Friction measurements of articular cartilage are important to determine the relative tribologic c... more Friction measurements of articular cartilage are important to determine the relative tribologic contributions made by synovial fluid or cartilage, and to assess the efficacy of therapies for preventing the development of post-traumatic osteoarthritis. Stanton's equation is the most frequently used formula for estimating the whole joint friction coefficient (μ) of an articular pendulum, and assumes pendulum energy loss through a mass-independent mechanism. This study examines if articular pendulum energy loss is indeed mass independent, and compares Stanton's model to an alternative model, which incorporates viscous damping, for calculating μ. Ten loads (25-100% body weight) were applied in a random order to an articular pendulum using the knees of adult male Hartley guinea pigs (n = 4) as the fulcrum. Motion of the decaying pendulum was recorded and μ was estimated using two models: Stanton's equation, and an exponential decay function incorporating a viscous damping coefficient. μ estimates decreased as mass increased for both models. Exponential decay model fit error values were 82% less than the Stanton model. These results indicate that μ decreases with increasing mass, and that an exponential decay model provides a better fit for articular pendulum data at all mass values. In conclusion, inter-study comparisons of articular pendulum μ values should not be made without recognizing the loads used, as μ values are mass dependent.
This study measured therapist behaviors in relation to subsequent habituation within exposure tas... more This study measured therapist behaviors in relation to subsequent habituation within exposure tasks, and also tested their direct and indirect relationships (via habituation) with clinical outcomes of exposure therapy. We observed 459 videotaped exposure tasks with 111 participants in three clinical trials for pediatric obsessive-compulsive disorder (POTS trials). Within exposure tasks, therapist behaviors and patient fear were coded continuously. Outcomes were habituation and post-treatment change in symptom severity, global improvement, and treatment response. More therapist behaviors that encourage approach-and less use of accommodation, unrelated talk, and externalizing language-predicted greater subsequent habituation during individual exposure tasks (exposure-level), and also predicted improved patient clinical outcomes via higher 'total dose' of habituation across treatment (patient-level indirect effect). For six of seven therapist behaviors analyzed, the relationship with subsequent habituation within exposure differed by patient fear (low, moderate, or high) at the time the behavior was used. Two therapist behaviors had direct effects in the opposite direction expected; more unrelated talk and less intensifying were associated with greater patient symptom reduction. Results shed light on the "black box" of insession exposure activities and point to specific therapist behaviors that may be important for clinical outcomes. These behaviors might be best understood in the context of changing patient
The Pediatric Obsessive-Compulsive Disorder Treatment Study II (POTS II) investigated the benefit... more The Pediatric Obsessive-Compulsive Disorder Treatment Study II (POTS II) investigated the benefit of serotonin reuptake inhibitor (SRI) augmentation with cognitive behavioral therapy (CBT). Primary outcomes focused on OCD symptom change and indicated benefit associated with a full course of CBT. Given that the majority of youth with OCD suffer from significant comorbid symptoms and impaired quality of life, the current study examined POTS II data for effects on secondary outcomes. Participants were 124 youth ages 7-17 years with a primary diagnosis of OCD who were partial responders to an adequate SRI trial. Participants were randomized to medication management, medication management plus instructions in cognitive behavioral therapy (CBT), or medication management plus full CBT. Acute effects on non-OCD anxiety, depression, inattention, hyperactivity, and quality of life were examined across treatment conditions. Improvement across treatment was observed for non-OCD anxiety, inatten...
Journal of consulting and clinical psychology, 2018
This study measured a variety of within-exposure fear changes and tested the relationship of each... more This study measured a variety of within-exposure fear changes and tested the relationship of each with treatment outcomes in exposure therapy. We coded 459 videotaped exposure tasks from 111 participants in 3 clinical trials for pediatric obsessive-compulsive disorder (OCD; POTS trials). Within exposures, fear level was observed continuously and alongside exposure process. Fear change metrics of interest were selected for relevance to mechanistic theory. Fear decreases were classified by function; nonhabituation decreases were associated with observed nonlearning processes (e.g., avoidance), whereas habituation decreases appeared to result from an internal and indirect process. Outcomes were posttreatment change in symptom severity, global improvement, and treatment response. Greater cumulative habituation across treatment was associated with larger reductions in symptom severity, greater global improvement, and increased odds of treatment response. Fear activation, fear variability...
