18 research outputs found

    Proteomic Profiling of Plasma Biomarkers Associated With Return to Sport Following Concussion: Findings From the NCAA and Department of Defense CARE Consortium

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    ObjectiveTo investigate the plasma proteomic profiling in identifying biomarkers related to return to sport (RTS) following a sport-related concussion (SRC).MethodsThis multicenter, prospective, case-control study was part of a larger cohort study conducted by the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium, athletes (n = 140) with blood collected within 48 h of injury and reported day to asymptomatic were included in this study, divided into two groups: (1) recovery <14-days (n = 99) and (2) recovery ≥14-days (n = 41). We applied a highly multiplexed proteomic technique that uses DNA aptamers assay to target 1,305 proteins in plasma samples from concussed athletes with <14-days and ≥14-days.ResultsWe identified 87 plasma proteins significantly dysregulated (32 upregulated and 55 downregulated) in concussed athletes with recovery ≥14-days relative to recovery <14-days groups. The significantly dysregulated proteins were uploaded to Ingenuity Pathway Analysis (IPA) software for analysis. Pathway analysis showed that significantly dysregulated proteins were associated with STAT3 pathway, regulation of the epithelial mesenchymal transition by growth factors pathway, and acute phase response signaling.ConclusionOur data showed the feasibility of large-scale plasma proteomic profiling in concussed athletes with a <14-days and ≥ 14-days recovery. These findings provide a possible understanding of the pathophysiological mechanism in neurobiological recovery. Further study is required to determine whether these proteins can aid clinicians in RTS decisions

    Proteomic Profiling of Plasma Biomarkers Associated With Return to Sport Following Concussion: Findings From the NCAA and Department of Defense CARE Consortium

    Get PDF
    ObjectiveTo investigate the plasma proteomic profiling in identifying biomarkers related to return to sport (RTS) following a sport-related concussion (SRC).MethodsThis multicenter, prospective, case-control study was part of a larger cohort study conducted by the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium, athletes (n = 140) with blood collected within 48 h of injury and reported day to asymptomatic were included in this study, divided into two groups: (1) recovery &lt;14-days (n = 99) and (2) recovery ≥14-days (n = 41). We applied a highly multiplexed proteomic technique that uses DNA aptamers assay to target 1,305 proteins in plasma samples from concussed athletes with &lt;14-days and ≥14-days.ResultsWe identified 87 plasma proteins significantly dysregulated (32 upregulated and 55 downregulated) in concussed athletes with recovery ≥14-days relative to recovery &lt;14-days groups. The significantly dysregulated proteins were uploaded to Ingenuity Pathway Analysis (IPA) software for analysis. Pathway analysis showed that significantly dysregulated proteins were associated with STAT3 pathway, regulation of the epithelial mesenchymal transition by growth factors pathway, and acute phase response signaling.ConclusionOur data showed the feasibility of large-scale plasma proteomic profiling in concussed athletes with a &lt;14-days and ≥ 14-days recovery. These findings provide a possible understanding of the pathophysiological mechanism in neurobiological recovery. Further study is required to determine whether these proteins can aid clinicians in RTS decisions

    Bifactor Model of the Sport Concussion Assessment Tool Symptom Checklist: Replication and Invariance Across Time in the CARE Consortium Sample

