Digital Commons Network^™

Anatomy, Physiology And Management Of Patients With Diffuse Pulmonary Arteriovenous Malformations, Tamara Lazic

Yale Medicine Thesis Digital Library

Diffuse pulmonary vascular malformations (PAVMs) are a small and understudied, but nevertheless important subset of the PAVM population of patients, associated with significant mortality and morbidity. A review of literature was undertaken to investigate the current understanding of diffuse PAVMs. This review demonstrated that no additional attempts to define diffuse PAVMs and describe their natural history was made before or after the in 2000 report by Faughnan et al {{51 Faughnan,M.E. 2000; }}. To further expand the findings from 2000, we performed a retrospective review of 36 patients (21 female, 15 male) with diffuse PAVMs from a cohort of 821 …

Differences In The Central Neural Activation Under Emotional Stress Across The Menstrual Cycle, Nayalya Lopushnyan

Yale Medicine Thesis Digital Library

The present study had several goals. First, we aimed to investigate the potential differences in the activation of the corticolimbic structures during emotional stress in healthy women across the menstrual cycle using stress imagery. Second, we searched for differences in the subjective anxiety under emotional stress across the menstrual cycle and tried to correlate the perceived level of anxiety to activation of the specific corticolimbic structures. Third, we attempted to compare central neural activation of women in follicular and in luteal phases of the menstrual cycle separately to that of men during emotional stress to investigate potential differences in neural …

Vesicles In Poiseuille Flow, Gerrit Danker, Petia M. Vlahovska, Chaouqi Misbah

Dartmouth Scholarship

Blood microcirculation critically depends on the migration of red cells towards the flow centerline. We identify theoretically the ratio of the inner over the outer fluid viscosities λ as a key parameter. At low λ, the vesicle deforms into a tank-treading ellipsoid shape far away from the flow centerline. The migration is always towards the flow centerline, unlike drops. Above a critical λ, the vesicle tumbles or breaths and migration is suppressed. A surprising coexistence of two types of shapes at the centerline, a bulletlike and a parachutelike shape, is predicted.

A Study Of Micrornas In Silico And In Vivo: Diagnostic And Therapeutic Applications In Cancer., Scott A Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

There is emerging evidence of the production in human tumors of abnormal levels of microRNAs (miRNAs), which have been assigned oncogenic and/or tumor-suppressor functions. While some miRNAs commonly exhibit altered amounts across tumors, more often, different tumor types produce unique patterns of miRNAs, related to their tissue of origin. The role of miRNAs in tumorigenesis underscores their value as mechanism-based therapeutic targets in cancer. Similarly, unique patterns of altered levels of miRNA production provide fingerprints that may serve as molecular biomarkers for tumor diagnosis, classification, prognosis of disease-specific outcomes and prediction of therapeutic responses.

The Relationship Between Cerebral Hemisphere Volume And Receptive Language Functioning In Dyslexia And Attention-Deficit Hyperactivity Disorder (Adhd)., Michelle Y. Kibby, Shital P. Pavawalla, Jill B. Fancher, Angela J. Naillon, George W. Hynd

Publications

Because poor comprehension has been associated with small cerebral volume and there is a high comorbidity between developmental dyslexia, attention-deficit hyperactivity disorder (ADHD), and specific language impairment, the goal of this study was to determine whether cerebral volume is reduced in dyslexia and attention-deficit hyperactivity disorder in general, as some suggest, or whether the reduction in volume corresponds to poor receptive language functioning, regardless of the diagnosis. Participants included 46 children with and without dyslexia and attention-deficit hyperactivity disorder, aged 8 to 12 years. Our results indicated that cerebral volume was comparable between those with and without dyslexia and attention-deficit …

Drug Abuse Treatment Beyond Prison Walls, Carl Leukefeld, Carrie B. Oser, Jennifer Havens, Michele Staton Tindall, Jennifer Mooney, Jamieson B. Duvall, Hannah Knudsen

Behavioral Science Faculty Publications

The period surrounding release from prison is a critical time for parolees, bearing the potential for a drug-free and crime-free life in the community but also high risks for recidivism and relapse to drugs. The authors describe two projects. The first illustrates the use of a formal Delphi process to elicit and combine the expertise of treatment providers, researchers, corrections personnel, and other stakeholders in a set of statewide guidelines for facilitating re-entry. The second project is a six-session intervention to enable women to protect themselves against acquiring or transmitting HIV in their intimate relationships.

