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Characteristics Of Clinical Shoulder Research Over The Last Decade: A Review Of Shoulder Articles In The Journal Of Bone & Joint Surgery From 2004 To 2014, Gary M. Gartsman, Brent J. Morris, R. Zackary Unger, Mitzi S. Laughlin, Hussein A. Elkousy, T. Bradley Edwards Mar 2015

Characteristics Of Clinical Shoulder Research Over The Last Decade: A Review Of Shoulder Articles In The Journal Of Bone & Joint Surgery From 2004 To 2014, Gary M. Gartsman, Brent J. Morris, R. Zackary Unger, Mitzi S. Laughlin, Hussein A. Elkousy, T. Bradley Edwards

Orthopaedic Surgery and Sports Medicine Faculty Publications

Background: The purpose of this study was to determine characteristics and trends in published shoulder research over the last decade in a leading orthopaedic journal.

Methods: We examined all clinical shoulder articles published in The Journal of Bone & Joint Surgery from 2004 to 2014. The number of citations, authorship, academic degrees of the authors, country and institution of origin, topic, level of evidence, positive or nonpositive outcome, and inclusion of validated patient-reported outcome measures were assessed for each article.

Results: Shoulder articles that included an author with an advanced research degree (MD [Doctor of Medicine] with a PhD …


Changes In Speckle Tracking Echocardiography Measures Of Ventricular Function After Percutaneous Implantation Of The Edwards Sapien Transcatheter Heart Valve In The Pulmonary Position., Shahryar M. Chowdhury, Ziyad M. Hijazi, John F. Rhodes, Saibal Kar, Raj Makkar, Michael Mullen, Qi-Ling Cao, Lazar Mandinov, Jason Buckley, Nicholas P. Pietris, Girish S. Shirali Mar 2015

Changes In Speckle Tracking Echocardiography Measures Of Ventricular Function After Percutaneous Implantation Of The Edwards Sapien Transcatheter Heart Valve In The Pulmonary Position., Shahryar M. Chowdhury, Ziyad M. Hijazi, John F. Rhodes, Saibal Kar, Raj Makkar, Michael Mullen, Qi-Ling Cao, Lazar Mandinov, Jason Buckley, Nicholas P. Pietris, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Patients with free pulmonary regurgitation or mixed pulmonary stenosis and regurgitation and severely dilated right ventricles (RV) show little improvement in ventricular function after pulmonary valve replacement when assessed by traditional echocardiographic markers. We evaluated changes in right and left ventricular (LV) function using speckle tracking echocardiography in patients after SAPIEN transcatheter pulmonary valve (TPV) placement.

METHODS: Echocardiograms were evaluated at baseline, discharge, 1 and 6 months after TPV placement in 24 patients from 4 centers. Speckle tracking measures of function included peak longitudinal strain, strain rate, and early diastolic strain rate. RV fractional area change, tricuspid annular plane …


Belief About Nicotine Selectively Modulates Value And Reward Prediction Error Signals In Smokers, Xiaosi Gu, Terry Lohrenz, Ramiro Salas, Philip R. Baldwin, Alireza Soltani Feb 2015

Belief About Nicotine Selectively Modulates Value And Reward Prediction Error Signals In Smokers, Xiaosi Gu, Terry Lohrenz, Ramiro Salas, Philip R. Baldwin, Alireza Soltani

Dartmouth Scholarship

Little is known about how prior beliefs impact biophysically described processes in the presence of neuroactive drugs, which presents a profound challenge to the understanding of the mechanisms and treatments of addiction. We engineered smokers' prior beliefs about the presence of nicotine in a cigarette smoked before a functional magnetic resonance imaging session where subjects carried out a sequential choice task. Using a model-based approach, we show that smokers' beliefs about nicotine specifically modulated learning signals (value and reward prediction error) defined by a computational model of mesolimbic dopamine systems. Belief of "no nicotine in cigarette" (compared with "nicotine in …


Predicting Functional And Regulatory Divergence Of A Drug Resistance Transporter Gene In The Human Malaria Parasite, Geoffrey H. Siwo, Asako Tan, Katrina A. Button-Simons, Upeka Samarakoon, Lisa A. Checkley, Richard S. Pinapati, Michael T. Ferdig Feb 2015

Predicting Functional And Regulatory Divergence Of A Drug Resistance Transporter Gene In The Human Malaria Parasite, Geoffrey H. Siwo, Asako Tan, Katrina A. Button-Simons, Upeka Samarakoon, Lisa A. Checkley, Richard S. Pinapati, Michael T. Ferdig

Dartmouth Scholarship

Background:

The paradigm of resistance evolution to chemotherapeutic agents is that a key coding mutation in a specific gene drives resistance to a particular drug. In the case of resistance to the anti-malarial drug chloroquine (CQ), a specific mutation in the transporter pfcrt is associated with resistance. Here, we apply a series of analytical steps to gene expression data from our lab and leverage 3 independent datasets to identify pfcrt-interacting genes. Resulting networks provide insights into pfcrt’s biological functions and regulation, as well as the divergent phenotypic effects of its allelic variants in different genetic backgrounds.

