Medicine and Health Sciences Commons^™

Susceptibility Of Anopheles Gambiae To Insecticides Used For Malaria Vector Control In Rwanda, Emmanuel Hakizimana, Corine Karema, Dunia Munyakanage, Gad Iranzi, John Githure, Jon Eric Tongren, Willem Takken, Agnes Binagwaho, Constantianus J.M. Koenraadt

Dartmouth Scholarship

Background:

The widespread emergence of resistance to pyrethroids is a major threat to the gains made in malaria control. To monitor the presence and possible emergence of resistance against a variety of insecticides used for malaria control in Rwanda, nationwide insecticide resistance surveys were conducted in 2011 and 2013.

Methods:

Larvae of Anopheles gambiae sensu lato mosquitoes were collected in 12 sentinel sites throughout Rwanda. These were reared to adults and analysed for knock-down and mortality using WHO insecticide test papers with standard diagnostic doses of the recommended insecticides. A sub-sample of tested specimens was analysed for the presence of …

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 …

Incidence And Duration Of Type-Specific Human Papillomavirus Infection In High-Risk Hpv-Naïve Women: Results From The Control Arm Of A Phase Ii Hpv-16/18 Vaccine Trial, Agnihotram V. Ramanakumar, Paulo Naud, Cecilia M. Roteli-Martins, Newton S. De Carvalho, Paola C. De Borba, Julio C. Teixeira, Mark Blatter, Anna-Barbara Moscicki, Diane M. Harper, Barbara Romanowski, Stephen K. Tyring, Brian Ramjattan, Anne Schuind, Gary Dubin, Eduardo L. Franco

Dartmouth Scholarship

OBJECTIVES:

Persistence of human papillomaviruses (HPVs) is necessary for cervical carcinogenesis. We evaluated incidence and duration of type-specific HPV infections and the influence of age and number of sexual partners.

METHODS:

Data were obtained from 553 women (15-25 years), who were seronegative and DNA-negative for high-risk HPV (HR-HPV) types and were enrolled in the placebo arm of a randomised trial of the HPV-16/18 vaccine (NCT00689741/NCT00120848). They were followed for 6.3 years. Cervicovaginal samples were self-collected at 3-month intervals for up to 27 months, and cervical samples were collected by clinicians at 6-month intervals until study end. …

Secretion Of Rhoptry And Dense Granule Effector Proteins By Nonreplicating Toxoplasma Gondii Uracil Auxotrophs Controls The Development Of Antitumor Immunity, Barbara A. Fox, Kiah L. Sanders, Leah M. Rommereim, Rebekah B. Guevara, David J. Bzik

Dartmouth Scholarship

Nonreplicating type I uracil auxotrophic mutants of Toxoplasma gondii possess a potent ability to activate therapeutic immunity to established solid tumors by reversing immune suppression in the tumor microenvironment. Here we engineered targeted deletions of parasite secreted effector proteins using a genetically tractable Δku80 vaccine strain to show that the secretion of specific rhoptry (ROP) and dense granule (GRA) proteins by uracil auxotrophic mutants of T. gondii in conjunction with host cell invasion activates antitumor immunity through host responses involving CD8α⁺ dendritic cells, the IL-12/interferon-gamma (IFN-γ) T_H1 axis, as well as CD4⁺ and CD8 …

Consistency Of Hemoglobin A1c Testing And Cardiovascular Outcomes In Medicare Patients With Diabetes, Philip P. Goodney, Karina A. Newhall, Kimon Bekelis, Daniel Gottlieb, Richard Comi, Sushela Chaudrain, Adrienne E. Faerber, Todd A. Mackenzie, Jonathan S. Skinner

Dartmouth Scholarship

Background:

Annual hemoglobin A1c testing is recommended for patients with diabetes mellitus. However, it is unknown how consistently patients with diabetes mellitus receive hemoglobin A1c testing over time, or whether testing consistency is associated with adverse cardiovascular outcomes.

Methods and Results:

We identified 1 574 415 Medicare patients (2002–2012) with diabetes mellitus over the age of 65. We followed each patient for a minimum of 3 years to determine their consistency in hemoglobin A1C testing, using 3 categories: low (testing in 0 or 1 of 3 years), medium (testing in 2 of 3 years), and high (testing in all 3 …

Costs Of Diagnostic And Preoperative Workup With And Without Breast Mri In Older Women With A Breast Cancer Diagnosis, Tracy Onega, Anna N.A Tosteson, Julie Weiss, Jennifer Alford-Teaster, Rebecca A. Hubbard, Louise M. Henderson, Karla Kerlikowske, Martha E. Goodrich, Cristina O'Donoghue, Karen J. Wernli, Wendy B. Demartini, Beth A. Virnig

