Multi-omics analysis reveals drivers of loss of ß-cell function after newly diagnosed autoimmune type 1 diabetes: An INNODIA multicenter study.

AIMS: Heterogeneity in the rate of ß-cell loss in newly diagnosed type 1 diabetes patients is poorly understood and creates a barrier to designing and interpreting disease-modifying clinical trials. Integrative analyses of baseline multi-omics data obtained after the diagnosis of type 1 diabetes may provide mechanistic insight into the diverse rates of disease progression after type 1 diabetes diagnosis. METHODS: We collected samples in a pan-European consortium that enabled the concerted analysis of five different omics modalities in data from 97 newly diagnosed patients. In this study, we used Multi-Omics Factor Analysis to identify molecular signatures correlating with post-diagnosis decline in ß-cell mass measured as fasting C-peptide. RESULTS: Two molecular signatures were significantly correlated with fasting C-peptide levels. One signature showed a correlation to neutrophil degranulation, cytokine signalling, lymphoid and non-lymphoid cell interactions and G-protein coupled receptor signalling events that were inversely associated with a rapid decline in ß-cell function. The second signature was related to translation and viral infection was inversely associated with change in ß-cell function. In addition, the immunomics data revealed a Natural Killer cell signature associated with rapid ß-cell decline. CONCLUSIONS: Features that differ between individuals with slow and rapid decline in ß-cell mass could be valuable in staging and prediction of the rate of disease progression and thus enable smarter (shorter and smaller) trial designs for disease modifying therapies as well as offering biomarkers of therapeutic effect.

Serum proteomics of mother-infant dyads carrying HLA-conferred type 1 diabetes risk.

In-utero and dietary factors make important contributions toward health and development in early childhood. In this respect, serum proteomics of maturing infants can provide insights into studies of childhood diseases, which together with perinatal proteomes could reveal further biological perspectives. Accordingly, to determine differences between feeding groups and changes in infancy, serum proteomics analyses of mother-infant dyads with HLA-conferred susceptibility to type 1 diabetes (n = 22), weaned to either an extensively hydrolyzed or regular cow's milk formula, were made. The LC-MS/MS analyses included samples from the beginning of third trimester, the time of delivery, 3 months postpartum, cord blood, and samples from the infants at 3, 6, 9, and 12 months. Correlations between ranked protein intensities were detected within the dyads, together with perinatal and age-related changes. Comparison with intestinal permeability data revealed a number of significant correlations, which could merit further consideration in this context.

Activity Diversity and Well-Being in Daily Life: Evidence for Heterogeneity Between Older Adults.

OBJECTIVES: Although higher activity diversity is associated with higher well-being at the between-person level, it is unknown whether a day with higher activity diversity is related to higher well-being within persons. Within 24 hr per day, there are a limited number of activities on which individuals could spend their time and energy. Personal resources could influence the expenditure of energy and thus the experience with daily activities. This study examined daily associations between activity diversity and well-being and whether age and self-related health moderated the associations. METHODS: For seven times per day over 2 weeks, 129 retired older adults (Mage = 73.9 years, SDage = 5.6) reported their present activity engagement and positive and negative affect. Daily activity diversity was operationalized as the number of different activity types reported per day. Daily positive and negative affect were assessed as the average of a range of high- and low-arousal affective states. Self-rated health was assessed with an item from the 12-Item Short-Form Health Survey at baseline. RESULTS: Multilevel models showed that daily activity diversity was unrelated, on average, to daily positive or negative affect at the between- and within-person levels. Daily activity diversity was associated with lower daily positive affect in participants with lower self-rated health, but the Johnson-Neyman regions of significance were outside of the range of observed data. DISCUSSION: Divergent patterns were observed in the within-person associations between activity diversity and well-being across participants. Results are discussed in the context of time use and well-being in older age.

Digital Care Program for Urinary Incontinence in Females: A Large-Scale, Prospective, Cohort Study.

