Digital Commons Network^™

Expression Of The Intestinal Biomarkers Guanylyl Cyclase C And Cdx2 In Poorly Differentiated Colorectal Carcinomas., Brody Winn, Rosemarie Tavares, Andres Matoso, Lelia Noble, Jacqueline Fanion, Scott A Waldman, Murray B Resnick

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Guanylyl cyclase C, a receptor for bacterial diarrheagenic enterotoxins, is expressed selectively by intestinal epithelium and is an endogenous downstream target of CDX2. The expression of Guanylyl cyclase C is preserved throughout the adenoma/carcinoma sequence in the colorectum. Detection of Guanylyl cyclase C expression by reverse transcriptase-polymerase chain reaction is currently being validated as a technique to identify occult lymph node metastases in patients with colorectal cancer and for circulating cells in the blood for postoperative surveillance. Although Guanylyl cyclase C is widely expressed by well-differentiated colorectal cancer, its expression in poorly differentiated colorectal cancer has not been evaluated. A …

A New Design For A Turing Test For Bots, Philip Hingston

Research outputs pre 2011

Interesting, human-like opponents add to the entertainment value of a video game, and creating such opponents is a difficult challenge for programmers. Can artificial intelligence and computational intelligence provide the means to convincingly simulate a human opponent? Or are simple programming tricks and deceptions more effective? To answer these questions, the author designed and organised a game bot programming competition, the BotPrize, in which competitors submit bots that try to pass a “Turing Test for Bots”. In this paper, we describe a new design for the competition, which will make it simpler to run, and, we hope, open up new …

The Transition From Medical Student To Junior Doctor: Today's Experiences Of Tomorrow's Doctors., Nicola Brennan, Oonagh Corrigan, Jon Allard, Julian Archer, Rebecca Barnes, Alan Bleakley, Tracey Collett, Bere Sr De

Peninsula Medical School

CONTEXT Medical education in the UK has recently undergone radical reform. Tomorrow's Doctors has prescribed undergraduate curriculum change and the Foundation Programme has overhauled postgraduate education. OBJECTIVES This study explored the experiences of junior doctors during their first year of clinical practice. In particular, the study sought to gain an understanding of how junior doctors experienced the transition from the role of student to that of practising doctor and how well their medical school education had prepared them for this. METHODS The study used qualitative methods comprising of semi-structured interviews and audio diary recordings with newly qualified doctors based at …

Negative Intrusive Thoughts And Dissociation As Risk Factors For Self-Harm., Helen Batey, Jon May, Jackie Andrade

School of Psychology

Relationships between self-harm and vulnerability factors were studied in a general population of 432 participants, of whom 30% reported some experience of self-harm. This group scored higher on dissociation and childhood trauma, had lower self-worth, and reported more negative intrusive thoughts. Among the non-harming group, 10% scored similarly to the self-harmers on the dissociation and self-worth scales, and engaged in potentially maladaptive behaviors that are not defined as indicating clinical self-harm, but experienced fewer negative intrusive thoughts. This group may be at risk of future self-harm if they begin to experience negative intrusive thoughts. If negative intrusive thoughts are playing …

Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets With Alopecia Resulting From A Novel Missense Mutation In The Dna-Binding Domain Of The Vitamin D Receptor., Peter J. Malloy, Jining Wang, Tarak Srivastava, David Feldman

Manuscripts, Articles, Book Chapters and Other Papers

The rare genetic recessive disease, hereditary vitamin D resistant rickets (HVDRR), is caused by mutations in the vitamin D receptor (VDR) that result in resistance to the active hormone 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3) or calcitriol). In this study, we examined the VDR from a young boy with clinical features of HVDRR including severe rickets, hypocalcemia, hypophosphatemia and partial alopecia. The pattern of alopecia was very unusual with areas of total baldness, adjacent to normal hair and regions of scant hair. The child failed to improve on oral calcium and vitamin D therapy but his abnormal chemistries and his bone X-rays normalized …