Dartmouth Scholarship

Background: Breast cancer in the U.S. - estimated at 232,670 incident cases in 2014 - has the highest aggregate economic burden of care relative to other female cancers. Yet, the amount of cost attributed to diagnostic/ preoperative work up has not been characterized. We examined the costs of imaging and biopsy among women enrolled in Medicare who did and did not receive diagnostic/preoperative Magnetic Resonance Imaging (MRI). Methods: Using Surveillance, Epidemiology and End Results (SEER)- Medicare data, we compared the per capita costs (PCC) based on amount paid, between diagnosis date and primary surgical treatment for a breast cancer diagnosis …

Cddo-Me Redirects Activation Of Breast Tumor Associated Macrophages, Michael S. Ball, Emilie P. Shipman, Hyunjung Kim, Karen T. Liby, Patricia A. Pioli

Dartmouth Scholarship

Tumor-associated macrophages can account for up to 50% of the tumor mass in breast cancer patients and high TAM density is associated with poor clinical prognosis. Because TAMs enhance tumor growth, development, and metastatic potential, redirection of TAM activation may have significant therapeutic benefit. Our studies in primary human macrophages and murine breast TAMs suggest that the synthetic oleanane triterpenoid CDDO-methyl ester (CDDO-Me) reprograms the activation profile of TAMs from tumor-promoting to tumor-inhibiting. We show that CDDO-Me treatment inhibits expression of IL-10 and VEGF in stimulated human M2 macrophages and TAMs but increases expression of TNF-α and IL-6. Surface expression …

Herpes Simplex Virus And Interferon Signaling Induce Novel Autophagic Clusters In Sensory Neurons, Sarah Katzenell, David A. Leib

Dartmouth Scholarship

Herpes simplex virus 1 (HSV-1) establishes lifelong infection in the neurons of trigeminal ganglia (TG), cycling between productive infection and latency. Neuronal antiviral responses are driven by type I interferon (IFN) and are crucial to controlling HSV-1 virulence. Autophagy also plays a role in this neuronal antiviral response, but the mechanism remains obscure. In this study, HSV-1 infection of murine TG neurons triggered unusual clusters of autophagosomes, predominantly in neurons lacking detectable HSV-1 antigen. Treatment of neurons with IFN-β induced a similar response, and cluster formation by infection or IFN treatment was dependent upon an intact IFN-signaling pathway. The autophagic …

Validating The Children’S Depression Inventory In The Context Of Rwanda, Agnes Binagwaho, Mary C. Smith Fawzi, Mawuena Agbonyitor, Sabin Nsanzimana, Corine Karema, Eric Remera, Vincent Mutabazi, Cyprien Shyirambere, Patrick Cyamatare, Cameron Nutt, Claire Wagner, Jeanine Condo, Nancy Misago, Yvonne Kayiteshonga

Dartmouth Scholarship

Background:

Depression is often co-morbid with chronic conditions, and when combined with HIV it can increase progression and reduce survival. A brief and accurate screening tool for depression among children living with HIV is necessary to increase access to mental health care and improve HIV-related outcomes in the long-term.

Methods:

A validation study was conducted, comparing the Children’s Depression Inventory (CDI) with a structured clinical assessment as the gold standard among children living with HIV ages 7-14 years in Rwanda. The response rate was 87 % and the analysis was performed among 100 study participants.

Results:

Twenty-five percent of children …

Is The Closest Facility The One Actually Used? An Assessment Of Travel Time Estimation Based On Mammography Facilities, Jennifer Alford-Teaster, Jane M. Lange, Rebecca A. Hubbard, Christoph I. Lee, Jennifer S. Haas, Xun Shi, Heather A. Carlos, Louise Henderson, Deirdre Hill, Anna N. A. Tosteson, Tracy Onega

Dartmouth Scholarship

Characterizing geographic access depends on a broad range of methods available to researchers and the healthcare context to which the method is applied. Globally, travel time is one frequently used measure of geographic access with known limitations associated with data availability. Specifically, due to lack of available utilization data, many travel time studies assume that patients use the closest facility. To examine this assumption, an example using mammography screening data, which is considered a geographically abundant health care service in the United States, is explored. This work makes an important methodological contribution to measuring access--which is a critical component of …

Incidence And In-Hospital Mortality Of Acute Kidney Injury (Aki) And Dialysis Requiring Aki (Aki-D) After Cardiac Catheterization In The National Inpatient Sample, Jeremiah R. Brown, Michael E. Rezaee, Elizabeth L. Nichols, Emily J. Marshall, Edward D. Siew, Michael E. Matheny

Dartmouth Scholarship

Background:

Acute kidney injury (AKI) and dialysis‐requiring AKI (AKI‐D) are common, serious complications of cardiac procedures.

