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The Predictive Value Of The Proliferation Marker Ki-67 In Patients With Fulminant Hepatic Failure, Ashesh P. Shah, Md, Upasana Joneja, Md, David Walls, Md, John Farber, Md

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

INTRODUCTION

In the United States, acute liver failure (ALF) affects an estimated 2,000 people per year and accounts for 6% of all liver transplants. Without transplantation, however, less than 50% of patients survive with medical management alone. Early identification of patients with survivable AFL is important to guiding their management and early referral to transplantation.

Studies have shown that the current prognostic scoring systems used for FHF, including the King’s College Criteria (KCC) and the Model for End- Stage Liver Disease (MELD), have poor sensitivity and negative predictive value for predicting outcome, highlighting a need for more accurate predictive models. …

A Rare Case Of A Systemic Non-Langerhans Histiocytosis Presenting With Diabetes Insipidus And A Tentorial Mass, Guilherme Barros, Ms, Kelly Krupa, Bs, Kristin Krupa, Bs, Ravichandra Madineni, Md, Lawrence C. Kenyon, Md, Phd, Christopher J Farrell, Md

JHN Journal

Introduction

The histiocytoses are a group of clinically diverse diseases distinguished from one another based on the specific immunophenotype of the lesional cells, implying derivation from the same precursor cell. Langerhans cell histiocytoses (LCH) diseases stem from abnormal dendritic cell lineages, while the non-Langerhans cell histiocytoses (non-LCH) are usually derived from an abnormal monocyte/macrophage cell line.1 Non-LCH with central nervous system (CNS) involvement is predictive of poor outcome. Histopathology is used to make a diagnosis of non-LCH. Immunohistochemistry and the clinical setting are used to differentiate between the various subtypes of non-LCH.1 The non-LCH can be divided into cutaneous non-LCH, …

Investigation Of Red-Cockaded Woodpeckers In Virginia: 2014 Report, M. D. Wilson, B D. Watts, C Lotts, F M. Smith, B J. Paxton

CCB Technical Reports

Red-cockaded woodpecker recovery at the Nature Conservancy’s Piney Grove Preserve has been a monumental achievement. Over the past 11 years, aspects of monitoring and management has worked together to more than triple the number of breeding groups from a modern low of 3 in 2000 to the 14 groups breeding there now. The current level of success has culminated from more than a decade long path of habitat management, cavity tree management, woodpecker population monitoring and translocation. It has been through the intelligent decision making and skill in the field from all partners involved in Red-cockaded Woodpecker management in Virginia …

Virginia Peregrine Falcon Monitoring And Management Program: Year 2015 Report, B. D. Watts, E K. Mojica

CCB Technical Reports

The Peregrine Falcon (Falco peregrinus) was believed to be extirpated as a breeding species in Virginia by the early 1960s. An aggressive restoration program was initiated in 1978 that included the release of 115 captive-reared birds on the Coastal Plain (1978-1985) and 127 birds in the mountains (1985-1993). This program resulted in the first breeding of the modern era in 1982. Since this time, the population has proceeded through a rapid establishment phase followed by a consolidation phase. However, more than 95% of all breeding activity over the past 30 years has occurred on the Coastal Plain with very limited …

Annual Report, 2014-2015, Connecticut College

Annual Reports

No abstract provided.

Mercury Speciation, Retention, And Abundance Of Genes Involved With Mercury Methylation In Fertilized Salt Marsh Sediments, Caroline Collins

Biology Honors Papers

Mercury (Hg) is a global pollutant which exists in both aquatic and terrestrial systems in three main forms including elemental Hg, ionic mercury, and methyl mercury, (MeHg), and Hg cycling plays an important role in ecosystems. Great Sippewisset Marsh, (GSM) in Falmouth MA has been chronically treated with fertilizer that contains heavy metals such as Hg in varying concentrations since the early 1970s and provides for an excellent location to study Hg contamination. The overall goal of this study is to analyze the key geochemical and microbial conditions that lead to MeHg production in the presence of the applied fertilizer. …

Changes In Zebrafish (Danio Rerio) Startle Responses Due To Stressors Related To Marine Bycatch, Margot Wilsterman

Biology Honors Papers

Marine bycatch is one of the most pressing issues that result from modern industrialized fishing. Scientists do not have good estimates of rates of cryptic mortality, which is the mortality of individuals that are not landed but die from interactions with fishing gear below the water surface. One of the main causes of cryptic mortality is depredation, which occurs after individuals have escaped through fishing equipment and are eaten by predators waiting close behind for an effortless meal. In this study the effects of scale loss, slime loss, and exhaustion on the startle response of zebrafish were examined. These stressors …

Annual Report, 2014-2015, Ammerman Center, Connecticut College

Annual Reports

No abstract provided.

