Research Interests: Immunology and Medicine
Research Interests: Adolescent, Medicine, Logistic Regression, Bone graft, Humans, and 15 moreFemur, Bone marrow, Boston, Clinical Sciences, Bone Marrow Transplantation, Humerus, Adult, Medical Records, Massachusetts General Hospital, Curettage, Bone Cyst, Logistic Models, Bone Transplantation, Adrenal cortex hormones, and Fractures Bone
The range of observable time-dependent mechanical behavior in AFM FD experiments is limited by sampling frequency 1/Δt and duration of the experiment tf. One should choose parameters that encompass both the minimum and maximum material... more
The range of observable time-dependent mechanical behavior in AFM FD experiments is limited by sampling frequency 1/Δt and duration of the experiment tf. One should choose parameters that encompass both the minimum and maximum material relaxation times.
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ABSTRACTThe anterior hypothalamic area (AHA) is a key brain region for orchestrating defensive behaviors. Here, we first examined AHA activity patterns during fear conditioning using in vivo functional imaging. We observed that neuronal... more
ABSTRACTThe anterior hypothalamic area (AHA) is a key brain region for orchestrating defensive behaviors. Here, we first examined AHA activity patterns during fear conditioning using in vivo functional imaging. We observed that neuronal activity in the AHA increases during both foot shock delivery and foot-shock associated auditory cues. Moreover, we used a combination of optogenetics and behavioral assays to determine the functional connectivity between the ventromedial hypothalamus (VMH) and the AHA. We found that photoactivation of the VMH→AHA pathway is aversive and triggers compulsive grooming behavior. Furthermore, we observed spatial and temporal changes of grooming behavior during the periods following VMH→AHA photoactivation. Interestingly, whole brain metabolic mapping using positron emission tomography (PET) combined with optogenetic activation of the VMH→AHA pathway in anesthetized mice revealed the amygdala as a downstream area activated by the stimulation of this pathw...
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Background: Interventions targeting physical activity and sedentary behavior concurrently in pregnancy may be an ideal strategy to reduce the risk of pregnancy complications. We assessed the feasibility, acceptability, and preliminary... more
Background: Interventions targeting physical activity and sedentary behavior concurrently in pregnancy may be an ideal strategy to reduce the risk of pregnancy complications. We assessed the feasibility, acceptability, and preliminary efficacy of a single-arm, remotely-delivered health coaching intervention to promote physical activity and reduce sedentary behavior in pregnancy.Methods: Women (n=34) between 8-12 weeks gestation were recruited to take part in the INcreasing Steps in PREgnancy (INSPiRE) study. Participants were given an activity tracker (Fitbit Inspire) and met virtually with their health coach throughout the second and third trimesters of pregnancy. Feasibility was based on enrollment, retention, and adherence rates. Acceptance was assessed using a process evaluation survey. Intervention efficacy was based on activPAL data obtained at baseline and the end of the second trimester. Results: Feasibility objectives were met, with greater than 70% enrollment, 97% retentio...
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Within a variety of stimuli, we selectively attend to the most emotionally relevant, often at a cost to the processing of the other stimuli. The emotional attentional blink (EAB) is an effect in which emotional distractor images capture... more
Within a variety of stimuli, we selectively attend to the most emotionally relevant, often at a cost to the processing of the other stimuli. The emotional attentional blink (EAB) is an effect in which emotional distractor images capture attention for several hundred milliseconds so that individuals cannot detect subsequent target images. In this study, we hoped to pinpoint the time course of the emotional capture of attention by creating a multi-target design based on Most and colleauges’ (2005) original EAB study. In Experiment 1, letters were presented on images following the distractor, and participants were asked to report which letter they first recalled seeing. We found that emotional distractor images, including erotic and gory conditions, induced greater deficits than non-emotional distractor images. In Experiment 2, participants reported not only the first letter they saw, but also the last number (presented before the distractor image) they saw. The task in Experiment 2 su...
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Resection of the distal fibula is used to treat malignant or benign locally aggressive tumors involving this region. Current reconstructive techniques are limited by undesirable functional deficits. The authors present a... more
Resection of the distal fibula is used to treat malignant or benign locally aggressive tumors involving this region. Current reconstructive techniques are limited by undesirable functional deficits. The authors present a part-retrospective and part-prospective case-comparison of 2 patient groups (study and control) treated for malignant or benign locally aggressive primary bone tumors of the distal fibula. Patients in the study group underwent a novel surgical technique involving distal transportation of the ipsilateral proximal portion of the fibula after periosteal dissection and osteotomy with subsequent proximal periosteal reconstruction. Patients in the control group underwent other limb-salvage or amputation procedures. Patients were evaluated at follow-up appointments for oncologic, radiographic, and functional outcomes. The groups had similar demographic and perioperative data. Operative time was longer in the study group. Radiographic union occurred in 75% of the study grou...