Results:

To …


Tumor Cell Targeting By Iron Oxide Nanoparticles Is Dominated By Different Factors In Vitro Versus In Vivo, Christian Ndong, Jennifer A. Tate, Warren C. Kett, Jaya Batra, Eugene Demidenko, Lionel D. Lewis, P. Jack Hoopes, Tillmann U. Gerngross, Karl E. Griswold Feb 2015

Tumor Cell Targeting By Iron Oxide Nanoparticles Is Dominated By Different Factors In Vitro Versus In Vivo, Christian Ndong, Jennifer A. Tate, Warren C. Kett, Jaya Batra, Eugene Demidenko, Lionel D. Lewis, P. Jack Hoopes, Tillmann U. Gerngross, Karl E. Griswold

Dartmouth Scholarship

Realizing the full potential of iron oxide nanoparticles (IONP) for cancer diagnosis and therapy requires selective tumor cell accumulation. Here, we report a systematic analysis of two key determinants for IONP homing to human breast cancers: (i) particle size and (ii) active vs passive targeting. In vitro, molecular targeting to the HER2 receptor was the dominant factor driving cancer cell association. In contrast, size was found to be the key determinant of tumor accumulation in vivo, where molecular targeting increased tumor tissue concentrations for 30 nm but not 100 nm IONP. Similar to the in vitro results, PEGylation …


The Effects Of Test-Enhanced Learning On Long-Term Retention In Aan Annual Meeting Courses., Douglas P Larsen, Andrew C Butler, Wint Y Aung, John R Corboy, Deborah I Friedman, Michael R Sperling Feb 2015

The Effects Of Test-Enhanced Learning On Long-Term Retention In Aan Annual Meeting Courses., Douglas P Larsen, Andrew C Butler, Wint Y Aung, John R Corboy, Deborah I Friedman, Michael R Sperling

Department of Neurology Faculty Papers

OBJECTIVE: We measured the long-term retention of knowledge gained through selected American Academy of Neurology annual meeting courses and compared the effects of repeated quizzing (known as test-enhanced learning) and repeated studying on that retention.

METHODS: Participants were recruited from 4 annual meeting courses. All participants took a pretest. This randomized, controlled trial utilized a within-subjects design in which each participant experienced 3 different postcourse activities with each activity performed on different material. Each key information point from the course was randomized in a counterbalanced fashion among participants to one of the 3 activities: repeated short-answer quizzing, repeated studying, and …


Scoliosis Related Information On The Internet In China: Can Patients Benefit From This Information?, Hongda Bao, Feng Zhu, Fei Wang, Zhen Liu, Mike H. Bao, Shouyu He, Zezhang Zhu, Yong Qiu Feb 2015

Scoliosis Related Information On The Internet In China: Can Patients Benefit From This Information?, Hongda Bao, Feng Zhu, Fei Wang, Zhen Liu, Mike H. Bao, Shouyu He, Zezhang Zhu, Yong Qiu

Dartmouth Scholarship

Background: There has been an increasing popularity of searching health related information online in recent years. Despite that considerable amount of scoliosis patients have shown interest in obtaining scoliosis information through Internet, previous studies have demonstrated poor quality of online information. However, this conclusion may vary depending on region and culture. Since China has a restricted Internet access outside of its borders, the aim of this study is to evaluate the quality of scoliosis information available online using recognized scoring systems and to analyze the Internet as a source of health information in China.

Methods: A survey-based questionnaire was distributed …


Modeling Neurovascular Coupling From Clustered Parameter Sets For Multimodal Eeg-Nirs, M. Tanveer Talukdar, H. Robert Frost, Solomon G. G. Diamond Feb 2015

Modeling Neurovascular Coupling From Clustered Parameter Sets For Multimodal Eeg-Nirs, M. Tanveer Talukdar, H. Robert Frost, Solomon G. G. Diamond

Dartmouth Scholarship

Despite significant improvements in neuroimaging technologies and analysis methods, the fundamental relationship between local changes in cerebral hemodynamics and the underlying neural activity remains largely unknown. In this study, a data driven approach is proposed for modeling this neurovascular coupling relationship from simultaneously acquired electroencephalographic (EEG) and near-infrared spectroscopic (NIRS) data. The approach uses gamma transfer functions to map EEG spectral envelopes that reflect time-varying power variations in neural rhythms to hemodynamics measured with NIRS during median nerve stimulation. The approach is evaluated first with simulated EEG-NIRS data and then by applying the method to experimental EEG-NIRS data measured from …