Polyglutamine Disruption Of The Huntingtin Exon 1 N Terminus Triggers A Complex Aggregation Mechanism, Ashwani K. Thakur, Murali Jayaraman, Rakesh Mishra, Monika Thakur, Veronique M. Chellgren, In-Ja L Byeon, Dalaver H. Anjum, Ravindra Kodali, Trevor P. Creamer, James F. Conway, Angela M. Gronenborn, Ronald Wetzel

Molecular and Cellular Biochemistry Faculty Publications

Simple polyglutamine (polyQ) peptides aggregate in vitro via a nucleated growth pathway directly yielding amyloid-like aggregates. We show here that the 17-amino-acid flanking sequence (HTT^NT) N-terminal to the polyQ in the toxic huntingtin exon 1 fragment imparts onto this peptide a complex alternative aggregation mechanism. In isolation, the HTT^NT peptide is a compact coil that resists aggregation. When polyQ is fused to this sequence, it induces in HTT^NT, in a repeat-length dependent fashion, a more extended conformation that greatly enhances its aggregation into globular oligomers with HTT^NT cores and exposed polyQ. In a second …

Bias For Consonantal Information Over Vocalic Information In 30-Month-Olds: Cross-Linguistic Evidence From French And English., Thierry Nazzi, Caroline Floccia, Bérangère Moquet, Joseph Butler

School of Psychology

Using a name-based categorization task, Nazzi found in 2005 that French-learning 20-month-olds can make use of one-feature consonantal contrasts between new labels but fail to do so with one-feature vocalic contrasts. This asymmetry was interpreted as developmental evidence for the proposal that consonants play a more important role than vowels at the lexical level. In the current study using the same task, we first show that by 30 months French-learning infants can make use of one-feature vocalic contrasts (e.g., /pize/-/pyze/). Second, we show that in a situation where infants must neglect either a consonantal one-feature change or a vocalic one-feature …

Long-Distance Delivery Of Bacterial Virulence Factors By Pseudomonas Aeruginosa Outer Membrane Vesicles, Jennifer M. Bomberger, Daniel P. Maceachran, Bonita A. Coutermarsh, Siying Ye, George A. O'Toole, Bruce A. Stanton, Frederick M. Ausubel

Dartmouth Scholarship

Bacteria use a variety of secreted virulence factors to manipulate host cells, thereby causing significant morbidity and mortality. We report a mechanism for the long-distance delivery of multiple bacterial virulence factors, simultaneously and directly into the host cell cytoplasm, thus obviating the need for direct interaction of the pathogen with the host cell to cause cytotoxicity. We show that outer membrane–derived vesicles (OMV) secreted by the opportunistic human pathogen Pseudomonas aeruginosa deliver multiple virulence factors, including β-lactamase, alkaline phosphatase, hemolytic phospholipase C, and Cif, directly into the host cytoplasm via fusion of OMV with lipid rafts in the host plasma …

Understanding Pitch Perception As A Hierarchical Process With Top-Down Modulation., E Balaguer-Ballester, Nr Clark, M Coath, K Krumbholz, Sl Denham

School of Psychology

Pitch is one of the most important features of natural sounds, underlying the perception of melody in music and prosody in speech. However, the temporal dynamics of pitch processing are still poorly understood. Previous studies suggest that the auditory system uses a wide range of time scales to integrate pitch-related information and that the effective integration time is both task- and stimulus-dependent. None of the existing models of pitch processing can account for such task- and stimulus-dependent variations in processing time scales. This study presents an idealized neurocomputational model, which provides a unified account of the multiple time scales observed …

Paracrine Sonic Hedgehog Signalling By Prostate Cancer Cells Induces Osteoblast Differentiation, Samantha M Zunich, Taneka Douglas, Maria Valdovinos, Tiffany Chang

Dartmouth Scholarship

Sonic hedgehog (Shh) and components of its signalling pathway have been identified in human prostate carcinoma and increased levels of their expression appear to correlate with disease progression and metastasis. The mechanism through which Shh signalling could promote metastasis in bone, the most common site for prostate carcinoma metastasis, has not yet been investigated. The present study determined the effect of Shh signalling between prostate cancer cells and pre-osteoblasts on osteoblast differentiation, a requisite process for new bone formation that characterizes prostate carcinoma metastasis.