Investigators conducted a prospective experimental study to evaluate the effect of team size and ... more Investigators conducted a prospective experimental study to evaluate the effect of team size and recovery exercises on individual providers' compression quality and exertion. Investigators hypothesized that 1) larger teams would perform higher quality compressions with less exertion per provider when compared to smaller teams; and 2) brief stretching and breathing exercises during rest periods would sustain compressor performance and mitigate fatigue. Methods: In Phase I, a volunteer cohort of pre-clinical medical students performed four minutes of continuous compressions on a Resusci-Anne manikin to gauge the spectrum of compressor performance in the subject population. Compression rate, depth, and chest recoil were measured. In Phase II, the highest-performing Phase I subjects were placed into 2-, 3-, and/or 4-compressor teams; 2-compressor teams were assigned either to control group (no recovery exercises) or intervention group (recovery exercises during rest). All Phase II teams participated in 20-minute simulations with compressor rotation every two minutes. Investigators recorded compression quality and real-time heart rate data, and calculated caloric expenditure from contact heart rate monitor measurements using validated physiologic formulas. Results: Phase I subjects delivered compressions that were 24.9% (IQR1-3: [0.5%-74.1%]) correct with a median rate of 112.0 (IQR1-3: [103.5-124.9]) compressions per minute and depth of 47.2 (IQR1-3: [35.7-55.2]) mm. In their first rotations, all Phase II subjects delivered compressions of similar quality and correctness (p=0.09). Bivariate analyses of 2-, 3-, and 4-compressor teams' subject compression characteristics by subsequent rotation did not identify significant differences within or across teams. On multivariate analyses, only subjects in 2-compressor teams exhibited significantly lower compression rates (control subjects; p<0.01), diminished chest release (intervention subjects; p=0.03), and greater exertion over successive rotations (both control [p≤0.03] and intervention [p≤0.02] subjects). Conclusion: During simulated resuscitations, 2-compressor teams exhibited increased levels of exertion relative to 3-and 4-compressor teams for comparable compression delivery. Stretching and breathing exercises intended to assist with compressor recovery exhibited mixed effects on compression performance and subject exertion. [
BACKGROUND The precise mechanisms whereby cardiovascular risk factors increase the risk of Alzhei... more BACKGROUND The precise mechanisms whereby cardiovascular risk factors increase the risk of Alzheimer’s disease (AD) have not been delineated. We reported that microvessels isolated from AD brains overexpress a diverse array of neurotoxic and inflammatory proteins, which is consistent with the process of vascular activation. In pre-clinical studies using AD animal models we showed that a vascular activation inhibitor reduced vascular-derived neuroinflammation and improved cognitive performance. Thrombin is a key mediator of cerebrovascular activation in AD. OBJECTIVE This study aims to investigate the safety and potential efficacy of the direct thrombin inhibitor dabigatran, in patients with mild cognitive impairment (MCI) or mild AD to decrease vascular-derived neuroinflammation and improve cognitive performance. METHODS Participants will be enrolled then evaluated quarterly throughout the 24-month study. This is a 24-month randomized-control, double-blind, placebo-controlled, multi...
Analyzing the reading grade level of online mental health information is an important first step ... more Analyzing the reading grade level of online mental health information is an important first step in ensuring that information is largely accessible by the general public, so as not to perpetuate existing health disparities across socioeconomic groups. The present study systematically examined grade level readability of mental health information related to various psychiatric diagnoses, obtained from six highly utilized mental health websites, using a general estimating equations approach. Results suggest that in general, the readability of mental health information is largely well-above the 6 th to 8 th grade level recommended by several national health organizations
Recent studies in the US and abroad suggest that boys are undergoing puberty at a younger age. It... more Recent studies in the US and abroad suggest that boys are undergoing puberty at a younger age. It is unknown if this secular trend extends to boys with central precocious puberty (CPP), who sit at the extreme end of the pubertal spectrum, and if neuroimaging should remain a standard diagnostic tool. Retrospective chart review of all boys with CPP seen by Endocrinology at a US pediatric hospital from 2001-2010. Fifty boys had pubertal onset at an average age of 7.31 years (95CI 6.83-7.89), though many did not present until nearly one year thereafter, by which time 30% were mid-to-late pubertal. Boys were predominantly non-Hispanic White and 64% were overweight/obese. The majority (64%) of boys had neurogenic CPP (CNS-CPP) with neurofibromatosis type I being the most common diagnosis. Diagnosis of CPP led to discovery of a neurogenic lesion in only 3 of 32 (9%) CNS-CPP cases. The remaining boys, with idiopathic CPP (36%), were indistinguishable from those with CNS-CPP aside from four ...
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, Jan 2, 2018
Up to 30% of patients with Crohn's disease (CD) require surgery within the first 5 years from... more Up to 30% of patients with Crohn's disease (CD) require surgery within the first 5 years from diagnosis. We investigated the recent risk of bowel surgery in an inception cohort of pediatric patients with CD and whether early use of biologics (tumor necrosis factor antagonists) alters later disease course. We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group registry on 1442 children (age, ≤16 y) diagnosed with CD from January 2002 through December 2014. Data were collected at diagnosis, 30 days following diagnosis, and then quarterly and during hospitalizations for up to 12 years. Our primary aim was to determine the 10-year risk for surgery in children with CD. Our secondary aim was to determine whether early use of biologics (<3 mo of diagnosis) affected risk of disease progression. The 10-year risk of first bowel surgery was 26%. The 5-year risk of bowel surgery did not change from 2002 through 2014, and remained between 13% and 14%....