The Role Of Chemotherapy In The Management Of Newly Diagnosed Brain Metastases: A Systematic Review And Evidence-Based Clinical Practice Guideline., Minesh P Mehta, Nina A Paleologos, Tom Mikkelsen, Paula D Robinson, Mario Ammirati, David W Andrews, Anthony L Asher, Stuart H Burri, Charles S Cobbs, Laurie E Gaspar, Douglas Kondziolka, Mark E Linskey, Jay S Loeffler, Michael Mcdermott, Jeffrey J Olson, Roy A Patchell, Timothy C Ryken, Steven N Kalkanis

Department of Neurosurgery Faculty Papers

TARGET POPULATION: This recommendation applies to adults with newly diagnosed brain metastases; however, the recommendation below does not apply to the exquisitely chemosensitive tumors, such as germinomas metastatic to the brain.

RECOMMENDATION: Should patients with brain metastases receive chemotherapy in addition to whole brain radiotherapy (WBRT)? Level 1 Routine use of chemotherapy following WBRT for brain metastases has not been shown to increase survival and is not recommended. Four class I studies examined the role of carboplatin, chloroethylnitrosoureas, tegafur and temozolomide, and all resulted in no survival benefit. Two caveats are provided in order to allow the treating physician to …

System Development For High Frequency Ultrasound-Guided Fluorescence Quantification Of Skin Layers, Josiah D. Gruber, Akshat Paliwal, Venkataramanan Krishnaswamy, Hamid Ghadyani

Dartmouth Scholarship

No abstract provided.

Recent Advances On Skin-Resident Stem/Progenitor Cell Functions In Skin Regeneration, Aging And Cancers And Novel Anti-Aging And Cancer Therapies., Murielle Mimeault, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Recent advances in skin-resident adult stem/progenitor cell research have revealed that these immature and regenerative cells with a high longevity provide critical functions in maintaining skin homeostasis and repair after severe injuries along the lifespan of individuals. The establishment of the functional properties of distinct adult stem/progenitor cells found in skin epidermis and hair follicles and extrinsic signals from their niches, which are deregulated during their aging and malignant transformation, has significantly improved our understanding on the etiopathogenesis of diverse human skin disorders and cancers. Particularly, enhanced ultraviolet radiation exposure, inflammation and oxidative stress and telomere attrition during chronological aging …

The Role Of Surgical Resection In The Management Of Newly Diagnosed Brain Metastases: A Systematic Review And Evidence-Based Clinical Practice Guideline., Steven N Kalkanis, Douglas Kondziolka, Laurie E Gaspar, Stuart H Burri, Anthony L Asher, Charles S Cobbs, Mario Ammirati, Paula D Robinson, David W Andrews, Jay S Loeffler, Michael Mcdermott, Minesh P Mehta, Tom Mikkelsen, Jeffrey J Olson, Nina A Paleologos, Roy A Patchell, Timothy C Ryken, Mark E Linskey

Department of Neurosurgery Faculty Papers

QUESTION: Should patients with newly-diagnosed metastatic brain tumors undergo open surgical resection versus whole brain radiation therapy (WBRT) and/or other treatment modalities such as radiosurgery, and in what clinical settings? Target population These recommendations apply to adults with a newly diagnosed single brain metastasis amenable to surgical resection. Recommendations Surgical resection plus WBRT versus surgical resection alone Level 1 Surgical resection followed by WBRT represents a superior treatment modality, in terms of improving tumor control at the original site of the metastasis and in the brain overall, when compared to surgical resection alone. Surgical resection plus WBRT versus SRS +/- …

Event-Related Potentials Dissociate Effects Of Salience And Space In Biased Competition For Visual Representation, Matthew R. Hilimire, Jeffrey R.W. Mounts, Nathan A. Parks, Paul M. Corballis

Psychology

Background: Selective visual attention is the process by which the visual system enhances behaviorally relevant stimuli and filters out others. Visual attention is thought to operate through a cortical mechanism known as biased competition. Representations of stimuli within cortical visual areas compete such that they mutually suppress each others' neural response. Competition increases with stimulus proximity and can be biased in favor of one stimulus (over another) as a function of stimulus significance, salience, or expectancy. Though there is considerable evidence of biased competition within the human visual system, the dynamics of the process remain unknown. Methodology/Principal Findings: Here, we …