Shbg Gene Polymorphism (Rs1799941) Associates With Metabolic Syndrome In Children And Adolescents, Marquitta J. White, Fatih Eren, Deniz Agirbasli, Scott M. Williams, Mehmet Agirbasli Feb 2015

Shbg Gene Polymorphism (Rs1799941) Associates With Metabolic Syndrome In Children And Adolescents, Marquitta J. White, Fatih Eren, Deniz Agirbasli, Scott M. Williams, Mehmet Agirbasli

Dartmouth Scholarship

Background: Metabolic syndrome (MetS) is a complex disorder characterized by coexistence of several cardiometabolic (CM) factors, i.e. hyperlipidemia, obesity, high blood pressure and insulin resistance. The presence of MetS is strongly associated with increased risk of cardiovascular disease (CVD). The syndrome was originally defined as an adult disorder, but MetS has become increasingly recognized in children and adolescents.

Methods: Genetic variants influence biological components common to the CM factors that comprise MetS. We investigated single locus associations between six single nucleotide polymorphisms (SNPs), previously shown to modulate lipid or sex hormone binding globulin (SHBG) levels, with MetS in a Turkish …


Efficacy Of Transoral Fundoplication Vs Omeprazole For Treatment Of Regurgitation In A Randomized Controlled Trial., John G. Hunter, Peter J. Kahrilas, Reginald C.W. Bell, Erik B. Wilson, Karim S. Trad, James P. Dolan, Kyle A. Perry, Brant K. Oelschlager, Nathaniel J. Soper, Brad E. Snyder, Miguel A. Burch, William Scott Melvin, Kevin M. Reavis, Daniel G. Turgeon, Eric S. Hungness, Brian S. Diggs Feb 2015

Efficacy Of Transoral Fundoplication Vs Omeprazole For Treatment Of Regurgitation In A Randomized Controlled Trial., John G. Hunter, Peter J. Kahrilas, Reginald C.W. Bell, Erik B. Wilson, Karim S. Trad, James P. Dolan, Kyle A. Perry, Brant K. Oelschlager, Nathaniel J. Soper, Brad E. Snyder, Miguel A. Burch, William Scott Melvin, Kevin M. Reavis, Daniel G. Turgeon, Eric S. Hungness, Brian S. Diggs

Surgery Faculty Publications

Background

The aim of this randomized, crossover study was to determine if transoral fundoplication (TF) could further improve clinical outcomes in partial responders to high-dose (HD) proton-pump inhibitor (PPI) therapy and to evaluate durability of TF.

Methods

In seven United States centers, patients with hiatal hernia ≤2 cm and abnormal esophageal acid exposure (EAE) were randomized to TF (n = 40) or HD PPIs (n = 23) group. At 6-month follow-up, PPI patients underwent crossover. We assessed clinical outcomes 6-month post TF in crossover patients (COP), as compared to 6-month of HD PPI therapy, and 12-month outcomes in patients initially …


Francis Daniels Moore: One Of The Brightest Minds In The Surgical Field., Sara L. Low, Bs, Charles J. Yeo, Md, Scott W. Cowan, Md, Ashesh P. Shah, Md Feb 2015

Francis Daniels Moore: One Of The Brightest Minds In The Surgical Field., Sara L. Low, Bs, Charles J. Yeo, Md, Scott W. Cowan, Md, Ashesh P. Shah, Md

Department of Surgery Gibbon Society Historical Profiles

Francis Daniels Moore was a pioneer ahead of his time who made numerous landmark contributions to the field of surgery, including the understanding of metabolic physiology during surgery, liver and kidney transplant, and the famous Study on Surgical Services of the United States (SOSSUS) report of 1975 that served for decades as a guideline for development of surgical residencies. He was the epitome of what a physician should be, a compassionate and dedicated surgeon, innovative scientist, and a medical professional dedicated to quality medical education across all specialties.