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Soft-tissue sarcomas are rare malignancies in children and adolescents, representing only 7.4 % of cancer cases in children <20 years of age. They are categorized into rhabdomyosarcomas (RMS) and non-rhabdomyosarcoma soft-tissue... more
Soft-tissue sarcomas are rare malignancies in children and adolescents, representing only 7.4 % of cancer cases in children <20 years of age. They are categorized into rhabdomyosarcomas (RMS) and non-rhabdomyosarcoma soft-tissue sarcomas (NRSTS). RMS of the extremities is associated with a poorer prognosis than RMS overall. Important negative prognostic factors are higher stage and clinical group, positive regional nodes, larger size, and greater tumor invasiveness. Overall survival for extremity RMS is around 70 % at five years, with significant variability based on clinical group. NRSTS is a heterogeneous group with frequent location in the extremities. Data are more limited in pediatric NRSTS, but general negative prognostic factors are extent of disease, tumor size, quality of resection, and grade. Survival ranges from 90 % for low-grade tumors to 15 % for patients presenting with metastatic disease. Further efforts to improve the outcome for extremity RMS and to research ped...
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Competitive athletes completed two studies of 2-h steady-state (SS) cycling at 70% peak O(2) uptake followed by 7 kJ/kg time trial (TT) with carbohydrate (CHO) intake before (2 g/kg) and during (6% CHO drink) exercise. In Study A, 12... more
Competitive athletes completed two studies of 2-h steady-state (SS) cycling at 70% peak O(2) uptake followed by 7 kJ/kg time trial (TT) with carbohydrate (CHO) intake before (2 g/kg) and during (6% CHO drink) exercise. In Study A, 12 subjects received either 6 mg/kg caffeine 1 h preexercise (Precaf), 6 x 1 mg/kg caffeine every 20 min throughout SS (Durcaf), 2 x 5 ml/kg Coca-Cola between 100 and 120 min SS and during TT (Coke), or placebo. Improvements in TT were as follows: Precaf, 3.4% (0.2-6.5%, 95% confidence interval); Durcaf, 3.1% (-0.1-6.5%); and Coke, 3.1% (-0.2-6.2%). In Study B, eight subjects received 3 x 5 ml/kg of different cola drinks during the last 40 min of SS and TT: decaffeinated, 6% CHO (control); caffeinated, 6% CHO; decaffeinated, 11% CHO; and caffeinated, 11% CHO (Coke). Coke enhanced TT by 3.3% (0.8-5.9%), with all trials showing 2.2% TT enhancement (0.5-3.8%; P < 0.05) due to caffeine. Overall, 1) 6 mg/kg caffeine enhanced TT performance independent of tim...
Research Interests: Chemistry, Animal Science, Exercise Physiology, Competition, Medicine, and 15 moreBiological Sciences, Humans, Bicycling, Caffeine, Applied, Blood, Male, Applied Physiology, Beverages, Adult, Carbohydrate metabolism, Drinking, Carbohydrate, Central nervous system stimulants, and Medical and Health Sciences
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Research Interests: Physiology, Nutrition and Dietetics, Medicine, Swimming, Humans, and 15 morePlacebo, Female, Male, Exercise, Dietary Supplements, Nutrients, Athletes, Adult, Athletic performance, Blood Lactate, Athlete, Physical Education and training, Carnosine, Ergogenic aid, and Central nervous system stimulants
Research Interests: Neurogenesis, Adult neurogenesis, Neurobiology of Learning and Memory, Medicine, Learning, and 15 moreHippocampus, Classical Conditioning, Cues, Animals, Male, Neurons, Dentate Gyrus, Analysis of Variance, Conditioning, Cell Survival, Blinking, Eyeblink Conditioning, Hippocampal formation, Cell count, and Medical and Health Sciences
Research Interests: Body Image, Adolescent, Medicine, Biomechanics of strength and conditioning, Physical Therapy, and 15 moreHumans, Strength and Conditioning, Body Composition, Male, Exercise, Attractiveness, The, Physical Fitness, Adult, Analysis of Variance, Interaction effect, Trunk, Training Program, Physical Education and training, and Control Group
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Research Interests: Adolescent, Medicine, Logistic Regression, Bone graft, Humans, and 15 moreFemur, Bone marrow, Boston, Clinical Sciences, Bone Marrow Transplantation, Humerus, Adult, Medical Records, Massachusetts General Hospital, Curettage, Bone Cyst, Logistic Models, Bone Transplantation, Adrenal cortex hormones, and Fractures Bone
