Kennedy Krieger Institute

This study examines how firms respond to shifts in economic policy uncertainty (EPU) by analyzing its impact on firm resilience. Using data from 2,660 Chinese A-share listed firms from 2010 to 2022, we find that higher firm-perceived policy uncertainty (FEPU) significantly weakens firm resilience. Drawing on real options and growth options perspectives, the results show that firms become less adaptable when uncertainty leads managers to behave more cautiously and when operational decisions—such as cash reserves and R&D spending—are distorted. Social media pressure, however, softens this negative effect by encouraging greater transparency and discipline. The findings also reveal substantial differences across ownership types, financial conditions, and industry characteristics. The study provides practical insights for managers and policymakers seeking to strengthen organizational resilience in uncertain environments and highlights the need to design governance and communication strategies that help firms remain adaptive when policy risks rise. • Corporate perceived policy uncertainty (FEPU) weakens firms’ ability to adapt and remain resilient. • Managerial behaviour and operations explain how uncertainty reduces resilience. • Social media pressure helps firms counteract the negative effects of FEPU. • Corporate resilience varies by ownership, financial strength, industry, and leadership traits. • Findings offer guidance for building stronger firms under rising policy risks.

ABSTRACTMost purposeful movements require the coordinated control of both hands, yet motor adaptation studies rely on highly constrained tasks that bear little resemblance to everyday bimanual actions. Here, we investigated how task demands shape control strategies during adaptation in a naturalistic bimanual object manipulation task. We tested 73 participants who lifted a virtual plate while we systematically distorted visual feedback of their right hand’s movement, creating a sensory conflict between arms. Compared to unimanual, bimanual lifting shifted learning away from feedforward adaptation toward use of feedback control—participants moved more slowly with gradual speed scaling, developed compensatory hand adjustments, and showed smaller aftereffects. Relaxing precision demands improved success and reduced feedback reliance, while minimizing interlimb sensory conflict diminished compensatory adjustments and restored plate aftereffects to unimanual levels. Bimanual contexts create distinct learning environments where precision demands and interlimb sensory conflict independently shape control strategy; this may inform bimanual training protocols.

Objective To examine the utility of implementing a neurorehabilitation intervention in pediatric psychology and neuropsychology training programs for building clinical competencies in neurorehabilitation. Method Using a convergent mixed methods approach, we surveyed neuropsychological and pediatric psychology trainees who completed training for the Teen Online Problem-Solving program (TOPS). The survey asked about training and competency on a 5-point Likert scale. Open-ended responses to “How has completing TOPS training changed how you practice as a psychologist?” were used for inductive thematic analyses. We surveyed site leaders and supervising psychologists at three hospitals (two in the United States and one in Canada) that integrated TOPS into their psychology training programs to provide case studies. Results 30 trainees completed the survey. Quantitatively, they indicated the TOPS program was a valuable part of training and improved understanding of neurological sequelae. Trainees endorsed that TOPS increased confidence and comfort working with adolescents and families and enhanced competency in delivering evidence-based interventions for neurodevelopmental disorders. Qualitative analyses yielded five themes: (1) enhanced clinical skills, (2) better tailoring to patients’ needs, (3) greater confidence delivering and adapting interventions, (4) equipping families with a helpful tool, and (5) informed feedback and recommendations for families. Conclusion Our mixed-methods analysis suggests that integrating evidence-based neurorehabilitation programs, such as TOPS, into neuropsychology and pediatric psychology training can build competencies, confidence, and interdisciplinary collaboration in neurorehabilitation.

Pediatric mental health prevalence rates have increased in recent years, while gaps remain in the number of available providers. Ongoing evaluation and understanding of treatment progress and engagement are critical to psychiatric care, and these details are often documented in the electronic health record (EHR). Given the utility of retrospective chart review (RCR) as a tool for psychiatrists, we developed a coding system examining common comorbid conditions (anxiety and attention-deficit/hyperactivity disorder [ADHD]) and adherence and evaluated interrater reliability. We created a coding system with a comprehensive manual and coding instructions that explore both symptom severity domains (anxiety, ADHD, and global) and adherence to medication. Codes were rated using Likert scales, and two independent raters coded all data. RCR was completed for 142 patients with a total of 1139 visits over 2 years. Weighted linear kappa statistics ranged between 0.77 and 0.95, and weighted quadratic kappa statistics ranged between 0.74 and 0.96, suggesting substantial to almost perfect agreement. Interrater agreement was highest for anxiety severity. We created a novel coding system for RCR and found substantial to almost perfect interrater reliability for assessing ADHD severity, anxiety severity, global severity, and medication adherence using psychiatry encounter notes documented in an EHR. Our coding system explores conditions that are often heterogeneous and have waxing and waning presentations, using a continuum that captures the complexity of symptoms. Future directions include utilization of coding systems to explore emotion and behavior change over time to optimize treatment.