Vivien Thomas: Master Craftsman, Gifted Teacher, And Unsung Hero., Alisha Joyner, B.S., Charles J. Yeo, Md, Pinckney J. Maxwell, Iv, Md Feb 2015

Vivien Thomas: Master Craftsman, Gifted Teacher, And Unsung Hero., Alisha Joyner, B.S., Charles J. Yeo, Md, Pinckney J. Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

The field of pediatric cardiovascular surgery gained international recognition in 1944 with the first successful correction of a tetralogy of Fallot congenital anomaly in a 15-month-old patient. Dr. Helen Taussig (1898 to 1986), a pediatrician at Johns Hopkins Hospital, recognized the need for the procedure. Dr. Alfred Blalock (1899 to 1964), Chief of Surgery at Johns Hopkins Hospital, is credited with performing the surgery. However, there is an unsung hero who for many years did not receive a single mention in the medical literature. Vivien Thomas (1910 to 1985) was Dr. Blalock’s research assistant who is said to have stood …


Lifelong Physical Exercise Delays Age-Associated Skeletal Muscle Decline., S Zampieri, L Pietrangelo, S Loefler, H Fruhmann, M Vogelauer, S Burggraf, A Pond, M Grim-Stieger, J Cvecka, M Sedliak, V Tirpáková, W Mayr, N Sarabon, K Rossini, L Barberi, M De Rossi, V Romanello, S Boncompagni, A Musarò, M Sandri, F Protasi, U Carraro, H Kern Feb 2015

Lifelong Physical Exercise Delays Age-Associated Skeletal Muscle Decline., S Zampieri, L Pietrangelo, S Loefler, H Fruhmann, M Vogelauer, S Burggraf, A Pond, M Grim-Stieger, J Cvecka, M Sedliak, V Tirpáková, W Mayr, N Sarabon, K Rossini, L Barberi, M De Rossi, V Romanello, S Boncompagni, A Musarò, M Sandri, F Protasi, U Carraro, H Kern

Publications

Aging is usually accompanied by a significant reduction in muscle mass and force. To determine the relative contribution of inactivity and aging per se to this decay, we compared muscle function and structure in (a) male participants belonging to a group of well-trained seniors (average of 70 years) who exercised regularly in their previous 30 years and (b) age-matched healthy sedentary seniors with (c) active young men (average of 27 years). The results collected show that relative to their sedentary cohorts, muscle from senior sportsmen have: (a) greater maximal isometric force and function, (b) better preserved fiber morphology and ultrastructure …


On Voxel-By-Voxel Accumulated Dose For Prostate Radiation Therapy Using Deformable Image Registration., Jialu Yu, Nicholas Hardcastle, Kyoungkeun Jeong, Edward T. Bender, Mark A. Ritter, Wolfgang A. Tomé Feb 2015

On Voxel-By-Voxel Accumulated Dose For Prostate Radiation Therapy Using Deformable Image Registration., Jialu Yu, Nicholas Hardcastle, Kyoungkeun Jeong, Edward T. Bender, Mark A. Ritter, Wolfgang A. Tomé

Department of Radiation Oncology Faculty Papers

Since delivered dose is rarely the same with planned, we calculated the delivered total dose to ten prostate radiotherapy patients treated with rectal balloons using deformable dose accumulation (DDA) and compared it with the planned dose. The patients were treated with TomoTherapy using two rectal balloon designs: five patients had the Radiadyne balloon (balloon A), and five patients had the EZ-EM balloon (balloon B). Prostate and rectal wall contours were outlined on each pre-treatment MVCT for all patients. Delivered fractional doses were calculated using the MVCT taken immediately prior to delivery. Dose grids were accumulated to the last MVCT using …


Improved Systemic Saturation After Ventricular Assist Device Implantation In A Patient With Decompensated Dextro-Transposition Of The Great Arteries After The Fontan Procedure, Ali Abdul Jabbar, Wayne J Franklin, Leo Simpson, Andrew B Civitello, Reynolds M Delgado, O H Frazier Feb 2015

Improved Systemic Saturation After Ventricular Assist Device Implantation In A Patient With Decompensated Dextro-Transposition Of The Great Arteries After The Fontan Procedure, Ali Abdul Jabbar, Wayne J Franklin, Leo Simpson, Andrew B Civitello, Reynolds M Delgado, O H Frazier

The Texas Heart Institute Journal

We report the successful implantation of a HeartMate II left ventricular assist device after a failed Fontan procedure in a patient with dextro-transposition of the great arteries. The patient had developed significant intrapulmonary arteriovenous shunting. Despite the theoretical risk of worsening intrapulmonary shunting due to the decrease in systemic vascular resistance after device implantation, our patient did well. He was discharged from the hospital in stable condition and had better oxygen saturation than before the device was implanted. To our knowledge, ours is the 2nd report of the use of a ventricular assist device after the failure of a Fontan …


Impact And Predictors Of Noncircular Left Ventricular Outflow Tract Shapes On Estimating Aortic Stenosis Severity By Means Of Continuity Equations, Nirmanmoh Bhatia, Buddhadeb Dawn, Tariq S Siddiqui, Marcus F Stoddard Feb 2015

Impact And Predictors Of Noncircular Left Ventricular Outflow Tract Shapes On Estimating Aortic Stenosis Severity By Means Of Continuity Equations, Nirmanmoh Bhatia, Buddhadeb Dawn, Tariq S Siddiqui, Marcus F Stoddard

The Texas Heart Institute Journal

Determining aortic stenosis (AS) severity is clinically important. Calculating aortic valve (AV) area by means of the continuity equation assumes a circular left ventricular outflow tract (LVOT). The full impact of this assumption in calculating AV area is unknown. Predictors of noncircular LVOT shape in patients with AS are undefined.

