Medicine and Health Sciences Commons^™

5-Hydroxymethylcytosine Localizes To Enhancer Elements And Is Associated With Survival In Glioblastoma Patients, Kevin C. Johnson, E. Andres Houseman, Jessica E. King, Katharine M. Von Herrmann, Camilo E. Fadu, Brock C. Christensen

Dartmouth Scholarship

Glioblastomas exhibit widespread molecular alterations including a highly distorted epigenome. Here, we resolve genome-wide 5-methylcytosine and 5-hydroxymethylcytosine in glioblastoma through parallel processing of DNA with bisulfite and oxidative bisulfite treatments. We apply a statistical algorithm to estimate 5-methylcytosine, 5-hydroxymethylcytosine and unmethylated proportions from methylation array data. We show that 5-hydroxymethylcytosine is depleted in glioblastoma compared with prefrontal cortex tissue. In addition, the genomic localization of 5-hydroxymethylcytosine in glioblastoma is associated with features of dynamic cell-identity regulation such as tissue-specific transcription and super-enhancers. Annotation of 5-hydroxymethylcytosine genomic distribution reveal significant associations with RNA regulatory processes, immune function, stem cell maintenance and …

Risk Of Medication Overuse Headache Across Classes Of Treatments For Acute Migraine, Kristian Thorlund, Christina Sun-Edelstein, Eric Druyts, Steve Kanters, Shanil Ebrahim, Rahul Bhambri, Elodie Ramos, Edward Mills, Michel Lanteri-Minet, Stewart Tepper

Dartmouth Scholarship

Background: The most commonly prescribed medications used to treat migraine acutely are single analgesics, ergots, opioids, and triptans. Due to varying mechanisms of action across drug classes, there is reason to believe that some classes may be less likely than others to elicit Medication Overuse Headache (MOH) than others. We therefore aimed to determine whether certain classes of acute migraine drugs are more likely to elicit MOH than others.

Methods: A comprehensive systematic literature was conducted to identify studies of varying designs that reported on MOH within the considered treatment classes. Only studies that reported MOH according to the International …

The Future Of Global Health Education: Training For Equity In Global Health, Lisa V. Adams, Claire M. Wagner, Cameron T. Nutt, Agnes Binagwaho

Dartmouth Scholarship

Background:

Among academic institutions in the United States, interest in global health has grown substantially: by the number of students seeking global health opportunities at all stages of training, and by the increase in institutional partnerships and newly established centers, institutes, and initiatives to house global health programs at undergraduate, public health and medical schools. Witnessing this remarkable growth should compel health educators to question whether the training and guidance that we provide to students today is appropriate, and whether it will be applicable in the next decade and beyond. Given that “global health” did not exist as an academic …

Dark Shadow Of The Long White Cloud: Neighborhood Safety Is Associated With Self-Rated Health And Cortisol During Pregnancy In Auckland, Aotearoa/New Zealand, Zaneta M. Thayer

Dartmouth Scholarship

Auckland, Aotearoa/New Zealand is a culturally and ethnically diverse city. Despite popular global conceptions regarding its utopian nature, the lived experience for many individuals in Auckland attests to the substantial social, economic, and health inequalities that exist there. In particular, rapidly rising home prices constrain housing decisions and force individuals to live in less desirable neighborhoods, with potential impacts on individual health. One of the pathways through which adverse neighborhood conditions could impact health is through alterations in the functioning of the hypothalamic pituitary adrenal (HPA)-axis, which regulates the physiological stress response. This paper evaluates the relationship between perceived …

Raman Spectroscopy Detects Distant Invasive Brain Cancer Cells Centimeters Beyond Mri Capability In Humans, Michael Jermyn, Joannie Desroches, Jeanne Mercier, Karl St-Arnaud

Dartmouth Scholarship

Surgical treatment of brain cancer is limited by the inability of current imaging capabilities such as magnetic resonance imaging (MRI) to detect the entirety of this locally invasive cancer. This results in residual cancer cells remaining following surgery, leading to recurrence and death. We demonstrate that intraoperative Raman spectroscopy can detect invasive cancer cells centimeters beyond pathological T1-contrast-enhanced and T2-weighted MRI signals. This intraoperative optical guide can be used to detect invasive cancer cells and minimize post-surgical cancer burden. The detection of distant invasive cancer cells beyond MRI signal has the potential to increase the effectiveness of surgery and directly …