Clinical Trial Of Tailored Activity And Eating Newsletters With Older Rural Women., Susan Noble Walker, Carol H. Pullen, Linda Boeckner, Patricia A. Hageman, Melody Hertzog, Maureen K. Oberdorfer, Matthew J. Rutledge

Journal Articles: College of Nursing

BACKGROUND: Unhealthy diet and lack of physical activity increase rural midlife and older women's risk of chronic diseases and premature death, and they are behind urban residents in meeting Healthy People 2010 objectives.

OBJECTIVES: The objective of this study was to compare a tailored intervention based on the Health Promotion Model with a generic intervention to increase physical activity and healthy eating among rural women.

METHODS: In a randomized-by-site, community-based, controlled, clinical trial, Wellness for Women, 225 women aged 50 to 69 years were recruited in two similar rural areas. Over 12 months, women received by mail either 18 generic …

What Is The Cost Of Maintaining A Kidney In Upper-Tract Transitional-Cell Carcinoma? An Objective Analysis Of Cost And Survival., Raymond W Pak, Eric J Moskowitz, Demetrius H Bagley

Department of Urology Faculty Papers

BACKGROUND AND PURPOSE: For many years, the gold standard in upper urinary tract transitional-cell carcinoma (UT-TCC) management has been nephroureterectomy with excision of the bladder cuff. Advances in endourologic instrumentation have allowed urologists to manage this malignancy. The feasibility and success of conservative measures for UT-TCC have been widely published, but there has not been an objective cost analysis performed to date. Our goal was to examine the direct costs of renal-sparing conservative measures v nephroureterectomy and subsequent chronic kidney disease (CKD) or end-stage renal disease (ESRD). Secondary analysis includes a discussion of survival and quality-of-life issues for both treatment …

Discovering The Complexities Of Adolescent Compliance To Treatment, Megan Song, Hatim A. Omar

Pediatrics Faculty Publications

To explore the challenges faced in enhancing adolescent treatment compliance and to understand the roles of key players in this endeavor: the adolescent, parent and healthcare provider. Obtaining compliance from adolescents requires collaboration from the adolescent, caregiver and provider and depends on well-established relationships between each person in the triad: adolescent-provider, adolescent-caregiver, and caregiver-provider. Ensuring and improving adherence to treatment by adolescents is a challenging task but crucial to overall health outcomes. It requires the collaboration of the adolescent, parent and physician to create the optimal treatment plan, specifically tailored to the adolescent. For the clinician, maintaining good communication and …

The Future (Or Lack Of Future) Of Personalized Prescription In Psychiatry, Jose De Leon

Psychiatry Faculty Publications

Rapid technological advances in genetics have created conceptual chaos regarding the genetics of drug response. Terms for differing concepts are used interchangeably: pharmacogenetics with pharmacogenomics, personalized medicine with personalized prescription. Biomarker has many definitions. The author prefers the concept of personalized prescription and uses it with implications beyond pharmacogenetics by considering all scientific information valid for prescribing medication. Genetics may not be crucial for all drugs. In this comprehensive view, clinicians must consider genetic, environmental and personal variables when prescribing medication and incorporate some basic pharmacological principles: (1) safety and efficacy, (2) pharmacokinetics and pharmacodynamics, (3) therapeutic window and prescriber's …

Iatrogenic Bile Duct Injury Associated With Anomalies Of The Right Hepatic Sectoral Ducts: A Misunderstood And Underappreciated Problem, Nitin Babel, Sujit Vijay Sakpal, Prakash Paragi, Jason Wellen, Stephen Feldman, Ronald Scott Chamberlain

Department of Surgery

Although laparoscopic cholecystectomy (LC) has been widely accepted as the standard of care, it continues to have a higher complication rate than open cholecystectomy. Bile duct injury with LC has often been attributed to surgical inexperience, but it is also clear that aberrant bile ducts are present in a significant number of patients who sustain biliary injuries during these procedures. We present three cases of right sectoral hepatic duct injuries which occurred during LC and provide a discussion of the conditions which are likely to lead to these injuries, as part of a strategy to prevent them.