In 109 adult patients with AS who underwent multiplanar transesophageal echocardiography, we calculated AV area by means of the standard continuity method and by a modified method involving planimetric LVOT area.

We found 54 circular, 37 horizontal-oval, 8 vertical-oval, and 10 irregular LVOTs. Area derived by direct planimetry correlated better …


Echocardiographic Versus Histologic Findings In Marfan Syndrome, Xiaoyan Gu, Yihua He, Zhian Li, Jiancheng Han, Jian Chen, J V Ian Nixon Feb 2015

Echocardiographic Versus Histologic Findings In Marfan Syndrome, Xiaoyan Gu, Yihua He, Zhian Li, Jiancheng Han, Jian Chen, J V Ian Nixon

The Texas Heart Institute Journal

This retrospective study attempted to establish the prevalence of multiple-valve involvement in Marfan syndrome and to compare echocardiographic with histopathologic findings in Marfan patients undergoing valvular or aortic surgery.

We reviewed echocardiograms of 73 Marfan patients who underwent cardiovascular surgery from January 2004 through October 2009. Tissue histology was available for comparison in 29 patients.

Among the 73 patients, 66 underwent aortic valve replacement or the Bentall procedure. Histologic findings were available in 29 patients, all of whom had myxomatous degeneration. Of 63 patients with moderate or severe aortic regurgitation as determined by echocardiography, 4 had thickened aortic valves. The …


Validation Of In Vivo 2d Displacements From Spiral Cine Dense At 3t, Gregory J. Wehner, Jonathan D. Suever, Christopher M. Haggerty, Linyuan Jing, David K. Powell, Sean M. Hamlet, Jonathan D. Grabau, Walter Dimitri Mojsejenko, Xiaodong Zhong, Frederick H. Epstein, Brandon K. Fornwalt Jan 2015

Validation Of In Vivo 2d Displacements From Spiral Cine Dense At 3t, Gregory J. Wehner, Jonathan D. Suever, Christopher M. Haggerty, Linyuan Jing, David K. Powell, Sean M. Hamlet, Jonathan D. Grabau, Walter Dimitri Mojsejenko, Xiaodong Zhong, Frederick H. Epstein, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Displacement Encoding with Stimulated Echoes (DENSE) encodes displacement into the phase of the magnetic resonance signal. Due to the stimulated echo, the signal is inherently low and fades through the cardiac cycle. To compensate, a spiral acquisition has been used at 1.5T. This spiral sequence has not been validated at 3T, where the increased signal would be valuable, but field inhomogeneities may result in measurement errors. We hypothesized that spiral cine DENSE is valid at 3T and tested this hypothesis by measuring displacement errors at both 1.5T and 3T in vivo.

METHODS: Two-dimensional spiral cine DENSE and tagged …


Designer Receptors Enhance Memory In A Mouse Model Of Down Syndrome, Ashley M. Fortress, Eric D. Hamlett, Elena M. Vazey, Gary Aston-Jones, Wayne A. Cass, Heather A. Boger, Ann-Charlotte E. Granholm Jan 2015

Designer Receptors Enhance Memory In A Mouse Model Of Down Syndrome, Ashley M. Fortress, Eric D. Hamlett, Elena M. Vazey, Gary Aston-Jones, Wayne A. Cass, Heather A. Boger, Ann-Charlotte E. Granholm

Neuroscience Faculty Publications

Designer receptors exclusively activated by designer drugs (DREADDs) are novel and powerful tools to investigate discrete neuronal populations in the brain. We have used DREADDs to stimulate degenerating neurons in a Down syndrome (DS) model, Ts65Dn mice. Individuals with DS develop Alzheimer's disease (AD) neuropathology and have elevated risk for dementia starting in their 30s and 40s. Individuals with DS often exhibit working memory deficits coupled with degeneration of the locus coeruleus (LC) norepinephrine (NE) neurons. It is thought that LC degeneration precedes other AD-related neuronal loss, and LC noradrenergic integrity is important for executive function, working memory, and attention. …


