Medicine and Health Sciences Commons^™

Smarter Vaccine Design Will Circumvent Regulatory T Cell-Mediated Evasion In Chronic Hiv And Hcv Infection, Leonard Moise, Frances Terry, Andres H. Gutierrez, Ryan Tassone, Phyllis Losikoff, Stephen H. Gregory, Chris Bailey-Kellogg

Dartmouth Scholarship

Despite years of research, vaccines against HIV and HCV are not yet available, due largely to effective viral immunoevasive mechanisms. A novel escape mechanism observed in viruses that cause chronic infection is suppression of viral-specific effector CD4(+) and CD8(+) T cells by stimulating regulatory T cells (Tregs) educated on host sequences during tolerance induction. Viral class II MHC epitopes that share a T cell receptor (TCR)-face with host epitopes may activate Tregs capable of suppressing protective responses. We designed an immunoinformatic algorithm, JanusMatrix, to identify such epitopes and discovered that among human-host viruses, chronic viruses appear more human-like than viruses …

Analysis Of Candida Albicans Mutants Defective In The Cdk8 Module Of Mediator Reveal Links Between Metabolism And Biofilm Formation, Allia K. Lindsay, Diana K. Morales, Zhongle Liu, Nora Grahl, Anda Zhang, Sven D. Willger, Lawrence C. Myers, Deborah A. Hogan

Dartmouth Scholarship

Candida albicans biofilm formation is a key virulence trait that involves hyphal growth and adhesin expression. Pyocyanin (PYO), a phenazine secreted by Pseudomonas aeruginosa, inhibits both C. albicans biofilm formation and development of wrinkled colonies. Using a genetic screen, we identified two mutants, ssn3Δ/Δ and ssn8Δ/Δ, which continued to wrinkle in the presence of PYO. Ssn8 is a cyclin-like protein and Ssn3 is similar to cyclin-dependent kinases; both proteins are part of the heterotetrameric Cdk8 module that forms a complex with the transcriptional co-regulator, Mediator. Ssn3 kinase activity was also required for PYO sensitivity as a kinase dead mutant maintained …

Contribution Of Teg49 Small Rna In The 5′ Upstream Transcriptional Region Of Sara To Virulence In Staphylococcus Aureus, Samin Kim, Dindo Reyes, Marie Beaume, Patrice Francois, Ambrose Cheung

Dartmouth Scholarship

High-throughput RNA sequencing technology has found the 5' untranslated region of sarA to contain two putative small RNAs (sRNAs), designated teg49 and teg48. Northern blot analysis disclosed that teg49 and teg48 were detectable within the P3-P1 and P1 sarA promoter regions, respectively. Focusing on teg49, we found that this sRNA, consisting of 196 nucleotides, is transcribed in the same direction as the sarA P3 transcript. The expression of both P3 and teg49 transcripts is dependent on sigB and cshA, which encodes a DEAD box RNA helicase. Within the sRNA teg49, there are two putative hairpin-loop structures, HP1 and HP2. Transversion …

Inpp4b Suppresses Prostate Cancer Cell Invasion, Myles C. Hodgson, Elena I. Deryugina, Egla Suarez, Sandra M. Lopez, Dong Lin, Hui Xue, Ivan P. Gorlov

Dartmouth Scholarship

INPP4B and PTEN dual specificity phosphatases are frequently lost during progression of prostate cancer to metastatic disease. We and others have previously shown that loss of INPP4B expression correlates with poor prognosis in multiple malignancies and with metastatic spread in prostate cancer.

We demonstrate that de novo expression of INPP4B in highly invasive human prostate carcinoma PC-3 cells suppresses their invasion both in vitro and in vivo. Using global gene expression analysis, we found that INPP4B regulates a number of genes associated with cell adhesion, the extracellular matrix, and the cytoskeleton. Importantly, de novo expressed INPP4B suppressed the proinflammatory chemokine …

Myeloid Derived Hypoxia Inducible Factor 1-Alpha Is Required For Protection Against Pulmonary Aspergillus Fumigatus Infection, Kelly M. Shepardson, Anupam Jhingran, Alayna Caffrey, Joshua J. Obar, Benjamin T. Suratt, Brent L. Berwin, Tobias M. Hohl, Robert A. Cramer

