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Galnt11 Is A Novel Galnac-Transferase That Glycosylates Notch1 Receptor To Specify Between Motor And Sensory Ciliary Fates In The Vertebrate Left-Right Organizer, Marko Boskovski

Yale Medicine Thesis Digital Library

Heterotaxy is a disease of abnormal left-right (LR) body patterning associated with congenital heart disease that has very poor outcomes. Despite advances in surgical management, the two most severe forms of heterotaxy, right and left atrial isomerism, have a 29% and 64% 5-year survival rate, respectively. Through copy number variant analysis of heterotaxy patients, GALNT11 was recently identified as a novel gene important in human LR development. However, the mechanism by which Galnt11 causes heterotaxy has not been elucidated. In order to discover the mechanism of GALNT11 in patterning the LR axis, I performed loss of function and gain of …

Emt Driven By Tgf-B Is A Significant Mediator Of Stenosis In Tissue Engineered Vascular Grafts, Daniel Rowe Duncan

Yale Medicine Thesis Digital Library

The development of an autologous tissue engineered vascular graft (TEVG) holds great promise for improving outcomes in congenital heart surgery. The first clinical trial showed that this approach is safe and effective but that the primary mode of failure is stenosis. In a C57BL/6 mouse model of unseeded TEVGs implanted as inferior vena cava interposition grafts, neovessels form in 2 weeks and patent grafts show endothelial and smooth muscle cell (SMC) layers, but occluded grafts show accumulation of SMCs. This suggests stenosis results from abnormal SMC in-growth in the neointima. Studies on fibrosis have shown that resident endothelial cells (EC) …

Blood Gases And Retinopathy Of Prematurity: The Extremely Low Gestational Age Newborn Study, Alisse Katherine Hauspurg

Yale Medicine Thesis Digital Library

BLOOD GASES AND RETINOPATHY OF PREMATURITY: THE EXTREMELY LOW GESTATIONAL AGE NEWBORN STUDY. Alisse K. Hauspurg and Richard A. Ehrenkranz. Department of Pediatrics, Yale University School of Medicine, New Haven, CT.

This study tested the hypothesis that preterm infants who had a blood gas derangement on at least 2 of the first 3 postnatal days are at increased risk for more severe retinopathy of prematurity (ROP). 1,042 infants born before 28 weeks gestational age (GA) were included. An infant was considered at risk if his/her blood gas measure was in the highest or lowest quartile for GA on at least …

Underrepresentation Of Females In Academia: A Relative Rate Index And System Dynamics Model, Nupur Garg

Yale Medicine Thesis Digital Library

Females continue to be significantly outnumbered by their male counterparts in the academic pipeline at the senior ranks. Confounding the problem is the inadequacy of tools used for measurement and analysis of it. A Relative Rate Index (RRI) is a better tool for measuring gender disparities of academic systems than calculating percentages of females in academia. An RRI determines the junctures and scales at which females fall out of the academic track. The RRIs for academic medicine departments at Yale were created using institutional records. Calculations indicate that the fallout for females in academia occurs from assistant to associate professor …

Analyzing Breast Tumor Response To Neoadjuvant Therapy By Pk Models Of Dynamic-­Contrast Enhanced Mr, Matthew Lidstrom

Yale Medicine Thesis Digital Library

Introduction: Pharmacokinetic modeling of contrast uptake by Dynamic-­‐Contrast Enhanced Magnetic Resonance Imaging studies has shown potential to predict the pathologic response to neoadjuvant therapy in breast cancer patients via several small studies. We will attempt to prospectively validate the performance of several previously published criteria in women undergoing neoadjuvant therapy with bevacizumab or trastuzumab.

Methods: 11 patients underwent dynamic contrast enhanced magnetic resonance imaging both before and after receiving one cycle of trastuzumab or bevacizumab neoadjuvant chemotherapy for a primary breast lesion of greater than two centimeters. By abstracting pharmacokinetic parameters (Ktrans) from each study, predictions for therapeutic response based …

Langerhans Cells Facilitate Mutagenesis And Squamous Cell Carcinoma, Badri Modi

Yale Medicine Thesis Digital Library

LANGERHANS CELLS FACILITATE MUTAGENESIS AND SQUAMOUS CELL CARCINOMA.

Badri G. Modi, Jason Neustadter, Julia Lewis, Renata Filler, Bernice Kwong, Swapna Reddy, Robert Tigelaar, Daniel Kaplan, Adrian Hayday, Michael Girardi. Department of Dermatology, Yale University, School of Medicine, New Haven, CT.