Continuing To Confront Copd International Surveys: Comparison Of Patient And Physician Perceptions About Copd Risk And Management, Ana M. Menezes, Sarah H. Landis, Meilan K. Han, Hana Muellerova, Zaurbek Aisanov, Thys Van Der Molen, Yeon-Mok Oh, Masakazu Ichinose, David M. Mannino, Kourtney J. Davis Jan 2015

Continuing To Confront Copd International Surveys: Comparison Of Patient And Physician Perceptions About Copd Risk And Management, Ana M. Menezes, Sarah H. Landis, Meilan K. Han, Hana Muellerova, Zaurbek Aisanov, Thys Van Der Molen, Yeon-Mok Oh, Masakazu Ichinose, David M. Mannino, Kourtney J. Davis

Preventive Medicine and Environmental Health Faculty Publications

PURPOSE: Using data from the Continuing to Confront COPD International Physician and Patient Surveys, this paper describes physicians' attitudes and beliefs regarding chronic obstructive pulmonary disease (COPD) prognosis, and compares physician and patient perceptions with respect to COPD.

METHODS: In 12 countries worldwide, 4,343 patients with COPD were identified through systematic screening of population samples, and 1,307 physicians who regularly saw patients with COPD were sampled from in-country professional databases. Both patients and physicians completed surveys about their COPD knowledge, beliefs, and perceptions; physicians answered further questions about diagnostic methods and treatment choices for COPD.

RESULTS: Most physicians (79%) responded …


Systems Level Analysis Of Systemic Sclerosis Shows A Network Of Immune And Profibrotic Pathways Connected With Genetic Polymorphisms, J. Matthew Mahoney, Jaclyn Taroni, Viktor Martyanov, Tammara A. A. Wood, Casey S. Greene, Patricia A. Pioli, Monique E. Hinchcliff, Michael L. Whitfield Jan 2015

Systems Level Analysis Of Systemic Sclerosis Shows A Network Of Immune And Profibrotic Pathways Connected With Genetic Polymorphisms, J. Matthew Mahoney, Jaclyn Taroni, Viktor Martyanov, Tammara A. A. Wood, Casey S. Greene, Patricia A. Pioli, Monique E. Hinchcliff, Michael L. Whitfield

Dartmouth Scholarship

Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited) are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes …


Trail-Based High Throughput Screening Reveals A Link Between Trail-Mediated Apoptosis And Glutathione Reductase, A Key Component Of Oxidative Stress Response., Dmitri Rozanov, Anton Cheltsov, Eduard Sergienko, Stefan Vasile, Vladislav Golubkov, Alexander E Aleshin, Trevor Levin, Elie Traer, Byron Hann, Julia Freimuth, Nikita Alexeev, Max A Alekseyev, Sergey P Budko, Hans Peter Bächinger, Paul Spellman Jan 2015

Trail-Based High Throughput Screening Reveals A Link Between Trail-Mediated Apoptosis And Glutathione Reductase, A Key Component Of Oxidative Stress Response., Dmitri Rozanov, Anton Cheltsov, Eduard Sergienko, Stefan Vasile, Vladislav Golubkov, Alexander E Aleshin, Trevor Levin, Elie Traer, Byron Hann, Julia Freimuth, Nikita Alexeev, Max A Alekseyev, Sergey P Budko, Hans Peter Bächinger, Paul Spellman

Computational Biology Institute

A high throughput screen for compounds that induce TRAIL-mediated apoptosis identified ML100 as an active chemical probe, which potentiated TRAIL activity in prostate carcinoma PPC-1 and melanoma MDA-MB-435 cells. Follow-up in silico modeling and profiling in cell-based assays allowed us to identify NSC130362, pharmacophore analog of ML100 that induced 65-95% cytotoxicity in cancer cells and did not affect the viability of human primary hepatocytes. In agreement with the activation of the apoptotic pathway, both ML100 and NSC130362 synergistically with TRAIL induced caspase-3/7 activity in MDA-MB-435 cells. Subsequent affinity chromatography and inhibition studies convincingly demonstrated that glutathione reductase (GSR), a key …


Mllt1 Yeats Domain Mutations In Clinically Distinctive Favourable Histology Wilms Tumours., Elizabeth J Perlman, Samantha Gadd, Stefan T Arold, Anand Radhakrishnan, Daniela S Gerhard, Jeffrey S. Dome, +19 Additional Authors Jan 2015

Mllt1 Yeats Domain Mutations In Clinically Distinctive Favourable Histology Wilms Tumours., Elizabeth J Perlman, Samantha Gadd, Stefan T Arold, Anand Radhakrishnan, Daniela S Gerhard, Jeffrey S. Dome, +19 Additional Authors