The tumor microenvironment is increasingly important in several tumors. We studied the relationsh... more The tumor microenvironment is increasingly important in several tumors. We studied the relationship of key players of immune microenvironment with clinicopathological parameters in gastric adenocarcinomas. Tissue microarrays were constructed from gastrectomy specimens, 2004-2013. Immunohistochemistry was performed for programmed death ligand 1 (PD-L1), indoleamine 2,3-dioxygenase (IDO), tryptophanyl-tRNA synthetase (WARS), guanylate-binding protein 5 (GBP5), tumor-infiltrating lymphocytes (TIL) expressing CD3/CD8/FoxP3/PD1, and mismatch repair proteins (MMRs) MLH1, PMS2, MSH2 and MSH6. Clinicopathological parameters and clinical follow-up were recorded. The study included 86 patients, median follow-up was 34 months (0-148). Tumor types were 45% tubular, 38% diffuse, 17% mixed. PD-L1 was positive in 70%, epithelial IDO in 58%, stromal IDO in 91%, epithelial WARS in 67%, stromal WARS in 100%, epithelial GBP5 in 53%, and stromal GBP5 in 71%. MMR-deficiency was found in 22%. There was n...
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, Jan 11, 2017
The purpose of this study was to develop a magnetic resonance T2 * relaxometry-based multiple lin... more The purpose of this study was to develop a magnetic resonance T2 * relaxometry-based multiple linear regression model to predict the structural properties of the healing anterior cruciate ligament (ACL) over a 24-week healing period following ACL repair in Yucatan minipigs. Two hypotheses were tested: (1) that a regression model based on ACL sub-volumes containing short and long T2 * relaxation times would outperform a competing model based on sub-volumes of short T2 * relaxation times only; and (2) that an optimized regression model would be capable of predicting ACL structural properties between 6 and 24 weeks post-repair. ACLs were imaged in 24 minipigs (8/group) at either 6, 12, or 24 weeks after ACL repair. The structural properties of the ACLs were determined from tensile failure tests. Four multiple linear regression models of increasing complexity were fitted to the data. Akaike Information Criterion values and Bland-Altman tests were used to compare model performance and to...
Introduction: The present study examined seizure clusters as a primary outcome in patients receiv... more Introduction: The present study examined seizure clusters as a primary outcome in patients receiving treatment for PNES. Cluster reduction is examined longitudinally using frequency threshold and statistical definitions of seizure cluster for patients. Possible risk factors for clustering will be examined along with clustering as a risk factor for poorer secondary outcomes. Methods: Participants were from a pilot randomized treatment trial for PNES where they received cognitive behavioral therapy-informed psychotherapy (CBT-ip), sertraline, combination therapy, or treatment as usual. Seizure data are from patients' seizure dairies. Results: Cluster reduction was observed for those receiving CBT-ip or combination treatment using all definitions of daily clusters and weekly clusters. No risk factors of clustering were observed. Those who were identified as having clusters during the trial had poorer secondary outcomes on several measures at baseline relative to those who were not identified as having clusters. Discussion: This is the first study known to the authors to not only examined seizure clusters as a primary outcome for those with PNES, but also the first study to suggest that CBT-ip and combination therapy may be effective in reducing the frequency of clusters.
Background: Anterior cruciate ligament (ACL) injuries pose a significant risk to the careers of p... more Background: Anterior cruciate ligament (ACL) injuries pose a significant risk to the careers of players in the National Football League (NFL). The relationships between draft round and position on return to play (RTP) among NFL players are not well understood, and the ability to return to preinjury performance levels remains unknown for most positions. Purpose: To test for differences in RTP rates and changes in performance after an ACL injury by position and draft round. We hypothesized that skilled positions would return at a lower rate compared to unskilled positions. We further hypothesized that early draft-round status would relate to a greater rate of RTP and that skilled positions and a lower draft round would correlate with decreased performance for players who return to sport.