Female urinary incontinence (UI) is highly prevalent in the US (>60%). Pelvic floor muscle training (PFMT) represents first-line care for UI; however, access and adherence challenges urge new care delivery models. This prospective cohort study investigates the feasibility and safety of a remote digital care program (DCP) combining education and PFMT with real-time biofeedback with an average duration of 10 weeks. The primary outcome was the change in the Urinary Impact Questionnaire-short form (UIQ-7) from baseline to program-end, calculated through latent growth curve analysis (LGCA). Secondary outcomes included the impact of pelvic conditions (PFIQ-7), depression (PHQ-9), anxiety (GAD-7), productivity impairment (WPAI), intention to seek additional healthcare, engagement, and satisfaction. Of the 326 participants who started the program, 264 (81.0%) completed the intervention. Significant improvement on UIQ-7 (8.8, 95%CI 4.7; 12.9, p < 0.001) was observed, corresponding to a response rate of 57.3%, together with improvements in all other outcomes and high satisfaction (8.9/10, SD 1.8). This study shows the feasibility and safety of a completely remote DCP with biofeedback managed asynchronously by a physical therapist to reduce UI-related symptoms in a real-world setting. Together, these findings may advocate for the exploration of this care delivery option to escalate access to proper and timely UI care.

A multi-modality and multi-dyad approach to measuring flexibility in psychotherapy.

INTRODUCTION: Flexibility, the ability of an individual to adapt to environmental changes in ways that facilitate goal attainment, has been proposed as a potential mechanism underlying psychopathology and psychotherapy. In psychotherapy, most findings are based on self-report measures that have important limitations. We propose a multimodal, multi-dyad approach based on a nonlinear dynamical systems framework to capture the complexity of this concept. METHOD: A new research paradigm was designed to explore the validity of the proposed conceptual model. The paradigm includes a psychotherapy-like social interaction, during which body movement and facial expressiveness data were collected. We analyzed the data using Hankel Alternative View of Koopmann analysis to reconstruct attractors of the observed behaviors and compare them. RESULTS: The patterns of behavior in the two cases differ, and differences in the reconstructed attractors correspond with differences in self-report measures and behavior in the interactions. CONCLUSIONS: The case studies show that information provided by a single modality is not enough to provide the full picture, and multiple modalities are needed. These observations can serve as an initial support for our claims that a multi-modal and multi-dyad approach to flexibility can address some of the issues of measurement in the field.

The potential of a multimodal digital care program in addressing healthcare inequities in musculoskeletal pain management.

Digital interventions have emerged as a solution for time and geographical barriers, however, their potential to target other social determinants of health is largely unexplored. In this post-hoc analysis, we report the impact of social deprivation on engagement and clinical outcomes after a completely remote multimodal musculoskeletal (MSK) digital care program managed by a culturally-sensitive clinical team. Patients were stratified in five categories according to their social deprivation index, and cross-referenced with their race/ethnicity, rurality and distance to healthcare facilities. From a total of 12,062 patients from all U.S. states, 8569 completed the program. Higher social deprivation was associated with greater baseline disease burden. We observed that all categories reported pain improvements (ranging from -2.0 95%CI -2.1, -1.9 to -2.1 95%CI -2.3, -1.9, p < 0.001) without intergroup differences in mean changes or responder rates (from 59.9% (420/701) to 66.6% (780/1172), p = 0.067), alongside reduction in analgesic consumption. We observed significant improvements in mental health and productivity across all categories, with productivity and non-work-related functional recovery being greater within the most deprived group. Engagement was high but varied slightly across categories. Together these findings highlight the importance of a patient-centered digital care program as a tool to address health inequities in musculoskeletal pain management. The idea of investigating social deprivation within a digital program provides a foundation for future work in this field to identify areas of improvement.

HIC1 interacts with FOXP3 multi protein complex: Novel pleiotropic mechanisms to regulate human regulatory T cell differentiation and function.

Transcriptional repressor, hypermethylated in cancer 1 (HIC1) participates in a range of important biological processes, such as tumor repression, immune suppression, embryonic development and epigenetic gene regulation. Further to these, we previously demonstrated that HIC1 provides a significant contribution to the function and development of regulatory T (Treg) cells. However, the mechanism by which it regulates these processes was not apparent. To address this question, we used affinity-purification mass spectrometry to characterize the HIC1 interactome in human Treg cells. Altogether 61 high-confidence interactors were identified, including IKZF3, which is a key transcription factor in the development of Treg cells. The biological processes associated with these interacting proteins include protein transport, mRNA processing, non-coding (ncRNA) transcription and RNA metabolism. The results revealed that HIC1 is part of a FOXP3-RUNX1-CBFB protein complex that regulates Treg signature genes thus improving our understanding of HIC1 function during early Treg cell differentiation.

Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes.

Better understanding of the early events in the development of type 1 diabetes is needed to improve prediction and monitoring of the disease progression during the substantially heterogeneous presymptomatic period of the beta cell damaging process. To address this concern, we used mass spectrometry-based proteomics to analyse longitudinal pre-onset plasma sample series from children positive for multiple islet autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n = 10) and compared these with similar measurements from matched children who were either positive for a single autoantibody (n = 10) or autoantibody negative (n = 10). Following statistical analysis of the longitudinal data, targeted serum proteomics was used to verify 11 proteins putatively associated with the disease development in a similar yet independent and larger cohort of children who progressed to the disease within 5 years of age (n = 31) and matched autoantibody negative children (n = 31). These data reiterated extensive age-related trends for protein levels in young children. Further, these analyses demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first islet autoantibody and remained relatively less abundant in children who progressed to type 1 diabetes, in comparison to autoantibody negative children.

The Mediating Role of Affective States in Short-Term Effects of Activity Engagement on Working Memory in Older Age.

INTRODUCTION: It has been shown that activity engagement is associated with cognitive ability in older age, but mechanisms behind the associations have rarely been examined. Following a recent study which showed short-term effects of activity engagement on working memory performance appearing 6 h later, this study examined the mediating role of affective states in this process. METHODS: For 7 times per day over 2 weeks, 150 Swiss older adults (aged 65-91 years) reported their present (sociocognitive/passive leisure) activities and affective states (high-arousal positive, low-arousal positive, high-arousal negative, and low-arousal negative) and completed an ambulatory working memory task on a smartphone. RESULTS: Multilevel vector autoregression models showed that passive leisure activities were associated with worse working memory performance 6 h later. Passive leisure activities were negatively associated with concurrent high-arousal positive affect (and high-arousal negative affect); high-arousal positive affect was negatively associated with working memory performance 6 h later. A Sobel test showed a significant mediation effect of high-arousal positive affect linking the time-lagged relationship between passive leisure activities and working memory. Additionally, sociocognitive activities were associated with better working memory performance 6 h later. Sociocognitive activities were associated with concurrent higher high- and low-arousal positive affect, which, however, were not associated with working memory performance 6 h later. Thus, a mediation related to sociocognitive activities was not found. DISCUSSION: Passive leisure activities could influence working memory performance through high-arousal positive affect within a timeframe of several hours. Results are discussed in relation to an emotional, and possibly a neuroendocrine, pathway explaining the time-lagged effects of affective states on working memory performance.

Targeted serum proteomics of longitudinal samples from newly diagnosed youth with type 1 diabetes distinguishes markers of disease and C-peptide trajectory.

AIMS/HYPOTHESIS: There is a growing need for markers that could help indicate the decline in beta cell function and recognise the need and efficacy of intervention in type 1 diabetes. Measurements of suitably selected serum markers could potentially provide a non-invasive and easily applicable solution to this challenge. Accordingly, we evaluated a broad panel of proteins previously associated with type 1 diabetes in serum from newly diagnosed individuals during the first year from diagnosis. To uncover associations with beta cell function, comparisons were made between these targeted proteomics measurements and changes in fasting C-peptide levels. To further distinguish proteins linked with the disease status, comparisons were made with measurements of the protein targets in age- and sex-matched autoantibody-negative unaffected family members (UFMs). METHODS: Selected reaction monitoring (SRM) mass spectrometry analyses of serum, targeting 85 type 1 diabetes-associated proteins, were made. Sera from individuals diagnosed under 18 years (n=86) were drawn within 6 weeks of diagnosis and at 3, 6 and 12 months afterwards (288 samples in total). The SRM data were compared with fasting C-peptide/glucose data, which was interpreted as a measure of beta cell function. The protein data were further compared with cross-sectional SRM measurements from UFMs (n=194). RESULTS: Eleven proteins had statistically significant associations with fasting C-peptide/glucose. Of these, apolipoprotein L1 and glutathione peroxidase 3 (GPX3) displayed the strongest positive and inverse associations, respectively. Changes in GPX3 levels during the first year after diagnosis indicated future fasting C-peptide/glucose levels. In addition, differences in the levels of 13 proteins were observed between the individuals with type 1 diabetes and the matched UFMs. These included GPX3, transthyretin, prothrombin, apolipoprotein C1 and members of the IGF family. CONCLUSIONS/INTERPRETATION: The association of several targeted proteins with fasting C-peptide/glucose levels in the first year after diagnosis suggests their connection with the underlying changes accompanying alterations in beta cell function in type 1 diabetes. Moreover, the direction of change in GPX3 during the first year was indicative of subsequent fasting C-peptide/glucose levels, and supports further investigation of this and other serum protein measurements in future studies of beta cell function in type 1 diabetes.

