Digital Commons Network^™

Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens And Patient Outcomes: An Individual Patient Data Meta-Analysis Of 9,153 Patients, Shama D. Ahuja, David Ashkin, Monika Avendano, Rita Banerjee, Melissa Bauer, Jamie N. Bayona

Dartmouth Scholarship

Dick Menzies and colleagues report findings from a collaborative, individual patient-level meta-analysis of treatment outcomes among patients with multidrug-resistant tuberculosis.

Background: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB.

The Ventricular Volume Variability Study Of The Pediatric Heart Network: Study Design And Impact Of Beat Averaging And Variable Type On The Reproducibility Of Echocardiographic Measurements In Children With Chronic Dilated Cardiomyopathy., Steven D. Colan, Girish S. Shirali, Renee Margossian, Dianne Gallagher, Karen Altmann, Charles Canter, Shan Chen, Fraser Golding, Elizabeth Radojewski, Michael Camitta, Michael Carboni, Jack Rychik, Mario Stylianou, Lloyd Y. Tani, Elif Seda Selamet Tierney, Yanli Wang, Lynn A. Sleeper, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Clinical trials often rely on echocardiographic measures of left ventricular size and function as surrogate end points. However, the quantitative impact of factors that affect the reproducibility of these measures is unknown. To address this issue, the National Heart, Lung, and Blood Institute-funded Pediatric Heart Network designed a longitudinal observational study of children with known or suspected dilated cardiomyopathy aged 0 to 22 years from eight pediatric clinical centers.

METHODS: Clinical data were collected together with 150 echocardiographic indices of left ventricular size and function. Separate observers performed duplicate echocardiographic imaging. Multiple observers performed measurements from three cardiac cycles …

Epoxide-Mediated Cifr Repression Of Cif Gene Expression Utilizes Two Binding Sites In Pseudomonas Aeruginosa, Alicia E. Ballok, Christopher D. Bahl, Emily L. Dolben, Allia K. Lindsay, Jessica D. St. Laurent, Deborah Hogan, Dean Madden, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa secretes an epoxide hydrolase virulence factor that reduces the apical membrane expression of ABC transporters such as the cystic fibrosis transmembrane conductance regulator (CFTR). This virulence factor, named CFTR inhibitory factor (Cif), is regulated by a TetR-family, epoxide-responsive repressor known as CifR via direct binding and repression. We identified two sites of CifR binding in the intergenic space between cifR and morB, the first gene in the operon containing the cif gene. We have mapped these binding sites and found they are 27 bp in length, and they overlap the -10 and +1 sites of both the cifR …

Shift Work And Vascular Events: Systematic Review And Meta-Analysis., Manav V Vyas, Amit X Garg, Arthur V Iansavichus, John Costella, Allan Donner, Lars E Laugsand, Imre Janszky, Marko Mrkobrada, Grace Parraga, Daniel G Hackam

Medical Biophysics Publications

OBJECTIVE: To synthesise the association of shift work with major vascular events as reported in the literature.

DATA SOURCES: Systematic searches of major bibliographic databases, contact with experts in the field, and review of reference lists of primary articles, review papers, and guidelines.

STUDY SELECTION: Observational studies that reported risk ratios for vascular morbidity, vascular mortality, or all cause mortality in relation to shift work were included; control groups could be non-shift ("day") workers or the general population.

DATA EXTRACTION: Study quality was assessed with the Downs and Black scale for observational studies. The three primary outcomes were myocardial infarction, …

A Prescription For The Epley Maneuver: Www.Youtube.Com?, Kevin A Kerber, James F Burke, Lesli E Skolarus, Brian C Callaghan, Terry D. Fife, Robert W Baloh, A Mark Fendrick

Neurology

OBJECTIVES: Video-sharing Web sites are being used for information about common conditions including dizziness. The Epley maneuver (EM) is a simple and effective treatment for benign paroxysmal positional vertigo (BPPV) of the posterior canal. However, the maneuver is underused in routine care. In this study, we aimed to describe and analyze the available information about the EM on youtube.com.