Dartmouth Scholarship

Hypoxia inducible factor 1α (HIF1α) is the mammalian transcriptional factor that controls metabolism, survival, and innate immunity in response to inflammation and low oxygen. Previous work established that generation of hypoxic microenvironments occurs within the lung during infection with the human fungal pathogen Aspergillus fumigatus. Here we demonstrate that A. fumigatus stabilizes HIF1α protein early after pulmonary challenge that is inhibited by treatment of mice with the steroid triamcinolone. Utilizing myeloid deficient HIF1α mice, we observed that HIF1α is required for survival and fungal clearance early following pulmonary challenge with A. fumigatus. Unlike previously reported research with bacterial …

Tissue-Protective Effects Of Nkg2a In Immune-Mediated Clearance Of Virus Infection, Kenneth H. Ely, Mitsuo Matsuoka, Matthew P. Deberge, Jessica A. Ruby, Jun Liu, Mark J. Schneider, Yan Wang, Young S. Hahn, Richard I. Enelow

Dartmouth Scholarship

Virus infection triggers a CD8⁺ T cell response that aids in virus clearance, but also expresses effector functions that may result in tissue injury. CD8⁺ T cells express a variety of activating and inhibiting ligands, though regulation of the expression of inhibitory receptors is not well understood. The ligand for the inhibitory receptor, NKG2A, is the non-classical MHC-I molecule Qa1^b, which may also serve as a putative restricting element for the T cell receptors of purported regulatory CD8⁺ T cells. We have previously shown that Qa1^b-null mice suffer considerably enhanced immunopathologic lung injury …

The Association Of The Vanin-1 N131s Variant With Blood Pressure Is Mediated By Endoplasmic Reticulum-Associated Degradation And Loss Of Function, Ya-Juan Wang, Bamidele O. Tayo, Anupam Bandyopadhyay, Heming Wang, Tao Feng, Nora Franceschini, Hua Tang, Jianmin Gao, Yun Ju Sung, The Cogent Bp Consortium, Robert C. Elston, Scott M. Williams, Richard S. Cooper, Ting-Wei Mu, Xiaofeng Zhu

Dartmouth Scholarship

High blood pressure (BP) is the most common cardiovascular risk factor worldwide and a major contributor to heart disease and stroke. We previously discovered a BP-associated missense SNP (single nucleotide polymorphism)–rs2272996–in the gene encoding vanin-1, a glycosylphosphatidylinositol (GPI)-anchored membrane pantetheinase. In the present study, we first replicated the association of rs2272996 and BP traits with a total sample size of nearly 30,000 individuals from the Continental Origins and Genetic Epidemiology Network (COGENT) of African Americans (P = 0.01). This association was further validated using patient plasma samples; we observed that the N131S mutation is associated with significantly lower plasma vanin-1 …

Role Of Adaptor Trfa And Clppc In Controlling Levels Of Ssra-Tagged Proteins And Antitoxins In Staphylococcus Aureus, Niles P. Donegan, Jonathan S. Marvin, Ambrose L. Cheung

Dartmouth Scholarship

Staphylococcus aureus responds to changing extracellular environments in part by adjusting its proteome through alterations of transcriptional priorities and selective degradation of the preexisting pool of proteins. In Bacillus subtilis, the proteolytic adaptor protein MecA has been shown to play a role in assisting with the proteolytic degradation of proteins involved in competence and the oxidative stress response. However, the targets of TrfA, the MecA homolog in S. aureus, have not been well characterized. In this work, we investigated how TrfA assists chaperones and proteases to regulate the proteolysis of several classes of proteins in S. aureus. …

Doctors’ Perspectives Of Informed Consent For Non‐Emergency Surgical Procedures: A Qualitative Interview Study, Fiona Wood, Sean Michael Martin, Andrew Carson-Stevens, Glyn Elwyn, Elizabeth Precious, Paul Kinnersley

Dartmouth Scholarship

Background: The need to involve patients more in decisions about their care, the ethical imperative and concerns about ligation and complaints has highlighted the issue of informed consent and how it is obtained. In order for a patient to make an informed decision about their treatment, they need appropriate discussion of the risks and benefits of the treatment.

Objectives: To explore doctors' perspectives of gaining informed consent for routine surgical procedures.

Design: Qualitative study using semi-structured interviews selected by purposive sampling. Data were analysed thematically.