Arthroscopy: The Journal of Arthroscopic & Related Surgery, 2017
Purpose: To investigate whether arthroscopy or stress radiography can identify instability result... more Purpose: To investigate whether arthroscopy or stress radiography can identify instability resulting from single-ligament injury of the ankle syndesmosis and to determine whether either modality is capable of differentiating between various levels of ligament injury. Methods: Syndesmotic/deltoid ligament sectioning was performed in 10 cadaver legs. Arthroscopic evaluation and fluoroscopic stress testing were completed after each sectioning. In group 1 (n ¼ 5), sectioning began with anteroinferior tibiofibular ligament (AITFL), then interosseous membrane (IOM), posteroinferior tibiofibular ligament (PITFL), and deltoid. In group 2 (n ¼ 5), this order was reversed. Measurements were made by determining the largest-sized probe that would fit in the anterior and posterior syndesmosis. Radiographic parameters included tibiofibular overlap/clear space and medial clear space. Results: No radiographic measurement proved useful in distinguishing between intact and transected AITFL. Anterior probe (AP) size reached significance when distinguishing between intact and AITFL-transected specimens (P < .0001). AP detected significant differences comparing single with 2-, 3-, and 4-ligament (AITFL, IOM, PITFL, deltoid) disruptions (P ¼ .05, <.0001, and <.0001, respectively). Significant differences were observed between 2-and 3/4-ligament (P ¼ .02) transections. Posterior probe (PP) size detected significant differences between intact and single-, double-, triple-, and complete ligament transections (P values .0006, <.0001, <.0001, <.001, respectively). PP detected significant differences between single-and double-, triple-, and complete ligament transection models (P ¼ .0075, .0010, and .0010, respectively). PP distinguished between 2-and 3/4ligament (P ¼ .03) transections. Conclusions: Stress radiography did not distinguish between intact and single-ligament disruption, and was unreliable in distinguishing between sequential transection models. Arthroscopy significantly predicted isolated disruption of the AITFL or deltoid ligaments. Also, probing was able to differentiate between most patterns of ligament injury, including sequential transections. Clinical Relevance: These data can aid surgeons during arthroscopy of the ankle when attempting to correlate intraoperative syndesmotic evaluation findings with the extent of ligament injury.
Introduction: The immune microenvironment is a prognostic factor for various malignancies. The si... more Introduction: The immune microenvironment is a prognostic factor for various malignancies. The significance of key players of this immune microenvironment including tumor-infiltrating lymphocytes and expression of programmed death-ligand 1 (PD-L1), indoleamine-2,3-dioxygenase (IDO), and tryptophanyl-tRNA synthetase (WARS) in gastrointestinal stromal tumors (GISTs) is largely unknown. Methods: Tissue microarrays were constructed from pathology files, 1996-2016. Immunohistochemistry for PD-L1, IDO, WARS was correlated with tumor size, mitoses, and outcomes. Tumor infiltrating lymphocytes (TILs) expressing CD3, CD4, CD8, FoxP3, and GBP5 were counted. Results: 129 GISTs were analyzed. Mean patient age was 62.5 years; 52.0% were male. Tumor location included 89 stomach (69.0%), 33 small bowel (25.6%), 7 other (5.4%). Mean tumor size was 5.6 cm; mean mitoses were 7.2/50HPF. Nineteen patients (15.0%) developed disease progression, to abdominal wall (n=8), liver (n=6), and elsewhere (n=5). Median progression-free survival was 56.6 months; 5 patients died of disease. PD-L1 was positive in 87/126 tumor samples (69.0%), 114/127 tumors were IDO-positive (89.8%), and 60/127 were positive for WARS (47.2%). PD-L1 was associated with increased size (p=0.01), necrosis (p=0.018), and mitoses (p=0.006). Disease progression was not associated with PD-L1 (p=0.44), IDO (p=0.14), or WARS (p=0.36) expression.
To explore early autonomic cardiac changes in pre-clinical Alzheimer's disease (AD), we have ... more To explore early autonomic cardiac changes in pre-clinical Alzheimer's disease (AD), we have evaluated electrocardiologic measures of vagal tone for 63 adults (ages 55-75) at rest, during cognitive testing, and then again at rest. All subjects had multiple risk factors for AD, and all completed amyloid PET scans (18F-Florbetapir) to determine amyloid positivity (Aβ+). No change in electrocardiographic measures were observed for Aβ+ participants under each testing condition, whereas Aβ-subjects showed an expected increase in vagal tone during the cognitive stress condition. These findings suggest an early relationship between cortical Aβ accumulation, a precursor to AD development, and autonomic cardiac function.
The Journal of bone and joint surgery. American volume, 2017
Sarcopenia is a condition of clinically relevant loss of muscle mass and function. Acetabular fra... more Sarcopenia is a condition of clinically relevant loss of muscle mass and function. Acetabular fractures in elderly patients are common and difficult to treat. This study aimed to determine if sarcopenia is common in elderly patients with acetabular fractures and correlates with lower-energy mechanisms of injury, higher rates of complications, and higher mortality than patients with normal muscle mass. The Rhode Island Hospital Trauma Database was queried for patients who were ≥60 years of age from 2005 to 2014 using the International Classification of Diseases, Ninth Revision, code for closed acetabular fracture, 808.0. Charts were retrospectively reviewed for demographic data, operative intervention, mechanism of injury, mortality, comorbidities, and other factors. Computed tomography (CT) was used to determine the muscle cross-sectional area and to calculate the skeletal muscle index. The database revealed 192 patients coded for acetabular fracture; of these, 181 were correctly di...