Does Diabetes Mellitus Influence Pathologic Complete Response And Tumor Downstaging After Neoadjuvant Chemoradiation For Esophageal And Gastroesophageal Cancer? A Two-Institution Report., Shayna L. Showalter, Ernest L. Rosato, P Rani Anne, Walter Scott, Edith Mitchell, Adam C. Berger

Department of Surgery Faculty Papers

BACKGROUND: Esophageal carcinoma is an aggressive disease that is often treated with neoadjuvant therapy followed by surgical resection. Diabetes mellitus (DM) has been associated with reduced efficacy of chemoradiation (CRT) in other gastrointestinal cancers. The goal of this study was to determine if DM affects response to neoadjuvant CRT in the management of gastroesophageal carcinoma.

METHODS: We retrospectively reviewed the esophageal cancer patient databases and subsequently analyzed those patients who received neoadjuvant CRT followed by surgical resection at two institutions, Thomas Jefferson University (TJUH) and Fox Chase Cancer Center (FCCC). Comparative analyses of rates of pathologic complete response rate (pCR) …

More Than Synaptic Plasticity: Role Of Nonsynaptic Plasticity In Learning And Memory, Riccardo Mozzachiodi, John H Byrne

Faculty, Staff and Student Publications

Decades of research on the cellular mechanisms of memory have led to the widely held view that memories are stored as modifications of synaptic strength. These changes involve presynaptic processes, such as direct modulation of the release machinery, or postsynaptic processes, such as modulation of receptor properties. Parallel studies have revealed that memories might also be stored by nonsynaptic processes, such as modulation of voltage-dependent membrane conductances, which are expressed as changes in neuronal excitability. Although in some cases nonsynaptic changes can function as part of the engram itself, they might also serve as mechanisms through which a neural circuit …

Social Support In An Internet Weight Loss Community, Kevin O Hwang, Allison J Ottenbacher, Angela P Green, M Roseann Cannon-Diehl, Oneka Richardson, Elmer V Bernstam, Eric J Thomas

Faculty, Staff and Student Publications

Purpose: To describe social support for weight loss shared by members of a large Internet weight loss community.

Methods: We conducted a mixed-methods study with surveys (n=193) and interviews (n=13) of community members along with a content analysis of discussion forum messages (n=1924 messages). Qualitative data were analyzed for social support themes.

Results: Survey respondents were primarily white (91.4%) and female (93.8%) with mean age 37.3 years and mean body mass index 30.9. They used forums frequently, with 56.8% reading messages, 36.1% replying to messages, and 18.5% posting messages to start a discussion related to weight loss on a daily …

Visuospatial Tasks Suppress Craving For Cigarettes., Jon May, Jackie Andrade, Nathalie Panabokke, David Kavanagh

School of Psychology

The Elaborated Intrusion (EI) theory of desire posits that visual imagery plays a key role in craving. We report a series of experiments testing this hypothesis in a drug addiction context. Experiment 1 showed that a mental visual imagery task with neutral content reduced cigarette craving in abstaining smokers, but that an equivalent auditory task did not. The effect of visual imagery was replicated in Experiment 2, which also showed comparable effects of non-imagery visual working memory interference. Experiment 3 showed that the benefit of visual over auditory interference was not dependent upon imagery being used to induce craving. Experiment …

Less Food For Thought. Impact Of Attentional Instructions On Intrusive Thoughts About Snack Foods., Jon May, Jackie Andrade, Helen Batey, Lisa Marie Berry, David J. Kavanagh

School of Psychology

Intrusive thoughts about food may play a role in unhealthy eating behaviours. Food-related thoughts that capture attention can lead to craving and further intrusive thoughts (Kavanagh, Andrade, & May, 2005). We tested whether diverting attention to mental images or bodily sensations would reduce the incidence of intrusive thoughts about snack foods. In two experiments, participants reported their thoughts in response to probes during three 10min periods. In the Baseline and Post-task period, participants were asked to let their mind wander. In the middle, Experimental, period, participants followed mind wandering (Control), thought diversion, or Thought Suppression instructions. Self-directed or Guided Imagery, …

Cellular Functions Of Fak Kinases: Insight Into Molecular Mechanisms And Novel Functions, M. D. Schaller

Faculty & Staff Scholarship

No abstract provided.