Pediatrics Faculty Publications

Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar …


Tom Regan On ‘Kind’ Arguments Against Animal Rights And For Human Rights, Nathan Nobis Jan 2015

Tom Regan On ‘Kind’ Arguments Against Animal Rights And For Human Rights, Nathan Nobis

Attitudes Towards Animals Collection

Tom Regan argues that human beings and some non-human animals have moral rights because they are “subjects of lives,” that is, roughly, conscious, sentient beings with an experiential welfare. A prominent critic, Carl Cohen, objects: he argues that only moral agents have rights and so animals, since they are not moral agents, lack rights. An objection to Cohen’s argument is that his theory of rights seems to imply that human beings who are not moral agents have no moral rights, but since these human beings have rights, his theory of rights is false, and so he fails to show that …


Identifying Cases Of Undiagnosed, Clinically Significant Copd In Primary Care: Qualitative Insight From Patients In The Target Population, Nancy K. Leidy, Katherine Kim, Elizabeth D. Bacci, Barbara P. Yawn, David M. Mannino, Byron M. Thomashow, R. Graham Barr, Stephen I. Rennard, Julia F. Houfek, Meilan K. Han, Catherine A. Meldrum, Barry J. Make, Russ P. Bowler, Anna W. Steenrod, Lindsey T. Murray, John W. Walsh, Fernando Martinez, High-Risk-Copd Screening Study Group Jan 2015

Identifying Cases Of Undiagnosed, Clinically Significant Copd In Primary Care: Qualitative Insight From Patients In The Target Population, Nancy K. Leidy, Katherine Kim, Elizabeth D. Bacci, Barbara P. Yawn, David M. Mannino, Byron M. Thomashow, R. Graham Barr, Stephen I. Rennard, Julia F. Houfek, Meilan K. Han, Catherine A. Meldrum, Barry J. Make, Russ P. Bowler, Anna W. Steenrod, Lindsey T. Murray, John W. Walsh, Fernando Martinez, High-Risk-Copd Screening Study Group

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations.

AIMS: This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care.

METHODS: Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care). Phase I: Eight focus groups and six telephone interviews were conducted to elicit descriptions of risk factors for COPD, recent or historical acute respiratory events, and symptoms to inform the …


Design Of A Multi-Center Immunophenotyping Analysis Of Peripheral Blood, Sputum And Bronchoalveolar Lavage Fluid In The Subpopulations And Intermediate Outcome Measures In Copd Study (Spiromics), Christine M. Freeman, Sean Crudgington, Valerie R. Stolberg, Jeanette P. Brown, Joanne Sonstein, Neil E. Alexis, Claire M. Doerschuk, Patricia V. Basta, Elizabeth E. Carretta, David J. Couper, Annette T. Hastie, Robert J. Kaner, Wanda K. O'Neal, Robert Paine, Stephen I. Rennard, Daichi Shimbo, Prescott G. Woodruff, Michelle Zeidler, Jeffrey L. Curtis Jan 2015

Design Of A Multi-Center Immunophenotyping Analysis Of Peripheral Blood, Sputum And Bronchoalveolar Lavage Fluid In The Subpopulations And Intermediate Outcome Measures In Copd Study (Spiromics), Christine M. Freeman, Sean Crudgington, Valerie R. Stolberg, Jeanette P. Brown, Joanne Sonstein, Neil E. Alexis, Claire M. Doerschuk, Patricia V. Basta, Elizabeth E. Carretta, David J. Couper, Annette T. Hastie, Robert J. Kaner, Wanda K. O'Neal, Robert Paine, Stephen I. Rennard, Daichi Shimbo, Prescott G. Woodruff, Michelle Zeidler, Jeffrey L. Curtis

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) is a multi-center longitudinal, observational study to identify novel phenotypes and biomarkers of chronic obstructive pulmonary disease (COPD). In a subset of 300 subjects enrolled at six clinical centers, we are performing flow cytometric analyses of leukocytes from induced sputum, bronchoalveolar lavage (BAL) and peripheral blood. To minimize several sources of variability, we use a "just-in-time" design that permits immediate staining without pre-fixation of samples, followed by centralized analysis on a single instrument.