Hands Up At Home: Militarized Masculinity And Police Officers Who Commit Intimate Partner Abuse, Leigh S. Goodmark

Faculty Scholarship

The deaths of Michael Brown and Eric Garner and the almost daily news stories about abusive and violent police conduct are currently prompting questions about the appropriate use of force by police officers. Moreover, the history of police brutality directed towards women is well documented. Most of that literature, however, captures the violence that police do in their public capacity, as officers of the state. This article examines the violence and abuse perpetrated by police in their private lives, against their intimate partners, although the public and private overlap significantly to the extent that the power and training provided to …

Marital Contracting In A Post-Windsor World, Martha M. Ertman

Faculty Scholarship

No abstract provided.

Respect And Dignity: A Conceptual Model For Patients In The Intensive Care Unit, Leslie Meltzer Henry, Cynda Rushton, Mary Catherine Beach, Ruth Faden

Faculty Scholarship

Although the concept of dignity is commonly invoked in clinical care, there is not widespread agreement—in either the academic literature or in everyday clinical conversations—about what dignity means. Without a framework for understanding dignity, it is difficult to determine what threatens patients’ dignity and, conversely, how to honor commitments to protect and promote it. This article aims to change that by offering the first conceptual model of dignity for patients in the intensive care unit. The conceptual model we present is based on the notion that there are three sources of patients’ dignity—their shared humanity, personal narratives, and autonomy—each of …

Imaging Brains, Changing Minds: How Pain Neuroimaging Can Inform The Law, Amanda C. Pustilnik

Faculty Scholarship

What would the law do differently if it could see into the black box of the mind? One of the most valuable things it might do is reform the ways it deals with pain. Pain is ubiquitous in law, from tort to torture, from ERISA to expert evidence. Yet legal doctrines grapple with pain poorly, embodying concepts that are generations out of date and that cast suspicion on pain sufferers as having a problem that is “all in their heads.”

Now, brain-imaging technologies are allowing scientists to see the brain in pain—and to reconceive of many types of pain as …

Effect Of Single Embryo Transfer On The Risk Of Preterm Birth Associated With In Vitro Fertilization, A. J. Fechner, K. R. Brown, N. Onwubalili, S. K. Jindal, G. Weiss, L. T. Goldsmith, P. G. Mcgovern

Journal Articles

To determine whether elective single embryo transfer (eSET) reduces the risk of preterm delivery associated with in vitro fertilization (IVF). This is an observational study of 3125 eSET cycles performed from 2008 to 2009 and reported to the Society for Assisted Reproductive Technology (SART) database. Preterm delivery rates were compared to the overall preterm delivery rate among all patients undergoing IVF over the same time period. The 3125 eSET cycles resulted in 1507 live births (live birth rate 48.2 %) Among these deliveries were 27 twins (1.8 %) and one set of triplets (0.07 %). The overall preterm delivery rate …

A Critical Role For The Host Mediator Macrophage Migration Inhibitory Factor In The Pathogenesis Of Malarial Anemia, M. A. Mcdevitt, J. Xie, S. Ganapathy-Kanniappan, J. Griffith, A. Liu, C. Mcdonald, P. Thuma, V. R. Gordeuk, C. N. Metz, R. Mitchell, J. Keefer, J. David, L. Leng, R. Bucala

Journal Articles

No abstract provided.