Research Interests: Magnetic Resonance Imaging, Medicine, Activities of Daily Living, Case Report, Osteoporosis, and 15 moreHumans, Femur, Female, Orthopedics, Clinical Sciences, Middle Aged, Humerus, Radiography, Bone Marrow Edema, Related, Predictive value of tests, Analgesics, Activity of Daily Living, Image Features, and Humeral Fractures
Research Interests: Neuroscience, Electrophysiology, Neurogenesis, Consciousness, Neural Networks, and 15 moreApoptosis, Neural Network, Medicine, Learning, Hippocampus, Classical Conditioning, Brain, Animals, Neurons, Alcohol Consumption, Declarative Memory, Learning Experience, Cell Survival, Aerobic Exercise, and Medical and Health Sciences
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Background: Pathological fractures could be prevented if reliable methods of fracture risk assessment were available. A multi-center, prospective study was conducted to identify significant predictors of physicians' treatment plan for... more
Background: Pathological fractures could be prevented if reliable methods of fracture risk assessment were available. A multi-center, prospective study was conducted to identify significant predictors of physicians' treatment plan for skeletal metastasis based on clinical fracture risk assessments and the proposed CT-based Rigidity Analysis (CTRA). Methods: Orthopaedic oncologists selected a treatment plan for 124 patients with 149 metastatic lesions based on Mirels method. Then, CTRA was performed and the results were provided to the physicians, who were asked to reassess their treatment plan. The pre- and post-CTRA treatment plans were compared to identify cases where the treatment plan was changed based on the CTRA report. Patients were followed for a 4 month period to establish the incidence of pathological fractures. Results: Pain, lesion type and lesion size were significant predictors of the pre-CTRA plan. After providing the CTRA results, physicians changed their plan fo...
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Research Interests: Sociology, Literacy, Information Literacy, Health, Healthcare, and 4 moreInformation, Digital, Seniors, and Marginalized
Key investigation efforts: Analysis of new aeromagnetic data will help identify and extend newly-discovered and known faults within forearc and arc upper crust of SW Washington and NW Oregon, roughly between Grays Harbor and Tillamook.... more
Key investigation efforts: Analysis of new aeromagnetic data will help identify and extend newly-discovered and known faults within forearc and arc upper crust of SW Washington and NW Oregon, roughly between Grays Harbor and Tillamook. Supporting analysis of LiDAR data will define neotectonic activity. These efforts will target new MT, ground-magnetic, and gravity transects across structures of interest, constrained by existing geologic mapping and seismic data, all leading to detailed 2-D models across important forearc structures. Combining 2-D models and map view interpretations will lead us to a 3-D model of upper-crustal structure. We will compare our structural map to indicators of subduction interface segmentation (e.g. tremor density, free-air gravity, offshore structure) to determine the causal association of upper-plate structure and interface segmentation/variations.
Low nadir CD4 T-cell counts in HIV+ patients are associated with high morbidity and mortality and lasting immune dysfunction, even after antiretroviral therapy (ART). The early events of immune recovery of T cells and B cells in severely... more
Low nadir CD4 T-cell counts in HIV+ patients are associated with high morbidity and mortality and lasting immune dysfunction, even after antiretroviral therapy (ART). The early events of immune recovery of T cells and B cells in severely lymphopenic HIV+ patients have not been fully characterized. In a cohort of lymphopenic (CD4 T-cell count < 100/µL) HIV+ patients, we studied mononuclear cells isolated from peripheral blood (PB) and lymph nodes (LN) pre-ART (n = 40) and 6-8 weeks post-ART (n = 30) with evaluation of cellular immunophenotypes; histology on LN sections; functionality of circulating T follicular helper (cTfh) cells; transcriptional and B-cell receptor profile on unfractionated LN and PB samples; and plasma biomarker measurements. A group of 19 healthy controls (HC, n = 19) was used as a comparator. T-cell and B-cell lymphopenia was present in PB pre-ART in HIV+ patients. CD4:CD8 and CD4 T- and B-cell PB subsets partly normalized compared to HC post-ART as viral loa...