CLN3 disease, also called Juvenile Neuronal Ceroid Lipofuscinosis (JNCL), or Batten disease, is an ultra‑rare, neurodegenerative lysosomal storage disorder generally affecting individuals during the first decade of life. There can be a delay in diagnosis or misdiagnosis due to a lack of awareness, and when the most common presenting symptom of visual loss is attributed to more common conditions affecting vision. We used a previously published Expert Mapping Tool (EMT) to identify multidisciplinary professionals with diagnostic or clinical management expertise, as well as patient advocates with experience of CLN3 disease. A systematic literature review of published evidence using the Preferred Reporting Items for Systematic Reviews and Meta‑Analyses (PRISMA) guidance was conducted independently and simultaneously to develop key clinical care statements. Each statement was based on the strength of the evidence. The statements formed the basis of an international modified-Delphi consensus process using a virtual meeting platform (Within3). Experts were asked to agree or disagree with each statement and suggest any changes. Statements that reached a consensus of 75% or over are the guiding statements within this manuscript. The processes and manuscript have been independently assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE II) criteria. Thirty‑nine international experts from eight specialities were identified, including a patient advocate. Fifty‑three recommendation statements were developed covering eleven domains: General statements, Diagnostics, Clinical Recommendations and Management, Assessments, Social Considerations, Ocular Management, Epilepsy/Seizures, Nutrition, Respiratory Health, Sleep and Rest, and End-of-Life Care. Consensus was reached after one round of voting for all except three statements. The overall AGREE II score for developing these recommendations was 6.4, where 1 represents the lowest and 7 is the highest quality. Currently, there are no comprehensive clinical recommendations for CLN3 disease. These recommendations provide a comprehensive, evidence- and consensus‑based tool that can be used by all healthcare professionals involved in the management of CLN3 disease and other similar neurodegenerative conditions. The goal is to address the unmet clinical need for CLN3 disease management and complement other information available.

Extraskeletal Ewing sarcoma (EES) is a variant of Ewing sarcoma that originates from soft tissues rather than bones. Our study aims to characterize the differences between EES and skeletal ES (SES) in the pediatric population. We conducted a retrospective review of children ≤ 18 years with ES recorded in the National Cancer Data Base (NCDB) from 2004 to 2022. Kaplan-Meier curves and Cox proportional hazards regression analysis were used to identify risk factors associated with survival. Among 7446 identified patients, 1016 (20.9%) had EES and 6430 (79.1%) had SES. EES patients were older (median 14 vs. 13 years, p = 0.007), more often female (46.9% vs. 41.2%, p = 0.0009), and had smaller tumors (7.5 vs. 8.0 cm, p = 0.003). Tumor distribution differed significantly, with EES was most frequent in the thorax (49.8%) and head and neck (11.8%), while SES more common in the lower limbs (30.2%) and pelvis (25.3%) (p < 0.0001). EES patients were more likely to receive surgery alone (4.2% vs. 1.8%) or a combination of surgery, chemotherapy, and radiation (25.9% vs. 20.7%) but less likely to receive chemotherapy and radiation without surgery (19.4% vs. 29.3%, p < 0.05). Five-year overall survival was similar between SES (72.2%) and EES (73.7%) (p = 0.70). Multivariable analysis confirmed EES was not an independent predictor of survival (aHR 0.94; 95% CI 0.81-1.10). Factors independently associated with mortality were older age, metastasis at diagnosis, and positive surgical margins. Demographic, treatment characteristics, and prognostic factors differ between pediatric patients with SES and EES. However, survival is similar between the two groups.

