Digital Commons Network^™

Development Of A Spirometry T-Score In The General Population, Sei Won Lee, Hyun Kuk Kim, Seunghee Baek, Ji-Ye Jung, Young Sam Kim, Jae Seung Lee, Sang-Do Lee, David M. Mannino, Yeon-Mok Oh

Preventive Medicine and Environmental Health Faculty Publications

Background and objective: Spirometry values may be expressed as T-scores in standard deviation units relative to a reference in a young, normal population as an analogy to the T-score for bone mineral density. This study was performed to develop the spirometry T-score.

Methods: T-scores were calculated from lambda-mu-sigma-derived Z-scores using a young, normal age reference. Three outcomes of all-cause death, respiratory death, and COPD death were evaluated in 9,101 US subjects followed for 10 years; an outcome of COPD-related health care utilization (COPD utilization) was evaluated in 1,894 Korean subjects followed for 4 years.

Results: The …

Project Achieve – Using Implementation Research To Guide The Evaluation Of Transitional Care Effectiveness, Jing Li, Jane Brock, Brian Jack, Brian Mittman, Mary Naylor, Joann Sorra, Glen P. Mays, Mark V. Williams, Arnold J. Stromberg, Heather M. Bush, Allison Scott, Robert Duff, Emily R. Clear, Hannah Keeler, Project Achieve

Internal Medicine Faculty Publications

Background: Poorly managed hospital discharges and care transitions between health care facilities can cause poor outcomes for both patients and their caregivers. Unfortunately, the usual approach to health care delivery does not support continuity and coordination across the settings of hospital, doctors’ offices, home or nursing homes. Though complex efforts with multiple components can improve patient outcomes and reduce 30-day readmissions, research has not identified which components are necessary. Also we do not know how delivery of core components may need to be adjusted based on patient, caregiver, setting or characteristics of the community, or how system redesign can be …

Modulating Foveal Representation Can Influence Visual Discrimination In The Periphery, Qing Yu, Won Mok Shim

Dartmouth Scholarship

A previous study by Williams et al. (2008) provided evidence for a novel form of feedback in the visual system, whereby peripheral information is contained in foveal retinotopic cortex. Beyond its possible implication for peripheral object recognition, few studies have examined the effect of a direct behavioral manipulation of the foveal feedback representation. To address this question, we measured participants' peripheral visual discrimination performance while modulating their foveal representation in a series of psychophysical experiments. On each trial, participants discriminated the identities of briefly presented novel, three-dimensional objects or the orientations of gratings in a peripheral location while fixating at …

Intact Cohesion, Anaphase, And Chromosome Segregation In Human Cells Harboring Tumor-Derived Mutations In Stag2, Jung-Sik Kim, Xiaoyuan He, Bernardo Orr, Gordana Wutz, Victoria Hill, Jan-Michael Peters, Duane A. Compton, Todd Waldman

Dartmouth Scholarship

Somatic mutations of the cohesin complex subunit STAG2 are present in diverse tumor types. We and others have shown that STAG2 inactivation can lead to loss of sister chromatid cohesion and alterations in chromosome copy number in experimental systems. However, studies of naturally occurring human tumors have demonstrated little, if any, correlation between STAG2 mutational status and aneuploidy, and have further shown that STAG2-deficient tumors are often euploid. In an effort to provide insight into these discrepancies, here we analyze the effect of tumor-derived STAG2 mutations on the protein composition of cohesin and the expected mitotic phenotypes of STAG2 …

Genome-Wide Annotation, Identification, And Global Transcriptomic Analysis Of Regulatory Or Small Rna Gene Expression In Staphylococcus Aureus, Ronan K. Carroll, Andy Weiss, William H. Broach, Richard E Wiemels, Austin B. Mogen, Kelly C. Rice, Lindsey N. Shaw

Molecular Biosciences Faculty Publications

In Staphylococcus aureus, hundreds of small regulatory or small RNAs (sRNAs) have been identified, yet this class of molecule remains poorly understood and severely understudied. sRNA genes are typically absent from genome annotation files, and as a consequence, their existence is often overlooked, particularly in global transcriptomic studies. To facilitate improved detection and analysis of sRNAs in S. aureus, we generated updated GenBank files for three commonly used S. aureus strains (MRSA252, NCTC 8325, and USA300), in which we added annotations for >260 previously identified sRNAs. These files, the first to include genome-wide annotation of sRNAs in S. aureus, were …