METHODS: The Immunophenotyping Core prepares 12-color antibody panels, which are shipped to the six Clinical Centers shortly before …


The Effect Of Statins On Blood Gene Expression In Copd, Ma'en Obeidat, Nick Fishbane, Yunlong Nie, Virginia Chen, Zsuzsanna Hollander, Scottj Tebbutt, Yohan Bossé, Raymond T. Ng, Bruce E. Miller, Bruce Mcmanus, Stephen I. Rennard, Peter D. Paré, Don D. Sin Jan 2015

The Effect Of Statins On Blood Gene Expression In Copd, Ma'en Obeidat, Nick Fishbane, Yunlong Nie, Virginia Chen, Zsuzsanna Hollander, Scottj Tebbutt, Yohan Bossé, Raymond T. Ng, Bruce E. Miller, Bruce Mcmanus, Stephen I. Rennard, Peter D. Paré, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: COPD is currently the fourth leading cause of death worldwide. Statins are lipid lowering agents with documented cardiovascular benefits. Observational studies have shown that statins may have a beneficial role in COPD. The impact of statins on blood gene expression from COPD patients is largely unknown.

OBJECTIVE: Identify blood gene signature associated with statin use in COPD patients, and the pathways underpinning this signature that could explain any potential benefits in COPD.

METHODS: Whole blood gene expression was measured on 168 statin users and 451 non-users from the ECLIPSE study using the Affymetrix Human Gene 1.1 ST microarray chips. …


The Development And Application Of An Oncology Therapy-Related Symptom Checklist For Adults (Trsc) And Children (Trsc-C) And E-Health Applications., Arthur R Williams, David D Williams, Phoebe D Williams, Farrokh Alemi, Hosai Hesham, Blaine Donley, Raya Kheirbek Jan 2015

The Development And Application Of An Oncology Therapy-Related Symptom Checklist For Adults (Trsc) And Children (Trsc-C) And E-Health Applications., Arthur R Williams, David D Williams, Phoebe D Williams, Farrokh Alemi, Hosai Hesham, Blaine Donley, Raya Kheirbek

Medicine Faculty Publications

BACKGROUND: Studies found that treatment symptoms of concern to oncology/hematology patients were greatly under-identified in medical records. On average, 11.0 symptoms were reported of concern to patients compared to 1.5 symptoms identified in their medical records. A solution to this problem is use of an electronic symptom checklist that can be easily accessed by patients prior to clinical consultations.

PURPOSE: Describe the oncology Therapy-Related Symptom Checklists for Adults (TRSC) and Children (TRSC-C), which are validated bases for e-Health symptom documentation and management. The TRSC has 25 items/symptoms; the TRSC-C has 30 items/symptoms. These items capture up to 80% of the …


Evidence For Distinct Coastal And Offshore Communities Of Bottlenose Dolphins In The North East Atlantic., Machiel G. Oudejans, Fleur Visser, Anneli Englund, Emer Rogan, Simon N. Ingram Jan 2015

Evidence For Distinct Coastal And Offshore Communities Of Bottlenose Dolphins In The North East Atlantic., Machiel G. Oudejans, Fleur Visser, Anneli Englund, Emer Rogan, Simon N. Ingram

School of Biological and Marine Sciences

Bottlenose dolphin stock structure in the northeast Atlantic remains poorly understood. However, fine scale photo-id data have shown that populations can comprise multiple overlapping social communities. These social communities form structural elements of bottlenose dolphin (Tursiops truncatus) [corrected] populations, reflecting specific ecological and behavioural adaptations to local habitats. We investigated the social structure of bottlenose dolphins in the waters of northwest Ireland and present evidence for distinct inshore and offshore social communities. Individuals of the inshore community had a coastal distribution restricted to waters within 3 km from shore. These animals exhibited a cohesive, fission-fusion social organisation, with repeated resightings …


Identifying A Gene Expression Signature Of Frequent Copd Exacerbations In Peripheral Blood Using Network Methods, Jarrett D. Morrow, Weiliang Qiu, Divya Chhabra, Stephen I. Rennard, Paula Belloni, Anton Belousov, Sreekumar G. Pillai, Craig P. Hersh Jan 2015

Identifying A Gene Expression Signature Of Frequent Copd Exacerbations In Peripheral Blood Using Network Methods, Jarrett D. Morrow, Weiliang Qiu, Divya Chhabra, Stephen I. Rennard, Paula Belloni, Anton Belousov, Sreekumar G. Pillai, Craig P. Hersh

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD), characterized by acute deterioration in symptoms, may be due to bacterial or viral infections, environmental exposures, or unknown factors. Exacerbation frequency may be a stable trait in COPD patients, which could imply genetic susceptibility. Observing the genes, networks, and pathways that are up- and down-regulated in COPD patients with differing susceptibility to exacerbations will help to elucidate the molecular signature and pathogenesis of COPD exacerbations.

METHODS: Gene expression array and plasma biomarker data were obtained using whole-blood samples from subjects enrolled in the Treatment of Emphysema With a Gamma-Selective Retinoid Agonist (TESRA) …