Friction measurements of articular cartilage are important to determine the relative tribologic c... more Friction measurements of articular cartilage are important to determine the relative tribologic contributions made by synovial fluid or cartilage, and to assess the efficacy of therapies for preventing the development of post-traumatic osteoarthritis. Stanton's equation is the most frequently used formula for estimating the whole joint friction coefficient (μ) of an articular pendulum, and assumes pendulum energy loss through a mass-independent mechanism. This study examines if articular pendulum energy loss is indeed mass independent, and compares Stanton's model to an alternative model, which incorporates viscous damping, for calculating μ. Ten loads (25-100% body weight) were applied in a random order to an articular pendulum using the knees of adult male Hartley guinea pigs (n = 4) as the fulcrum. Motion of the decaying pendulum was recorded and μ was estimated using two models: Stanton's equation, and an exponential decay function incorporating a viscous damping coefficient. μ estimates decreased as mass increased for both models. Exponential decay model fit error values were 82% less than the Stanton model. These results indicate that μ decreases with increasing mass, and that an exponential decay model provides a better fit for articular pendulum data at all mass values. In conclusion, inter-study comparisons of articular pendulum μ values should not be made without recognizing the loads used, as μ values are mass dependent.
This study measured therapist behaviors in relation to subsequent habituation within exposure tas... more This study measured therapist behaviors in relation to subsequent habituation within exposure tasks, and also tested their direct and indirect relationships (via habituation) with clinical outcomes of exposure therapy. We observed 459 videotaped exposure tasks with 111 participants in three clinical trials for pediatric obsessive-compulsive disorder (POTS trials). Within exposure tasks, therapist behaviors and patient fear were coded continuously. Outcomes were habituation and post-treatment change in symptom severity, global improvement, and treatment response. More therapist behaviors that encourage approach-and less use of accommodation, unrelated talk, and externalizing language-predicted greater subsequent habituation during individual exposure tasks (exposure-level), and also predicted improved patient clinical outcomes via higher 'total dose' of habituation across treatment (patient-level indirect effect). For six of seven therapist behaviors analyzed, the relationship with subsequent habituation within exposure differed by patient fear (low, moderate, or high) at the time the behavior was used. Two therapist behaviors had direct effects in the opposite direction expected; more unrelated talk and less intensifying were associated with greater patient symptom reduction. Results shed light on the "black box" of insession exposure activities and point to specific therapist behaviors that may be important for clinical outcomes. These behaviors might be best understood in the context of changing patient
The Pediatric Obsessive-Compulsive Disorder Treatment Study II (POTS II) investigated the benefit... more The Pediatric Obsessive-Compulsive Disorder Treatment Study II (POTS II) investigated the benefit of serotonin reuptake inhibitor (SRI) augmentation with cognitive behavioral therapy (CBT). Primary outcomes focused on OCD symptom change and indicated benefit associated with a full course of CBT. Given that the majority of youth with OCD suffer from significant comorbid symptoms and impaired quality of life, the current study examined POTS II data for effects on secondary outcomes. Participants were 124 youth ages 7-17 years with a primary diagnosis of OCD who were partial responders to an adequate SRI trial. Participants were randomized to medication management, medication management plus instructions in cognitive behavioral therapy (CBT), or medication management plus full CBT. Acute effects on non-OCD anxiety, depression, inattention, hyperactivity, and quality of life were examined across treatment conditions. Improvement across treatment was observed for non-OCD anxiety, inatten...
Journal of consulting and clinical psychology, 2018
This study measured a variety of within-exposure fear changes and tested the relationship of each... more This study measured a variety of within-exposure fear changes and tested the relationship of each with treatment outcomes in exposure therapy. We coded 459 videotaped exposure tasks from 111 participants in 3 clinical trials for pediatric obsessive-compulsive disorder (OCD; POTS trials). Within exposures, fear level was observed continuously and alongside exposure process. Fear change metrics of interest were selected for relevance to mechanistic theory. Fear decreases were classified by function; nonhabituation decreases were associated with observed nonlearning processes (e.g., avoidance), whereas habituation decreases appeared to result from an internal and indirect process. Outcomes were posttreatment change in symptom severity, global improvement, and treatment response. Greater cumulative habituation across treatment was associated with larger reductions in symptom severity, greater global improvement, and increased odds of treatment response. Fear activation, fear variability...