Does Travel Time To A Radiation Facility Impact Patient Decision-Making Regarding Treatment For Prostrate Cancer? A Study Of The New Hampshire State Cancer Registry, Fady Ghali, Maria Celaya, Michael Laviolette, Johann Ingimarsson, Heather Carlos, Judy R. Rees, Elias Hyams

Dartmouth Scholarship

Purpose: We sought to determine whether further distance from a radiation center is associated with lower utilization of external beam radiation therapy (XRT). Methods: We retrospectively identified patients with a new diagnosis of localized prostate cancer (CaP) within the New Hampshire State Cancer Registry from 2004 to 2011. Patients were categorized by age, D’Amico risk category, year of treatment, marital status, season of diagnosis, urban/rural residence, and driving time to the nearest radiation facility. Treatment decisions were stratified into those requiring multiple trips (XRT) or a single trip (surgery or brachytherapy). Multivariable regression analysis was performed. Results: A total of …

Maternal Arsenic Exposure And Gestational Diabetes And Glucose Intolerance In The New Hampshire Birth Cohort Study, Shohreh F. Farzan, Anala Gossai, Yu Chen, Lisa Chasan-Taber, Emily Baker, Margaret Karagas

Dartmouth Scholarship

Background: Gestational diabetes mellitus (GDM) is a major pregnancy complication with detrimental effects for both mothers and their children. Accumulating evidence has suggested a potential role for arsenic (As) exposure in the development of GDM, but current studies have not assessed As exposure from water, urine or toenail samples.

Methods: We investigated the association between As exposure and risk of glucose intolerance and GDM among 1151 women enrolled in the New Hampshire Birth Cohort Study. Arsenic was measured in home well water and via biomarkers (i.e., maternal urine collected ~24–28 weeks gestation and toenail clippings collected 2 weeks postpartum).

Results: …

Constitutively Activated Pi3k Accelerates Tumor Initiation And Modifies Histopathology Of Breast Cancer, M. R. Sheen, J. D. Marotti, M. J. Allegrezza, M. Rutkowski, J. R. Conejo-Garcia, S. Fiering

Dartmouth Scholarship

The gene encoding phosphatidylinositol 3-kinase catalytic subunit α-isoform (PIK3CA, p110α) is frequently activated by mutation in human cancers. Based on detection in some breast cancer precursors, PIK3CA mutations have been proposed to have a role in tumor initiation. To investigate this hypothesis, we generated a novel mouse model with a Cre-recombinase regulated allele of p110α (myristoylated-p110α, myr-p110α) along with p53fl/fl deletion and KrasG12D also regulated by Cre-recombinase. After instillation of adenovirus-expressing Cre-recombinase into mammary ducts, we found that myr-p110α accelerated breast tumor initiation in a copy number-dependent manner. Breast tumors induced by p53fl/fl;KrasG12D with no or one copy of myr-p110α …

Application Of Rnai-Induced Gene Expression Profiles For Prognostic Prediction In Breast Cancer, Yue Wang, Kenneth . M. K. Mark, Matthew H. Ung, Arminja Kettenbach, Todd Miller, Wei Xu, Wenqing Cheng Cheng, Tian Xia, Chao Cheng

Dartmouth Scholarship

Homologous recombination (HR) is the primary pathway for repairing double-strand DNA breaks implicating in the development of cancer. RNAi-based knockdowns of BRCA1 and RAD51 in this pathway have been performed to investigate the resulting transcriptomic profiles. Here we propose a computational framework to utilize these profiles to calculate a score, named RNA-Interference derived Proliferation Score (RIPS), which reflects cell proliferation ability in individual breast tumors. RIPS is predictive of breast cancer classes, prognosis, genome instability, and neoadjuvant chemosensitivity. This framework directly translates the readout of knockdown experiments into potential clinical applications and generates a robust biomarker in breast cancer.

Signaling Through Lrg1, Rho1 And Pkc1 Governs Candida Albicans Morphogenesis In Response To Diverse Cues, Jinglin L. Xie, Nora Grahl, Trevor Sless, Michelle Leach, Sang Hu Kim, Deborah Hogan

Dartmouth Scholarship

The capacity to transition between distinct morphological forms is a key virulence trait for diverse fungal pathogens. A poignant example of a leading opportunistic fungal pathogen of humans for which an environmentally responsive developmental program underpins virulence is Candida albicans. C. albicans mutants that are defective in the transition between yeast and filamentous forms typically have reduced virulence. Although many positive regulators of C. albicans filamentation have been defined, there are fewer negative regulators that have been implicated in repression of filamentation in the absence of inducing cues. To discover novel negative regulators of filamentation, we screened …