METHODS: A YouTube search was performed on August 31, 2011, for videos that demonstrated the entire EM. Detailed data were abstracted from each video and corresponding Web site. Videos were rated on the accuracy of the maneuver by 2 authors, with …

Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M. Vaske, Kimberly N. White, Tanya L. Cohen, Helene C. Vervoort, Karen Tenney, Frederick A. Valeriote, Leonard F. Bjeldanes, Phillip Crews

Natural Sciences and Mathematics | Faculty Scholarship

A nuclear factor-κB (NF-κB) luciferase assay has been employed to identify the bengamides, previously known for their anti-tumor activity, as a new class of immune modulators. A unique element of this study was that the bengamide analogs were isolated from two disparate sources, Myxococcus virescens (bacterium) and Jaspis coriacea (sponge). Comparative LC-MS/ELSD and NMR analysis facilitated the isolation of M. viriscens derived samples of bengamide E (8) and two congeners, bengamide E' (13) and F' (14) each isolated as an insperable mixture of diastereomers. Additional compounds drawn from the UC, Santa Cruz repository allowed expansion of the structure activity relationship …

Multivoxel Patterns In Face-Sensitive Temporal Regions Reveal An Encoding Schema Based On Detecting Life In A Face, Christine E. Looser, Jyothi S. Guntupalli, Thalia Wheatley

Dartmouth Scholarship

More than a decade of research has demonstrated that faces evoke prioritized processing in a ‘core face network’ of three brain regions. However, whether these regions prioritize the detection of global facial form (shared by humans and mannequins) or the detection of life in a face has remained unclear. Here, we dissociate form-based and animacy-based encoding of faces by using animate and inanimate faces with human form (humans, mannequins) and dog form (real dogs, toy dogs). We used multivariate pattern analysis of BOLD responses to uncover the representational similarity space for each area in the core face network. Here, we …

Drugs For Preventing Red Blood Cell Dehydration In People With Sickle Cell Disease., Srikanth Nagalla, Samir K Ballas

Department of Medicine Faculty Papers

BACKGROUND: Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs.

OBJECTIVES: To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells.

SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials …

The Human Phosphotyrosine Signaling Network: Evolution And Hotspots Of Hijacking In Cancer., Lei Li, Chabane Tibiche, Cong Fu, Tomonori Kaneko, Michael F. Moran, Martin Schiller, Shawn Shun-Cheng Li, Edwin Wang

Life Sciences Faculty Research

Phosphotyrosine (pTyr) signaling, which plays a central role in cell-cell and cell-environment interactions, has been considered to be an evolutionary innovation in multicellular metazoans. However, neither the emergence nor the evolution of the human pTyr signaling system is currently understood. Tyrosine kinase (TK) circuits, each of which consists of a TK writer, a kinase substrate, and a related reader, such as Src homology (SH) 2 domains and pTyr-binding (PTB) domains, comprise the core machinery of the pTyr signaling network. In this study, we analyzed the evolutionary trajectories of 583 literature-derived and 50,000 computationally predicted human TK circuits in 19 representative …

Analytic Lymph Node Number Establishes Staging Accuracy By Occult Tumor Burden In Colorectal Cancer., Terry Hyslop, David S. Weinberg, Stephanie Schulz, Alan Barkun, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND AND OBJECTIVES: Recurrence in lymph node-negative (pN0) colorectal cancer suggests the presence of undetected occult metastases. Occult tumor burden in nodes estimated by GUCY2C RT-qPCR predicts risk of disease recurrence. This study explored the impact of the number of nodes analyzed by RT-qPCR (analytic) on the prognostic utility of occult tumor burden.

METHODS: Lymph nodes (range: 2-159) from 282 prospectively enrolled pN0 colorectal cancer patients, followed for a median of 24 months (range: 2-63), were analyzed by GUCY2C RT-qPCR. Prognostic risk categorization defined using occult tumor burden was the primary outcome measure. Association of prognostic variables and risk category …

Systemic Sclerosis Disease Modification Clinical Trials Design: Quo Vadis?, Fabian A. Mendoza, Md, Lynette L Keyes-Elstein, Sergio A. Jimenez

Scleroderma Center Faculty Papers

The purpose of this manuscript is to discuss relevant aspects of clinical trials for Systemic Sclerosis (SSc) and to identify important considerations for the design of SSc disease modification clinical trials. Placebo randomized controlled trials with appropriate identification of SSc patients with diffuse progressive SSc skin involvement of recent onset, along with a rescue strategy for patients with worsening lung and skin involvement are suggested. If change in skin thickening is a major outcome of the study, the selection of patients with recent onset of disease and a predetermined degree of skin involvement are crucial requirements. The trial duration should …

