Cortical modulations before lower limb motor blocks are associated with freezing of gait in Parkinson's disease: an EEG source localization study.

BACKGROUND: Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) characterized by paroxysmal episodes in which patients are unable to step forward. A research priority is identifying cortical changes before freezing in PD-FOG. METHODS: We tested 19 patients with PD who had been assessed for FOG (n=14 with FOG and 5 without FOG). While seated, patients stepped bilaterally on pedals to progress forward through a virtual hallway while 64-channel EEG was recorded. We assessed cortical activities before and during lower limb motor blocks (LLMB), defined as a break in rhythmic pedaling, and stops, defined as movement cessation following an auditory stop cue. This task was selected because LLMB correlates with FOG severity in PD and allows recording of high-quality EEG. Patients were tested after overnight withdrawal from dopaminergic medications ("off" state) and in the "on" medications state. EEG source activities were evaluated using individual MRI and standardized low resolution brain electromagnetic tomography (sLORETA). Functional connectivity was evaluated by phase lag index between seeds and pre-defined cortical regions of interest. RESULTS: EEG source activities for LLMB vs. cued stops localized to right posterior parietal area (Brodmann area 39), lateral premotor area (Brodmann area 6), and inferior frontal gyrus (Brodmann area 47). In these areas, PD-FOG (n=14) increased alpha rhythms (8-12 Hz) before LLMB vs. typical stepping, whereas PD without FOG (n=5) decreased alpha power. Alpha rhythms were linearly correlated with LLMB severity, and the relationship became an inverted U-shape when assessing alpha rhythms as a function of percent time in LLMB in the "off" medication state. Right inferior frontal gyrus and supplementary motor area connectivity was observed before LLMB in the beta band (13-30 Hz). This same pattern of connectivity was seen before stops. Dopaminergic medication improved FOG and led to less alpha synchronization and increased functional connections between frontal and parietal areas. CONCLUSIONS: Right inferior parietofrontal structures are implicated in PD-FOG. The predominant changes were in the alpha rhythm, which increased before LLMB and with LLMB severity. Similar connectivity was observed for LLMB and stops between the right inferior frontal gyrus and supplementary motor area, suggesting that FOG may be a form of "unintended stopping." These findings may inform approaches to neurorehabilitation of PD-FOG.

Tob Regulates the Timing of Sleep Onset at Night in Drosophila.

Sleep is regulated by homeostatic sleep drive and the circadian clock. While tremendous progress has been made in elucidating the molecular components of the core circadian oscillator, the output mechanisms by which this robust oscillator generates rhythmic sleep behavior remain poorly understood. At the cellular level, growing evidence suggests that subcircuits in the master circadian pacemaker suprachiasmatic nucleus (SCN) in mammals and in the clock network in Drosophila regulate distinct aspects of sleep. Thus, to identify novel molecules regulating the circadian timing of sleep, we conducted a large-scale screen of mouse SCN-enriched genes in Drosophila Here, we show that Tob (Transducer of ERB-B2) regulates the timing of sleep onset at night in female fruit flies. Knockdown of Tob pan-neuronally, either constitutively or conditionally, advances sleep onset at night. We show that Tob is specifically required in "evening neurons" (the LNds and the fifth s-LNv) of the clock network for proper timing of sleep onset. Tob levels cycle in a clock-dependent manner in these neurons. Silencing of these "evening" clock neurons results in an advanced sleep onset at night, similar to that seen with Tob knockdown. Finally, sharp intracellular recordings demonstrate that the amplitude and kinetics of LNd postsynaptic potentials (PSPs) cycle between day and night, and this cycling is attenuated with Tob knockdown in these cells. Our data suggest that Tob acts as a clock output molecule in a subset of clock neurons to potentiate their activity in the evening and enable the proper timing of sleep onset at night.

Effect of aerobic exercise training on pulse wave velocity in adults with and without long-term conditions: a systematic review and meta-analysis.