Metabolic Resting-State Brain Networks In Health And Disease, P. G. Spetsieris, J. H. Ko, C. C. Tang, A. Nazem, W. Sako, S. Peng, Y. Ma, V. Dhawan, D. Eidelberg

Journal Articles

The delineation of resting state networks (RSNs) in the human brain relies on the analysis of temporal fluctuations in functional MRI signal, representing a small fraction of total neuronal activity. Here, we used metabolic PET, which maps nonfluctuating signals related to total activity, to identify and validate reproducible RSN topographies in healthy and disease populations. In healthy subjects, the dominant (first component) metabolic RSN was topographically similar to the default mode network (DMN). In contrast, in Parkinson's disease (PD), this RSN was subordinated to an independent disease-related pattern. Network functionality was assessed by quantifying metabolic RSN expression in cerebral blood …

Implications Of Epigenetic Variability Within A Cell Population For "Cell Type" Classification, I. Tabansky, J. N.H. Stern, D. W. Pfaff

Journal Articles

Here, we propose a new approach to defining nerve "cell types" in reaction to recent advances in single cell analysis. Among cells previously thought to be equivalent, considerable differences in global gene expression and biased tendencies among differing developmental fates have been demonstrated within multiple lineages. The model of classifying cells into distinct types thus has to be revised to account for this intrinsic variability. A "cell type" could be a group of cells that possess similar, but not necessarily identical properties, variable within a spectrum of epigenetic adjustments that permit its developmental path toward a specific function to be …

Parkinson's Disease-Related Spatial Covariance Pattern Identified With Resting-State Functional Mri, T. Wu, Y. Ma, Z. Zheng, S. Peng, X. Wu, D. Eidelberg, P. Chan

Journal Articles

In this study, we sought to identify a disease-related spatial covariance pattern of spontaneous neural activity in Parkinson's disease using resting-state functional magnetic resonance imaging (MRI). Time-series data were acquired in 58 patients with early to moderate stage Parkinson's disease and 54 healthy controls, and analyzed by Scaled Subprofile Model Principal Component Analysis toolbox. A split-sample analysis was also performed in a derivation sample of 28 patients and 28 control subjects and validated in a prospective testing sample of 30 patients and 26 control subjects. The topographic pattern of neural activity in Parkinson's disease was characterized by decreased activity in …

First-In-Human, Phase 1, Randomized, Dose-Escalation Trial With Recombinant Anti-Il-20 Monoclonal Antibody In Patients With Psoriasis, A. B. Gottlieb, J. G. Krueger, M. Sandberg Lundblad, M. Gothberg, B. E. Skolnick

Journal Articles

BACKGROUND: The current trial was a first-in-human clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the recombinant monoclonal anti-interleukin-20 (IL-20) antibody, NNC0109-0012, which targets the inflammatory cytokine IL-20. METHODS: In total, 48 patients aged 18 to 75 years with moderate to severe stable chronic plaque psoriasis with affected body surface area >/=15% and physician global assessment score >/=3 were enrolled in this randomized, double-blind, multicenter, placebo-controlled, phase 1 dose-escalation trial. Patients were randomized within each single dose cohort (0.01, 0.05, 0.2, 0.6, 1.5, or 3.0 mg/kg) or multiple dose cohort (0.05, 0.2, 0.5, 1.0, or 2.0 …

Mesothelioma Patients With Germline Bap1 Mutations Have 7-Fold Improved Long-Term Survival, F. Baumann, E. Flores, A. Napolitano, S. Kanodia, E. Taioli, H. Pass, H. Yang, M. Carbone

Journal Articles

BRCA1-associated protein-1 (BAP1) mutations cause a new cancer syndrome, with a high rate of malignant mesothelioma (MM). Here, we tested the hypothesis that MM associated with germline BAP1 mutations has a better prognosis compared with sporadic MM. We compared survival among germline BAP1 mutation MM patients with that of all MM (N = 10 556) recorded in the United States Surveillance, Epidemiology, and End Results (SEER) data from 1973 to 2010. We identified 23 MM patients-11 alive-with germline BAP1 mutations and available data on survival. Ten patients had peritoneal MM, ten pleural MM and three MM in both locations. Thirteen …

Circulating Adipokines And Inflammatory Markers And Postmenopausal Breast Cancer Risk, M. J. Gunter, T. Wang, M. Cushman, X. Xue, S. Wassertheil-Smoller, H. D. Strickler, T. E. Rohan, J. E. Manson, A. Mctiernan, G. Y. Ho, +5 Additional Authors

Journal Articles

BACKGROUND: Adipokines and inflammation may provide a mechanistic link between obesity and postmenopausal breast cancer, yet epidemiologic data on their associations with breast cancer risk are limited. METHODS: In a case-cohort analysis nested within the Women's Health Initiative Observational Study, a prospective cohort of postmenopausal women, baseline plasma samples from 875 incident breast cancer case patients and 839 subcohort participants were tested for levels of seven adipokines, namely leptin, adiponectin, resistin, interleukin-6, tumor necrosis factor-alpha, hepatocyte growth factor, and plasminogen activator inhibitor-1, and for C-reactive protein (CRP), an inflammatory marker. Data were analyzed by multivariable Cox modeling that included established …

Emerging Novel Therapies For Heart Failure, A. M. Szema, S. Dang, J. C. Li

Journal Articles

No abstract provided.