Reconstructing Representations Of Dynamic Visual Objects In Early Visual Cortex, Edmund Chong, Ariana M. Familiar, Won Mok Shim

Dartmouth Scholarship

As raw sensory data are partial, our visual system extensively fills in missing details, creating enriched percepts based on incomplete bottom-up information. Despite evidence for internally generated representations at early stages of cortical processing, it is not known whether these representations include missing information of dynamically transforming objects. Long-range apparent motion (AM) provides a unique test case because objects in AM can undergo changes both in position and in features. Using fMRI and encoding methods, we found that the “intermediate” orientation of an apparently rotating grating, never presented in the retinal input but interpolated during AM, is reconstructed in population-level, …

Variability Of Brain Death Policies In The United States, David M. Greer, Hilary H. Wang, Jennifer D. Robinson, Panayiotis N. Varelas, Galen V. Henderson, Eelco Fm Wijdicks

Neurology Articles

IMPORTANCE: Brain death is the irreversible cessation of function of the entire brain, and it is a medically and legally accepted mechanism of death in the United States and worldwide. Significant variability may exist in individual institutional policies regarding the determination of brain death. It is imperative that brain death be diagnosed accurately in every patient. The American Academy of Neurology (AAN) issued new guidelines in 2010 on the determination of brain death.

OBJECTIVE: To evaluate if institutions have adopted the new AAN guidelines on the determination of brain death, leading to policy changes.

DESIGN, SETTING, AND PARTICIPANTS: Fifty-two organ …

Initial Benchmarking Of The Quality Of Medical Care In Childhood-Onset Systemic Lupus Erythematosus., Rina Mina, Julia G. Harris, Marisa S. Klein-Gitelman, Simone Appenzeller, Maraisa Centeville, Diane Eskra, Jennifer L. Huggins, Anne L. Johnson, Raju Khubchandani, Prachi Khandekar, Jiha Lee, Hai Mei Liu, Joshua D. Pendl, Clovis A. Silva, Marco F. Silva, Ahmad I. Zaal, Esi Morgan Dewitt, Stacy P. Ardoin, Hermine I. Brunner

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To assess the quality of medical care in childhood-onset systemic lupus erythematosus (SLE) at tertiary pediatric rheumatology centers as measured by observance of SLE quality indicators (SLE-QIs).

METHODS: International consensus has been achieved for childhood-onset SLE-QIs capturing medical care provision in 9 domains: diagnostic testing, education of cardiovascular (CV) risk and lifestyles, lupus nephritis (LN), medication management, bone health, ophthalmologic surveillance, transition, pregnancy, and vaccination. Using medical record information, the level of performance of these childhood-onset SLE-QIs was assessed in childhood-onset SLE populations treated at 4 tertiary pediatric rheumatology centers in the US, 2 in Brazil, and 1 center …

A Targeted Genetic Association Study Of Epithelial Ovarian Cancer Susceptibility, Madalene Earp, Stacey J. Winham, Nicholas Larson, Jennifer B. Permuth, Hugues Sicotte, Jeremy Chien, Hoda Anton-Culver, Elisa V. Bandera, Andrew Berchuck, Linda S. Cook, Daniel Cramer, Jennifer A. Doherty

Dartmouth Scholarship

BACKGROUND:

Genome-wide association studies have identified several common susceptibility alleles for epithelial ovarian cancer (EOC). To further understand EOC susceptibility, we examined previously ungenotyped candidate variants, including uncommon variants and those residing within known susceptibility loci.

RESULTS:

At nine of eleven previously published EOC susceptibility regions (2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13), novel variants were identified that were more strongly associated with risk than previously reported variants. Beyond known susceptibility regions, no variants were found to be associated with EOC risk at genome-wide statistical significance (p <5x10(-8)), nor were any significant after Bonferroni correction for 17,000 variants (p< 3x10-6).