Optical Tracer Size Differences Allow Quantitation Of Active Pumping Rate Versus Stokes–Einstein Diffusion In Lymphatic Transport, Alisha V. Dsouza, Kayla Marra, Jason R. Gunn, Kimberley S. Samkoe, Brian W. Pogue

Dartmouth Scholarship

Lymphatic uptake of interstitially administered agents occurs by passive convective–diffusive inflow driven by interstitial concentration and pressure, while the downstream lymphatic transport is facilitated by active propulsive contractions of lymphatic vessel walls. Near-infrared fluorescence imaging in mice was used to measure these central components of lymphatic transport for the first time, using two different-sized molecules––methylene blue (MB) and fluorescence-labeled antibody immunoglobulin G (IgG)-IRDye 680RD. This work confirms the hypothesis that lymphatic passive inflow and active propulsion rates can be separated based upon the relative differences in Stokes–Einstein diffusion coefficient. This coefficient specifically affects the passive-diffusive uptake when the interstitial volume …

A Novel Genetic Variant In Long Non-Coding Rna Gene Nexn-As1 Is Associated With Risk Of Lung Cancer, Hua Yuan, Hongliang Liu, Zhensheng Liu, Kouros Owzar

Dartmouth Scholarship

Lung cancer etiology is multifactorial, and growing evidence has indicated that long non-coding RNAs (lncRNAs) are important players in lung carcinogenesis. We performed a large-scale meta-analysis of690,564 SNPs in 15,531 autosomal lncRNAs by using datasets from six previously published genome-wideassociation studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung (TRICL) consortiumin populations of European ancestry. Previously unreported significant SNPs (P value < 1 × 10−7) were further validated in two additional independent lung cancer GWAS datasets from Harvard University anddeCODE. In the final meta-analysis of all eight GWAS datasets with 17,153 cases and 239,337 controls, a novel risk SNP rs114020893 in the lncRNA NEXN-AS1 region at 1p31.1 remained statistically significant(odds ratio = 1.17; 95% confidence interval = 1.11–1.24; P = 8.31 × 10−9). In further in silico analysis,rs114020893 was predicted to change the secondary structure of the lncRNA. Our finding indicates that SNP rs114020893 of NEXN-AS1 at 1p31.1 may contribute to lung cancer susceptibility.

Throat Swabs And Sputum Culture As Predictors Of P. Aeruginosa Or S. Aureus Lung Colonization In Adult Cystic Fibrosis Patients, Darius Seidler, Mary Griffin, Amanda Nymon, Katja Koeppen, Alix Ashare

Dartmouth Scholarship

Background:

Due to frequent infections in cystic fibrosis (CF) patients, repeated respiratory cultures are obtained to inform treatment. When patients are unable to expectorate sputum, clinicians obtain throat swabs as a surrogate for lower respiratory cultures. There is no clear data in adult subjects demonstrating the adequacy of throat swabs as a surrogate for sputum or BAL. Our study was designed to determine the utility of throat swabs in identifying lung colonization with common organisms in adults with CF.

Methods:

Adult CF subjects (n = 20) underwent bronchoscopy with BAL. Prior to bronchoscopy, a throat swab was obtained. A sputum …

Use Of A Multiplex Transcript Method For Analysis Of Pseudomonas Aeruginosa Gene Expression Profiles In The Cystic Fibrosis Lung, Alex H. Gifford, Sven D. Willger, Emily L. Dolben, Lisa A. Moulton, Dana Dorman, Heather Bean, Jane Hill, Thomas Hampton, Alix Ashare, Deborah Hogan

Dartmouth Scholarship

The discovery of therapies that modulate Pseudomonas aeruginosa virulence or that can eradicate chronic P. aeruginosa lung infections associated with cystic fibrosis (CF) will be advanced by an improved understanding of P. aeruginosa behavior in vivo We demonstrate the use of multiplexed Nanostring technology to monitor relative abundances of P. aeruginosa transcripts across clinical isolates, in serial samples, and for the purposes of comparing microbial physiology in vitro and in vivo The expression of 75 transcripts encoded by genes implicated in CF lung disease was measured in a variety of P. aeruginosa strains as well as RNA serial sputum samples …

Pyrimidine Pathway-Dependent And -Independent Functions Of The Toxoplasma Gondii Mitochondrial Dihydroorotate Dehydrogenase, Miryam Andrea Hortua Triana, Daniela Cajiao Herrera, Barbara H. Zimmermann, Barbara A. Fox, David Bzik