New Best1 Mutations In Autosomal Recessive Bestrophinopathy, A. T. Fung, S. Yzer, N. Goldberg, H. Wang, M. Nissen, A. Giovannini, J. E. Merriam, E. N. Bukanova, L. A. Yannuzzi, R. Allikmets, +2 Additional Authors

Journal Articles

PURPOSE: To report the ocular phenotype in patients with autosomal recessive bestrophinopathy and carriers, and to describe novel BEST1 mutations. METHODS: Patients with clinically suspected and subsequently genetically proven autosomal recessive bestrophinopathy underwent full ophthalmic examination and investigation with fundus autofluorescence imaging, spectral domain optical coherence tomography, electroretinography, and electrooculography. Mutation analysis of the BEST1 gene was performed through direct Sanger sequencing. RESULTS: Five affected patients from four families were identified. Mean age was 16 years (range, 6-42 years). All affected patients presented with reduced visual acuity and bilateral, hyperautofluorescent subretinal yellowish deposits within the posterior pole. Spectral domain optical …

Lifitegrast Ophthalmic Solution 5.0% Versus Placebo For Treatment Of Dry Eye Disease: Results Of The Randomized Phase Iii Opus-2 Study, J. Tauber, P. Karpecki, R. Latkany, J. Luchs, J. Martel, K. Sall, A. Raychaudhuri, V. Smith, C. P. Semba

Journal Articles

PURPOSE: Lifitegrast is an integrin antagonist that decreases T-cell-mediated inflammation associated with dry eye disease (DED). We report the results of OPUS-2, a phase III study evaluating the efficacy and safety of lifitegrast compared with placebo for the treatment of DED. DESIGN: A 12-week, multicenter, randomized, prospective, double-masked, placebo-controlled clinical trial. PARTICIPANTS: Adults aged >/=18 years with use of artificial tears within 30 days, inferior corneal staining score >/=0.5 (0-4 scale), Schirmer tear test (without anesthesia) >/=1 and/=40 (0-100 visual analogue scale [VAS]). METHODS: Subjects were randomized 1:1 after 14-day placebo run-in to lifitegrast ophthalmic solution 5.0% or placebo twice …

Ld Score Regression Distinguishes Confounding From Polygenicity In Genome-Wide Association Studies, B. K. Bulik-Sullivan, P. R. Loh, H. K. Finucane, S. Ripke, J. Yang, N. Patterson, M. J. Daly, A. L. Price, B. M. Neale, A. Malhotra

Journal Articles

Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from a true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of the …

A Common Polymorphism In Scn2a Predicts General Cognitive Ability Through Effects On Pfc Physiology, M. A. Scult, J. W. Trampush, F. Zheng, E. D. Conley, T. Lencz, A. K. Malhotra, D. Dickinson, D. R. Weinberger, A. R. Hariri

Journal Articles

Here we provide novel convergent evidence across three independent cohorts of healthy adults (n = 531), demonstrating that a common polymorphism in the gene encoding the alpha2 subunit of neuronal voltage-gated type II sodium channels (SCN2A) predicts human general cognitive ability or "g." Using meta-analysis, we demonstrate that the minor T allele of a common polymorphism (rs10174400) in SCN2A is associated with significantly higher "g" independent of gender and age. We further demonstrate using resting-state fMRI data from our discovery cohort (n = 236) that this genetic advantage may be mediated by increased capacity for information processing between the dorsolateral …

Association Of A Schizophrenia Risk Variant At The Drd2 Locus With Antipsychotic Treatment Response In First-Episode Psychosis, J. P. Zhang, D. G. Robinson, Juan Gallego, M. John, J. Yu, J. Addington, M. Tohen, John Kane, Anil Malhotra, T. Lencz