The Role Of Stereotactic Radiosurgery In The Management Of Patients With Newly Diagnosed Brain Metastases: A Systematic Review And Evidence-Based Clinical Practice Guideline., Mark E Linskey, David W Andrews, Anthony L Asher, Stuart H Burri, Douglas Kondziolka, Paula D Robinson, Mario Ammirati, Charles S Cobbs, Laurie E Gaspar, Jay S Loeffler, Michael Mcdermott, Minesh P Mehta, Tom Mikkelsen, Jeffrey J Olson, Nina A Paleologos, Roy A Patchell, Timothy C Ryken, Steven N Kalkanis

Department of Neurosurgery Faculty Papers

QUESTION: Should patients with newly-diagnosed metastatic brain tumors undergo stereotactic radiosurgery (SRS) compared with other treatment modalities? Target population These recommendations apply to adults with newly diagnosed solid brain metastases amenable to SRS; lesions amenable to SRS are typically defined as measuring less than 3 cm in maximum diameter and producing minimal (less than 1 cm of midline shift) mass effect. Recommendations SRS plus WBRT vs. WBRT alone Level 1 Single-dose SRS along with WBRT leads to significantly longer patient survival compared with WBRT alone for patients with single metastatic brain tumors who have a KPS > or = 70.Level 1 …

The Relationship Between Mosquito Abundance And Rice Field Density In The Republic Of Korea, Erin E. Richards, Penny Masuoka, David Brett-Major, Matthew Smith, Terry A. Klein, Heung Chul Kim, Assaf Anyamba, John Grieco

Journal Articles: Epidemiology

BACKGROUND: Japanese encephalitis virus (JEV), the causative agent of Japanese encephalitis (JE), is endemic to the Republic of Korea (ROK) where unvaccinated United States (U.S.) military Service members, civilians and family members are stationed. The primary vector of the JEV in the ROK is Culex tritaeniorhynchus. The ecological relationship between Culex spp. and rice fields has been studied extensively; rice fields have been shown to increase the prevalence of Cx. tritaeniorhynchus. This research was conducted to determine if the quantification of rice field land cover surrounding U.S. military installations in the ROK should be used as a parameter in a …

The Novel Endosomal Membrane Protein Ema Interacts With The Class C Vps-Hops Complex To Promote Endosomal Maturation, Sungsu Kim, Yogesh P. Wairkar, Richard W. Daniels, Aaron Diantonio

Open Access Publications

Endosomal maturation is critical for accurate and efficient cargo transport through endosomal compartments. Here we identify a mutation of the novel Drosophila gene, ema (endosomal maturation defective) in a screen for abnormal synaptic overgrowth and defective protein trafficking. Ema is an endosomal membrane protein required for trafficking of fluid-phase and receptor-mediated endocytic cargos. In the ema mutant, enlarged endosomal compartments accumulate as endosomal maturation fails, with early and late endosomes unable to progress into mature degradative late endosomes and lysosomes. Defective endosomal down-regulation of BMP signaling is responsible for the abnormal synaptic overgrowth. Ema binds to and genetically interacts with …

Definitions Of The Phenotypic Manifestations Of Sickle Cell Disease., Samir K Ballas, Susan Lieff, Lennette J Benjamin, Carlton D Dampier, Matthew M Heeney, Carolyn Hoppe, Cage S Johnson, Zora R Rogers, Kim Smith-Whitley, Winfred C Wang, Marilyn J Telen