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    Background: Identifying separate dimensions of concussion symptoms may inform a precision medicine approach to treatment. It was previously reported that a bifactor model identified distinct acute postconcussion symptom dimensions. Purpose: To replicate previous findings of a bifactor structure of concussion symptoms in the Concussion Assessment Research and Education (CARE) Consortium sample, examine measurement invariance from pre- to postinjury, and evaluate whether factors are associated with other clinical and biomarker measures. Study design: Cohort study (Diagnosis); Level of evidence, 2. Methods: Collegiate athletes were prospectively evaluated using the Sport Concussion Assessment Tool-3 (SCAT-3) during preseason (N = 31,557); 2789 were followed at <6 hours and 24 to 48 hours after concussion. Item-level SCAT-3 ratings were analyzed using exploratory and confirmatory factor analyses. Bifactor and higher-order models were compared for their fit and interpretability. Measurement invariance tested the stability of the identified factor structure across time. The association between factors and criterion measures (clinical and blood-based markers of concussion severity, symptom duration) was evaluated. Results: The optimal structure for each time point was a 7-factor bifactor model: a General factor, on which all items loaded, and 6 specific factors-Vestibulo-ocular, Headache, Sensory, Fatigue, Cognitive, and Emotional. The model manifested strict invariance across the 2 postinjury time points but only configural invariance from baseline to postinjury. From <6 to 24-48 hours, some dimensions increased in severity (Sensory, Fatigue, Emotional), while others decreased (General, Headache, Vestibulo-ocular). The factors correlated with differing clinical and biomarker criterion measures and showed differing patterns of association with symptom duration at different time points. Conclusion: Bifactor modeling supported the predominant unidimensionality of concussion symptoms while revealing multidimensional properties, including a large dominant General factor and 6 independent factors: Headache, Vestibulo-ocular, Sensory, Cognitive, Fatigue, and Emotional. Unlike the widely used SCAT-3 symptom severity score, which declines gradually after injury, the bifactor model revealed separable symptom dimensions that have distinct trajectories in the acute postinjury period and different patterns of association with other markers of injury severity and outcome. Clinical relevance: The SCAT-3 total score remains a valuable, robust index of overall concussion symptom severity, and the specific factors identified may inform management strategies. Because some symptom dimensions continue to worsen in the first 24 to 48 hours after injury (ie, Sensory, Fatigue, Emotional), routine follow-up in this time frame may be valuable to ensure that symptoms are managed effectively

    Fairness in ambulance routing for post disaster management

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    Disaster management generally includes the post-disaster stage, which consists of the actions taken in response to the disaster damages. These actions include the employment of emergency plans and assigned resources to (i) rescue affected people immediately, (ii) deliver personnel, medical care and equipment to the disaster area, and (iii) aid to prevent the infrastructural and environmental losses. In the response phase, humanitarian logistics directly influence the efficiency of the relief operation. Ambulances routing problem is defined as employing the optimisation tools to manage the flow of ambulances for finding the best ambulance tours to transport the injured to hospitals. Researchers pointed out the importance of equity and fairness in humanitarian relief services: managing the operations of ambulances in the immediate aftermath of a disaster must be done impartially and efficiently to rescue affected people with different priority in accordance with the restrictions. Our research aim is to find the best ambulance tours to transport the patients during a disaster in relief operations while considering fairness and equity to deliver services to patients in balance. The problem is formulated as a new variant of the team orienteering problem with hierarchical objectives to address also the efficiency issue. Due to the limitation of solving the proposed model using a general-purpose solver, we propose a new hybrid algorithm based on a machine learning and neighbourhood search. Based on a new set of realistic benchmark instances, our quantitative analysis proves that our algorithm is capable to largely reduce the solution running time especially when the complexity of the problem increases. Further, a comparison between the fair solution and the system optimum solution is also provided

    Neuropsychological Functioning in Bilateral versus Unilateral Temporal Lobe Epilepsy

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    Although relatively specific anatomo-electro-clinical features of temporal lobe epilepsy (TLE) with bilateral ictal involvement (bitemporal epilepsy—BTLE) have been described, differentiating between BTLE and unilateral TLE (UTLE) remains challenging. Surgery is often the treatment of choice for drug-resistant UTLE, whereas its use is more controversial in BTLE. It is currently unclear whether neuropsychological assessment can contribute to the differential diagnosis. We retrospectively reviewed the neuropsychological evaluation of 46 consecutive patients with refractory TLE. Eighteen patients were diagnosed with BTLE on the basis of ictal electro-clinical data, in particular a video EEG recording of at least one seizure simultaneously involving the two temporal lobes without the possibility of lateralizing its onset or at least two different seizures independently arising from the two temporal lobes. Twenty-eight patients were classified as UTLE. Presurgery evaluation data were used in this study. Compared with UTLE, BTLE was associated with a lower intelligence quotient (IQ) and more severe impairment in long-term memory, the latter remaining significant even after controlling for IQ. No significant differences were found between right and left UTLE. In conclusion, BTLE and UTLE are associated with relatively distinct neuropsychological profiles, further supporting their classification as different disorders within the TLE spectrum