METHODS:

A customized genotyping array was used to assess over …

Fracture Burden And Risk Factors In Childhood Ckd: Results From The Ckid Cohort Study., Michelle R. Denburg, Juhi Kumar, Thomas Jemielita, Ellen R. Brooks, Amy Skversky, Anthony A. Portale, Isidro B. Salusky, Bradley A. Warady, Susan L. Furth, Mary B. Leonard

Manuscripts, Articles, Book Chapters and Other Papers

Childhood chronic kidney disease (CHD) poses multiple threats to bone accrual; however, the associated fracture risk is not well characterized. This prospective cohort study included 537 CKD in Children (CKiD) participants. Fracture histories were obtained at baseline, at years 1, 3, and 5 through November 1, 2009, and annually thereafter. We used Cox regression analysis of first incident fracture to evaluate potential correlates of fracture risk. At enrollment, median age was 11 years, and 16% of patients reported a prior fracture. Over a median of 3.9 years, 43 males and 24 females sustained incident fractures, corresponding to 395 (95% confidence …

Genetic Loci Associated With Renal Function Measures And Chronic Kidney Disease In Children: The Pediatric Investigation For Genetic Factors Linked With Renal Progression Consortium., Matthias Wuttke, Craig S. Wong, Elke Wühl, Daniel Epting, Li Luo, Anselm Hoppmann, Anke Doyon, Yong Li, Gkdgen Consortium, Betül Sözeri, Daniela Thurn, Martin Helmstädter, Tobias B. Huber, Tom D. Blydt-Hansen, Albrecht Kramer-Zucker, Otto Mehls, Anette Melk, Uwe Querfeld, Susan L. Furth, Bradley A. Warady, Franz Schaefer, Anna Köttgen

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Chronic kidney disease (CKD) in children is characterized by rapid progression and a high incidence of end-stage renal disease and therefore constitutes an important health problem. While unbiased genetic screens have identified common risk variants influencing renal function and CKD in adults, the presence and identity of such variants in pediatric CKD are unknown.

METHODS: The international Pediatric Investigation for Genetic Factors Linked with Renal Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) and Cardiovascular …

Endosteal Biologic Augmentation For Surgical Fixation Of Displaced Femoral Neck Fractures, Lionel E Lazaro, Jacqueline F Birnbaum, Nadja A Farshad-Amacker, David L Helfet, Hollis G Potter, Dean G Lorich

Faculty, Staff and Student Publications

OBJECTIVES: To report outcomes of a cohort with displaced femoral neck fractures (FNFs) treated with a length/angle-stable construct augmented with an endosteal fibular allograft serving as a biologic dowel.

DESIGN: Prospective.

SETTING: Level I Trauma Center.

PATIENTS: The study group consists of 27 patients with isolated FNF surgically treated by a single surgeon.

INTERVENTION: Open reduction of the femoral neck, fixed with a length- and angle-stable construct of 2 fully threaded cannulated screws augmented with an endosteal fibular allograft serving as a biologic dowel.

MAIN OUTCOME MEASUREMENTS: Clinical and radiographic outcomes of the fixation construct and the viability of both …

Assessing Knowledge Of, And Attitudes To, Hiv/Aids Among University Students In The United Arab Emirates, Dalia Haroun, Ola El Saleh, Lesley Wood, Rola Mechli, Nada Al Marzouqi, Samir Anouti

All Works

© 2016 Haroun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: The Middle East and North Africa (MENA) region is among the top two regions in the world with the fastest growing HIV epidemic. In this context, risks and vulnerability are high as the epidemic is on the rise with evidence indicating significantly increasing HIV prevalence, new HIV infections and AIDS-related deaths. Objective: The aim of the survey was to assess …

Down-Regulation Of Placental Neuropilin-1 In Fetal Growth Restriction., Dev Maulik, Alok De, Louis Ragolia, Jodi Evans, Dmitry Grigoryev, Kamani Lankachandra, David Mundy, Jolene Muscat, Mary M. Gerkovich, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Fetal growth restriction (FGR) is associated with adverse outcomes extending from fetal to adult life, and thus, constitutes a major health care challenge. Fetuses with progressive growth restriction show increasing impedance in the umbilical artery flow, which may become absent during end-diastole. Absent end-diastolic flow (AEDF) is associated with adverse perinatal outcomes including stillbirths and perinatal asphyxia. Placentas from such pregnancies demonstrate deficient fetoplacental vascular branching. Current evidence, moreover, indicates an antiangiogenic state in maternal circulation in several pregnancy complications including preeclampsia, small-for-gestational-age births, fetal death, and preterm labor. The angiogenic mediators in maternal circulation are predominantly of placental …