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Background Resource utilization among emergency department (ED) patients with possible coronary chest pain is highly variable. Methods and Results Controlled cohort study amongst 21 EDs of an integrated healthcare system examining the... more
Background Resource utilization among emergency department (ED) patients with possible coronary chest pain is highly variable. Methods and Results Controlled cohort study amongst 21 EDs of an integrated healthcare system examining the implementation of a graded coronary risk stratification algorithm (RISTRA‐ACS [risk stratification for acute coronary syndrome]). Thirteen EDs had access to RISTRA‐ACS within the electronic health record (RISTRA sites) beginning in month 24 of a 48‐month study period (January 2016 to December 2019); the remaining 8 EDs served as contemporaneous controls. Study participants had a chief complaint of chest pain and serum troponin measurement in the ED. The primary outcome was index visit resource utilization (observation unit or hospital admission, or 7‐day objective cardiac testing). Secondary outcomes were 30‐day objective cardiac testing, 60‐day major adverse cardiac events (MACE), and 60‐day MACE‐CR (MACE excluding coronary revascularization). Differe...
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Background Idiopathic CD4 Lymphocytopenia (ICL) is a rare immunodeficiency characterized by an absolute CD4+ T count of < 300 cells/µL, in absence of HIV-infection or any other known cause. Patients with ICL have an increased risk of... more
Background Idiopathic CD4 Lymphocytopenia (ICL) is a rare immunodeficiency characterized by an absolute CD4+ T count of < 300 cells/µL, in absence of HIV-infection or any other known cause. Patients with ICL have an increased risk of opportunistic infections. The prevalence, natural history, and spectrum of Human Papillomaviruses (HPV) associated diseases in ICL patients are unknown. Methods ICL patients were enrolled in a prospective observational study (N = 90). Demographic, clinical, and immunologic data were analyzed by nonparametric Methods. Immunophenotyping was performed by flow cytometry. Results The median age of ICL patients was 48 years, 47% were women, and 92% were Caucasian. Sixty-five percent of patients had at least one opportunistic infection, with HPV being the most prevalent (34.4%), followed by cryptococcal disease (22%), shingles (15.5%), molluscum contagiosum (8.8%), Histoplasma capsulatum (4.4%), Mycobacterium avium complex (4.4%), and progressive multifocal...
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The highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers. In the current study, the authors describe the clinical course of... more
The highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers. In the current study, the authors describe the clinical course of children with locally advanced TRK fusion sarcoma who were treated preoperatively with larotrectinib and underwent subsequent surgical resection. A total of 24 children were treated on a pediatric phase 1 trial of larotrectinib (ClinicalTrials.gov identifier NCT02637687). Five children who had a documented TRK fusion sarcoma and underwent surgical resection were included in the current analysis. Tumor response (Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1) and surgical outcomes were collected prospectively. A total of 5 patients (median age, 2 years; range, 0.4-12 years) had locally advanced infantile fibrosarcoma (3 patients) or soft-tissue sarcoma (2 patients). Four patients had disease that was refractory to standard therapy. All 5 ...
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Given the high mortality experienced by patients who deteriorate outside the intensive care unit, issues related to patient preferences around escalation of care are common. However, the literature on early warning systems (EWSs) provides... more
Given the high mortality experienced by patients who deteriorate outside the intensive care unit, issues related to patient preferences around escalation of care are common. However, the literature on early warning systems (EWSs) provides limited information on how respecting patient preferences can be incorporated into clinical workflows. In this report, we describe how we developed workflows for integrating supportive care with an automated EWS in the context of a 2‐hospital pilot. We used the Institute for Healthcare Improvement's Plan‐Do‐Study‐Act approach to achieve consensus with clinicians and administrators. The workflows will serve as the basis for dissemination to an additional 19 hospitals. We were successful in integrating an automated EWS with supportive care. Our workflows take local resource availability into account and have been well received by hospitalists, nurses, and families. Our work demonstrates that one can achieve integration of proactive supportive car...
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SummaryBackground: The Pulmonary Embolism (PE) Severity Index identifies emergency department (ED) patients with acute PE that can be safely managed without hospitalization. However, the Index comprises 11 weighted variables, complexity... more
SummaryBackground: The Pulmonary Embolism (PE) Severity Index identifies emergency department (ED) patients with acute PE that can be safely managed without hospitalization. However, the Index comprises 11 weighted variables, complexity that can impede its integration into contextual work-flow.Objective: We designed a computerized version of the PE Severity Index (e-Index) to automatically extract the required variables from discrete fields in the electronic health record (EHR). We tested the e-Index on the study population to determine its accuracy compared with a gold standard generated by physician abstraction of the EHR on manual chart review.Methods: This retrospective cohort study included adults with objectively-confirmed acute PE in four community EDs from 2010–2012. Outcomes included performance characteristics of the e-Index for individual values, the number of cases requiring physician editing, and the accuracy of the e-Index risk category (low vs. higher).Results: For th...