Medicine and Health Sciences Commons^™

Dueling Biological And Social Contagions, Feng Fu, Nicholas A. Christakis, James H. Fowler

Dartmouth Scholarship

Numerous models explore how a wide variety of biological and social phenomena spread in social networks. However, these models implicitly assume that the spread of one phenomenon is not affected by the spread of another. Here, we develop a model of “dueling contagions”, with a particular illustration of a situation where one is biological (influenza) and the other is social (flu vaccination). We apply the model to unique time series data collected during the 2009 H1N1 epidemic that includes information about vaccination, flu, and face-to-face social networks. The results show that well- connected individuals are more likely to get vaccinated, …

Hyper-Methylated Loci Persisting From Sessile Serrated Polyps To Serrated Cancers, Angeline S. Andrew, John A. Baron, Lynn F. Butterfly, Arief A. Suriawinata, Gregory J. Tsongalis, Christina M. Robinson, Christopher I. Amos

Dartmouth Scholarship

Although serrated polyps were historically considered to pose little risk, it is now understood that progression down the serrated pathway could account for as many as 15%–35% of colorectal cancers. The sessile serrated adenoma/polyp (SSA/P) is the most prevalent pre-invasive serrated lesion. Our objective was to identify the CpG loci that are persistently hyper-methylated during serrated carcinogenesis, from the early SSA/P lesion through the later cancer phases of neoplasia development. We queried the loci hyper-methylated in serrated cancers within our rightsided SSA/Ps from the New Hampshire Colonoscopy Registry, using the Illumina Infinium Human Methylation 450 k panel to comprehensively assess …

Boosting Of Hiv Envelope Cd4 Binding Site Antibodies With Long Variable Heavy Third Complementarity Determining Region In The Randomized Double Blind Rv305 Hiv-1 Vaccine Trial, David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman

Dartmouth Scholarship

The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is antigenic for the unmutated common ancestor of V1V2 broadly neutralizing antibody (bnAbs), no plasma bnAb activity was induced. The RV305 (NCT01435135) HIV-1 clinical trial was a placebo-controlled randomized double-blinded study that assessed the safety and efficacy of vaccine boosting on B cell repertoires. HIV-1- uninfected RV144 vaccine recipients were reimmunized 6–8 years later with AIDSVAX B/E gp120 alone, ALVAC-HIV alone, or a combination of ALVAC-HIV and AIDSVAX B/E gp120 …

Potent Single-Domain Antibodies That Arrest Respiratory Syncytial Virus Fusion Protein In Its Prefusion State, Iebe Rossey, Morgan Gilman, Stephanie Kabeche, Koen Sedeyn, Daniel Wrapp

Dartmouth Scholarship

Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs …

Evaluating Collaborate In A Clinical Setting: Analysis Of Mode Effects On Scores, Response Rates And Costs Of Data Collection, Paul J. Barr, Rachel C. Forcino, Rachel Thompson, Elissa M. Ozanne, Roger Arend, Molly Ganger Castaldo, A. James O'Malley, Glyn Elwyn

Dartmouth Scholarship

Shared decision-making (SDM) has become a policy priority, yet its implementation is not routinely assessed. To address this gap we tested the delivery of CollaboRATE, a 3-item patient reported experience measure of SDM, via multiple survey modes.To assess CollaboRATE response rates and respondent characteristics across different modes of administration, impact of mode and patient characteristics on SDM performance and cost of administration per response in a real-world primary care practice.Observational study design, with repeated assessment of SDM performance using CollaboRATE in a primary care clinic over 15 months of data collection. Different modes of administration were introduced sequentially including paper, …

Disability In Long-Term Care Residents Explained By Prevalent Geriatric Syndromes, Not Long-Term Care Home Characteristics: A Cross-Sectional Study, Natasha E. Lane, Walter P. Wodchis, Cynthia M. Boyd, Thérèse A. Stukel

Dartmouth Scholarship

Self-care disability is dependence on others to conduct activities of daily living, such as bathing, eating and dressing. Among long-term care residents, self-care disability lowers quality of life and increases health care costs. Understanding the correlates of self-care disability in this population is critical to guide clinical care and ongoing research in Geriatrics. This study examines which resident geriatric syndromes and chronic conditions are associated with residents’ self-care disability and whether these relationships vary across strata of age, sex and cognitive status. It also describes the proportion of variance in residents’ self-care disability that is explained by residents’ geriatric syndromes …

Neighborhood Environment And Falls Among Community-Dwelling Older Adults, Emily Nicklett, Matthew Lohman, Matthew Smith

Dartmouth Scholarship

Falls present a major challenge to active aging, but the relationship between neighborhood factors and falls is poorly understood. This study examined the relationship between fall events and neighborhood factors, including neighborhood social cohesion (sense of belonging, trust, friendliness, and helpfulness) and physical environment (vandalism/graffiti, rubbish, vacant/deserted houses, and perceived safety walking home at night).