Randomized-controlled trial assessing a digital care program versus conventional physiotherapy for chronic low back pain.

Low back pain (LBP) is the world's leading cause of years lived with disability. Digital exercise-based interventions have shown great potential in the management of musculoskeletal conditions, promoting access and easing the economic burden. However, evidence of their effectiveness for chronic LBP (CLBP) management compared to in-person physiotherapy has yet to be unequivocally established. This randomized controlled trial (RCT) aims to compare the clinical outcomes of patients with CLBP following a digital intervention versus evidence-based in-person physiotherapy. Our results demonstrate that patient satisfaction and adherence were high and similar between groups, although a significantly lower dropout rate is observed in the digital group (11/70, 15.7% versus 24/70, 34.3% in the conventional group; P = 0.019). Both groups experience significant improvements in disability (primary outcome), with no differences between groups in change from baseline (median difference: -0.55, 95% CI: -2.42 to 5.81, P = 0.412) or program-end scores (-1.05, 95% CI: -4.14 to 6.37; P = 0.671). Likewise, no significant differences between groups are found for secondary outcomes (namely pain, anxiety, depression, and overall productivity impairment). This RCT demonstrates that a remote digital intervention for CLBP can promote the same levels of recovery as evidence-based in-person physiotherapy, being a potential avenue to ease the burden of CLBP.

Comparing Digital to Conventional Physical Therapy for Chronic Shoulder Pain: Randomized Controlled Trial.

BACKGROUND: Chronic shoulder pain (CSP) is a common condition with various etiologies, including rotator cuff disorders, adhesive capsulitis, shoulder instability, and shoulder arthritis. It is associated with substantial disability and psychological distress, resulting in poor productivity and quality of life. Physical therapy constitutes the mainstay treatment for CSP, but several barriers exist in accessing care. In recent years, telerehabilitation has gained momentum as a potential solution to overcome such barriers. It has shown numerous benefits, including improving access and convenience, promoting patient adherence, and reducing costs. However, to date, no previous randomized controlled trial has compared fully remote digital physical therapy to in-person rehabilitation for nonoperative CSP. OBJECTIVE: The aim of this study is to compare clinical outcomes between digital physical therapy and conventional in-person physical therapy in patients with CSP. METHODS: We conducted a single-center, parallel-group, randomized controlled trial involving 82 patients with CSP referred for outpatient physical therapy. Participants were randomized into digital or conventional physical therapy (8-week interventions). The digital intervention consisted of home exercise, education, and cognitive behavioral therapy (CBT), using a device with movement digitalization for biofeedback and asynchronous physical therapist monitoring through a cloud-based portal. The conventional group received in-person physical therapy, including exercises, manual therapy, education, and CBT. The primary outcome was the change (baseline to 8 weeks) in function and symptoms using the short-form of Disabilities of the Arm, Shoulder, and Hand questionnaire. Secondary outcome measures included self-reported pain, surgery intent, analgesic intake, mental health, engagement, and satisfaction. All questionnaires were delivered electronically. RESULTS: A total of 90 participants were randomized into digital or conventional physical therapy, with 82 receiving the allocated intervention. Both groups experienced significant improvements in function measured by the short-form of the Disabilities of the Arm, Shoulder, and Hand questionnaire, with no differences between groups (-1.8, 95% CI -13.5 to 9.8; P=.75). For secondary outcomes, no differences were observed in surgery intent, analgesic intake, and mental health or worst pain. Higher reductions were observed in average and least pain in the conventional group, which, given the small effect sizes (least pain 0.15 and average pain 0.16), are unlikely to be clinically meaningful. High adherence and satisfaction were observed in both groups, with no adverse events. CONCLUSIONS: This study shows that fully remote digital programs can be viable care delivery models for CSP given their scalability and effectiveness, assessed through comparison with high-dosage in-person rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04636528); https://clinicaltrials.gov/study/NCT04636528.