Journal Articles

Findings from the Psychiatric Genomics Consortium genome-wide association study (GWAS) showed that variation at the DRD2 locus is associated with schizophrenia risk. However, the functional significance of rs2514218, the top DRD2 single nucleotide polymorphism in the GWAS, is unknown. Dopamine D2 receptor binding is a common mechanism of action for all antipsychotic drugs, and DRD2 variants were related to antipsychotic response in previous studies. The present study examined whether rs2514218 genotype could predict antipsychotic response, including efficacy and adverse events, in a cohort of patients with first episode of psychosis treated with either risperidone or aripiprazole for 12 weeks. Subjects …

Clinical And Functional Outcomes After 2 Years In The Early Detection And Intervention For The Prevention Of Psychosis Multisite Effectiveness Trial, W. R. Mcfarlane, B. Levin, L. Travis, F. L. Lucas, S. Lynch, M. Verdi, Barbara Cornblatt, S. F. Taylor, A. M. Auther, E. Spring, +11 Additional Authors

Journal Articles

OBJECTIVE: To test effectiveness of the Early Detection, Intervention, and Prevention of Psychosis Program in preventing the onset of severe psychosis and improving functioning in a national sample of at-risk youth. METHODS: In a risk-based allocation study design, 337 youth (age 12-25) at risk of psychosis were assigned to treatment groups based on severity of positive symptoms. Those at clinically higher risk (CHR) or having an early first episode of psychosis (EFEP) were assigned to receive Family-aided Assertive Community Treatment (FACT); those at clinically lower risk (CLR) were assigned to receive community care. Between-groups differences on outcome variables were adjusted …

Missing-In-Metastasis Regulates Cell Motility And Invasion Via Ptpdelta-Mediated Changes In Src Activity, F. Chaudhary, R. Lucito, N. K. Tonks

Journal Articles

MIM (Missing-in-Metastasis), also known as MTSS1 (metastasis suppressor 1), is a scaffold protein that is down-regulated in multiple metastatic cancer cell lines compared with non-metastatic counterparts. MIM regulates cytoskeletal dynamics and actin polymerization, and has been implicated in the control of cell motility and invasion. MIM has also been shown to bind to a receptor PTP (protein tyrosine phosphatase), PTPdelta, an interaction that may provide a link between tyrosine-phosphorylation-dependent signalling and metastasis. We used shRNA-mediated gene silencing to investigate the consequences of loss of MIM on the migration and invasion of the MCF10A mammary epithelial cell model of breast cancer. …

Multirater Agreement Of The Causes Of Anterior Cruciate Ligament Reconstruction Failure: A Radiographic And Video Analysis Of The Mars Cohort, M. J. Matava, R. A. Arciero, K. M. Baumgarten, J. A. Hannafin, B. S. Miller, C. W. Nissen, T. N. Taft, B. R. Wolf, E. B. Hershman, R. W. Wright, +3 Additional Authors

Journal Articles

BACKGROUND: Anterior cruciate ligament (ACL) reconstruction failure occurs in up to 10% of cases. Technical errors are considered the most common cause of graft failure despite the absence of validated studies. Limited data are available regarding the agreement among orthopaedic surgeons regarding the causes of primary ACL reconstruction failure and accuracy of graft tunnel placement. HYPOTHESIS: Experienced knee surgeons have a high level of interobserver reliability in the agreement about the causes of primary ACL reconstruction failure, anatomic graft characteristics, and tunnel placement. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: Twenty cases of revision ACL reconstruction were …

Romidepsin In Peripheral And Cutaneous T-Cell Lymphoma: Mechanistic Implications From Clinical And Correlative Data, S. E. Bates, R. Eisch, A. Ling, D. Rosing, M. Turner, S. Pittaluga, H. M. Prince, M. H. Kirschbaum, S. L. Allen, R. L. Piekarz, +15 Additional Authors

Journal Articles

Romidepsin is an epigenetic agent approved for the treatment of patients with cutaneous or peripheral T-cell lymphoma (CTCL and PTCL). Here we report data in all patients treated on the National Cancer Institute 1312 trial, demonstrating long-term disease control and the ability to retreat patients relapsing off-therapy. In all, 84 patients with CTCL and 47 with PTCL were enrolled. Responses occurred early, were clinically meaningful and of very long duration in some cases. Notably, patients with PTCL receiving romidepsin as third-line therapy or later had a comparable response rate (32%) of similar duration as the total population (38%). Eight patients …