Intestinal Microbiota And Weight-Gain In Preterm Neonates, Silvia Arboleya, Pablo Martinez-Camblor, Gonzalo Solís, Marta Suárez

Dartmouth Scholarship

The involvement of the gut microbiota on weight-gain and its relationship with childhood undernutrition and growth has been reported. Thus, the gut microbiota constitutes a potential therapeutic target for preventing growth impairment. However, our knowledge in this area is limited. In this study we aimed at evaluating the relationship among early microbiota, growth, and development in preterm infants. To this end we assessed the levels of specific microorganisms by qPCR, and those of short chain fatty acids by mean of gas-chromatography, in feces from 63 preterm newborns and determined their weight-gain during the first months. The statistical analyses performed indicate …

Association Of Igg4 Response And Autoimmune Pancreatitis With Intraductal Papillary-Mucinous Neoplasms, Amin A. Hedayat, Mikhail Lisovsky, Arief A. Suriawinata

Dartmouth Scholarship

Objectives: Concurrent intraductal papillary-mucinous neoplasm (IPMN) and autoimmune pancreatitis (AIP) was observed in a patient (index case) at our institution. Cases of coincidental IPMN and type 1 AIP and concurrent ductal adenocarcinoma (PDAC) and AIP have been previously reported. In this study we evaluate the hypothesis that IPMN elicits an IgG4 response. Methods: Twenty-one pancreases (including the index case) with IPMN resected at our institution were studied. H&E stained slides were reviewed and blocks of peritumoral pancreas were immunostained with IgG4 to look for IgG4-positive plasma cells. Results: We found evidence of variable IgG4 overexpression in 4/21 (19%) of IPMN. …

Role Of Cyclic Di-Gmp And Exopolysaccharide In Type Iv Pilus Dynamics, Jan Ribbe, Amy E. Baker, Sebastian Euler, George A. O'Toole, Berenike Maier

Dartmouth Scholarship

For Pseudomonas aeruginosa, levels of cyclic di-GMP (c-di-GMP) govern the transition from the planktonic state to biofilm formation. Type IV pili (T4P) are crucial determinants of biofilm structure and dynamics, but it is unknown how levels of c-di-GMP affect pilus dynamics. Here, we scrutinized how c-di-GMP affects molecular motor properties and adhesive behavior of T4P. By means of retraction, T4P generated forces of ∼30 pN. Deletion mutants in the proteins with known roles in biofilm formation, swarming motility, and exopolysaccharide (EPS) production (specifically, the diguanylate cyclases sadC and roeA or the c-di-GMP phosphodiesterase bifA) showed only modest effects on …

Donation After Brain Circulation Determination Of Death, Anne L. Dalle Ave, James L. Bernat

Dartmouth Scholarship

Background:

The fundamental determinant of death in donation after circulatory determination of death is the cessation of brain circulation and function. We therefore propose the term donation after brain circulation determination of death [DBCDD].

Results:

In DBCDD, death is determined when the cessation of circulatory function is permanent but before it is irreversible, consistent with medical standards of death determination outside the context of organ donation. Safeguards to prevent error include that: 1] the possibility of auto-resuscitation has elapsed; 2] no brain circulation may resume after the determination of death; 3] complete circulatory cessation is verified; and 4] the cessation …

Implementation Research On Community Health Workers’ Provision Of Maternal And Child Health Services In Rural Liberia, Peter W. Luckow, Avi Kenny, Emily White, Madeleine Ballard, Lorenzo Dorr, Kirby Erlandson, Benjamin Grant, Alice Johnson, Breanna Lorenzen, Subarna Mukherjee

Dartmouth Scholarship

OBJECTIVE:

To assess changes in the use of essential maternal and child health services in Konobo, Liberia, after implementation of an enhanced community health worker (CHW) programme.

METHODS:

The Liberian Ministry of Health partnered with Last Mile Health, a nongovernmental organization, to implement a pilot CHW programme with enhanced recruitment, training, supervision and compensation. To assess changes in maternal and child health-care use, we conducted repeated cross-sectional cluster surveys before (2012) and after (2015) programme implementation.