Managing Musculoskeletal Pain in Older Adults Through a Digital Care Solution: Secondary Analysis of a Prospective Clinical Study.

BACKGROUND: Aging is closely associated with an increased prevalence of musculoskeletal conditions. Digital musculoskeletal care interventions emerged to deliver timely and proper rehabilitation; however, older adults frequently face specific barriers and concerns with digital care programs (DCPs). OBJECTIVE: This study aims to investigate whether known barriers and concerns of older adults impacted their participation in or engagement with a DCP or the observed clinical outcomes in comparison with younger individuals. METHODS: We conducted a secondary analysis of a single-arm investigation assessing the recovery of patients with musculoskeletal conditions following a DCP for up to 12 weeks. Patients were categorized according to age: ≤44 years old (young adults), 45-64 years old (middle-aged adults), and ≥65 years old (older adults). DCP access and engagement were evaluated by assessing starting proportions, completion rates, ability to perform exercises autonomously, assistance requests, communication with their physical therapist, and program satisfaction. Clinical outcomes included change between baseline and program end for pain (including response rate to a minimal clinically important difference of 30%), analgesic usage, mental health, work productivity, and non-work-related activity impairment. RESULTS: Of 16,229 patients, 12,082 started the program: 38.3% (n=4629) were young adults, 55.7% (n=6726) were middle-aged adults, and 6% (n=727) were older adults. Older patients were more likely to start the intervention and to complete the program compared to young adults (odds ratio [OR] 1.72, 95% CI 1.45-2.06; P<.001 and OR 2.40, 95% CI 1.97-2.92; P<.001, respectively) and middle-aged adults (OR 1.22, 95% CI 1.03-1.45; P=.03 and OR 1.38, 95% CI 1.14-1.68; P=.001, respectively). Whereas older patients requested more technical assistance and exhibited a slower learning curve in exercise performance, their engagement was higher, as reflected by higher adherence to both exercise and education pieces. Older patients interacted more with the physical therapist (mean 12.6, SD 18.4 vs mean 10.7, SD 14.7 of young adults) and showed higher satisfaction scores (mean 8.7, SD 1.9). Significant improvements were observed in all clinical outcomes and were similar between groups, including pain response rates (young adults: 949/1516, 62.6%; middle-aged adults: 1848/2834, 65.2%; and older adults: 241/387, 62.3%; P=.17). CONCLUSIONS: Older adults showed high adherence, engagement, and satisfaction with the DCP, which were greater than in their younger counterparts, together with significant clinical improvements in all studied outcomes. This suggests DCPs can successfully address and overcome some of the barriers surrounding the participation and adequacy of digital models in the older adult population.

The short-term effects of activity engagement on working memory performance in older age.

Does a single bout of activity engagement have short-term effects on cognition in daily life? Using a smartphone-based ambulatory assessment design, this study examined the duration of the effects of three types of activities (i.e., sociocognitive, passive leisure, and physical activities) on working memory performance. For seven times per day (i.e., approximately every 2 hr) over 15 days, 150 healthy older adults (aged 65-91 years) in Switzerland reported their present activities and completed working memory assessments. In an examination of within-person concurrent associations, results from a multilevel model showed that passive leisure activities were negatively associated with working memory. Extending this to time-lagged dynamics, results from multilevel vector autoregression models showed that the negative effect of passive leisure activities and a positive effect of sociocognitive activities on working memory performance appeared 6 hr later and faded out completely by 8 hr later. Follow-up analyses showed that the time-lagged effects of activity engagement were evident among relatively younger individuals with lower levels of formal education. In sum, our findings suggest that a single bout of activity engagement has an impact on cognitive performance as quickly as 6 hr. In line with the "use it or lose it" hypothesis, our findings highlight the importance of continuous and active engagement in sociocognitive activities in older age. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Engagement and Utilization of a Complete Remote Digital Care Program for Musculoskeletal Pain Management in Urban and Rural Areas Across the United States: Longitudinal Cohort Study.