Reevaluating The Imaging Definition Of Tumor Progression: Perfusion Mri Quantifies Recurrent Glioblastoma Tumor Fraction, Pseudoprogression, And Radiation Necrosis To Predict Survival., Leland S Hu, Jennifer M Eschbacher, Joseph E Heiserman, Amylou C Dueck, William R Shapiro, Seban Liu, John P Karis, Kris A Smith, Stephen W Coons, Peter Nakaji, Robert F Spetzler, Burt G Feuerstein, Josef Debbins, Leslie C Baxter

Neurosurgery

INTRODUCTION: Contrast-enhanced MRI (CE-MRI) represents the current mainstay for monitoring treatment response in glioblastoma multiforme (GBM), based on the premise that enlarging lesions reflect increasing tumor burden, treatment failure, and poor prognosis. Unfortunately, irradiating such tumors can induce changes in CE-MRI that mimic tumor recurrence, so called post treatment radiation effect (PTRE), and in fact, both PTRE and tumor re-growth can occur together. Because PTRE represents treatment success, the relative histologic fraction of tumor growth versus PTRE affects survival. Studies suggest that Perfusion MRI (pMRI)-based measures of relative cerebral blood volume (rCBV) can noninvasively estimate histologic tumor fraction to predict …

B-Vitamin Deficiency In Patients Treated With Antiepileptic Drugs., Scott Mintzer, Christopher T Skidmore, Michael R Sperling

Department of Neurology Faculty Papers

Enzyme-inducing antiepileptic drugs (AEDs) produce many alterations in metabolism, including vitamin levels. Whether they produce clinically relevant deficiency of B vitamins has rarely been assessed. We obtained B-vitamin levels in patients who were being converted from an inducing AED (phenytoin or carbamazepine) to a non-inducing AED (levetiracetam, lamotrigine, or topiramate), with measurements both before and ≥ 6 weeks after the switch. A group of normal subjects underwent the same studies. Neither folate nor B12 deficiency was seen in any patient. Vitamin B6 deficiency was found in 16/33 patients (48%) taking inducers, compared to 1/11 controls (9%; p=0.031). After switch to …

Intermediate-Term Mortality And Cardiac Transplantation In Infants With Single-Ventricle Lesions: Risk Factors And Their Interaction With Shunt Type., James S. Tweddell, Lynn A. Sleeper, Richard G. Ohye, Ismee A. Williams, Lynn Mahony, Christian Pizarro, Victoria L. Pemberton, Peter C. Frommelt, Scott M. Bradley, James F. Cnota, Jennifer Hirsch, Paul M. Kirshbom, Jennifer S. Li, Nancy Pike, Michael Puchalski, Chitra Ravishankar, Jeffrey P. Jacobs, Peter C. Laussen, Brian W. Mccrindle, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: The study objective was to identify factors associated with death and cardiac transplantation in infants undergoing the Norwood procedure and to determine differences in associations that might favor the modified Blalock-Taussig shunt or a right ventricle-to-pulmonary artery shunt.

METHODS: We used competing risks methodology to analyze death without transplantation, cardiac transplantation, and survival without transplantation. Parametric time-to-event modeling and bootstrapping were used to identify independent predictors.

RESULTS: Data from 549 subjects (follow-up, 2.7 ± 0.9 years) were analyzed. Mortality risk was characterized by early and constant phases; transplant was characterized by only a constant phase. Early phase factors associated …

Parent Or Community: Where Do 20-Month-Olds Exposed To Two Accents Acquire Their Representation Of Words?, Caroline Floccia, Luche C Delle, Samantha Durrant, Joseph Butler, Jeremy Goslin

School of Psychology

The recognition of familiar words was evaluated in 20-month-old children raised in a rhotic accent environment to parents that had either rhotic or non-rhotic accents. Using an Intermodal Preferential Looking task children were presented with familiar objects (e.g. 'bird') named in their rhotic or non-rhotic form. Children were only able to identify familiar words pronounced in a rhotic accent, irrespective of their parents' accent. This suggests that it is the local community rather than parental input that determines accent preference in the early stages of acquisition. Consequences for the architecture of the early lexicon and for models of word learning …

Associations Between Toenail Arsenic Concentration And Dietary Factors In A New Hampshire Ppopulation, Joann F. Gruber, Margaret R. Karagas, Diane Gilbert-Diamond, Pamela J. Bagley, M Scot Zens, Vicki Sayarath, Tracy Punshon, J Steven Morris, Kathryn L. Cottingham

Dartmouth Scholarship

Background: Dietary factors such as folate, vitamin B12, protein, and methionine are important for the excretion of arsenic via one-carbon metabolism in undernourished populations exposed to high levels of arsenic via drinking water. However, the effects of dietary factors on toenail arsenic concentrations in well-nourished populations exposed to relatively low levels of water arsenic are unknown.