FINDINGS:

Between 2012 and 2015, 54 CHWs, seven peer supervisors and three clinical supervisors were trained to serve a population of 12 127 people …

Regulation Of Sterol Biosynthesis In The Human Fungal Pathogen Aspergillus Fumigatus: Opportunities For Therapeutic Development, Sourabh Dhingra, Robert A. Cramer

Dartmouth Scholarship

Sterols are a major component of eukaryotic cell membranes. For human fungal infections caused by the filamentous fungus Aspergillus fumigatus, antifungal drugs that target sterol biosynthesis and/or function remain the standard of care. Yet, an understanding of A. fumigatus sterol biosynthesis regulatory mechanisms remains an under developed therapeutic target. The critical role of sterol biosynthesis regulation and its interactions with clinically relevant azole drugs is highlighted by the basic helix loop helix (bHLH) class of transcription factors known as Sterol Regulatory Element Binding Proteins (SREBPs). SREBPs regulate transcription of key ergosterol biosynthesis genes in fungi including A. fumigatus. …

Caesarean Sections And For-Profit Status Of Hospitals: Systematic Review And Meta-Analysis, Ilir Hoxha, Lamprini Syrogiannouli, Xhyljeta Luta, Kali Tal, David C. Goodman

Dartmouth Scholarship

Objective: Financial incentives may encourage private for-profit providers to perform more caesarean section (CS) than non-profit hospitals. We therefore sought to determine the association of for-profit status of hospital and odds of CS.

Design: Systematic review and meta-analysis. Data sources: MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews from the first year of records through February 2016. Eligibility criteria: To be eligible, studies had to report data to allow the calculation of ORs of CS comparing private for-profit hospitals with public or private non-profit hospitals in a specific geographic area. Outcomes: The prespecified primary outcome was the adjusted OR …

The Fatty Acid Regulator Fadr Influences The Expression Of The Virulence Cascade In The El Tor Biotype Of Vibrio Cholerae By Modulating The Levels Of Toxt Via Two Different Mechanisms, Gabriela Kovacikova, Wei Lin, Ronald K. Taylor, Karen Skorupski

Dartmouth Scholarship

FadR is a master regulator of fatty acid (FA) metabolism that coordinates the pathways of FA degradation and biosynthesis in enteric bacteria. We show here that a ΔfadR mutation in the El Tor biotype of Vibrio cholerae prevents the expression of the virulence cascade by influencing both the transcription and the posttranslational regulation of the master virulence regulator ToxT. FadR is a transcriptional regulator that represses the expression of genes involved in FA degradation, activates the expression of genes involved in unsaturated FA (UFA) biosynthesis, and also activates the expression of two operons involved in saturated FA (SFA) biosynthesis. …

Familial Lung Cancer: A Brief History From The Earliest Work To The Most Recent Studies, Anthony Musolf, Claire Simpson, Mariza De Andrade, Diptasri Mandal, Colette Gaba, Ping Yang, Yafang Li

Dartmouth Scholarship

Lung cancer is the deadliest cancer in the United States, killing roughly one of four cancer patients in 2016. While it is well-established that lung cancer is caused primarily by environmental effects (particularly tobacco smoking), there is evidence for genetic susceptibility. Lung cancer has been shown to aggregate in families, and segregation analyses have hypothesized a major susceptibility locus for the disease. Genetic association studies have provided strong evidence for common risk variants of small-to-moderate effect. Rare and highly penetrant alleles have been identified by linkage studies, including on 6q23–25. Though not common, some germline mutations have also been identified …

A Comparison Between Lynch Syndrome And Sporadic Colorectal Cancer Survivors’ Satisfaction With Their Healthcare Providers, Allison M. Burton-Chase, Wendy M. Parker, Katrina M. Polivka, Ellen R. Gritz

Dartmouth Scholarship

This study evaluated provider satisfaction in a sample of colorectal cancer (CRC) survivors with and without Lynch syndrome (LS). Participants were case–case-matched CRC survivors with (n=75) or without (n=75) LS (mean age of 55; range: 27–93). Participants completed a mailed questionnaire assessing demographics, clinical characteristics, healthcare utilization, psychosocial variables, and provider satisfaction. LS CRC survivors reported lower provider satisfaction scores on three subscales of the Primary Care Assessment Survey: communication (78.14 vs. 83.96; P<0.05), interpersonal treatment (78.58 vs. 85.30; P<0.05), and knowledge of the patient (60.34 vs. 69.86; P<0.01). Among LS CRC survivors, predictors for mean communication and trust subscale scores were location of treatment and socioeconomic status. Higher mean depression scores also were associated with trust, while social support predicted higher satisfaction with communication. Sporadic CRC survivor satisfaction is driven largely by age (communication, interpersonal treatment) and patient anxiety (communication), while seeing a provider more often was associated with increased satisfaction with knowledge of the patient. LS CRC survivors reported lower levels of provider satisfaction than sporadic CRC survivors. LS survivors who received care at The University of Texas MD Anderson Cancer Center, a comprehensive cancer center (CCC), reported higher satisfaction than those receiving care at other institutions. Depressive symptoms and socioeconomic status may impact provider satisfaction ratings. Exploration of other potential predictors of provider satisfaction should be examined in this population. Additionally, further research is needed to examine the potential impact of provider satisfaction on adherence to medical recommendations in LS CRC survivors, particularly those being treated outside of CCCs.