Mrn Complex Function In The Repair Of Chromosomal Rag-Mediated Dna Double-Strand Breaks, Beth A. Helmink, Andrea L. Bredemeyer, Baeck-Seung Lee, Ching-Yu Huang, Girdhar G. Sharma, Laura M. Walker, Jeffrey J. Bednarski, Wan-Ling Lee, Tej K. Pandita, Craig H. Bassing, Barry P. Sleckman

Open Access Publications

The Mre11-Rad50-Nbs1 (MRN) complex functions in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) at postreplicative stages of the cell cycle. During HR, the MRN complex functions directly in the repair of DNA DSBs and in the initiation of DSB responses through activation of the ataxia telangiectasia-mutated (ATM) serine-threonine kinase. Whether MRN functions in DNA damage responses before DNA replication in G0/G1 phase cells has been less clear. In developing G1-phase lymphocytes, DNA DSBs are generated by the Rag endonuclease and repaired during the assembly of antigen receptor genes by the process of V(D)J recombination. Mice and …

Antibiotic Prophylaxis For Leptospirosis, David Brett-Major, Robert J. Lipnick

Journal Articles: Epidemiology

BACKGROUND: Leptospira infection is a global zoonosis with significant health impact for agricultural workers and those persons whose work or recreation takes them into endemic areas.

OBJECTIVES: This systematic review assessed the current literature for evidence for or against use of antibiotic prophylaxis against Leptospira infection (leptospirosis).

SEARCH STRATEGY: The authors searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and SCI-Expanded as well as relevant professional society meeting abstracts until January 2009.

SELECTION CRITERIA: Prospective, randomised clinical trials studying antibiotic prophylaxis against leptospirosis were selected.

DATA …

Improving Follow-Up Of Abnormal Cancer Screens Using Electronic Health Records: Trust But Verify Test Result Communication, Hardeep Singh, Lindsey Wilson, Laura A Petersen, Mona K Sawhney, Brian Reis, Donna Espadas, Dean F Sittig

Faculty, Staff and Student Publications

BACKGROUND: Early detection of colorectal cancer through timely follow-up of positive Fecal Occult Blood Tests (FOBTs) remains a challenge. In our previous work, we found 40% of positive FOBT results eligible for colonoscopy had no documented response by a treating clinician at two weeks despite procedures for electronic result notification. We determined if technical and/or workflow-related aspects of automated communication in the electronic health record could lead to the lack of response.

METHODS: Using both qualitative and quantitative methods, we evaluated positive FOBT communication in the electronic health record of a large, urban facility between May 2008 and March 2009. …

Rationale And Design Of A Trial Of Angiotensin-Converting Enzyme Inhibition In Infants With Single Ventricle., Daphne T. Hsu, Seema Mital, Chitra Ravishankar, Renee Margossian, Jennifer S. Li, Lynn A. Sleeper, Richard V. Williams, Jami C. Levine, Brian W. Mccrindle, Andrew M. Atz, Darlene Servedio, Lynn Mahony, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors are known to improve clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology show abnormalities in ventricular function as well as poor growth. The ability of an ACE inhibitor to preserve ventricular function and improve growth in these infants is unknown.

METHODS: The Pediatric Heart Network designed a randomized, double-blind trial to compare outcomes in infants with single-ventricle physiology receiving enalapril or placebo. Neonates < or =45 days old were eligible. The primary outcome is weight-for-age Z-score at 14 months of age. Secondary outcomes include other measures of somatic growth, laboratory and functional measures of heart failure, developmental indices, measures of ventricular size and function, and the relationship of the renin-angiotensin-aldosterone system genotype to the response to enalapril. The incidence and spectrum of adverse events will also be compared between treatment groups.