Dartmouth Scholarship

Dihydroorotate dehydrogenase (DHODH) mediates the fourth step of de novo pyrimidine biosynthesis and is a proven drug target for inducing immunosuppression in therapy of human disease as well as a rapidly emerging drug target for treatment of malaria. In Toxoplasma gondii, disruption of the first, fifth, or sixth step of de novo pyrimidine biosynthesis induced uracil aux- otrophy. However, previous attempts to generate uracil auxotrophy by genetically deleting the mitochondrion-associated DHODH of T. gondii (Tg DHODH) failed. To further address the essentiality of Tg DHODH, mutant gene alleles deficient in Tg DHODH activity were designed to ablate the enzyme activity. …

Implementing An Mhealth System For Substance Use Disorders In Primary Care: A Mixed Methods Study Of Clinicians’ Initial Expectations And First Year Experiences, Marie-Louise Mares, David H. Gustafson, Joseph E. Glass, Andrew Quanbeck, Helene Mcdowell, Fiona Mctavish, Amy Atwood, Lisa Marsch

Dartmouth Scholarship

Millions of Americans need but don’t receive treatment for substance use, and evidence suggests that addiction-focused interventions on smart phones could support their recovery. There is little research on implementation of addiction-related interventions in primary care, particularly in Federally Qualified Health Centers (FQHCs) that provide primary care to underserved populations. We used mixed methods to examine three FQHCs’ implementation of Seva, a smart-phone app that offers patients online support/discussion, health-tracking, and tools for coping with cravings, and offers clinicians information about patients’ health tracking and relapses. We examined (a) clinicians' initial perspectives about implementing Seva, and (b) the first year …

Lifestyle And Other Factors Explain One-Half Of The Variability In The Serum 25-Hydroxyvitamin D Response To Cholecalciferol Supplementation In Healthy Adults, Judy R. Rees, Leila A. Mott, Elizabeth L. Barry, John A. Baron

Dartmouth Scholarship

Background: Many factors have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentrations in observational studies, with variable consistency. However, less information is available on factors affecting the magnitude of changes in serum 25(OH)D resulting from vitamin D supplementation. Objective: This study aimed to identify factors associated with the serum 25(OH)D response to supplementation with 1000 IU cholecalciferol/d during the first year of a large, multicenter, randomized, placebo-controlled colorectal adenoma chemoprevention trial. Methods: Eligible older adults who were not vitamin D–deficient [serum 25(OH)D12 ng/mL] were randomly assigned in a modified 2 3 2 factorial design to 1 of 4 groups: daily …

Immune- And Nonimmune-Compartment-Specific Interferon Responses Are Critical Determinants Of Herpes Simplex Virus-Induced Generalized Infections And Acute Liver Failure, Zachary M. Parker, Tracy Jo Pasieka, George A. Parker, David A. Leib

Dartmouth Scholarship

The interferon (IFN) response to viral pathogens is critical for host survival. In humans and mouse models, defects in IFN responses can result in lethal herpes simplex virus 1 (HSV-1) infections, usually from encephalitis. Although rare, HSV-1 can also cause fulminant hepatic failure, which is often fatal. Although herpes simplex encephalitis has been extensively studied, HSV-1 generalized infections and subsequent acute liver failure are less well understood. We previously demonstrated that IFN-αβγR-/- mice are exquisitely susceptible to liver infection following corneal infection with HSV-1. In this study, we used bone marrow chimeras of IFN-αβγR-/- (AG129) and wild-type (WT; 129SvEv) mice …

Pharmacy Use By Dual-Eligible Non-Elderly Veterans With Private Healthcare Insurance, Brian C. Lund, Mary E. Charlton, Alan N. West

Dartmouth Scholarship

The Veterans Health Administration (VHA) is the largest nationally integrated healthcare system in the United States, operating 168 medical centers and more than 1000 community based outpatient clinics. However, many veterans seek care outside the VHA system, particularly when they are also covered by state or federal programs such as Medicare or Medicaid, or have access to private health insurance, often through employment. Concerted efforts have been made to facilitate communication and coordinate care between VHA and private sector healthcare, but concurrent use of these systems adds to an already fragmented U.S health care system.

Dying Among Older Adults In Switzerland: Who Dies In Hospital, Who Dies In A Nursing Home?, Xhyljeta Luta, Radoslaw Panczak, Maud Maessen, Matthias Egger, David Goodman

Dartmouth Scholarship

Background: Institutional deaths (hospitals and nursing homes) are an important issue because they are often at odds with patient preference and associated with high healthcare costs. The aim of this study was to examine deaths in institutions and the role of individual, regional, and healthcare supply characteristics in explaining variation across Swiss Hospital Service Areas (HSAs).