Department of Medicine Faculty Papers

Sickle cell disease (SCD) is a pleiotropic genetic disorder of hemoglobin that has profound multiorgan effects. The low prevalence of SCD ( approximately 100,000/US) has limited progress in clinical, basic, and translational research. Lack of a large, readily accessible population for clinical studies has contributed to the absence of standard definitions and diagnostic criteria for the numerous complications of SCD and inadequate understanding of SCD pathophysiology. In 2005, the Comprehensive Sickle Cell Centers initiated a project to establish consensus definitions of the most frequently occurring complications. A group of clinicians and scientists with extensive expertise in research and treatment of …

Impact Of Workplace Based Assessment On Doctors' Education And Performance: A Systematic Review., A Miller, J Archer

Peninsula Medical School

To investigate the literature for evidence that workplace based assessment affects doctors' education and performance.

A Review Of Human Factors Principles For The Design And Implementation Of Medication Safety Alerts In Clinical Information Systems., Shobha Phansalkar, Judy Edworthy, Elizabeth Hellier, Diane L. Seger, Angela Schedlbauer, Anthony J. Avery, David W. Bates

School of Psychology

The objective of this review is to describe the implementation of human factors principles for the design of alerts in clinical information systems. First, we conduct a review of alarm systems to identify human factors principles that are employed in the design and implementation of alerts. Second, we review the medical informatics literature to provide examples of the implementation of human factors principles in current clinical information systems using alerts to provide medication decision support. Last, we suggest actionable recommendations for delivering effective clinical decision support using alerts. A review of studies from the medical informatics literature suggests that many …

The Principled Control Of False Positives In Neuroimaging, Craig M. Bennett, George L. Wolford, Michael B. Miller

Dartmouth Scholarship

An incredible amount of data is generated in the course of a functional neuroimaging experiment. The quantity of data gives us improved temporal and spatial resolution with which to evaluate our results. It also creates a staggering multiple testing problem. A number of methods have been created that address the multiple testing problem in neuroimaging in a principled fashion. These methods place limits on either the familywise error rate (FWER) or the false discovery rate (FDR) of the results. These principled approaches are well established in the literature and are known to properly limit the amount of false positives across …

Chylomicrons Promote Intestinal Absorption And Systemic Dissemination Of Dietary Antigen (Ovalbumin) In Mice, Yuehui Wang, Sarbani Ghoshal, Martin Ward, Willem De Villiers, Jerold Woodward, Erik Eckhardt

Internal Medicine Faculty Publications

BACKGROUND: A small fraction of dietary protein survives enzymatic degradation and is absorbed in potentially antigenic form. This can trigger inflammatory responses in patients with celiac disease or food allergies, but typically induces systemic immunological tolerance (oral tolerance). At present it is not clear how dietary antigens are absorbed. Most food staples, including those with common antigens such as peanuts, eggs, and milk, contain long-chain triglycerides (LCT), which stimulate mesenteric lymph flux and postprandial transport of chylomicrons through mesenteric lymph nodes (MLN) and blood. Most dietary antigens, like ovalbumin (OVA), are emulsifiers, predicting affinity for chylomicrons. We hypothesized that chylomicron …

Regulation Of Cellular Protein Phosphatase-1 (Pp1) By Phosphorylation Of The Cpi-17 Family, C-Kinase-Activated Pp1 Inhibitors., Masumi Eto

Department of Molecular Physiology and Biophysics Faculty Papers

The regulatory circuit controlling cellular protein phosphatase-1 (PP1), an abundant group of Ser/Thr phosphatases, involves phosphorylation of PP1-specific inhibitor proteins. Malfunctions of these inhibitor proteins have been linked to a variety of diseases, including cardiovascular disease and cancer. Upon phosphorylation at Thr(38), the 17-kDa PP1 inhibitor protein, CPI-17, selectively inhibits a specific form of PP1, myosin light chain phosphatase, which transduces multiple kinase signals into the phosphorylation of myosin II and other proteins. Here, the mechanisms underlying PP1 inhibition and the kinase/PP1 cross-talk mediated by CPI-17 and its related proteins, PHI, KEPI, and GBPI, are discussed.