RESULTS: A total of 1,245 neonates were screened and 533 (43%) were eligible. The consent rate was 43%; 230 subjects were enrolled. Parental reluctance to …

Regional And Foreign Accent Processing In English: Can Listeners Adapt?, Caroline Floccia, Joseph Butler, Jeremy Goslin, Lucy Ellis

School of Psychology

Recent data suggest that the first presentation of a foreign accent triggers a delay in word identification, followed by a subsequent adaptation. This study examines under what conditions the delay resumes to baseline level. The delay will be experimentally induced by the presentation of sentences spoken to listeners in a foreign or a regional accent as part of a lexical decision task for words placed at the end of sentences. Using a blocked design of accents presentation, Experiment 1 shows that accent changes cause a temporary perturbation in reaction times, followed by a smaller but long-lasting delay. Experiment 2 shows …

Elevated Expression Of L-Selectin Ligand In Lymph Node-Derived Human Prostate Cancer Cells Correlates With Increased Tumorigenicity., Prakash Radhakrishnan, Ming-Fong Lin, Pi-Wan Cheng

Journal Articles: Biochemistry & Molecular Biology

Human prostate cancer LNCaP cells including C-33 and C-81 cells were originally derived from the lymph nodes of a patient with metastatic prostate cancer. These two cells were employed for characterization of L-selectin ligand and in vitro tumorigenicity, because they mimic the clinical conditions of early and late-stage human prostate cancer. C-81 cells exhibit higher in vitro migratory and invasive properties as compared with C-33 cells. We find that the L-selectin ligand and mucin glycan-associated MECA-79 epitope were elevated in C-81 cells. An increase of these glycotopes positively correlates with elevated tumorigenicity and expression of key glycosyl- and sulfotransferase genes. …

Evidence For Menstrual Cycle Shifts In Women’S Preferences For Masculinity: A Response To Harris (In Press) “Menstrual Cycle And Facial Preferences Reconsidered", Lisa Debruine, Benedict C. Jones, David Frederick, Martie Haselton, Ian S. Penton-Voak, David I. Perrett

Psychology Faculty Articles and Research

Over the last decade, a growing literature has shown that women in the fertile phase of the menstrual cycle demonstrate stronger preferences for men with masculine traits than they do when in the non-fertile phases of the cycle (see Gangestad and Thornhill, 2008 and Jones et al., 2008 for recent reviews). In a recent article, Harris (in press; Sex Roles) failed to replicate this increase in women's preferences for masculine faces when women are near ovulation. Harris represented her study as one of only three studies on the topic, and as the largest of the existing studies. There are, however, …

Lung Cancer In A U.S. Population With Low To Moderate Arsenic Exposure, Julia Heck

Dartmouth Scholarship

No abstract provided.

Quality Improvement In Small Office Settings: An Examination Of Successful Practices., Daniel Wolfson, Elizabeth Bernabeo, Brian Leas, Shoshanna Sofaer, Gregory Pawlson, Donna Pillittere

College of Population Health Faculty Papers

BACKGROUND: Physicians in small to moderate primary care practices in the United States (U.S.) (<25>physicians) face unique challenges in implementing quality improvement (QI) initiatives, including limited resources, small staffs, and inadequate information technology systems 23,36. This qualitative study sought to identify and understand the characteristics and organizational cultures of physicians working in smaller practices who are actively engaged in measurement and quality improvement initiatives.

METHODS: We undertook a qualitative study, based on semi-structured, open-ended interviews conducted with practices (N = 39) that used performance data to drive quality improvement activities.

RESULTS: Physicians indicated that benefits to performing measurement and …

Quality Improvement In Small Office Settings: An Examination Of Successful Practices., Daniel Wolfson, Elizabeth Bernabeo, Brian Leas, Shoshanna Sofaer, Gregory Pawlson, Donna Pillittere

College of Population Health Faculty Papers

BACKGROUND: Physicians in small to moderate primary care practices in the United States (U.S.) (<25 >physicians) face unique challenges in implementing quality improvement (QI) initiatives, including limited resources, small staffs, and inadequate information technology systems 23,36. This qualitative study sought to identify and understand the characteristics and organizational cultures of physicians working in smaller practices who are actively engaged in measurement and quality improvement initiatives.