Supporting Shared Decision-Making For Older People With Multiple Health And Social Care Needs: A Protocol For A Realist Synthesis To Inform Integrated Care Models, Frances Bunn, Claire Goodman, Jill Manthorpe, Marie-Anne Durand, Isabel Hodkinson, Greta Rait, Paul Millac, Sue L. Davies, Bridget Russell, Patricia Wilson

Dartmouth Scholarship

Introduction: Including the patient or user perspective is a central organising principle of integrated care. Moreover, there is increasing recognition of the importance of strengthening relationships among patients, carers and practitioners, particularly for individuals receiving substantial health and care support, such as those with long-term or multiple conditions. The overall aims of this synthesis are to provide a context-relevant understanding of how models to facilitate shared decision-making (SDM) might work for older people with multiple health and care needs, and how they might be applied to integrated care models.

Methods and analysis: The synthesis draws on the principles of realist …

Neutralization Of Diverse Human Cytomegalovirus Strains Conferred By Antibodies Targeting Viral Gh/Gl/Pul128-131 Pentameric Complex, Sha Ha, Fengsheng Li, Matthew C. Troutman, Daniel C. Freed, Aimin Tang, John W. Loughney, Dai Wang, I-Ming Wang, Josef Vlasak, David C. Nickle, Richard R. Rustandi, Melissa Hamm, Pete A. Dephillips, Ningyan Zhang, Jason S. Mclellan, Stuart P. Adler, Michael A. Mcvoy, Zhiqiang An, Tong-Ming Fu

Dartmouth Scholarship

Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex glycoprotein H (gH)/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross-neutralize the field strains of HCMV, remains a challenge. In this study, with a panel of neutralizing antibodies from three healthy human donors with natural HCMV infection or a …

Telemedicine And Primary Care Obesity Management In Rural Areas– Innovative Approach For Older Adults?, John A. Batsis, Sarah N. Pletcher, James E. Stahl

Dartmouth Scholarship

Background:

The growing prevalence of obesity is paralleling a rise in the older adult population creating an increased risk of functional impairment, nursing home placement and early mortality. The Centers for Medicare and Medicaid recognized the importance of treating obesity and instituted a benefit in primary care settings to encourage intensive behavioral therapy in beneficiaries by primary care clinicians. This benefit covers frequent, brief, clinic visits designed to address older adult obesity.

Discussion:

We describe the challenges in the implementation and delivery into real-world settings. The challenges in rural settings that have the fastest growing elderly population, high obesity rates, …

Ehlers-Danlos Syndrome Hypermobility Type Is Associated With Rheumatic Diseases, Kyla R. Rodgers, Jiang Gui, Mary Beth P. Dinulos, Richard C. Chou

Dartmouth Scholarship

We retrospectively analyzed electronic medical records of patients with Ehlers-Danlos Syndrome hypermobility type (HEDS), including demographic information, workup, rheumatological diagnoses in order to determine its association with rheumatological conditions. HEDS Patients were stratified according to level of workup received (no additional work (physical exam only) = NWU, limited workup = LWU, comprehensive workup = CWU)). HEDS patients were predominantly female (21:4, F:M). The percentage of patients with at least one rheumatological condition was significantly correlated with level of workup (NWU, 9.2%; LWU, 33.3%, CWU, 67.1%; p-value < 0.0001). The HLA-B27 antigen was more prevalent (p-value < 2.2 × 10 –8 ) in the CWU HEDS patients (23.9%) than in the general population of the United States (6.1%). HEDS with CWU were associated with more rheumatological conditions (i.e. psoriasis, ankylosing spondylitis, rheumatoid arthritis, fibromyalgia) than those with NWU or LWU. In conclusion, HEDS is associated with complicated rheumatological conditions, which are uncovered by comprehensive workup. These conditions require different clinical management strategies than HEDS, and left untreated could contribute to the pain or even physical disability (i.e. joint erosions) in HEDS patients. While the mechanisms underlying these associations are unknown, it is important that all HEDS patients receive adequate workup to ensure a complete clinical understanding for the best care strategy possible.