The Genetic Interacting Landscape Of 63 Candidate Genes In Major Depressive Disorder: An Explorative Study, Magnus Lekman, Ola Hössjer, Peter Andrews, Henrik Källberg, Daniel Uvehag, Dennis Charney, Husseini Manji, John A. Rush, Frances J. Mcmahon, Jason H Moore, Ingrid Kockum

Dartmouth Scholarship

Background:

Genetic contributions to major depressive disorder (MDD) are thought to result from multiple genes interacting with each other. Different procedures have been proposed to detect such interactions. Which approach is best for explaining the risk of developing disease is unclear.

This study sought to elucidate the genetic interaction landscape in candidate genes for MDD by conducting a SNP-SNP interaction analysis using an exhaustive search through 3,704 SNP-markers in 1,732 cases and 1,783 controls provided from the GAIN MDD study. We used three different methods to detect interactions, two logistic regressions models (multiplicative and additive) and one data mining and …

A Dietary-Wide Association Study (Dwas) Of Environmental Metal Exposure In Us Children And Adults, Matthew A. Davis, Diane Gilbert-Diamond, Margaret R. Karagas, Zhigang Li, Jason H. Moore, Scott M. Williams, H. Robert Frost

Dartmouth Scholarship

Background: A growing body of evidence suggests that exposure to toxic metals occurs through diet but few studies have comprehensively examined dietary sources of exposure in US populations.

Purpose: Our goal was to perform a novel dietary-wide association study (DWAS) to identify specific dietary sources of lead, cadmium, mercury, and arsenic exposure in US children and adults.

Methods: We combined data from the National Health and Nutrition Examination Survey with data from the US Department of Agriculture’s Food Intakes Converted to Retail Commodities Database to examine associations between 49 different foods and environmental metal exposure. Using blood and urinary biomarkers …

Facilitated Detection Of Social Cues Conveyed By Familiar Faces, Matteo Visconti Di Oleggio Castello, J. Swaroop Guntupalli, Hua Yang, M. Ida Gobbini

Dartmouth Scholarship

Recognition of the identity of familiar faces in conditions with poor visibility or over large changes in head angle, lighting and partial occlusion is far more accurate than recognition of unfamiliar faces in similar conditions. Here we used a visual search paradigm to test if one class of social cues transmitted by faces—direction of another’s attention as conveyed by gaze direction and head orientation—is perceived more rapidly in personally familiar faces than in unfamiliar faces. We found a strong effect of familiarity on the detection of these social cues, suggesting that the times to process these signals in familiar faces …

Comparative Performance Information Plays No Role In The Referral Behaviour Of Gps, Nicole A. B. M. Ketelaar, Marjan J. Faber, Glyn Elwyn, Gert P. Westert

Dartmouth Scholarship

Comparative performance information (CPI) about the quality of hospital care is information used to identify high-quality hospitals and providers. As the gatekeeper to secondary care, the general practitioner (GP) can use CPI to reflect on the pros and cons of the available options with the patient and choose a provider best fitted to the patient’s needs. We investigated how GPs view their role in using CPI to choose providers and support patients.

Method: We used a mixed-method, sequential, exploratory design to conduct explorative interviews with 15 GPs about their referral routines, methods of referral consideration, patient involvement, and the role …

Hybrid Photomultiplier Tube And Photodiode Parallel Detection Array For Wideband Optical Spectroscopy Of The Breast Guided By Magnetic Resonance Imaging, Fadi El-Ghussein, Michael A. Mastanduno, Shudong Jiang, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

A new optical parallel detection system of hybrid frequency and continuous-wave domains was developed to improve the data quality and accuracy in recovery of all breast optical properties. This new system was deployed in a previously existing system for magnetic resonance imaging (MRI)-guided spectroscopy, and allows incorporation of additional near-infrared wavelengths beyond 850 nm, with interlaced channels of photomultiplier tubes (PMTs) and silicon photodiodes (PDs). The acquisition time for obtaining frequency-domain data at six wavelengths (660, 735, 785, 808, 826, and 849 nm) and continuous-wave data at three wavelengths (903, 912, and 948 nm) is 12 min. The dynamic ranges …

Nuclear Glycolytic Enzyme Enolase Of Toxoplasma Gondii Functions As A Transcriptional Regulator, Thomas Mouveaux, Gabrielle Oria, Elisabeth Werkmeister, Christian Slomianny, Barbara A. Fox, David J. Bzik, Stanislas Tomavo