Methods: Retrospective study of individuals ≥66 years old who died in a Swiss institution (hospital or nursing homes) in 2010. Using a two-level logistic regression analysis we examined the amount of variation across HSAs adjusting for individual, regional and healthcare supply measures. The outcome …

In The Information Age, Do Dementia Caregivers Get The Information They Need? Semi-Structured Interviews To Determine Informal Caregivers’ Education Needs, Barriers, And Preferences, Kendra Peterson, Howard Hahn, Amber J. Lee, Catherine A. Madison, Alireza Atri

Dartmouth Scholarship

Most patients with dementia or cognitive impairment receive care from family members, often untrained for this challenging role. Caregivers may not access publicly available caregiving information, and caregiver education programs are not widely implemented clinically. Prior large surveys yielded broad quantitative understanding of caregiver information needs, but do not illuminate the in-depth, rich, and nuanced caregiver perspectives that can be gleaned using qualitative methodology. We aimed to understand perspectives about information sources, barriers and preferences, through semi-structured interviews with 27 caregivers. Content analysis identified important themes

Multiobjective Guided Priors Improve The Accuracy Of Near-Infrared Spectral Tomography For Breast Imaging, Jinchao Feng, Shudong Jiang, Junqing Xu, Yan Zhao, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

An image reconstruction regularization approach for magnetic resonance imaging-guided near-infrared spectral tomography has been developed to improve quantification of total hemoglobin (HbT) and water. By combining prior information from dynamic contrast enhanced (DCE) and diffusion weighted (DW) MR images, the absolute bias errors of HbT and water in the tumor were reduced by 22% and 18%, 21% and 6%, and 10% and 11%, compared to that in the no-prior, DCE- or DW-guided reconstructed images in three-dimensional simulations, respectively. In addition, the apparent contrast values of HbT and water were increased in patient image reconstruction from 1.4 and 1.4 (DCE) or …

Heterogeneity Among Isolates Reveals That Fitness In Low Oxygen Correlates With Aspergillus Fumigatus Virulence, Caitlin H. Kowalski, Sarah R. Beattie, Kevin K. Fuller, Elizabeth A. Mcgurk, Yi-Wei Tang, Tobias Hohl, Joshua Obar, Robert Cramer Jr.

Dartmouth Scholarship

Previous work has shown that environmental and clinical isolates of Aspergillus fumigatus represent a diverse population that occupies a variety of niches, has extensive genetic diversity, and exhibits virulence heterogeneity in a number of animal models of invasive pulmonary aspergillosis (IPA). However, mechanisms explaining differences in virulence among A. fumigatus isolates remain enigmatic. Here, we report a significant difference in virulence of two common lab strains, CEA10 and AF293, in the murine triamcinolone immunosuppression model of IPA, in which we previously identified severe low oxygen microenvironments surrounding fungal lesions. Therefore, we hypothesize that the ability to thrive within these lesions …

Epithelial Cell Integrin Β1 Is Required For Developmental Angiogenesis In The Pituitary Gland, Kathleen M. Scully, Dorota Skowronska-Krawczyk, Michal Krawczyk, Daria Merkurjev, Havilah Taylor, Antonia Livolsi, Jessica Tollkuhn, Radu V. Stan, Michael G. Rosenfeld

Dartmouth Scholarship

As a key component of the vertebrate neuroendocrine system, the pituitary gland relies on the progressive and coordinated development of distinct hormone-producing cell types and an invading vascular network. The molecular mechanisms that drive formation of the pituitary vasculature, which is necessary for regulated synthesis and secretion of hormones that maintain homeostasis, metabolism, and endocrine function, remain poorly understood. Here, we report that expression of integrin β1 in embryonic pituitary epithelial cells is required for angiogenesis in the developing mouse pituitary gland. Deletion of pituitary epithelial integrin β1 before the onset of angiogenesis resulted in failure of invading endothelial cells …

Time Trends And Predictors Of Abnormal Postoperative Body Temperature In Infants Transported To The Intensive Care Unit, Hedwig Schroeck, Angela K. Lyden, Wendy L. Benedict, Satya Krishna Ramachandran