Investigators conducted a prospective experimental study to evaluate the effect of team size and ... more Investigators conducted a prospective experimental study to evaluate the effect of team size and recovery exercises on individual providers' compression quality and exertion. Investigators hypothesized that 1) larger teams would perform higher quality compressions with less exertion per provider when compared to smaller teams; and 2) brief stretching and breathing exercises during rest periods would sustain compressor performance and mitigate fatigue. Methods: In Phase I, a volunteer cohort of pre-clinical medical students performed four minutes of continuous compressions on a Resusci-Anne manikin to gauge the spectrum of compressor performance in the subject population. Compression rate, depth, and chest recoil were measured. In Phase II, the highest-performing Phase I subjects were placed into 2-, 3-, and/or 4-compressor teams; 2-compressor teams were assigned either to control group (no recovery exercises) or intervention group (recovery exercises during rest). All Phase II teams participated in 20-minute simulations with compressor rotation every two minutes. Investigators recorded compression quality and real-time heart rate data, and calculated caloric expenditure from contact heart rate monitor measurements using validated physiologic formulas. Results: Phase I subjects delivered compressions that were 24.9% (IQR1-3: [0.5%-74.1%]) correct with a median rate of 112.0 (IQR1-3: [103.5-124.9]) compressions per minute and depth of 47.2 (IQR1-3: [35.7-55.2]) mm. In their first rotations, all Phase II subjects delivered compressions of similar quality and correctness (p=0.09). Bivariate analyses of 2-, 3-, and 4-compressor teams' subject compression characteristics by subsequent rotation did not identify significant differences within or across teams. On multivariate analyses, only subjects in 2-compressor teams exhibited significantly lower compression rates (control subjects; p<0.01), diminished chest release (intervention subjects; p=0.03), and greater exertion over successive rotations (both control [p≤0.03] and intervention [p≤0.02] subjects). Conclusion: During simulated resuscitations, 2-compressor teams exhibited increased levels of exertion relative to 3-and 4-compressor teams for comparable compression delivery. Stretching and breathing exercises intended to assist with compressor recovery exhibited mixed effects on compression performance and subject exertion. [
BACKGROUND The precise mechanisms whereby cardiovascular risk factors increase the risk of Alzhei... more BACKGROUND The precise mechanisms whereby cardiovascular risk factors increase the risk of Alzheimer’s disease (AD) have not been delineated. We reported that microvessels isolated from AD brains overexpress a diverse array of neurotoxic and inflammatory proteins, which is consistent with the process of vascular activation. In pre-clinical studies using AD animal models we showed that a vascular activation inhibitor reduced vascular-derived neuroinflammation and improved cognitive performance. Thrombin is a key mediator of cerebrovascular activation in AD. OBJECTIVE This study aims to investigate the safety and potential efficacy of the direct thrombin inhibitor dabigatran, in patients with mild cognitive impairment (MCI) or mild AD to decrease vascular-derived neuroinflammation and improve cognitive performance. METHODS Participants will be enrolled then evaluated quarterly throughout the 24-month study. This is a 24-month randomized-control, double-blind, placebo-controlled, multi...
Analyzing the reading grade level of online mental health information is an important first step ... more Analyzing the reading grade level of online mental health information is an important first step in ensuring that information is largely accessible by the general public, so as not to perpetuate existing health disparities across socioeconomic groups. The present study systematically examined grade level readability of mental health information related to various psychiatric diagnoses, obtained from six highly utilized mental health websites, using a general estimating equations approach. Results suggest that in general, the readability of mental health information is largely well-above the 6 th to 8 th grade level recommended by several national health organizations
Recent studies in the US and abroad suggest that boys are undergoing puberty at a younger age. It... more Recent studies in the US and abroad suggest that boys are undergoing puberty at a younger age. It is unknown if this secular trend extends to boys with central precocious puberty (CPP), who sit at the extreme end of the pubertal spectrum, and if neuroimaging should remain a standard diagnostic tool. Retrospective chart review of all boys with CPP seen by Endocrinology at a US pediatric hospital from 2001-2010. Fifty boys had pubertal onset at an average age of 7.31 years (95CI 6.83-7.89), though many did not present until nearly one year thereafter, by which time 30% were mid-to-late pubertal. Boys were predominantly non-Hispanic White and 64% were overweight/obese. The majority (64%) of boys had neurogenic CPP (CNS-CPP) with neurofibromatosis type I being the most common diagnosis. Diagnosis of CPP led to discovery of a neurogenic lesion in only 3 of 32 (9%) CNS-CPP cases. The remaining boys, with idiopathic CPP (36%), were indistinguishable from those with CNS-CPP aside from four ...
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, Jan 2, 2018
Up to 30% of patients with Crohn's disease (CD) require surgery within the first 5 years from... more Up to 30% of patients with Crohn's disease (CD) require surgery within the first 5 years from diagnosis. We investigated the recent risk of bowel surgery in an inception cohort of pediatric patients with CD and whether early use of biologics (tumor necrosis factor antagonists) alters later disease course. We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group registry on 1442 children (age, ≤16 y) diagnosed with CD from January 2002 through December 2014. Data were collected at diagnosis, 30 days following diagnosis, and then quarterly and during hospitalizations for up to 12 years. Our primary aim was to determine the 10-year risk for surgery in children with CD. Our secondary aim was to determine whether early use of biologics (<3 mo of diagnosis) affected risk of disease progression. The 10-year risk of first bowel surgery was 26%. The 5-year risk of bowel surgery did not change from 2002 through 2014, and remained between 13% and 14%....