RATIONALE: There is conflicting evidence whether aerobic exercise training (AET) reduces pulse wave velocity (PWV) in adults with and without long-term conditions (LTCs). OBJECTIVE: To explore whether PWV improves with AET in adults with and without LTC, to quantify the magnitude of any effect and understand the influence of the exercise prescription. DATA SOURCES: CENTRAL, MEDLINE and EMBASE were among the databases searched. ELIGIBILITY CRITERIA: We included studies with a PWV measurement before and after supervised AET of at least 3 weeks duration. Exclusion criteria included resistance exercise and alternative measures of arterial stiffness. DESIGN: Controlled trials were included in a random effects meta-analysis to explore the effect of AET on PWV. Uncontrolled studies were included in a secondary meta-analysis and meta-regression exploring the effect of patient and programme factors on change in PWV. The relevant risk of bias tool was used for each study design. RESULTS: 79 studies (n=3729) were included: 35 controlled studies (21 randomised control trials (RCT) (n=1240) and 12 non-RCT (n=463)) and 44 uncontrolled (n=2026). In the controlled meta- analysis, PWV was significantly reduced following AET (mean (SD) 11 (7) weeks) in adults with and without LTC (mean difference -0.63; 95% CI -0.82 to -0.44; p<0.0001). PWV was similarly reduced between adults with and without LTC (p<0.001). Age, but not specific programme factors, was inversely associated with a reduction in PWV -0.010 (-0.020 to -0.010) m/s, p<0.001. DISCUSSION: Short-term AET similarly reduces PWV in adults with and without LTC. Whether this effect is sustained and the clinical implications require further investigation.

Demographics, distribution and experiences of UK clinical academic trainees using GMC NTS Survey data.

Involvement in research plays an integral role in the delivery of high-quality patient care, benefitting doctors, patients and employers. It is important that access to clinical academic training opportunities are inclusive and equitable. To better understand the academic trainee population, distribution of academic posts and their reported experience of clinical training, we analysed 53 477 anonymous responses from General Medical Council databases and the 2019 National Training Survey. Academic trainees are more likely to be men, and the gender divide begins prior to graduation. There are very low numbers of international medical graduates and less than full-time academic trainees. A small number of UK universities produce a greater prevalence of doctors successfully appointed to academic posts; subsequent academic training also clusters around these institutions. At more senior levels, academic trainees are significantly more likely to be of white ethnicity, although among UK graduates, no ethnicity differences were seen. Foundation academic trainees report a poorer experience of some aspects of their clinical training placements, with high workloads reported by all academic trainees. Our work highlights important disparities in the demographics of the UK clinical academic trainee population and raises concerns that certain groups of doctors face barriers accessing and progressing in UK academic training pathways.

The Social Shapes Test as a Self-Administered, Online Measure of Social Intelligence: Two Studies with Typically Developing Adults and Adults with Autism Spectrum Disorder.

The Social Shapes Test (SST) is a measure of social intelligence which does not use human faces or rely on extensive verbal ability. The SST has shown promising validity among adults without autism spectrum disorder (ASD), but it is uncertain whether it is suitable for adults with ASD. We find measurement invariance between adults with (n = 229) or without ASD (n = 1,049) on the 23-item SST. We also find that adults without ASD score higher on the SST than adults with ASD (d = 0.21). We also provide two, 14-item versions which demonstrated good parallel test-retest reliability and are positively related to scores on the Frith-Happé task. The SST is suitable for remote, online research studies.

Self-selection as an explanation for general mental ability test score differences between mobile and nonmobile devices in observational studies.

Past studies have reported divergent results regarding the effect of mobile devices on general mental ability (GMA) test scores. We investigate selection bias as an explanation for this inconsistency in GMA score differences between applicants using mobile or nonmobile devices reported in observational and lab studies. We initially found that mobile test-takers scored 0.58 SD lower than nonmobile test-takers in an operational sample of 76,948 applicants across over 400 occupations. However, we found that mobile device use was more prevalent among applicants with lower educational attainment and within jobs of lower complexity. These factors, among others, could potentially confound the observed GMA score differences between devices. The device effect shrank to d = 0.25 after controlling for selection bias in device choice using propensity score weighing. As an alternative, we also used poststratification to control for selection bias and this yielded an even weaker device effect (d = 0.10). Our results indicate that the large device effects obtained in prior operational studies are possibly inflated by selection bias. Therefore, it is important to control for these demographic and occupational differences between self-selected device groups when analyzing operational data for research purposes. Propensity score weighing and poststratification appear useful for reducing the impact of selection bias in real-world, observational data. We also strongly recommend the use of random assignment to prevent selection bias when evaluating device effects for new or adapted GMA or similar ability tests. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Using game-like animations of geometric shapes to simulate social interactions: An evaluation of group score differences.

This study introduces a novel, game-like method for measuring social intelligence: the Social Shapes Test. Unlike other existing video or game-based tests, the Shapes Test uses animations of abstract shapes to represent social interactions. We explore demographic differences in Shapes Test scores compared to a written situational judgment test. Gender and race/ethnicity only had meaningful effects on written SJT scores while no effects were found for Shapes Test scores. This pattern of results remained after controlling for general mental ability and English language exposure. We also found metric invariance between demographic groups for both tests. Our results demonstrate the potential for using animated shape tasks as an alternative to written SJTs when designing future game-based assessments.