Methods: As part of a population-based case-control study of skin and bladder cancer from the USA, we evaluated relationships between consumption of dietary factors and arsenic concentrations in toenail clippings. Consumption of each dietary factor was determined from a validated food frequency questionnaire. We …

Loss Of Intranetwork And Internetwork Resting State Functional Connections With Alzheimer's Disease Progression, Mathew R. Brier, Jewell B. Thomas, Abraham Z. Snyder, Tammie L. Benzinger, Dongyang Zhang, Marcus E. Raichle, David M. Holtzman, John C. Morris, Beau M. Ances

Open Access Publications

Alzheimer's disease (AD) is the most common cause of dementia. Much is known concerning AD pathophysiology but our understanding of the disease at the systems level remains incomplete. Previous AD research has used resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) to assess the integrity of functional networks within the brain. Most studies have focused on the default-mode network (DMN), a primary locus of AD pathology. However, other brain regions are inevitably affected with disease progression. We studied rs-fcMRI in five functionally defined brain networks within a large cohort of human participants of either gender (n = 510) that ranged in …

Resilience In The Face Of Disaster: Prevalence And Longitudinal Course Of Mental Disorders Following Hurricane Ike, Robert H. Pietrzak, Melissa Tracy, Sandro Galea, Dean G. Kilpatrick, Kenneth J. Ruggiero, Jessica L. Hamblen, Steven M. Southwick, Fran H. Norris

Dartmouth Scholarship

Objectives: Natural disasters may increase risk for a broad range of psychiatric disorders, both in the short- and in the medium-term. We sought to determine the prevalence and longitudinal course of posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), depression, and suicidality in the first 18 months after Hurricane Ike.

Methods: Six hundred fifty-eight adults representative of Galveston and Chambers Counties, Texas participated in a random, population-based survey. The initial assessment was conducted 2 to 5 months after Hurricane Ike struck Galveston Bay on September 13, 2008. Follow-up assessments were conducted at 5 to 9 and 14 …

What's New In Spine Surgery., Keith H Bridwell, Paul A Anderson, Scott D Boden, Alexander R Vaccaro, Jeffrey C Wang

Rothman Institute Papers

No abstract provided.

Live-Cell Monitoring Of Periodic Gene Expression In Synchronous Human Cells Identifies Forkhead Genes Involved In Cell Cycle Control, Gavin D. Grant, Joshua Gamsby, Viktor Martyanov, Lionel Brooks, Lacy K. George, J. Matthew Mahoney, Jennifer J. Loros, Jay C. Dunlap, Michael L. Whitfield

Dartmouth Scholarship

We developed a system to monitor periodic luciferase activity from cell cycle-regulated promoters in synchronous cells. Reporters were driven by a minimal human E2F1 promoter with peak expression in G1/S or a basal promoter with six Forkhead DNA-binding sites with peak expression at G2/M. After cell cycle synchronization, luciferase activity was measured in live cells at 10-min intervals across three to four synchronous cell cycles, allowing unprecedented resolution of cell cycle-regulated gene expression. We used this assay to screen Forkhead transcription factors for control of periodic gene expression. We confirmed a role for FOXM1 and identified two novel cell cycle …

Consumption Of Pornographic Materials Among Hong Kong Early Adolescents: A Replication, Daniel T. L. Shek, Cecilia M. S. Ma

Pediatrics Faculty Publications

Consumption of pornographic materials was examined in 3,638 secondary 2 students in Hong Kong. Results showed that over 80% of the respondents had never consumed pornographic materials in the past year. Internet pornography was the most common medium that adolescents used when viewing pornographic materials. Males reported a higher level of pornography consumption than did females. Participants who were born in mainland China were more likely to consume pornographic materials than their Hong Kong counterparts. Regardless of the types of pornographic materials, the levels of pornography consumption significantly increased over time. Results also showed that higher levels of positive youth …