Polyaromatic hydrocarbons (PAHs) are prevalent, potent carcinogens, and 7,12-dimethylbenz[a]anthracene (DMBA) is a model PAH widely used to model epithelial carcinogenesis. To achieve mutagenic effects, DMBA must be activated to DMBA-trans-3,4-diol via cytochrome p450 (CYP) 1B1, and this intermediate is the penultimate carcinogen responsible for inducing the signature mutation in the Hras oncogene. Recently, we observed that mice deficient in Langerhans …

Golgi & Eres Biogenesis In The Malaria-Causing Parasite Plasmodium Falciparum, Michelle Morales

Yale Medicine Thesis Digital Library

GOLGI AND ERES BIOGENESIS IN THE MALARIA-CAUSING PARASITE PLASMODIUM FALCIPARUM. Michelle Morales, Susann Herrmann and Tim-Wolf Gilberger, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. Sponsored by Choukri Ben Mamoun, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.

Plasmodium falciparum, the parasite causing the most severe form of human malaria, continues to bear a global burden of morbidity and mortality. No vaccine is available and resistance is emerging and expanding to all classes of existing antimalarials. Relatively little is known about the secretory pathway of P. falciparum, which has the ability to export proteins to specialized …

High-Resolution Time-Frequency Analysis Of Neurovascular Responses To Ischemic Challenges, Frederick Romberg

Yale Medicine Thesis Digital Library

The identification and delineation of oscillatory patterns of blood flow associated with cerebral autoregulation mechanisms is the focus of three specific aims. 1) Identify a superior spectral analysis method for the identification of activity due to cholinergic oscillatory control of the microvasculature (COC_micvasc) and compare the effectiveness of the Hilbert-Huang transform (HHT), the smoothed pseudo Wigner-Ville (SPWV) distribution, and the variable-frequency complex demodulation (VFCDM) method to detect such activity. 2) Determine if changes in forehead microcirculation as monitored by noninvasive laser Doppler flowmetry may provide a reliable indication of the adequacy of cerebral blood flow during progressive simulated …

Acute Constipation In Children Receiving Chemotherapy For Cancer, Jonathan Season

Yale Medicine Thesis Digital Library

ACUTE CONSTIPATION IN CHILDREN RECEIVING CHEMOTHERAPY FOR CANCER.

J. Hale Season, Farzana D. Pashankar, Joseph McNamara, and Dinesh S. Pashankar. Sections of Pediatric Gastroenterology and Pediatric Hematology-Oncology, Department of Pediatrics, Yale University, School of Medicine, New Haven, CT.

We hypothesized that the prevalence of constipation amongst children on chemotherapy would be high, and that certain pharmacologic interventions commonly used in this population (especially vinca alkaloids, narcotic analgesics, and ondansetron) would be associated with constipation. We also hypothesized that constipation would be perceived as an important problem with a significant impact on lifestyle. We prospectively studied 61 children receiving chemotherapy for …

Cellular Response To Prosthetic Wear Debris Differs In Rheumatoid Versus Non-Rheumatoid Arthritis, Anant Vasudevan

Yale Medicine Thesis Digital Library

Anant Vasudevan, Edward F. DiCarlo, Timothy Wright, Dan Chen, Mark. P Figgie, Steven R. Goldring, Lisa A. Mandl. Department of Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, New York, NY. (Sponsored by Carrie Swigart, Department of Orthopaedics and Rehabilitation, Yale University School of Medicine).

In the setting of inflammatory arthritis, the histopathologic reaction to foreign body wear debris generated from a failing arthroplasty has not been definitively characterized. This study examined whether patients with rheumatoid arthritis (RA) demonstrate different patterns of prosthetic wear or cellular responses to implant wear debris compared to patients without inflammatory joint disease. Thirty-eight …

Foretelling The Future Of Prognostication: A Historically Inspired Domain-Based Approach For The Elderly, John Thomas

Yale Medicine Thesis Digital Library

FORETELLING THE FUTURE OF PROGNOSTICATION: A HISTORICALLY INSPIRED DOMAIN-BASED APPROACH FOR THE ELDERLY

John M. Thomas and Terri R. Fried. Section of Geriatrics, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.

Hypothesis: 1) Physicians' decisions to discuss hospice as an option for terminally ill patients are based on a limited approach to prognostication that excludes many patients who may benefit from discussions. 2) Identifying broader domains of health most important for prognostication, as an alternative to calculating life expectancy or mortality risk, might encourage prognostication and improve physician-patient communication.