Dartmouth Scholarship

Apicomplexan parasites including Toxoplasma gondii have complex life cycles within different hosts and their infectivity relies on their capacity to regulate gene expression. However, little is known about the nuclear factors that regulate gene expression in these pathogens. Here, we report that T. gondii enolase TgENO2 is targeted to the nucleus of actively replicating parasites, where it specifically binds to nuclear chromatin in vivo. Using a ChIP-Seq technique, we provide evidence for TgENO2 enrichment at the 5′ untranslated gene regions containing the putative promoters of 241 nuclear genes. Ectopic expression of HA-tagged TgENO1 or TgENO2 led to changes in …

Disrupted Human–Pathogen Co-Evolution: A Model For Disease, Nuri Kodaman, Rafal S. Sobota, Robertino Mera, Barbara G. Schneider, Scott M. Williams

Dartmouth Scholarship

A major goal in infectious disease research is to identify the human and pathogenic genetic variants that explain differences in microbial pathogenesis. However, neither pathogenic strain nor human genetic variation in isolation has proven adequate to explain the heterogeneity of disease pathology. We suggest that disrupted co-evolution between a pathogen and its human host can explain variation in disease outcomes, and that genome-by-genome interactions should therefore be incorporated into genetic models of disease caused by infectious agents. Genetic epidemiological studies that fail to take both the pathogen and host into account can lead to false and misleading conclusions about disease …

Genome-Wide Dna Methylation Profiles In Progression To In Situ And Invasive Carcinoma Of The Breast With Impact On Gene Transcription And Prognosis, Thomas Fleischer, Arnoldo Frigessi, Kevin C. Johnson, Hege Edvardsen, Nizar Touleimat, Jovana Klajic, Margit Lh Riis, Vilde D. Haakensen, Fredrik Wärnberg, Bjørn Naume, Åslaug Helland, Anne-Lise Børresen-Dale, Jörg Tost, Brock C. Christensen, Vessela N. Kristensen

Dartmouth Scholarship

Background: Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive breast carcinoma. DNA methylation alterations are thought to be an early event in progression of cancer, and may prove valuable as a tool in clinical decision making and for understanding neoplastic development. Results: We generate genome-wide DNA methylation profiles of 285 breast tissue samples representing progression of cancer, and validate methylation changes between normal and DCIS in an independent dataset of 15 normal and 40 DCIS samples. We also validate a prognostic signature on 583 breast cancer samples from The Cancer Genome Atlas. Our analysis reveals …

Sensitivity Of Mri-Guided Near-Infrared Spectroscopy Clinical Breast Exam Data And Its Impact On Diagnostic Performance, Michael A. Mastanduno, Junqing Xu, Fadi El-Ghussein, Shudong Jiang, Hong Yin, Yan Zhao, Kelly E. Michaelson, Ke Wang, Fang Ren, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

In this study, data from breast MRI-guided near infrared spectroscopy (NIRS) exams delivered to 44 patients scheduled for surgical resection (ending in 16 benign and 28 malignant diagnoses) were analyzed using a spatial sensitivity metric to quantify the adequacy of the optical measurements for interrogating the tumor region of interest, as derived from the concurrent MRI scan. Along with positional sensitivity, the incorporation of spectral priors and the selection of an appropriate regularization parameter in the image reconstruction were considered, and found to influence the diagnostic accuracy of the recovered images. Once optimized, the MRI/NIRS data was able to differentiate …

Infection With Mers-Cov Causes Lethal Pneumonia In The Common Marmoset, Darryl Falzarano, Emmie De Wit, Friederike Feldmann, Angela L. Rasmussen, Atsushi Okumura, Xinxia Peng, Matthew J. Thomas, Neeltje Van Doremalen, Elaine Haddock, Lee Nagy, Rachel Lacasse, Tingting Liu, Jiang Zhu, Jason S. Mclellan, Dana P. Scott, Michael G. Katze, Heinz Feldmann, Vincent J. Munster

Dartmouth Scholarship

The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia …

Relating Gene Expression Evolution With Cpg Content Changes, Huan Yang, Dawei Li, Chao Cheng

Dartmouth Scholarship

Background:

Previous studies have shown that CpG dinucleotides are enriched in a subset of promoters and the CpG content of promoters is positively correlated with gene expression levels. But the relationship between divergence of CpG content and gene expression evolution has not been investigated. Here we calculate the normalized CpG (nCpG) content in DNA regions around transcription start site (TSS) and transcription terminal site (TTS) of genes in nine organisms, and relate them with expression levels measured by RNA-seq.