The Annual Burden Of Seasonal Influenza In The Us Veterans Affairs Population, Yinong Young-Xu, Robertus Van Aalst, Ellyn Russo, Jason K. H. Lee, Ayman Chit

Dartmouth Scholarship

Seasonal influenza epidemics have a substantial public health and economic burden in the United States (US). On average, over 200,000 people are hospitalized and an estimated 23,000 people die from respiratory and circulatory complications associated with seasonal influenza virus infections each year. Annual direct medical costs and indirect productivity costs across the US have been found to average respectively at $10.4 billion and $16.3 billion. The objective of this study was to estimate the economic impact of severe influenza-induced illness on the US Veterans Affairs population. The five-year study period included 2010 through 2014. Influenza-attributed outcomes were estimated with a …

Pseudomonas Aeruginosa Sabotages The Generation Of Host Proresolving Lipid Mediators, Becca A. Flitter, Kelli L. Hvorecny, Emiko Ono, Taylor Eddens

Dartmouth Scholarship

Recurrent Pseudomonas aeruginosa infections coupled with robust, damaging neutrophilic inflammation characterize the chronic lung disease cystic fibrosis (CF). The proresolving lipid mediator, 15-epi lipoxin A4 (15-epi LXA4), plays a critical role in limiting neutrophil activation and tissue inflammation, thus promoting the return to tissue homeostasis. Here, we show that a secreted P. aeruginosa epoxide hydrolase, cystic fibrosis transmembrane conductance regulator inhibitory factor (Cif), can disrupt 15-epi LXA4 transcellular biosynthesis and function. In the airway, 15-epi LXA4 production is stimulated by the epithelial-derived eicosanoid 14,15-epoxyeicosatrienoic acid (14,15-EET). Cif sabotages the production of 15-epi LXA4 by rapidly hydrolyzing 14,15-EET into its cognate …

Genetic Risk For Obesity Predicts Nucleus Accumbens Size And Responsivity To Real-World Food Cues, Kristina Rapuano, Amanda Zieselman, William Kelley, James Sargent, Todd Heatherton, Diane Gilbert-Diamond

Dartmouth Scholarship

Obesity is a major public health concern that involves an interaction between genetic susceptibility and exposure to environmental cues (e.g., food marketing); however, the mechanisms that link these factors and contribute to unhealthy eating are unclear. Using a well-known obesity risk polymorphism (FTO rs9939609) in a sample of 78 children (ages 9-12 y), we observed that children at risk for obesity exhibited stronger responses to food commercials in the nucleus accumbens (NAcc) than children not at risk. Similarly, children at a higher genetic risk for obesity demonstrated larger NAcc volumes. Although a recessive model of this polymorphism best predicted body …

An Investigation Of Professionalism Reflected By Student Comments On Formative Virtual Patient Encounters, Ting Dong, William Kelly, Meredith Hays, Norman B. Berman

Dartmouth Scholarship

Background: This study explored the use of virtual patient generated data by investigating the association between students’ unprofessional patient summary statements, which they entered during an on-line virtual patient case, and detection of their future unprofessional behavior.

Method: At the USUHS, students complete a number of virtual patient encounters, including a patient summary, to meet the clerkship requirements of Internal Medicine, Family Medicine, and Pediatrics. We reviewed the summary statements of 343 students who graduated in 2012 and 2013. Each statement was rated with regard to four features: Unprofessional, Professional, Equivocal (could be construed as unprofessional), and Unanswered (students did …

Your Teaching Strategy Matters: How Engagement Impacts Application In Health Information Literacy Instruction, Heather A. Johnson, Laura C. Barrett

Dartmouth Scholarship

The purpose of this study was to compare two pedagogical methods, active learning and passive instruction, to determine which is more useful in helping students to achieve the learning outcomes in a one-hour research skills instructional session.

Management Of Urinoma Formation After Laparoscopic Cryoablation Of Renal Cyst, Shawn X. Li, Lawrence M. Dagrosa, Vernon M. Pais Jr

Dartmouth Scholarship

Aim: To describe the presentation and management of a urinoma developing as a complication of laparoscopic cryoablation of a Bosniak III renal cyst.

Case: A 74-year-old woman presented with acute onset of severe left lower abdominal pain 1 day after a laparoscopic cryoablation of a 3 cm multilobular left cystic renal mass. CT revealed a perinephric fluid collection adjacent to the lower pole of the left kidney with active urinary extravasation seen on retrograde pyelogram, confirming the presence of an urinoma. A retrograde ureteral stent was placed with complete resolution of symptoms and the patient was discharged on the first …