Aims: 1) To examine the association between …

Actigraphy Sleep Patterns: Relationships To Body Mass Index And Physical Activity In Minority Children, Kathryn Wynne

Yale Medicine Thesis Digital Library

Previous research suggests that short sleep duration and later bedtimes are associated with higher body mass index (BMI) and lower physical activity levels in children. We sought to determine if objective measurements of sleep duration and timing were correlated with BMI percentile and/or physical activity measures in low-income, minority children. Data were collected from 104 8- to 10-year-old children (58% female; 88.5% Latino or African-American; 51.9% overweight or obese) who were instructed to wear an accelerometer at their waists for 1 week. Data were manually analyzed to determine average sleep-onset (i.e. bedtime), sleep-offset (i.e. wake time), sleep duration, and minutes …

An Incompletely Penetrant Col7a1 Mutation Causes Dystrophic Epidermolysis Bullosa And Epidermolysis Bullosa Pruriginosa, Catherine Yang

Yale Medicine Thesis Digital Library

Epidermolysis bullosa pruriginosa (EBP) is a rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by intense pruritus, nodular or lichenoid lesions, and violaceous linear scarring most prominent on the extensor extremities. Remarkably, identical mutations in COL7A1, which encodes an anchoring fibril protein present at the dermal-epidermal junction, can cause both DEB and EBP with either autosomal dominant or recessive inheritance. We present one family with both dystrophic and pruriginosa phenotypes of epidermolysis bullosa. The proband is a 19-year-old Caucasian female who initially presented in childhood with lichenoid papules affecting her extensor limbs and intense pruritus consistent with EBP. Her maternal …

The Prevalence Of Hpv Associated Disease In Women Under Age 21: Who Will Be Missed Under The New Cervical Cancer Screening Guidelines?, Amanda Decew

Yale School of Nursing Digital Theses

Objective: To quantify the number of adolescent females <21 with pre-cancerous cervical lesions or cervical intraepithelial neoplasia (CIN) 2+/AIS in the state of Connecticut and identify any correlates which may be associated with CIN 3.

Methods: CIN 2+/AIS precancerous cervical lesions are a reportable condition in the State of Connecticut for the purpose of public health surveillance. A subset of this data (681 women) under 21 years of age was analyzed for the years 2008-2010.

Results: Of the 681 records, 478 (70.2%) women had CIN 2, 92 had CIN 2/3 (13.5%), and 110 (16.2%) had CIN 3. The highest annual rates for CIN 2+/AIS were found in Litchfield (342.98/100,000) and New London (287.85/100,000) counties. CIN 3 occurred at an average rate statewide of 38.6/100,000 per year for …

The Prevalence Of Hpv Associated Disease In Women Under Age 21: Who Will Be Missed Under The New Cervical Cancer Screening Guidelines?, Amanda Decew

Public Health Theses

Objective: To quantify the number of adolescent females <21 with pre-cancerous cervical lesions or cervical intraepithelial neoplasia (CIN) 2+/AIS in the state of Connecticut and identify any correlates which may be associated with CIN 3.

Methods: CIN 2+/AIS precancerous cervical lesions are a reportable condition in the State of Connecticut for the purpose of public health surveillance. A subset of this data (681 women) under 21 years of age was analyzed for the years 2008-2010.

Results: Of the 681 records, 478 (70.2%) women had CIN 2, 92 had CIN 2/3 (13.5%), and 110 (16.2%) had CIN 3. The highest annual rates for CIN 2+/AIS were found in Litchfield (342.98/100,000) and New London (287.85/100,000) counties. CIN 3 occurred at an average rate statewide of 38.6/100,000 per year for …

Epigenetic Events Suggest A Distinct Molecular Pathogenesis In Braf-Associated Papillary Thyroid Cancer, Ogechukwu Eze

Yale Medicine Thesis Digital Library

EPIGENETIC EVENTS SUGGEST A DISTINCT MOLECULAR PATHOGENESIS IN BRAF-ASSOCIATED PAPILLARY THYROID CANCER.

Ogechukwu Eze, Lee Starker, William Long, Robert Udelsman, Peyman Björklund, and Tobias Carling. Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.

