, where participants are mostly abstinent. It is therefore unclear whether the BEAT is valid for use in outpatient settings, where participants may be actively using substances. The effects of acute intoxication and withdrawal have the potential to alter the results of the BEAT. The current study sought to establish construct and criterion validity of the BEAT in an outpatient substance use disorder sample and to detect its sensitivity to substance use over the previous 24 hours and also over the past month. A total of 74 clients of a New South Wales-based outpatient substance use disorder service participated in the current study. Construct validity was demonstrated by significant correlations between the BEAT and three performance-based tests of executive functioning. Criterion validity was established in that the BEAT discriminated between those deemed impaired or not on a criterion composite measure of executive functioning. Test operating characteristics (88% sensitivity, 69% specificity, 44% PPV, and 95% NPV) were also established relative to this composite measure as a reference standard. The BEAT was insensitive to use/abstinence over the previous 24 hours and the past month.

Quantitative assay to analyze neutralization and inhibition of authentic Middle East respiratory syndrome coronavirus

To date, there is no licensed vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV). Therefore, MERS-CoV is one of the diseases targeted by the Coalition for Epidemic Preparedness Innovations (CEPI) vaccine development programs and has been classified as a priority disease by the World Health Organization (WHO). An important measure of vaccine immunogenicity and antibody functionality is the detection of virus-neutralizing antibodies. We have developed and optimized a microneutralization assay (MNA) using authentic MERS-CoV and standardized automatic counting of virus foci. Compared to our standard virus neutralization assay, the MNA showed improved sensitivity when analyzing 30 human sera with good correlation of results (Spearman’s correlation coefficient r = 0.8917, p value < 0.0001). It is important to use standardized materials, such as the WHO international standard (IS) for anti-MERS-CoV immunoglobulin G, to compare the results from clinical trials worldwide. Therefore, in addition to the neutralizing titers (NT50 = 1384, NT80 = 384), we determined the IC50 and IC80 of WHO IS in our MNA to be 0.67 IU/ml and 2.6 IU/ml, respectively. Overall, the established MNA is well suited to reliably quantify vaccine-induced neutralizing antibodies with high sensitivity.

Arrow of time and gravitational entropy in collapse

Abstract We investigate the status of the gravitational arrow of time in the case of a spherical collapse of a fluid that conducts heat and radiates energy. In particular, we examine the results obtained by W. B. Bonnor in his 1985 paper where he found that the gravitational arrow of time was opposite to the thermodynamic arrow of time. The measure of gravitational epoch function $P$ used by Bonnor was given by the ratio of the Weyl square to the Ricci square. In this paper, we have assumed the measure of gravitational entropy $P_{1}$ to be given by the ratio of the Weyl scalar to the Kretschmann scalar. Our analysis indicates that Bonnor's result seems to be validated, i.e., the gravitational arrow and the thermodynamic arrow of time point in opposite directions. This strengthens the opinion that the Weyl proposal of gravitational entropy applies only to the universe as a whole (provided that we exclude the white wholes).

Global longitudinal strain as a predictor of mortality in patients with cardiogenic shock