Telemedicine Patient Satisfaction Dimensions Moderated by Patient Demographics.

BACKGROUND: A multi-dimensional telemedicine patient satisfaction measure is utilized to provide managerial insights into where service improvements are needed and factors that impact patient service perceptions. This research explores the influence of patient demographics on telemedicine satisfaction. Four dimensions of telemedicine patient satisfaction (health benefits, patient-centered care, monetary costs, and non-monetary costs) were compared across patient gender, income, and education levels. METHODS: A survey of 440 US telemedicine patients on patient satisfaction was measured with Likert scale items to create a multi-dimensional construct using the SERVQUAL model. MANOVA, ANOVA, and linear contrasts were used to examine the impact of patient demographics on telemedicine satisfaction dimensions. RESULTS: The findings revealed that patient demographic characteristics moderated various dimensions of their telemedicine experience satisfaction. Satisfaction with telemedicine health benefits was moderated by patient gender and income levels. Patient-centered care was moderated by patient gender, income, and education levels. Satisfaction with the monetary cost of telemedicine was associated with patient gender and education level. Patient education level influenced their satisfaction with telemedicine non-monetary costs. DISCUSSION: Notable trends include generally higher patient satisfaction for women and those with lower education levels. Patient income showed mixed trends regarding the four dimensions of patient satisfaction. Improvements in patient health literacy along with customized services may improve telemedicine patient care satisfaction and health outcomes. CONCLUSIONS: Measuring telemedicine patient satisfaction with a multi-dimensional assessment tool provides insights into how patient demographics influence perceptions of services received. The findings highlighted perceptions of telemedicine patient satisfaction dimensions that differed across patient demographics and provided insights into their overall impact on telemedicine patient satisfaction.

Longitudinal evaluations of somatosensory-motor inhibition in Dopa-responsive dystonia.

INTRODUCTION: GCH1 mutations have been linked to decreased striatal dopamine and development of dopa-responsive dystonia (DRD) and Parkinsonism. Sensory and sensorimotor integration impairments have been documented in various forms of dystonia. DRD patients with confirmed GCH1 mutations have demonstrated normal short-latency afferent inhibition (SAI), a measure of sensorimotor inhibition, under chronic dopaminergic replacement therapy (DRT), but reduced inhibition after a single l-dopa dose following 24 h withdrawal. Studies have revealed normal SAI in other forms of dystonia but reductions with DRT in Parkinson's disease. Longitudinal changes in sensorimotor inhibition are unknown. METHODS: We analyzed sensorimotor inhibition using two different measures: SAI and somatosensory-motor inhibition using dual-site transcranial magnetic stimulation (ds-TMS). SAI was measured using digit stimulation 25 ms prior to contralateral primary motor cortex (M1) TMS. DS-TMS was measured using TMS over the somatosensory cortex 1 or 2.5 ms prior to ipsilateral M1 stimulation. A total of 20 GCH1 mutation carriers and 20 age-matched controls were included in the study. SAI and ds-TMS were evaluated in GCH1 mutation carriers both OFF and ON DRT compared to controls. Furthermore, longitudinal changes of SAI were examined in a subset of the same individuals that were measured âˆ¼five years earlier. RESULTS: Neither SAI nor ds-TMS were significantly different in GCH1 mutation carriers relative to controls. No effects of DRT on SAI or ds-TMS were seen but SAI decreased over time in mutation carriers OFF DRT. CONCLUSION: Our longitudinal results suggest changes in SAI that could be associated with plasticity changes in sensorimotor networks.

Demographics, distribution and experiences of UK clinical academic trainees using GMC NTS Survey data.

Involvement in research plays an integral role in the delivery of high-quality patient care, benefitting doctors, patients and employers. It is important that access to clinical academic training opportunities are inclusive and equitable. To better understand the academic trainee population, distribution of academic posts and their reported experience of clinical training, we analysed 53 477 anonymous responses from General Medical Council databases and the 2019 National Training Survey. Academic trainees are more likely to be men, and the gender divide begins prior to graduation. There are very low numbers of international medical graduates and less than full-time academic trainees. A small number of UK universities produce a greater prevalence of doctors successfully appointed to academic posts; subsequent academic training also clusters around these institutions. At more senior levels, academic trainees are significantly more likely to be of white ethnicity, although among UK graduates, no ethnicity differences were seen. Foundation academic trainees report a poorer experience of some aspects of their clinical training placements, with high workloads reported by all academic trainees. Our work highlights important disparities in the demographics of the UK clinical academic trainee population and raises concerns that certain groups of doctors face barriers accessing and progressing in UK academic training pathways.