Internet Addiction Phenomenon In Early Adolescents In Hong Kong, Daniel T. L. Shek, Lu Yu

Pediatrics Faculty Publications

The present study investigated the prevalence and demographic correlates of Internet addiction in Hong Kong adolescents as well as the change in related behavior at two time points over a one-year interval. Two waves of data were collected from a large sample of students (Wave 1: 3,328 students, age = 12.59 ± 0.74 years; Wave 2: 3,580 students, age = 13.50 ± 0.75 years) at 28 secondary schools in Hong Kong. Comparable to findings at Wave 1 (26.4%), 26.7% of the participants met the criterion of Internet addiction at Wave 2 as measured by Young's 10-item Internet Addiction Test. The …

Autophagy And Senescence In Cancer-Associated Fibroblasts Metabolically Supports Tumor Growth And Metastasis Via Glycolysis And Ketone Production., Claudia Capparelli, Carmela Guido, Diana Whitaker-Menezes, Phd, Gloria Bonuccelli, Renee Balliet, Timothy G Pestell, Allison F Goldberg, Richard Pestell, Anthony Howell, Sharon Sneddon, Ruth Birbe, Aristotelis Tsirigos, Ubaldo E. Martinez-Outshoorn, Federica Sotgia, Michael P. Lisanti

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Senescent fibroblasts are known to promote tumor growth. However, the exact mechanism remains largely unknown. An important clue comes from recent studies linking autophagy with the onset of senescence. Thus, autophagy and senescence may be part of the same physiological process, known as the autophagy-senescence transition (AST). To test this hypothesis, human fibroblasts immortalized with telomerase (hTERT-BJ1) were stably transfected with autophagy genes (BNIP3, CTSB or ATG16L1). Their overexpression was sufficient to induce a constitutive autophagic phenotype, with features of mitophagy, mitochondrial dysfunction and a shift toward aerobic glycolysis, resulting in L-lactate and ketone body production. Autophagic fibroblasts also showed …

Amygdala Responses To Averted Vs Direct Gaze Fear Vary As A Function Of Presentation Speed, Reginald B. Adams, Robert G. Franklin Jr, Kestutis Kveraga, Nalini Ambady, Robert E. Kleck, Paul J. Whalen, Nouchine Hadjikhani, Anthony J. Nelson

Dartmouth Scholarship

We examined whether amygdala responses to rapidly presented fear expressions are preferentially tuned to averted vs direct gaze fear and conversely whether responses to more sustained presentations are preferentially tuned to direct vs averted gaze fear. We conducted three functional magnetic resonance imaging (fMRI) studies to test these predictions including: Study 1: a block design employing sustained presentations (1 s) of averted vs direct gaze fear expressions taken from the Pictures of Facial Affect; Study 2: a block design employing rapid presentations (300 ms) of these same stimuli and Study 3: a direct replication of these studies in the context …

Neurological Soft Signs In Persons With Amnestic Mild Cognitive Impairment And The Relationships To Neuropsychological Functions, Hui-Jie Li, Peng-Yun Wang, Yang Jiang, Raymond C.K. Chan, Hua-Li Wang, Juan Li

Behavioral Science Faculty Publications

BACKGROUND: Neurological abnormalities have been reported in people with amnestic mild cognitive impairment (aMCI). The current study aimed to examine the prevalence of neurological soft signs (NSS) in this clinical group and to examine the relationship of NSS to other neuropsychological performances.

METHODS: Twenty-nine people with aMCI and 28 cognitively healthy elderly people were recruited for the present study. The NSS subscales (motor coordination, sensory integration, and disinhibition) of the Cambridge Neurological Inventory and a set of neuropsychological tests were administered to all the participants.

RESULTS: People with aMCI exhibited significantly more motor coordination signs, disinhibition signs, and total NSS …

School Day Segmented Physical Activity Patterns Of High And Low Active Children, Stuart J. Fairclough, Aaron Beighle, Heather Erwin, Nicola D. Ridgers

Kinesiology and Health Promotion Faculty Publications

BACKGROUND: Variability exists in children's activity patterns due to the association with environmental, social, demographic, and inter-individual factors. This study described accelerometer assessed physical activity patterns of high and low active children during segmented school week days whilst controlling for potential correlates.