Dartmouth Scholarship

Background: Despite increasing adoption of active warming methods over the recent years, little is known about the effectiveness of these interventions on the occurrence of abnormal postoperative temperatures in sick infants. Methods: Preoperative and postoperative temperature readings, patient characteristics, and procedural factors of critically ill infants at a single institution were retrieved retrospectively from June 2006 until May 2014. The primary endpoints were the incidence and trend of postoperative hypothermia and hyperthermia on arrival at the intensive care units. Univariate and adjusted analyses were performed to identify factors independently associated with abnormal postoperative temperatures. Results: 2,350 cases were included. 82% …

Trustworthy Patient Decision Aids: A Qualitative Analysis Addressing The Risk Of Competing Interests, Glyn Elwyn, Michelle Dannenberg, Arianna Blaine, Urbashi Poddar, Marie-Anne Durand

Dartmouth Scholarship

OBJECTIVE:

Our aim in this study was to examine the competing interest policies and procedures of organisations who develop and maintain patient decision aids.

DESIGN:

Descriptive and thematic analysis of data collected from a cross-sectional survey of patient decision aid developer's competing interest policies and disclosure forms.

RESULTS:

We contacted 25 organisations likely to meet the inclusion criteria. 12 eligible organisations provided data. 11 organisations did not reply and 2 declined to participate. Most patient decision aid developers recognise the need to consider the issue of competing interests. Assessment processes vary widely and, for the most part, are insufficiently robust …

Effects Of Breast Density And Compression On Normal Breast Tissue Hemodynamics Through Breast Tomosynthesis Guided Near-Infrared Spectral Tomography, Kelly E. Michaelsen, Venkataramanan Krishnaswamy, Linxi Shi, Srinivasan Vedantham, Andrew Karellas, Brian W. Pogue, Keith D. Paulsen, Steven P. Poplack

Dartmouth Scholarship

Optically derived tissue properties across a range of breast densities and the effects of breast compression on estimates of hemoglobin, oxygen metabolism, and water and lipid concentrations were obtained from a coregistered imaging system that integrates near-infrared spectral tomography (NIRST) with digital breast tomosynthesis (DBT). Image data were analyzed from 27 women who underwent four IRB approved NIRST/DBT exams that included fully and mildly compressed breast acquisitions in two projections—craniocaudal (CC) and mediolateral-oblique (MLO)—and generated four data sets per patient (full and moderate compression in CC and MLO views). Breast density was correlated with HbT (r=0.64, p=0.001), water (r=0.62, p=0.003), …

Microdose Fluorescence Imaging Of Aby-029 On An Operating Microscope Adapted By Custom Illumination And Imaging Modules, Jonathan T. Elliott, Alisha V. Dsouza, Kayla Marra, Brian W. Pogue, David Roberts, Keith Paulsen

Dartmouth Scholarship

Fluorescence guided surgery has the potential to positively impact surgical oncology; current operating microscopes and stand-alone imaging systems are too insensitive or too cumbersome to maximally take advantage of new tumor-specific agents developed through the microdose pathway. To this end, a custom-built illumination and imaging module enabling picomolar-sensitive near-infrared fluorescence imaging on a commercial operating microscope is described. The limits of detection and system specifications are characterized, and in vivo efficacy of the system in detecting ABY-029 is evaluated in a rat orthotopic glioma model following microdose injections, showing the suitability of the device for microdose phase 0 clinical trials.

Using Foreign Virtual Patients With Medical Students In Germany: Are Cultural Differences Evident And Do They Impede Learning?, Jens Walldorf, Tina Jähnert, Norman B. Berman, Martin R. Fischer

Dartmouth Scholarship

Learning with virtual patients (VPs) is considered useful in medical education for fostering clinical reasoning. As the authoring of VPs is highly demanding, an international exchange of cases might be desirable. However, cultural differences in foreign VPs might hamper learning success.

Requirements For Pseudomonas Aeruginosa Type I-F Crispr-Cas Adaptation Determined Using A Biofilm Enrichment Assay, Gary E. Heussler, Jon L. Miller, Courtney E. Price, Alan J. Collins

Dartmouth Scholarship

CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR-associated protein) systems are diverse and found in many archaea and bacteria. These systems have mainly been characterized as adaptive immune systems able to protect against invading mobile genetic elements, including viruses. The first step in this protection is acquisition of spacer sequences from the invader DNA and incorporation of those sequences into the CRISPR array, termed CRISPR adaptation. Progress in understanding the mechanisms and requirements of CRISPR adaptation has largely been accomplished using overexpression of cas genes or plasmid loss assays; little work has focused on endogenous CRISPR-acquired immunity from viral predation. …