    Immediate Removal From Activity After Sport-Related Concussion Is Associated With Shorter Clinical Recovery and Less Severe Symptoms in Collegiate Student-Athletes

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    Timely removal from activity after concussion symptoms remains problematic despite heightened awareness. Previous studies indicated potential adverse effects of continuing to participate in physical activity immediately after sustaining a concussion. Hypothesis/Purpose: The purpose was to determine the effect of timing of removal from play after concussion on clinical outcomes. It was hypothesized that immediate removal from activity after sport-related concussion (SRC) would be associated with less time missed from sport, a shorter symptomatic period, and better outcomes on acute clinical measures. Cohort study; Level of evidence, 3. Data were reported from the National Collegiate Athletic Association and Department of Defense Grand Alliance: Concussion Awareness, Research, and Education (CARE) Consortium. Participants with 506 diagnosed SRCs from 18 sports and 25 institutions and military service academies were analyzed and classified as either immediate removal from activity (I-RFA) or delayed removal from activity (D-RFA). Outcomes of interest included time missed from sport attributed to their SRC, symptom duration, and clinical assessment scores. There were 322 participants (63.6%) characterized as D-RFA. I-RFA status was associated with significantly less time missed from sport ( R change = .022-.024, P < .001 to P = .001) and shorter symptom duration ( R change = .044-.046, P < .001 [all imputations]) while controlling for other SRC recovery modifiers. These athletes missed approximately 3 fewer days from sport participation. I-RFA athletes had significantly less severe acute SRC symptoms and were at lower risk of recovery taking ≥14 days (relative risk = .614, P < .001, small-medium effect size) and ≥21 days (relative risk = .534, P = .010, small effect size). I-RFA is a protective factor associated with less severe acute symptoms and shorter recovery after SRC. Conveying this message to athletes, coaches, and others involved in the care of athletes may promote timely injury reporting

    Maternal distress and child neuroendocrine and immune regulation

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    RATIONALE: Neuroendocrine-immune regulation is essential for maintaining health. Early-life adversity may cause dysregulation in the neuroendocrine-immune network through repeated activation of the stress response, thereby increasing disease risk. OBJECTIVE: This paper examined the extent to which maternal psychological well-being moderates neuroendocrine-immune relations in children. METHODS: We used data from a laboratory-based study of mothers and their five-year old children (n=125 mother-child pairs) conducted from 2011–2013 in Baltimore, Maryland. Child saliva was assayed for markers of immune function (i.e., cytokines: interleukin [IL]-1β, IL-6, IL-8, tumor necrosis factor alpha [TNF-α]) and hypothalamic-pituitary-adrenal activity (i.e., cortisol). A composite score for depressive symptoms, anxiety, and parenting stress characterized maternal psychological distress. Multilevel mixed models examined the relationship between maternal psychological well-being and child neuroendocrine-immune relations. RESULTS: Significant cytokine × maternal distress interactions indicated that as maternal distress increased, expected inverse cytokine-cortisol relations within children became weaker for IL-1β, IL-6, and TNF-α. Sex-stratified models revealed that these interactions were only significant among girls. Among boys, there were inverse cytokine-cortisol relations for all cytokines, and, while in the same direction as observed among girls, the cytokine × maternal distress interactions were non-significant. CONCLUSION: The findings suggest that maternal distress is associated with child neuroendocrine-immune relations in saliva and may alter the sensitivity of inflammatory immune processes to cortisol's inhibitory effects. This desensitization may place the child at risk for inflammatory diseases. The findings support efforts for the early detection and treatment of at-risk mothers to protect maternal and child health and well-being
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