The tumor microenvironment is increasingly important in several tumors. We studied the relationsh... more The tumor microenvironment is increasingly important in several tumors. We studied the relationship of key players of immune microenvironment with clinicopathological parameters in gastric adenocarcinomas. Tissue microarrays were constructed from gastrectomy specimens, 2004-2013. Immunohistochemistry was performed for programmed death ligand 1 (PD-L1), indoleamine 2,3-dioxygenase (IDO), tryptophanyl-tRNA synthetase (WARS), guanylate-binding protein 5 (GBP5), tumor-infiltrating lymphocytes (TIL) expressing CD3/CD8/FoxP3/PD1, and mismatch repair proteins (MMRs) MLH1, PMS2, MSH2 and MSH6. Clinicopathological parameters and clinical follow-up were recorded. The study included 86 patients, median follow-up was 34 months (0-148). Tumor types were 45% tubular, 38% diffuse, 17% mixed. PD-L1 was positive in 70%, epithelial IDO in 58%, stromal IDO in 91%, epithelial WARS in 67%, stromal WARS in 100%, epithelial GBP5 in 53%, and stromal GBP5 in 71%. MMR-deficiency was found in 22%. There was n...
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, Jan 11, 2017
The purpose of this study was to develop a magnetic resonance T2 * relaxometry-based multiple lin... more The purpose of this study was to develop a magnetic resonance T2 * relaxometry-based multiple linear regression model to predict the structural properties of the healing anterior cruciate ligament (ACL) over a 24-week healing period following ACL repair in Yucatan minipigs. Two hypotheses were tested: (1) that a regression model based on ACL sub-volumes containing short and long T2 * relaxation times would outperform a competing model based on sub-volumes of short T2 * relaxation times only; and (2) that an optimized regression model would be capable of predicting ACL structural properties between 6 and 24 weeks post-repair. ACLs were imaged in 24 minipigs (8/group) at either 6, 12, or 24 weeks after ACL repair. The structural properties of the ACLs were determined from tensile failure tests. Four multiple linear regression models of increasing complexity were fitted to the data. Akaike Information Criterion values and Bland-Altman tests were used to compare model performance and to...
Introduction: The present study examined seizure clusters as a primary outcome in patients receiv... more Introduction: The present study examined seizure clusters as a primary outcome in patients receiving treatment for PNES. Cluster reduction is examined longitudinally using frequency threshold and statistical definitions of seizure cluster for patients. Possible risk factors for clustering will be examined along with clustering as a risk factor for poorer secondary outcomes. Methods: Participants were from a pilot randomized treatment trial for PNES where they received cognitive behavioral therapy-informed psychotherapy (CBT-ip), sertraline, combination therapy, or treatment as usual. Seizure data are from patients' seizure dairies. Results: Cluster reduction was observed for those receiving CBT-ip or combination treatment using all definitions of daily clusters and weekly clusters. No risk factors of clustering were observed. Those who were identified as having clusters during the trial had poorer secondary outcomes on several measures at baseline relative to those who were not identified as having clusters. Discussion: This is the first study known to the authors to not only examined seizure clusters as a primary outcome for those with PNES, but also the first study to suggest that CBT-ip and combination therapy may be effective in reducing the frequency of clusters.
Background: Anterior cruciate ligament (ACL) injuries pose a significant risk to the careers of p... more Background: Anterior cruciate ligament (ACL) injuries pose a significant risk to the careers of players in the National Football League (NFL). The relationships between draft round and position on return to play (RTP) among NFL players are not well understood, and the ability to return to preinjury performance levels remains unknown for most positions. Purpose: To test for differences in RTP rates and changes in performance after an ACL injury by position and draft round. We hypothesized that skilled positions would return at a lower rate compared to unskilled positions. We further hypothesized that early draft-round status would relate to a greater rate of RTP and that skilled positions and a lower draft round would correlate with decreased performance for players who return to sport.