Results:

The nCpG content of TSS shows a bimodal distribution in all organisms except platypus, whereas the nCpG content of TTS …

Mst1 Directs Myosin Iia Partitioning Of Low And Higher Affinity Integrins During T Cell Migration, Xiaolu Xu, Emily R. Jaeger, Xinxin Wang, Erica Lagler-Ferrez, Serge Batalov, Nancy L. Mathis, Tim Wiltshire, John R. Walker, Michael P. Cooke, Karsten Sauer, Yina H. Huang

Dartmouth Scholarship

Chemokines promote T cell migration by transmitting signals that induce T cell polarization and integrin activation and adhesion. Mst1 kinase is a key signal mediator required for both of these processes; however, its molecular mechanism remains unclear. Here, we present a mouse model in which Mst1 function is disrupted by a hypomorphic mutation. Microscopic analysis of Mst1-deficient CD4 T cells revealed a necessary role for Mst1 in controlling the localization and activity of Myosin IIa, a molecular motor that moves along actin filaments. Using affinity specific LFA-1 antibodies, we identified a requirement for Myosin IIa-dependent contraction in the precise …

Placental Fkbp5 Genetic And Epigenetic Variation Is Associated With Infant Neurobehavioral Outcomes In The Richs Cohort, Alison G. Paquette, Barry M. Lester, Devin C. Koestler, Corina Lesseur, David A. Armstrong, Carmen J. Marsit

Dartmouth Scholarship

Adverse maternal environments can lead to increased fetal exposure to maternal cortisol, which can cause infant neurobehavioral deficits. The placenta regulates fetal cortisol exposure and response, and placental DNA methylation can influence this function. FK506 binding protein (FKBP5) is a negative regulator of cortisol response, FKBP5 methylation has been linked to brain morphology and mental disorder risk, and genetic variation of FKBP5 was associated with post-traumatic stress disorder in adults. We hypothesized that placental FKBP5 methylation and genetic variation contribute to gene expression control, and are associated with infant neurodevelopmental outcomes assessed using the Neonatal Intensive Care Unit (NICU) Network …

Co-Infection With Hpv Types From The Same Species Provides Natural Cross-Protection From Progression To Cervical Cancer, Rafal S. Sobota, Doreen Ramogola-Masire, Scott M. Williams, Nicola M. Zetola

Dartmouth Scholarship

The worldwide administration of bivalent and quadrivalent HPV vaccines has resulted in cross-protection against non-vaccine HPV types. Infection with multiple HPV types may offer similar cross-protection in the natural setting. We hypothesized that infections with two or more HPV types from the same species, and independently, infections with two or more HPV types from different species, associate with protection from high-grade lesions.

Epoxide-Mediated Differential Packaging Of Cif And Other Virulence Factors Into Outer Membrane Vesicles, A. E. Ballok, L. M. Filkins, J.. M. Bomberger, B. A. Stanton, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa produces outer membrane vesicles (OMVs) that contain a number of secreted bacterial proteins, including phospholipases, alkaline phosphatase, and the CFTR inhibitory factor (Cif). Previously, Cif, an epoxide hydrolase, was shown to be regulated at the transcriptional level by epoxides, which serve as ligands of the repressor, CifR. Here, we tested whether epoxides have an effect on Cif levels in OMVs. We showed that growth of P. aeruginosa in the presence of specific epoxi

The Impact Of Waist Circumference On Function And Physical Activity In Older Adults: Longitudinal Observational Data From The Osteoarthritis Initiative, John A. Batsis, Alicia J. Zbehlik, Laura K. Barre, Todd A. Mackenzie, Stephen J. Bartels

Dartmouth Scholarship

Background: We previously demonstrated that BMI is associated with functional decline and reduced quality of life. While BMI in older adults is fraught with challenges, waist circumference (WC) is a marker of visceral adiposity that can also predict mortality. However, its association with function and quality of life in older adults is not well understood and hence we sought to examine the impact of WC on six-year outcomes.