METHODS: Two hundred and twenty-three children (mean age: 10.7 ± 0.3 yrs, 55.6% girls, 18.9% overweight/obese) from 8 north-west England primary schools wore ActiGraph GT1M accelerometers for 7 consecutive days during autumn of 2009. ActiGraph counts were converted to minutes of moderate (MPA), vigorous (VPA) and moderate-to-vigorous (MVPA) physical activity. Children were classified as high active (HIGH) or …

Is Mri Better Than Ct For Detecting A Vascular Component To Dementia? A Systematic Review And Meta-Analysis., Rebecca Beynon, Jonathan A.C. Sterne, Gordon Wilcock, Marcus Likeman, Roger M. Harbord, Margaret Astin, Margaret Burke, Alysson Bessell, Yoav Ben-Shlomo, James Hawkins, William Hollingworth, Penny Whiting

School of Psychology

BACKGROUND: Identification of causes of dementia soon after symptom onset is important, because appropriate treatment of some causes of dementia can slow or halt its progression or enable symptomatic treatment where appropriate. The accuracy of MRI and CT, and whether MRI is superior to CT, in detecting a vascular component to dementia in autopsy confirmed and clinical cohorts of patients with VaD, combined AD and VaD ("mixed dementia"), and AD remain unclear. We conducted a systematic review and meta-analysis to investigate this question. METHODS: We searched eight databases and screened reference lists to identify studies addressing the review question. We …

Human Genome-Wide Association And Mouse Knockout Approaches Identify Platelet Supervillin As An Inhibitor Of Thrombus Formation Under Shear Stress., Leonard C. Edelstein, Elizabeth J. Luna, Ian B. Gibson, Molly Bray, Ying Jin, Altaf Kondkar, Srikanth Nagalla, Nacima Hadjout-Rabi, Tara C. Smith, Daniel Covarrubias, Stephen N. Jones, Firdos Ahmad, Moritz Stolla, Xianguo Kong, Zhiyou Fang, Wolfgang Bergmeier, Chad Shaw, Suzanne M. Leal, Paul Bray

Department of Medicine Faculty Papers

BACKGROUND: High shear force critically regulates platelet adhesion and thrombus formation during ischemic vascular events. To identify genetic factors that influence platelet thrombus formation under high shear stress, we performed a genome-wide association study and confirmatory experiments in human and animal platelets.

METHODS AND RESULTS: Closure times in the shear-dependent platelet function analyzer (PFA)-100 were measured on healthy, nondiabetic European Americans (n=125) and blacks (n=116). A genome-wide association (P

CONCLUSIONS: We show for the first time that (1) platelets contain supervillin; (2) platelet thrombus formation in the PFA-100 is associated with human SVIL variants and low SVIL expression; and (3) …

Participants' Evaluation Of The Project P.A.T.H.S.: Are Findings Based On Different Datasets Consistent?, Daniel T. L. Shek, Rachel C. F. Sun

Pediatrics Faculty Publications

Subjective outcome evaluation findings based on the perspective of the participants of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in nine datasets collected from 2005 to 2009 (n = 206, 313 program participants) were examined in this paper. Based on the consolidated data with schools as units, results showed that the participants generally had positive perceptions of the program, implementers, and benefits of the program. More than four-fifths of the participants regarded the program as beneficial to their holistic development. Multiple regression analysis revealed that the perceived qualities of the program and the program implementers predicted perceived …

Selective Impact Of Hiv Disease Progression On The Innate Immune System In The Human Female Reproductive Tract, Timothy Lahey, Mimi Ghosh, John V. Fahey, Zheng Shen, Lucy R. Mukura, Yan Song, Susan Cu-Uvin, Kenneth H. Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira

Dartmouth Scholarship

Background: We have previously demonstrated intrinsic anti-HIV activity in cervicovaginal lavage (CVL) from HIV-infected women with high CD4 counts and not on antiretroviral therapy. However, the impact of HIV disease progression on CVL innate immune responses has not been delineated.

Methods: CVL from 57 HIV-infected women not on antiretroviral therapy were collected by washing the cervicovaginal area with 10 ml of sterile normal saline. We characterized subject HIV disease progression by CD4 count strata: >500 cells/µl, 200-500 cells/µl, or <200 cells/µl of blood. To assess CVL anti-HIV activity, we incubated TZM-bl cells with HIV plus or minus CVL. Antimicrobials, cytokines, chemokines and anti-gp160 HIV IgG antibodies were measured by ELISA and Luminex.