BACKGROUND: Musculoskeletal (MSK) conditions are the number one cause of disability worldwide. Digital care programs (DCPs) for MSK pain management have arisen as alternative care delivery models to circumvent challenges in accessibility of conventional therapy. Despite the potential of DCPs to reduce inequities in accessing care, the outcomes of such interventions in rural and urban populations have yet to be studied. OBJECTIVE: The aim of this study was to assess the impact of urban or rural residency on engagement and clinical outcomes after a multimodal DCP for MSK pain. METHODS: This study consists of an ad hoc analysis of a decentralized single-arm investigation into engagement and clinical-related outcomes after a multimodal DCP in patients with MSK conditions. Patients were coded according to their zip codes to a specific rural-urban commuting area code and grouped into rural and urban cohorts. Changes in their engagement and clinical outcomes from baseline to program end were assessed. Latent growth curve analysis was performed to estimate change trajectories adjusting for the following covariates: age, gender, BMI, employment status, and pain acuity. Outcomes included engagement, self-reported pain, and the results of the Generalized Anxiety Disorder 7-item, Patient Health Questionnaire 9-item, and Work Productivity and Activity Impairment scales. A minimum clinically important difference (MCID) of 30% was considered for pain. RESULTS: Patients with urban and rural residency across the United States participated in the program (n=9992). A 73.8% (7378/9992) completion rate was observed. Both groups reported high satisfaction scores and similar engagement with exercise sessions, with rural residents showing higher engagement with educational content (P<.001) and higher program completion rates (P=.02). All groups showed a significant improvement in all clinical outcomes, including pain, mental health, and work productivity, without statistically significant intergroup differences. The percentage of patients meeting the MCID was similar in both groups (urban: 67.1%, rural: 68.3%; P=.30). CONCLUSIONS: This study advocates for the utility of a DCP in improving access to MSK care in urban and rural areas alike, showcasing its potential to promote health equity. High engagement, satisfaction, and completion rates were noted in both groups, as well as significant improvements in clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04092946; https://clinicaltrials.gov/ct2/show/NCT04092946.

Sleep Disturbance in Musculoskeletal Conditions: Impact of a Digital Care Program.

Background: Musculoskeletal (MSK) pain is highly prevalent worldwide, resulting in significant disability, and comorbid sleep disturbances. Digital therapy for MSK pain can provide significant improvements in care access, alongside pain and disability reductions. However, studies on the effect of such programs on sleep are lacking. Purpose: To evaluate the impact on pain-related sleep impairment after a 12-week remote multimodal digital care program (DCP) for MSK conditions. Patients and Methods: This is an ad-hoc analysis of a decentralized single-arm study into engagement and clinical outcomes after a DCP for MSK rehabilitation. Patients were stratified by baseline sleep disturbance, based on sleep questions in the questionnaires: Oswestry Disability Index, Neck Disability Index, and the Quick Disabilities of the Arm, Shoulder and Hand questionnaire. Additional outcomes were pain, Generalized Anxiety Disorder 7-item scale, Patient Health 9-item questionnaire, Work Productivity, and Activity Impairment, and program engagement. Results: At baseline, 5749 patients reported sleep disturbance (78.0% of eligible patients). These reported significantly worse clinical outcomes at baseline than patients without sleep disturbance (all p<0.001). Patients with comorbid sleep disturbance showed improvements in sleep, with a significant proportion reporting full recovery at program completion: 56% of patients with upper limb conditions (including 10% of patients with severe sleep disturbance at baseline), and 24% with spine conditions. These patients also reported significant improvements in all clinical outcomes at program completion. Engagement and satisfaction were high, and also higher than in patients without sleep impairment. Conclusion: This is the first study of its kind investigating the effect of a completely remote DCP for MSK pain on sleep. Patients reporting comorbid sleep disturbance had significant improvement in sleep, alongside pain, mental health and work productivity at program completion. The results suggest that a DCP for MSK pain can improve sleep disturbances in patients with upper limb and spine conditions.

Daily activity diversity and daily working memory in community-dwelling older adults.