Methods: We identified adults aged ≥60 years from the longitudinal Osteoarthritis Initiative and stratified the cohort into quartiles based on WC. Our primary outcome measures of function at six year follow-up included: …

The Influence Of Race/Ethnicity And Place Of Service On Breast Reconstruction For Medicare Beneficiaries With Mastectomy, Tracy Onega, Julie Weiss, Karla Kerlikowske, Karen Wernli

Dartmouth Scholarship

Racial disparities in breast reconstruction for breast cancer are documented. Place of service has contributed to disparities in cancer care; but the interaction of race/ethnicity and place of service has not been explicitly examined. We examined whether place of service modified the effect of race/ethnicity on receipt of reconstruction. We included women with a mastectomy for incident breast cancer in SEER-Medicare from 2005-2009. Using Medicare claims, we determined breast reconstruction within 6 months. Facility characteristics included: rural/urban location, teaching status, NCI Cancer Center designation, cooperative oncology group membership, Disproportionate Share Hospital (DSH) status, and breast surgery volume. Using multivariable logistic …

Appropriate Development Of The Liver Treg Compartment Is Modulated By The Microbiota And Requires Tgf-Β And Myd88, Ann Maria, Kathryn A. English, James D. Gorham

Dartmouth Scholarship

Neither the early postnatal development of the liver Treg compartment nor the factors that regulate its development has been characterized. We compared the early developmental patterns of Treg cell accumulation in murine liver, thymus, and spleen. A FoxP3EGFP reporter mouse was employed to identify Treg cells. Mononuclear cells were isolated from organs postnatally, stained for CD4, and examined by flow cytometry to enumerate FoxP3+CD4hi cells. To assess roles for TGF-��1, MyD88, and TLR2, gene specific knockout pups were generated from heterozygous breeders. To test the role of commensal bacteria, pregnant dams were administered antibiotics during gestation and after parturition.The pattern …

Diagnosis-Specific Readmission Risk Prediction Using Electronic Health Data: A Retrospective Cohort Study, Courtney Hebert, Chaitanya Shivade, Randi Foraker, Jared Wasserman, Caryn Roth, Hagop Mekhjan, Stanley Lemeshow, Peter Embi

Dartmouth Scholarship

Background: Readmissions after hospital discharge are a common occurrence and are costly for both hospitals and patients. Previous attempts to create universal risk prediction models for readmission have not met with success. In this study we leveraged a comprehensive electronic health record to create readmission-risk models that were institution- and patient- specific in an attempt to improve our ability to predict readmission. Methods: This is a retrospective cohort study performed at a large midwestern tertiary care medical center. All patients with a primary discharge diagnosis of congestive heart failure, acute myocardial infarction or pneumonia over a two-year time period were …

The Role Of Melanin Concentrating Hormone (Mch) In The Central Chemoreflex: A Knockdown Study By Sirna In The Lateral Hypothalamus In Rats, Ningjing Li, Eugene Nattie, Aihua Li

Dartmouth Scholarship

Melanin concentrating hormone (MCH), a neuropeptide produced mainly in neurons localized to the lateral hypothalamic area (LHA), has been implicated in the regulation of food intake, energy balance, sleep state, and the cardiovascular system. Hypothalamic MCH neurons also have multisynaptic connections with diaphragmatic motoneurons and project to many central chemoreceptor sites. However, there are few studies of MCH involvement in central respiratory control. To test the hypothesis that MCH plays a role in the central chemoreflex, we induced a down regulation of MCH in the central nervous system by knocking down the MCH precursor (pMCH) mRNA in the LHA using …

Making A Decision About Trial Participation: The Feasibility Of Measuring Deliberation During The Informed Consent Process For Clinical Trials, Katie Gillies, Glyn Elwyn, Jonathan Cook

Dartmouth Scholarship

Background:

Informed consent of trial participants is both an ethical and a legal requirement. When facing a decision about trial participation, potential participants are provided with information about the trial and have the opportunity to have any questions answered before their degree of ‘informed-ness’ is assessed, usually subjectively, and before they are asked to sign a consent form. Currently, standardised methods for assessing informed consent have tended to be focused on aspects of understanding and associated outcomes, rather than on the process of consent and the steps associated with decision-making.

Methods:

Potential trial participants who were approached regarding participation in …