Pharmacogenetic Allele Nomenclature: International Workgroup Recommendations For Test Result Reporting., L V. Kalman, Jag Agúndez, M Lindqvist Appell, J L. Black, G C. Bell, S Boukouvala, C Bruckner, E Bruford, K Caudle, S A. Coulthard, A K. Daly, Al Del Tredici, J T. Den Dunnen, K Drozda, R E. Everts, D Flockhart, R R. Freimuth, Andrea Gaedigk, H Hachad, T Hartshorne, M Ingelman-Sundberg, T E. Klein, V M. Lauschke, D R. Maglott, H L. Mcleod, G A. Mcmillin, U A. Meyer, D J. Müller, D A. Nickerson, W S. Oetting, M Pacanowski, V M. Pratt, M V. Relling, A Roberts, W S. Rubinstein, K Sangkuhl, M Schwab, S A. Scott, S C. Sim, R K. Thirumaran, L H. Toji, R F. Tyndale, Rhn Van Schaik, M Whirl-Carrillo, Ktj Yeo, U M. Zanger

Manuscripts, Articles, Book Chapters and Other Papers

This article provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward.

Physical Examination Findings Among Children And Adolescents With Obesity: An Evidence-Based Review., Sarah Armstrong, Suzanne Lazorick, Sarah Hampl, Joseph A. Skelton, Charles Wood, David Collier, Eliana M. Perrin

Manuscripts, Articles, Book Chapters and Other Papers

Overweight and obesity affects 1 in 3 US children and adolescents. Clinical recommendations have largely focused on screening guidelines and counseling strategies. However, the physical examination of the child or adolescent with obesity can provide the clinician with additional information to guide management decisions. This expert-based review focuses on physical examination findings specific to children and adolescents with obesity. For each physical examination element, the authors define the finding and its prevalence among pediatric patients with obesity, discuss the importance and relevance of the finding, describe known techniques to assess severity, and review evidence regarding the need for additional evaluation. …

Binomial Regression With A Misclassified Covariate And Outcome, Sheng Luo, Wenyaw Chan, Michelle A Detry, Paul J Massman, R S. Doody

Faculty, Staff and Students Publications

Misclassification occurring in either outcome variables or categorical covariates or both is a common issue in medical science. It leads to biased results and distorted disease-exposure relationships. Moreover, it is often of clinical interest to obtain the estimates of sensitivity and specificity of some diagnostic methods even when neither gold standard nor prior knowledge about the parameters exists. We present a novel Bayesian approach in binomial regression when both the outcome variable and one binary covariate are subject to misclassification. Extensive simulation results under various scenarios and a real clinical example are given to illustrate the proposed approach. This approach …

Cutting The Cost Of Health Care: The Physician's Role, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Predator Diet And Trophic Position Modified With Altered Habitat Morphology, Alexander Tewfik, Susan S. Bell, Kevin S. Mccann, Kristina Morrow

Integrative Biology Faculty and Staff Publications

Empirical patterns that emerge from an examination of food webs over gradients of environmental variation can help to predict the implications of anthropogenic disturbance on ecosystems. This “dynamic food web approach” is rarely applied at the coastal margin where aquatic and terrestrial systems are coupled and human development activities are often concentrated. We propose a simple model of ghost crab (Ocypode quadrata) feeding that predicts changing dominant prey (Emerita talpoida, Talorchestia sp., Donax variablis) along a gradient of beach morphology and test this model using a suite of 16 beaches along the Florida, USA coast. …

Diagnostic Value Of End Tidal Capnography In Patients With Hyperglycemia In The Emergency Department., Ralphe Bou Chebl, Bryan Madden, Justin Belsky, Elie Harmouche, Lenar Yessayan

Emergency Medicine Articles

BACKGROUND: Diabetic Ketoacidosis (DKA) is a potentially life-threatening emergency that requires prompt diagnosis and treatment. In paediatric populations an end tidal capnography value greater than 36 mmHg was found to be 100 % sensitive in ruling out DKA.