Methods and Results:

We evaluated 3 633 762 (17 765 214 weighted population) cardiac catheterization or percutaneous coronary intervention (PCI) hospital discharges from the nationally representative National Inpatient Sample to determine annual population incidence rates for AKI and AKI‐D in the United States from 2001 to 2011. Odds ratios for both conditions and associated in‐hospital mortality were calculated for each year in the study period using multiple logistic regression. The number of cardiac catheterization or PCI cases resulting in AKI rose almost 3‐fold from …

The Relationship Between Foot Arch Measurements And Walking Parameters In Children, Simone V. Gill, Sara Keimig, Damian Kelty-Stephen, Ya-Ching Hung, Jeremy M. Desilva

Dartmouth Scholarship

Walking mechanics are influenced by body morphology. Foot arch height is one aspect of body morphology central to walking. However, generalizations about the relationship between arch height and walking are limited due to previous methodologies used for measuring the arch and the populations that have been studied. To gain the knowledge needed to support healthy gait in children and adults, we need to understand this relationship in unimpaired, typically developing children and adults using dynamic measures. The purpose of the current study was to examine the relationship between arch height and gait in a sample of healthy children and adults …

Genetic Susceptibility Loci Of Idiopathic Interstitial Pneumonia Do Not Represent Risk For Systemic Sclerosis: A Case Control Study In Caucasian Patients, Minghua Wu, Shervin Assassi, Gloria A. Salazar, Claudia Pedroza, Olga Y. Gorlova, Wei V. Chen, Julio Charles, Miranda L. Taing, Kelley Liao, Fredrick M. Wigley

Dartmouth Scholarship

Background: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) has phenotypic similarities to lung involvement in idiopathic interstitial pneumonia (IIP). We aimed to assess whether genetic susceptibility loci recently identified in the large IIP genome-wide association studies (GWASs) were also risk loci for SSc overall or severity of ILD in SSc. Methods: A total of 2571 SSc patients and 4500 healthy controls were investigated from the US discovery GWAS and additional US replication cohorts. Thirteen IIP-related selected single nucleotide polymorphisms (SNPs) were genotyped and analyzed for their association with SSc. Results: We found an association of SSc with the SNP rs6793295 …

Integrative Analysis Of Breast Cancer Reveals Prognostic Haematopoietic Activity And Patient-Specific Immune Response Profiles, Frederick S. Varn, Erik H. Andrews, David W. Mullins, Chao Cheng

Dartmouth Scholarship

Transcriptional programmes active in haematopoietic cells enable a variety of functions including dedifferentiation, innate immunity and adaptive immunity. Understanding how these programmes function in the context of cancer can provide valuable insights into host immune response, cancer severity and potential therapy response. Here we present a method that uses the transcriptomes of over 200 murine haematopoietic cells, to infer the lineage-specific haematopoietic activity present in human breast tumours. Correlating this activity with patient survival and tumour purity reveals that the transcriptional programmes of many cell types influence patient prognosis and are found in environments of high lymphocytic infiltration. Collectively, these …

Stress Granules And Rna Processing Bodies Are Novel Autoantibody Targets In Systemic Sclerosis, Michael E. Johnson, Andrew V. Grassetti, Jaclyn N. Taroni, Shawn M. Lyons, Devin Schweppe, Jessica K. Gordon, Robert F. Speira, Robert Lafyatis, Paul J. Anderson, Scott A. Gerber, Michael L. Whitfield

Dartmouth Scholarship

Autoantibody profiles represent important patient stratification markers in systemic sclerosis (SSc). Here, we performed serum-immunoprecipitations with patient antibodies followed by mass spectrometry (LC-MS/MS) to obtain an unbiased view of all possible autoantibody targets and their associated molecular complexes recognized by SSc.

Placental Epigenetics In Children’S Environmental Health, Carmen Marsit

Dartmouth Scholarship

There is a growing interest in understanding the mechanisms that drive the developmental origins of health and disease, and the role of epigenetic regulation has risen to the forefront of these studies. In particular, the placenta may be a model organ to consider as a mediator of the impact of the environment on developmental programming of children's health, as this organ plays a critical role in directing development and regulating the fetal environment. Several recent studies have begun to examine how environmental toxicant exposures can impact the placental epigenome, focusing on studies of DNA methylation and microRNA expression. This review …

Regional Implementation Of A Pediatric Cardiology Syncope Algorithm Using Standardized Clinical Assessment And Management Plans (Scamps) Methodology, Yvonne Paris, Olga H. Toro‐Salazar, Naomi S. Gauthier, Kathleen Rotondo, Lucy Arnold, Rose Hamershock, David E. Saudek, David R. Fulton, Ashley Renaud, Mark E. Alexander, New England Congenital Cardiology Association (Necca

Dartmouth Scholarship

Background:

Pediatric syncope is common. Cardiac causes are rarely found. We describe and assess a pragmatic approach to these patients first seen by a pediatric cardiologist in the New England region, using Standardized Clinical Assessment and Management Plans (SCAMPs).

Methods and Results:

Ambulatory patients aged 7 to 21 years initially seen for syncope at participating New England Congenital Cardiology Association practices over a 2.5‐year period were evaluated using a SCAMP. Findings were iteratively analyzed and the care pathway was revised. The vast majority (85%) of the 1254 patients had typical syncope. A minority had exercise‐related or more problematic symptoms. Guideline‐defined …