Papillary thyroid cancer (PTC) associated with a somatic V-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutation has been associated with a more aggressive phenotype (i.e. extrathyroidal extension, lymph node metastasis, high TNM stage and recurrence) than those with wildtype (WT) BRAF. The underlying molecular mechanism for this association is incompletely clarified. Epigenetic alterations, such as DNA methylation participate with genetic abnormalities …

A Survey Assessing The Contributing Factors To Substance Abuse Treatment In U.S. Corrections Settings, Michael Soule

Yale Medicine Thesis Digital Library

In light of the dramatic rise in incarceration due to the "War on Drugs," we explored the contributing factors to substance abuse treatment (SAT) programming - in particular, evidence-based treatments like medication assisted therapy (MAT) - implementation in United States correctional settings (including jails, prisons, and community corrections facilities). We hypothesized that current funding availability would be the primary factor preventing and contributing to program implementation, but further hypothesized that an array of secondary factors such as overcrowding, geographic location, facility type, and attitudes and knowledge about MAT would also play a role. We mailed a survey to an enriched …

The Legacy Of Gordon Arthur Riley (1911–1985) And The Development Of Mathematical Models In Biological Oceanography, Thomas R. Anderson, Wendy C. Gentleman

Journal of Marine Research

Gordon Arthur Riley (1911–1985) is remembered for his pioneering work in the development of marine ecosystem models during the mid-20th century. Using models that were necessarily simple because of the limited understanding of plankton physiology at the time, as well as the fact that calculations had to be done by hand, Riley studied the processes that control plankton stocks, production, and nutrient cycling, notably at Georges Bank. His great achievement lay not so much in the simulation of plankton dynamics per se, but rather in bringing to the fore the concept of using modeling as a means of explaining …

Detailed Internal Wave Mixing Above A Deep-Ocean Slope, Hans Van Haren, Louis Gostiaux

Journal of Marine Research

Turbulent vertical eddy diffusivity (K_z) and dissipation rate (ε) are estimated between 0.5 and 50 m above the sloping side of Great Meteor Seamount, Canary Basin, using 101 moored temperature sensors, 1-mK precision, sampling at 1 Hz. Effectively, detailed observed time-depth temperature images are split in two: a statically stable and a turbulence image. Tides dominate the temperature variations, but the local bottom slope is supercritical to motions at semidiurnal frequencies. Averaged over a fortnight, the observed overall time-depth mean Kz = 3±1 × 10^–3 m² s^–1 and ε = 1.5±0.7 × 10^–7 W …

A Tribute To Doreen Orciari, George Veronis

Journal of Marine Research

With her retirement this year Doreen Orciari will end her 36th year at Yale, 32 of them as editorial assistant at the Journal of Marine Research. She came to work for me as my secretary in December, 1976, when I was chairman of the Department of Geology and Geophysics. It turns out that she was the best Christmas present that I have ever had. Doreen was born and raised as an Irish Catholic in New Haven and spent her youth in somewhat of a dysfunctional family. She spent 12 years amid Catholic nuns who served to add structure to her …

The Rise And Fall Of Crassostrea Virginica Oyster Reefs: The Role Of Disease And Fishing In Their Demise And A Vignette On Their Management, Eric N. Powell, John M. Klinck, Kathryn Ashton-Alcox, Eileen E. Hofmann, Jason Morson

Journal of Marine Research

We describe a model designed to simulate the shell carbonate budget of an oyster reef. We identify five parameters descriptive of basic characteristics of the shell carbonate budget of a reef that limit simulation accuracy. Two describe the TAZ (taphonomically-active zone) and the distribution of shell carbonate within it. One is the taphonomic rate in the TAZ. Two determine the volume contribution of shell carbonate and the taphonomic loss rate within the reef framework. For Mid-Atlantic estuaries, model simulations suggest that reef accretion only occurs if oyster abundance is near carrying capacity. Simulations further suggest that reef accretion is infeasible …

Baroclinic Instability Of An Idealized Tidal Mixing Front, K. H. Brink

Journal of Marine Research

Tidal mixing fronts separate vertically homogenized waters from stratified ambient waters. The linear and nonlinear baroclinic stability of an idealized tidal mixing front is treated here in the parameter range that is stable with regard to symmetric instabilities and that has no bottom friction. All model configurations considered are unstable, and the dependence on bottom slope, stratification and other parameters is similar to that suggested by models (such as that of Blumsack and Gierasch, 1972) with much simpler configurations. The finite-amplitude evolution of the instabilities is treated using a primitive equation numerical model. The initial length scale and growth rate …

Hurricane Wake Restratification Rates Of One-, Two- And Three-Dimensional Processes, S. Haney, S. Bachman, B. Cooper, S. Kupper, K. Mccaffrey, L. Van Roekel, S. Stevenson, B. Fox-Kemper