Profiling the secretome for biomarkers offers an attractive, minimally invasive strategy to detect and monitor cancer. Several challenges, however, must be overcome, including the broad dynamic range of biomolecules in the secretome and the requirement for selective detection of tumor-associated markers. Here, we employed a metabolic glycoengineering (MGE) strategy, using 1,3,4-O-Bu3ManNAz, an azido-tagged, bio-orthogonal metabolic precursor of sialic acid, to label the glycome of pancreatic near-normal and cancer cells to improve conventional LC-MS/MS proteomics-based biomarker discovery. By using this "MGE-LC-MS/MS" approach that incorporates MGE enrichment into conventional LC-MS/MS proteomics, we identified several unique proteins from the secretomes of cancer cells evaluated in vitro. In addition to proteins known to be secreted, we identified several putatively intracellular, non-N-glycosylated proteins, such as β-glucocerebrosidase and paladin, linked to pancreatic cancer (PC) as well as proteins associated with extracellular vesicles (EVs) in PC, such as dCTP pyrophosphatase 1. The identification of EV-associated proteins was consistent with our discovery that ManNAc analogs used in the MGE-LC-MS/MS workflow enhance EV production, creating a more complete secretome profile of PC cells. Pointing toward clinical relevance, we used MGE-LC-MS/MS to enrich PC-derived glycoproteins from plasma harvested from mice bearing xenografted human pancreatic tumors, unambiguously demonstrating that this approach can interrogate the secretomes of cancer cells for biomarker discovery. Finally, we discovered that MGE dramatically improved the production of EVs, which both aids in biomarker discovery (this study) and holds potential to facilitate biomanufacturing of these nascent drugs.

Suicide is a leading cause of death worldwide, yet the biological mechanisms underlying suicide remain poorly understood. A clearer understanding at the molecular level is essential for developing objective biomarkers and targeted interventions. In this study, we used transcriptomic profiling to investigate gene expression patterns associated with suicidal thoughts and behaviors across peripheral blood (n=264) and postmortem brain tissue from two prefrontal regions (dorsolateral prefrontal cortex, DLPFC; subgenual anterior cingulate cortex, sgACC) of individuals with and without psychiatric illness (n=249). Peripheral analyses revealed broad transcriptional changes associated with suicidal thoughts and behaviors, marked by dysregulated immune-related and inflammatory processes. Longitudinal modeling further revealed gene co-expression modules that predicted future suicide attempts over a 12-month follow-up, highlighting processes related to apoptosis, mitochondrial function, and immune regulation. By contrast, transcriptomic analyses of postmortem tissue derived from the DLPFC and sgACC revealed largely suppressed neuroimmune activity. Gene co-expression analyses in the brain identified suicide-associated modules enriched for synaptic plasticity, oxidative stress, and neuroimmune function, some of which displayed regional specificity. Cross-tissue comparison showed minimal gene-level overlap between brain and blood, although shared pathway-level themes emerged in immune, sensory, and cellular stress processes. Taken together, these findings suggest that suicide is associated with distinct but functionally convergent transcriptional alterations across brain and blood. By integrating tissue-specific and systems-level molecular signatures, this work provides insight into the biological architecture of suicide and lays the groundwork for developing novel biomarkers and therapeutic targets to improve prevention and treatment outcomes.

Monotonous tasks are common in academic and professional settings, yet sustaining motivation and effort in such contexts remains a persistent challenge. This research examined whether inserting a brief episode of interest into an otherwise boring, incentivized task could replenish cognitive and motivational resources and sustain effort. Two competing accounts were tested. The contrast-effect hypothesis predicted that once interest was withdrawn, the remaining rewards would lose their impact, and effort would diminish. In contrast, the transfer-effect hypothesis proposed that prior interest would leave a motivational trace that preserves the effectiveness of the rewards. Study 1 (behavioral study) employed a typing task, while Study 2 (fMRI study) used a social preference guessing task, both with performance-contingent monetary incentives. In both studies, participants in the experimental group completed a boring-interesting-boring sequence, whereas those in the control group experienced a boring-neutral-boring sequence. Across two studies, results consistently supported the transfer-effect hypothesis, demonstrating that prior interest enhanced subsequent engagement, effort, and reward sensitivity, even when monetary incentives were reduced. Neuroimaging results further revealed activity in regions involved in reward processing (e.g., anterior cingulate cortex, anterior insula) and attentional control (e.g., lateral occipital cortex, inferior parietal lobule) even after interest was removed, suggesting a lingering motivational effect of interest. These findings integrate reinforcement learning and interest theories and suggest a practical strategy: sandwiching brief, interest-enhancing episodes between boring rewarded tasks can serve as a motivational reset, enabling effort and persistence in low-stimulation environments.