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Aarhus University Dagmar Marshalls Fond. Background The assessment of left ventricular (LV) function through transthoracic echocardiography (TTE) is essential for guiding diagnosis and treatment in cases of cardiogenic shock (CS). Myocardial global longitudinal strain (GLS) provides an objective and reproducible measure of systolic function, independently predicting outcomes in acute heart failure, regardless of left ventricular ejection fraction (LVEF). However, whether assessment of GLS can predict mortality in patients with CS remains unknown. Purpose In this study, we aimed to evaluate the prognostic significance of GLS in patients with CS. Methods Data from cardiac intensive care unit (CICU) patients admitted between 2007 and 2018 with CS who received vasoactive agents and/or mechanical circulatory support were analysed. GLS (as absolute values) and biplane LVEF were measured via TTE performed within 24 hours of CICU admission. Patients with CS were categorised based on the GLS quartile: mild (GLS &amp;gt;9.7%), moderate (7.0% &amp;lt; GLS &amp;lt;9.6%), severe (5.0% &amp;lt; GLS &amp;lt; 6.9%), and very severe (GLS ≤ 4.9%). CICU and in-hospital mortality were compared across GLS categories, and the relationship between GLS and mortality was assessed using multivariable logistic regression. Results The study included 626 patients with a median age of 68.6 years, a median LVEF of 31% (IQR 24 to 40%), and a median GLS of 7.0% (IQR 5.0 to 9.7%). In-hospital mortality was 29.1%. As GLS deteriorated, there was an increasing need for vasopressors (P&amp;lt;0.001). Patients with progressively lower GLS exhibited significantly higher CICU and in-hospital mortality across the GLS quartiles (Figure A; P&amp;lt;0.001). Patients in the severe (adjusted OR 2.67; p&amp;lt;0.001) and very severe category (adjusted OR 3.54; P&amp;lt;0.001) had significantly increased risk of in-hospital death compared with mild category. In multivariable analysis, every 1% decrease in GLS corresponded to a 14% higher risk of in-hospital mortality (P&amp;lt;0.001). Finally, GLS outperformed LVEF for discrimination of in-hospital mortality (P=0.002), and when both measurements were included in the same multivariable model, only GLS remained significant. When patients were divided according to whether they had GLS and/or LVEF below the median value, patients with low GLS had higher mortality irrespective of the LVEF (Figure B). Conclusion In patients with CS, GLS assessment surpasses LVEF in its prognostic value and improves risk stratification. Routine evaluation of GLS should be considered for patients with CS.Figure AFigure B

Cross-sectional associations between patterns and composition of upright and stepping events with physical function: insights from The Maastricht Study

IntroductionAge-related declines in physical functioning have significant implications for health in later life. Physical activity (PA) volume is associated with physical function, but the importance of the pattern in which PA is accumulated is unclear. This study investigates associations between accelerometer-determined daily PA patterns, including composition and temporal distribution (burstiness) of upright and stepping events, with physical function.MethodsData was from participants who wore an activPAL3 accelerometer as part of The Maastricht Study. Exposures included a suite of metrics describing the composition and the temporal distribution (burstiness) of upright and sedentary behaviour. Physical function outcomes included the six-minute walk test (6MWT), timed chair-stand test (TCST), grip strength (GS), and SF-36 physical functioning sub-scale (SF-36pf). Multivariable linear regression models were used to assess associations, adjusting for covariates including overall PA volume (daily step count).ResultsParticipants(n = 6085) had 6 or 7 days of valid data. Upright and stepping event metrics were associated with physical function outcomes, even after adjusting PA volume. Higher sedentary burstiness was associated with better function (6MWT, TCST, and SF-36pf), as was duration and step volume of stepping events (6MWT, TCST, GS, and SF-36pf), step-weighted cadence (6MWT, TCST, and SF-36pf). Number of stepping events was associated with poorer function (6MWT, GS, and SF-36pf), as was upright event burstiness (SF-36pf). Associations varied according to sex.ConclusionOur study reveals that diverse patterns of physical activity accumulation exhibit distinct associations with various measures of physical function, irrespective of the overall volume. Subsequent investigations should employ longitudinal and experimental studies to examine how changing patterns of physical activity may affect physical function, and other health outcomes.

Sexual Function After Gender Affirming Surgery

Abstract Purpose of Review Sexual function and satisfaction in the transgender community is a nascent field with a paucity of data due to the fast paced nature of improving upon surgical technique and variety of patient experiences. The authors aim to review the current literature for areas of success as well as areas of improvement in order to better the sexual health of the transgender community. Recent Findings Gender dysphoria is a feeling of distress experienced by those whose gender assigned at birth is not in line with their gender identity. While social transition to the desired gender can suffice for some, medical and surgical interventions are often sought out to achieve gender euphoria, the decrease or absence of gender dysphoria. Often, issues with sexual function and satisfaction can trigger gender dysphoria, especially prior to social, medical, or surgical transition. Summary Surgical genital gender affirmation has been the most studied in terms of sexual function and improvement of gender dysphoria. Surgical complications, hormonal changes, and other organic causes of sexual dysfunction can still interfere with one’s overall sexual satisfaction. A validated measure of sexual function for trans men and trans women is needed to better assess outcomes.