Volumetric measurements are preferred in the evaluation of mutant IDH inhibition in non-enhancing diffuse gliomas: Evidence from a phase I trial of ivosidenib.

BACKGROUND: Since IDH-mutant (mIDH) low-grade gliomas (LGGs) progress slowly and have a relatively long survival, there is a significant need for earlier measurements of clinical benefit. Guidance using the LGG RANO criteria recommends serial bidirectional (2D) measurements on a single slice; however, questions remain as to whether volumetric (3D) measurements are better, since they would allow for more accurate measurements in irregular shaped lesions and allow readers to better assess areas of subtle change. METHODS: Twenty-one (out of 24) non-enhancing, recurrent mIDH1 LGGs were enrolled in a phase I, multicenter, open-label study of oral ivosidenib (NCT02073994), and with imaging pre- and post-treatment as part of this exploratory ad hoc analysis. 2D and 3D measurements on T2-weighted FLAIR images were centrally evaluated at an imaging contract research organization using a paired read and forced adjudication paradigm. The effects of 2D vs 3D measurements on progression-free survival (PFS), growth rate measurement variability, and reader concordance and adjudication rates were quantified. RESULTS: 3D volumetric measurements showed significantly longer estimated PFS (P = .0181), more stable (P = .0063) and considerably slower measures of tumor growth rate (P = .0037), the highest inter-reader agreement (weighted kappa = 0.7057), and significantly lower reader discordance rates (P = .0002) with 2D LGG RANO. CONCLUSION: 3D volumetric measurements are better for determining response assessment in LGGs due to more stable measures of tumor growth rates (ie, less "yo-yo-ing" of measurements over time), highest inter-reader agreement, and lowest reader discordance rates. Continued evaluation in future studies is warranted to determine whether these measurements reflect clinical benefit.

Actual vs Documented Advance Care Planning in a Primary Care Clinic.

Introduction: Advance care planning (ACP) is a complex and multifaceted entity that has significant impact on patient care. ACP takes many forms, may be underbilled, and can have significant ramifications on quality care metrics. We performed a retrospective chart review for patients over 70 years in age in our family medicine resident clinic to evaluate the ways in which ACP is charted and the gap between billed and nonbilled ACP. Methods: The first 50 patients over 70 years in age seen between August 25, 2020 and September 25, 2020 were selected for standardized chart review. Billing for ACP was defined as Current Procedural Terminology codes=-10 codes 99497 or 99498. Primary outcomes were the percentage of patients with ACP and incidence of ACP documents. Secondary outcome was the proportion of documented ACP conversations in office visits which had billing for ACP. Results: Forty-eight patients over 70 years in age were identified with an average age of 80.9 years old. Forty-one of 48 patients (85.4%) had some form of ACP and 12 (25%) had formal ACP documents. Of 25 patients with documented ACP conversations in office visits, eleven patients (44%) had ACP which had been formally billed. Conclusion: The majority of our patients had some form of ACP ranging from inpatient discussions of code status to outpatient visits regarding end-of-life care. However, ACP was underbilled in our practice. Physicians are often evaluated based on quality care metrics such as billed ACP which may not accurately reflect the work physicians are doing.

Developmental Histories Facilitating the Emergence of Creative Scientific Expertise: The Role of Developed Cognitive Talents, Education, and Social and Cultural Contexts.

Understanding how individual and contextual factors collectively contribute to the developmental histories that facilitate the emergence of creative expertise in science is improved by considering the contribution of the broad structure of developed cognitive abilities to creativity, prospective research on the high achieving or gifted students who may choose careers in and end up as creative scientists later in life, as well as retrospective studies of established creative scientists themselves and what their educational histories reveal. We first review and elaborate on these connections as documented in research which explore the development of talent, including cognitive mechanisms that include math and spatial reasoning and science related educational opportunities. We propose a research thought experiment that utilizes the multi-trait, multi-method matrix, and bifactor modeling to help understand the true overlap between measurement structures of cognitive and creative aptitudes. Then we explore the social and cultural contexts that may facilitate and/or hinder creative solutions in science through the lens of how these ecosystems influence talent development for gifted students and also the production of elite scientists. Based on this review, some policies will be suggested that may enhance the development of scientific creativity and broader societal innovation and expand the pipeline to include and fully develop the talents of disadvantaged students and provide nurturing environments to improve the likelihood of the emergence of scientific creative expertise.

Prevalence and early-life determinants of mid-life multimorbidity: evidence from the 1970 British birth cohort.