Journal of Marine Research

The restratification of the cold wakes of Tropical Cyclones Fanapi, Frances, Igor and Katrina are examined based on derived scalings for processes that can restore the hurricane wake toward the precyclone conditions. The different restoration processes depend on the parameters of the wake: depth, width, buoyancy anomaly and wind stress. The parameters needed are derived for each wake from satellite and climatological data. The scalings are based on model results and existing parameterizations, including air-sea heat fluxes (one-dimensional) Ekman buoyancy fluxes (two-dimensional) and mixed layer eddies (three-dimensional). The dominant surface restoration occurs by a combination of surface fluxes and Ekman …

Computational Phylogenetics And The Internal Structure Of Pama-Nyungan, Claire Bowern, Quentin Atkinson

Linguistics Faculty Publications

No abstract provided.

Medicine@Yale June 2012 Volume 8, Issue 3, Yale School Of Medicine Office Of Communications

Medicine@Yale - development newsletter

Medicine@Yale : advancing biomedical science, education and health care was a print and online newsletter which published news about academics, research and philanthropy for alumni, donors, faculty, students and the general public. It was initially published 6 times a year and then changed to a quarterly schedule. The first issue came out June/Jul. 2005. The final issue was published in May/June 2022, vol. 17, issue 1. Published by Yale School of Medicine, Office of Communications.

Medicine@Yale November/December 2012 Volume 8, Issue 5, Yale School Of Medicine Office Of Communications

Medicine@Yale - development newsletter

Medicine@Yale : advancing biomedical science, education and health care was a print and online newsletter which published news about academics, research and philanthropy for alumni, donors, faculty, students and the general public. It was initially published 6 times a year and then changed to a quarterly schedule. The first issue came out June/Jul. 2005. The final issue was published in May/June 2022, vol. 17, issue 1. Published by Yale School of Medicine, Office of Communications.

Parental Perception Of Child Weight Status In Wangcheng District, Hunan Province, People's Republic Of China, Nichole Buswell

Yale School of Nursing Digital Theses

Objectives: This cross-sectional, quantitative study was designed to describe the prevalence of overweight and obesity in a sample of schoolchildren (age 9-11 years) in central southern China. It also described parental attitudes about childhood overweight, physical activity, and eating patterns. In addition, this study described parental perception of and concern about their child's weight status.

Methods: This study was conducted in June 2011 at three elementary schools located in Wangcheng District, a suburb of Changsha, the capital city of Hunan Province. Child anthropometric data were collected, after which surveys were distributed to be brought home for completion by parents/caregivers.

Results: …

Anticholinergic Impact On Cognition In Schizophrenia, Catherine Underwood

Yale School of Nursing Digital Theses

This secondary analysis examined the relationship between the total anticholinergic load and scores on cognitive tests in 94 patients diagnosed with schizophrenia or schizoaffective disorder. Cognitive impairment is a core feature of schizophrenia, and studies have shown that it is a strong predictor of functional outcomes in this population. Anticholinergic medications have been demonstrated to have a negative impact on cognition. Some antipsychotic medications have anticholinergic properties, and anticholinergic medications are often prescribed to patients with schizophrenia to treat or prevent extrapyramidal side effects of antipsychotics. We did not find any significant correlations between anticholinergic load as measured by benztropine …

Yale School Of Medicine Facts & Figures 2012, Yale School Of Medicine Office Of Communications

Facts & Figures – annual Yale School of Medicine numbers

Provided by the Office of Communications, the Facts and Figures brochure is produced annually as a way to provide a snapshot of key facts and data related to the School of Medicine as well as the Medical Campus. This includes enrollment data, research activity, financial summaries, and more.

Circulation And Behavior Controls On Dispersal Of Eastern Oyster (Crassostrea Virginica) Larvae In Delaware Bay, Diego A. Narváez, John N. Klinck, Eric N. Powell, Eileen E. Hofmann, John Wilkin, Dale B. Haidvogel

Journal of Marine Research

The relative contributions of the spring-neap tides, river discharge and vertical behavior to the dispersal of eastern oyster (Crassostrea virginica) larvae in Delaware Bay is investigated with a coupled circulation-individual-based larvae model. The coupled model simulates larval growth and behavior along particle trajectories using temperature and salinity conditions obtained from an implementation of the Regional Ocean Model System (ROMS) for Delaware Bay. Particles, representing oyster larvae, are released at five-day intervals during the spawning seasons (mid-June to mid-September) of 1984, 1985, 1986, 2000 and 2001 from areas that correspond to natural oyster reefs in Delaware Bay. Successful larvae …