OBJECTIVE: Cross-sectional and long-term longitudinal studies have shown that engagement in diverse activities benefits cognitive performance in older age, but it is unknown whether the beneficial effect holds within persons on a daily basis. This study examines the within-person association between activity diversity and working memory on the same day and its time-lagged directionality between days. It also examines the effects of potential moderators on the within-person association, including age, education, processing speed, and crystallized intelligence, to understand who may benefit more from daily activity diversity. METHOD: We examined smartphone-based ambulatory assessment data from 150 community-dwelling older adults (aged 65-91 years) from Switzerland. Participants reported their present activity and completed a working memory task (i.e., numerical updating) seven times per day over 15 days. Activity diversity was calculated on a daily level and scores of working memory were averaged within a day. Age, education, processing speed, and crystallized intelligence were assessed in the laboratory at baseline. RESULTS: Multilevel models showed that, within persons, higher daily activity diversity was positively associated with higher daily working memory. Moreover, the prior day's greater activity diversity led to that day's higher working memory, but not vice versa. There were no moderating effects of age, education, and crystallized intelligence, but partial evidence of a moderating effect of processing speed. CONCLUSIONS: Our results on within-person concurrent and time-lagged associations between daily activity diversity and daily working memory strengthen the existing evidence on the beneficial effect of activity diversity on older adults' cognitive performance. Results are discussed in the context of cognitive reserve theory. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Extracting Nonlinear Dynamics from Psychological and Behavioral Time Series Through HAVOK Analysis.

Analytical methods derived from nonlinear dynamical systems, complexity, and chaos theories offer researchers a framework for in-depth analysis of time series data. However, relatively few studies involving time series data obtained from psychological and behavioral research employ such methods. This paucity of application is due to a lack of general analysis frameworks for modeling time series data with strong nonlinear components. In this article, we describe the potential of Hankel alternative view of Koopman (HAVOK) analysis for solving this issue. HAVOK analysis is a unified framework for nonlinear dynamical systems analysis of time series data. By utilizing HAVOK analysis, researchers may model nonlinear time series data in a linear framework while simultaneously reconstructing attractor manifolds and obtaining a secondary time series representing the amount of nonlinear forcing occurring in a system at any given time. We begin by showing the mathematical underpinnings of HAVOK analysis and then show example applications of HAVOK analysis for modeling time series data derived from real psychological and behavioral studies.

Effects of Mass Shootings on Mental Illness Stigma in the United States.

Although the vast majority of people with mental illness (PWMI) are not violent, Americans tend to think they are more dangerous than the general population. Because negative media portrayals may contribute to stigma, we used time-series analyses to examine changes in the public's perceived dangerousness of PWMI around six mass shootings whose perpetrators were reported to have a mental illness. From 2011 to 2019, 38,094 U.S. participants completed an online study assessing implicit and explicit perceived dangerousness of PWMI. There were large, upward spikes in perceived dangerousness the week of the Sandy Hook mass shooting that were relatively short-lived. However, there was not a consistent pattern of effects for other events analyzed, and any other spikes observed were smaller. Effects tended to be larger for explicit versus implicit perceived dangerousness. Sandy Hook seemed to temporarily worsen perceived dangerousness of PWMI, but this pattern was not observed for other mass shootings.

The children's brain tumor network (CBTN) - Accelerating research in pediatric central nervous system tumors through collaboration and open science.

Pediatric brain tumors are the leading cause of cancer-related death in children in the United States and contribute a disproportionate number of potential years of life lost compared to adult cancers. Moreover, survivors frequently suffer long-term side effects, including secondary cancers. The Children's Brain Tumor Network (CBTN) is a multi-institutional international clinical research consortium created to advance therapeutic development through the collection and rapid distribution of biospecimens and data via open-science research platforms for real-time access and use by the global research community. The CBTN's 32 member institutions utilize a shared regulatory governance architecture at the Children's Hospital of Philadelphia to accelerate and maximize the use of biospecimens and data. As of August 2022, CBTN has enrolled over 4700 subjects, over 1500 parents, and collected over 65,000 biospecimen aliquots for research. Additionally, over 80 preclinical models have been developed from collected tumors. Multi-omic data for over 1000 tumors and germline material are currently available with data generation for > 5000 samples underway. To our knowledge, CBTN provides the largest open-access pediatric brain tumor multi-omic dataset annotated with longitudinal clinical and outcome data, imaging, associated biospecimens, child-parent genomic pedigrees, and in vivo and in vitro preclinical models. Empowered by NIH-supported platforms such as the Kids First Data Resource and the Childhood Cancer Data Initiative, the CBTN continues to expand the resources needed for scientists to accelerate translational impact for improved outcomes and quality of life for children with brain and spinal cord tumors.