Identifying Blood Biomarkers And Physiological Processes That Distinguish Humans With Superior Performance Under Psychological Stress., Amanda M. Cooksey, Nausheen Momen, Russell Stocker, Shane C. Burgess

CVM Publications

BACKGROUND: Attrition of students from aviation training is a serious financial and operational concern for the U.S. Navy. Each late stage navy aviator training failure costs the taxpayer over $1,000,000 and ultimately results in decreased operational readiness of the fleet. Currently, potential aviators are selected based on the Aviation Selection Test Battery (ASTB), which is a series of multiple-choice tests that evaluate basic and aviation-related knowledge and ability. However, the ASTB does not evaluate a person's response to stress. This is important because operating sophisticated aircraft demands exceptional performance and causes high psychological stress. Some people are more resistant to …

Documentation Of Body Mass Index And Control Of Associated Risk Factors In A Large Primary Care Network, Stephanie A. Rose, Alexander Turchin, Richard W. Grant, James B. Meigs

Internal Medicine Faculty Publications

BACKGROUND: Body mass index (BMI) will be a reportable health measure in the United States (US) through implementation of Healthcare Effectiveness Data and Information Set (HEDIS) guidelines. We evaluated current documentation of BMI, and documentation and control of associated risk factors by BMI category, based on electronic health records from a 12-clinic primary care network.

METHODS: We conducted a cross-sectional analysis of 79,947 active network patients greater than 18 years of age seen between 7/05 - 12/06. We defined BMI category as normal weight (NW, 18-24.9 kg/m²), overweight (OW, 25-29.9), and obese (OB, ≥ 30). We measured documentation …

Effects Of Caregiver Burden And Satisfaction On Affect Of Older End-Stage Renal Disease Patients And Their Spouses, Maureen Wilson-Genderson, Rachel A Pruchno, Francine P Cartwright

Rowan-Virtua School of Osteopathic Medicine Departmental Research

We examined the extent to which a 2-factor model of affect explains how the burdens and satisfactions experienced by caregivers influence their own well-being and that of the spouses for whom they provide care. Using data from 315 older patients with end-stage renal disease and their spouses, we extended tests of Lawton et al.'s (1991) 2-factor model both longitudinally and dyadically. Multilevel modeling analyses partially support the 2-factor model. Consistent with the model, mean caregiver burden has a stronger effect on both caregiver and patient negative affect than does mean caregiver satisfaction. Contrary to the model, mean caregiver satisfaction has …

Changes In Self-Schema Structure In Cognitive Therapy For Major Depressive Disorder: A Randomized Clinical Trial., David J A Dozois, Peter J Bieling, Irene Patelis-Siotis, Lori Hoar, Susan Chudzik, Katie Mccabe, Henny A Westra

Psychology Publications

Negative cognitive structure (particularly for interpersonal content) has been shown in some research to persist past a current episode of depression and potentially to be a stable marker of vulnerability for depression (D. J. A. Dozois, 2007; D. J. A. Dozois & K. S. Dobson, 2001a). Given that cognitive therapy (CT) is highly effective for treating the acute phase of a depressive episode and that this treatment also reduces the risk of relapse and recurrence, it is possible that CT may alter these stable cognitive structures. In the current study, patients were randomly assigned to CT+ pharmacotherapy (n = 21) …

Adding A Motivational Interviewing Pretreatment To Cognitive Behavioral Therapy For Generalized Anxiety Disorder: A Preliminary Randomized Controlled Trial., Henny A Westra, Hal Arkowitz, David J A Dozois

Psychology Publications

Seventy-six individuals with a principal diagnosis of generalized anxiety disorder (GAD) were randomly assigned to receive either an MI pretreatment or no pretreatment (NPT), prior to receiving CBT. Significant group differences favoring the MI-CBT group were observed on the hallmark GAD symptom of worry and on therapist-rated homework compliance, which mediated the impact of treatment group on worry reduction. Adding MI pretreatment to CBT was specifically and substantively beneficial for individuals with high worry severity at baseline. There was evidence of relapse at 6-month follow-up for high severity individuals who received MI-CBT, but significant moderator effects favoring the high severity …