Arthroscopy: The Journal of Arthroscopic & Related Surgery, 2017
Purpose: To investigate whether arthroscopy or stress radiography can identify instability result... more Purpose: To investigate whether arthroscopy or stress radiography can identify instability resulting from single-ligament injury of the ankle syndesmosis and to determine whether either modality is capable of differentiating between various levels of ligament injury. Methods: Syndesmotic/deltoid ligament sectioning was performed in 10 cadaver legs. Arthroscopic evaluation and fluoroscopic stress testing were completed after each sectioning. In group 1 (n ¼ 5), sectioning began with anteroinferior tibiofibular ligament (AITFL), then interosseous membrane (IOM), posteroinferior tibiofibular ligament (PITFL), and deltoid. In group 2 (n ¼ 5), this order was reversed. Measurements were made by determining the largest-sized probe that would fit in the anterior and posterior syndesmosis. Radiographic parameters included tibiofibular overlap/clear space and medial clear space. Results: No radiographic measurement proved useful in distinguishing between intact and transected AITFL. Anterior probe (AP) size reached significance when distinguishing between intact and AITFL-transected specimens (P < .0001). AP detected significant differences comparing single with 2-, 3-, and 4-ligament (AITFL, IOM, PITFL, deltoid) disruptions (P ¼ .05, <.0001, and <.0001, respectively). Significant differences were observed between 2-and 3/4-ligament (P ¼ .02) transections. Posterior probe (PP) size detected significant differences between intact and single-, double-, triple-, and complete ligament transections (P values .0006, <.0001, <.0001, <.001, respectively). PP detected significant differences between single-and double-, triple-, and complete ligament transection models (P ¼ .0075, .0010, and .0010, respectively). PP distinguished between 2-and 3/4ligament (P ¼ .03) transections. Conclusions: Stress radiography did not distinguish between intact and single-ligament disruption, and was unreliable in distinguishing between sequential transection models. Arthroscopy significantly predicted isolated disruption of the AITFL or deltoid ligaments. Also, probing was able to differentiate between most patterns of ligament injury, including sequential transections. Clinical Relevance: These data can aid surgeons during arthroscopy of the ankle when attempting to correlate intraoperative syndesmotic evaluation findings with the extent of ligament injury.
Introduction: The immune microenvironment is a prognostic factor for various malignancies. The si... more Introduction: The immune microenvironment is a prognostic factor for various malignancies. The significance of key players of this immune microenvironment including tumor-infiltrating lymphocytes and expression of programmed death-ligand 1 (PD-L1), indoleamine-2,3-dioxygenase (IDO), and tryptophanyl-tRNA synthetase (WARS) in gastrointestinal stromal tumors (GISTs) is largely unknown. Methods: Tissue microarrays were constructed from pathology files, 1996-2016. Immunohistochemistry for PD-L1, IDO, WARS was correlated with tumor size, mitoses, and outcomes. Tumor infiltrating lymphocytes (TILs) expressing CD3, CD4, CD8, FoxP3, and GBP5 were counted. Results: 129 GISTs were analyzed. Mean patient age was 62.5 years; 52.0% were male. Tumor location included 89 stomach (69.0%), 33 small bowel (25.6%), 7 other (5.4%). Mean tumor size was 5.6 cm; mean mitoses were 7.2/50HPF. Nineteen patients (15.0%) developed disease progression, to abdominal wall (n=8), liver (n=6), and elsewhere (n=5). Median progression-free survival was 56.6 months; 5 patients died of disease. PD-L1 was positive in 87/126 tumor samples (69.0%), 114/127 tumors were IDO-positive (89.8%), and 60/127 were positive for WARS (47.2%). PD-L1 was associated with increased size (p=0.01), necrosis (p=0.018), and mitoses (p=0.006). Disease progression was not associated with PD-L1 (p=0.44), IDO (p=0.14), or WARS (p=0.36) expression.
To explore early autonomic cardiac changes in pre-clinical Alzheimer's disease (AD), we have ... more To explore early autonomic cardiac changes in pre-clinical Alzheimer's disease (AD), we have evaluated electrocardiologic measures of vagal tone for 63 adults (ages 55-75) at rest, during cognitive testing, and then again at rest. All subjects had multiple risk factors for AD, and all completed amyloid PET scans (18F-Florbetapir) to determine amyloid positivity (Aβ+). No change in electrocardiographic measures were observed for Aβ+ participants under each testing condition, whereas Aβ-subjects showed an expected increase in vagal tone during the cognitive stress condition. These findings suggest an early relationship between cortical Aβ accumulation, a precursor to AD development, and autonomic cardiac function.
The Journal of bone and joint surgery. American volume, 2017
Sarcopenia is a condition of clinically relevant loss of muscle mass and function. Acetabular fra... more Sarcopenia is a condition of clinically relevant loss of muscle mass and function. Acetabular fractures in elderly patients are common and difficult to treat. This study aimed to determine if sarcopenia is common in elderly patients with acetabular fractures and correlates with lower-energy mechanisms of injury, higher rates of complications, and higher mortality than patients with normal muscle mass. The Rhode Island Hospital Trauma Database was queried for patients who were ≥60 years of age from 2005 to 2014 using the International Classification of Diseases, Ninth Revision, code for closed acetabular fracture, 808.0. Charts were retrospectively reviewed for demographic data, operative intervention, mechanism of injury, mortality, comorbidities, and other factors. Computed tomography (CT) was used to determine the muscle cross-sectional area and to calculate the skeletal muscle index. The database revealed 192 patients coded for acetabular fracture; of these, 181 were correctly di...
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Papers by Jason Machan