METHODS: We undertook a qualitative study, based on semi-structured, open-ended interviews conducted with practices (N = 39) that used performance data to drive quality improvement activities.

RESULTS: Physicians indicated that benefits to performing measurement and …

Evaluation Of The Stability And Validity Of Participant Samples Recruited Over The Internet., Daniel Z Lieberman

Psychiatry and Behavioral Sciences Faculty Publications

Research conducted via the Internet has the potential to reach important clinical populations of participants who would not participate in traditional studies. Concerns exist, however, about the validity of samples recruited in this manner, especially when participants are anonymous and never have contact with study staff. This study evaluated two anonymous samples that were recruited over the Internet to test an online program designed to help problem drinkers. The two studies were conducted 3 years apart, and different recruitment strategies were utilized. Despite these differences, the two samples were highly similar in demographic and clinical features. Correlations that have been …

Meeting Report: Methylmercury In Marine Ecosystems—From Sources To Seafood Consumers, Celia Y. Chen, Nancy Serrell, David C. Evers, Bethany J. Fleishman, Kathleen F. Lambert, Jeri Weiss, Robert P. Mason, Michael S. Bank

Dartmouth Scholarship

Mercury and other contaminants in coastal and open-ocean ecosystems are an issue of great concern globally and in the United States, where consumption of marine fish and shellfish is a major route of human exposure to methylmercury (MeHg). A recent National Institute of Environmental Health Sciences–Superfund Basic Research Program workshop titled “Fate and Bioavailability of Mercury in Aquatic Ecosystems and Effects on Human Exposure,” convened by the Dartmouth Toxic Metals Research Program on 15–16 November 2006 in Durham, New Hampshire, brought together human health experts, marine scientists, and ecotoxicologists to encourage cross-disciplinary discussion between ecosystem and human health scientists and …

Androgen-Independent Prostate Cancer Cells Acquire The Complete Steroidogenic Potential Of Synthesizing Testosterone From Cholesterol., Paulette R. Dillard, Ming-Fong Lin, Shafiq A. Khan

Journal Articles: Biochemistry & Molecular Biology

The proliferation and differentiation of normal prostate epithelial cells depends upon the action of androgens produced by the testis. Prostate cancers retain the ability to respond to androgens in the initial stages of cancer development, but progressively become independent of exogenous androgens in advanced stages of the disease while maintaining the expression of functional androgen receptor (AR). In the present study, we have determined the potential of prostate cancer cells to synthesize androgens from cholesterol which may be involved in intracrine regulation of AR in advanced stages of the disease. Established androgen-independent prostate cancer cell lines, PC3 and DU145 cells, …

The Parkinson's Disease Protein Α-Synuclein Disrupts Cellular Rab Homeostasis, Aaron D. Gitler, Brooke J. Bevis, James Shorter, Katherine E. Strathearn, Shusei Hamamichi, Linhui Julie Su, Kim A. Caldwell, Guy A. Caldwell, Jean-Christophe Rochet, J. Michael Mccaffrey, Charles Barlowe, Susan Lindquist

Dartmouth Scholarship

α-Synuclein (α-syn), a protein of unknown function, is the most abundant protein in Lewy bodies, the histological hallmark of Parkinson's disease (PD). In yeast α-syn inhibits endoplasmic reticulum (ER)-to-Golgi (ER→Golgi) vesicle trafficking, which is rescued by overexpression of a Rab GTPase that regulates ER→Golgi trafficking. The homologous Rab1 rescues α-syn toxicity in dopaminergic neuronal models of PD. Here we investigate this conserved feature of α-syn pathobiology. In a cell-free system with purified transport factors α-syn inhibited ER→Golgi trafficking in an α-syn dose-dependent manner. Vesicles budded efficiently from the ER, but their docking or fusion to Golgi membranes was inhibited. Thus, …