BACKGROUND: We sought to: [1] estimate the prevalence of multimorbidity at age 46-48 in the 1970 British Cohort Study-a nationally representative sample in mid-life; and [2] examine the association between early-life characteristics and mid-life multimorbidity. METHOD: A prospective longitudinal birth cohort of a community-based sample from the 1970 British Cohort Study (BCS70). Participants included all surviving children born in mainland Britain in a single week in April 1970; the analytical sample included those with valid data at age 46-48 (n = 7951; 2016-2018). The main outcome was multimorbidity, which was operationalised as a binary indicator of two or more long-term health conditions where at least one of these conditions was of physical health. It also included symptom complexes (e.g., chronic pain), sensory impairments, and alcohol problems. RESULTS: Prevalence of mid-life multimorbidity was 33.8% at age 46-48. Those with fathers from unskilled social occupational class (vs professional) at birth had 43% higher risk of mid-life multimorbidity (risk ratio = 1.43, 95% confidence interval 1.15 to 1.77). After accounting for potential child and family confounding, an additional kilogram of birthweight was associated with 10% reduced risk of multimorbidity (risk ratio = 0.90, 95% confidence interval 0.84 to 0.96); a decrease of one body mass index point at age 10 was associated with 3% lower risk (risk ratio = 1.03, 95% confidence interval 1.01 to 1.05); one standard deviation higher cognitive ability score at age 10 corresponded to 4% lower risk (risk ratio = 0.96, 95% confidence interval 0.91 to 1.00); an increase of one internalising problem at age 16 was equated with 4% higher risk (risk ratio = 1.04, 95% confidence interval 1.00 to 1.08) and of one externalising problem at age 16 with 6% higher risk (risk ratio = 1.06, 1.03 to 1.09). CONCLUSION: Prevalence of multimorbidity was high in mid-life (33.8% at age 46-48) in Britain. Potentially modifiable early-life exposures, including early-life social circumstances, cognitive, physical and emotional development, were associated with elevated risk of mid-life multimorbidity.

Contrasting effects of d-amphetamine and atomoxetine on measures of impulsive action and choice.

Amphetamine (AMP) and atomoxetine (ATX) represent two of the most widely studied drug treatments used in the investigation of impulsive behaviour. While both drugs have relatively well defined effects in tests designed to investigate impulsive action (e.g. 5-choice task; 5-CSRTT), the effects of both drugs in tests of impulsive choice (e.g. delay discounting) are less consistent. In the present study both AMP and ATX were tested in a rodent gambling task (rGT) and delay discounting in rats separately trained to either an ascending or descending delay schedule. Effects of both drugs were compared to measures of impulsive action (premature (PREM) responses) and perseverative (PSV) responses measured in the 5-choice and rGT tasks. Consistent with previous studies, AMP (0.1-1 mg/kg) increased both PREM and PSV responses, and ATX (0.5-2 mg/kg) reduced both measures in the 5-choice and rGT tasks. At equivalent doses ATX had no reliable effect on choice behaviour in either the rGT or delay discounting suggesting a null effect of this drug on impulsive choice and risky decision making. The effects of AMP were more complex, with a subtle shift in preference to a low risk (P1) choice in the rGT, and an effect on discounting that was unrelated to reinforcer value, but instead dependent on delay sequence and baseline choice preference. One aspect to these outcomes is to highlight the importance of multiple methodological factors when assessing drug effects on complex behaviours such as impulsive choice, and question what are the most appropriate test conditions under which to examine these drugs on discounting.

Can You Ever Be Too Smart for Your Own Good? Comparing Linear and Nonlinear Effects of Cognitive Ability on Life Outcomes.

Despite a long-standing expert consensus about the importance of cognitive ability for life outcomes, contrary views continue to proliferate in scholarly and popular literature. This divergence of beliefs presents an obstacle for evidence-based policymaking and decision-making in a variety of settings. One commonly held idea is that greater cognitive ability does not matter or is actually harmful beyond a certain point (sometimes stated as > 100 or 120 IQ points). We empirically tested these notions using data from four longitudinal, representative cohort studies comprising 48,558 participants in the United States and United Kingdom from 1957 to the present. We found that ability measured in youth has a positive association with most occupational, educational, health, and social outcomes later in life. Most effects were characterized by a moderate to strong linear trend or a practically null effect (mean R2 range = .002-.256). Nearly all nonlinear effects were practically insignificant in magnitude (mean incremental R2 = .001) or were not replicated across cohorts or survey waves. We found no support for any downside to higher ability and no evidence for a threshold beyond which greater scores cease to be beneficial. Thus, greater cognitive ability is generally advantageous-and virtually never detrimental.