METHODS: A cross sectional observational study of adults ≥ 17 years of age presenting to the emergency department between January 2014 and May 2014 with glucose > 550 mg/dL. In all patients, nasal capnography and venous blood gas analysis were performed prior to any insulin or intravenous fluid administration. The diagnosis of DKA was based on the presence of anion gap metabolic acidosis, …

Gap Junction Mediated Mirna Intercellular Transfer And Gene Regulation: A Novel Mechanism For Intercellular Genetic Communication, Liang Zong, Yan Zhu, Ruqiang Liang, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Intercellular genetic communication is an essential requirement for coordination of cell proliferation and differentiation and has an important role in many cellular processes. Gap junction channels possess large pore allowing passage of ions and small molecules between cells. MicroRNAs (miRNAs) are small regulatory RNAs that can regulate gene expression broadly. Here, we report that miRNAs can pass through gap junction channels in a connexin-dependent manner. Connexin43 (Cx43) had higher permeability, whereas Cx30 showed little permeability to miRNAs. In the tested connexin cell lines, the permeability to miRNAs demonstrated: Cx43 > Cx26/30 > Cx26 > Cx31 > Cx30 = Cx-null. However, consistent with a uniform …

Gender Representation In The Vision Sciences: A Longitudinal Study, Emily A. Cooper, Ana Radonjic

Dartmouth Scholarship

Understanding the current status and historical trends of gender representation within a research field is an important component of fostering a diverse and inclusive scientific community. Here, we report on the gender representation of a large sample of the vision science research community—the attendees of the Annual Meeting of the Vision Sciences Society (VSS). Our analysis shows that the majority of scientists at all career levels in our sample are male. This imbalance is most pronounced for the senior scientists, whereas predoctoral students are nearly balanced between the genders. Historically, the gender imbalance was larger than it is at present, …

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 …

Association Of Dna Methylation At Cpt1a Locus With Metabolic Syndrome In The Genetics Of Lipid Lowering Drugs And Diet Network (Goldn) Study, Mithun Das, Jin Sha, Bertha Hidalgo, Stella Aslibekyan, Anh N. Do, Degui Zhi, Dianjianyi Sun, Tao Zhang, Shengxu Li, Wei Chen, Sathanur R. Srinivasan, Hemant K. Tiwari, Devin Absher, Jose M. Ordovas, Gerald S. Berenson, Donna K. Arnett, Marguerite R. Irvin

Epidemiology and Environmental Health Faculty Publications

In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10⁻⁷ was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = …

Ehugs: Enhanced Hierarchical Unbiased Graph Shrinkage For Efficient Groupwise Registration, Guorong Wu, Xuewei Peng, Shihui Ying, Qian Wang, Pew-Thian Yap, Dan Shen, Dinggang Shen

Mathematics and Statistics Faculty Publications

Effective and efficient spatial normalization of a large population of brain images is critical for many clinical and research studies, but it is technically very challenging. A commonly used approach is to choose a certain image as the template and then align all other images in the population to this template by applying pairwise registration. To avoid the potential bias induced by the inappropriate template selection, groupwise registration methods have been proposed to simultaneously register all images to a latent common space. However, current groupwise registration methods do not make full use of image distribution information for more accurate registration. …

Targeting Wnt/Β-Catenin Pathway In Hepatocellular Carcinoma Treatment, Valery Vilchez, Lilia M. Turcios, Francesc Marti, Roberto Gedaly

Surgery Faculty Publications

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Liver cancer is generally related to hepatitis B or C infection and cirrhosis. Usually, patients with HCC are asymptomatic and are diagnosed at late stages when surgical treatment is no longer suitable. Limited treatment options for patients with advanced HCC are a major concern. Therefore, there is an urge for finding novel therapies to treat HCC. Liver cancer is highly heterogeneous and involved deregulation of several signaling pathways. Wnt/β-catenin pathway is frequently upregulated in HCC and it is implicated in maintenance of tumor initiating cells, drug …

Transdiagnostic Psychiatric Symptoms And Event-Related Potentials Following Rewarding And Aversive Outcomes, Jeffrey S. Bedwell, Geoffrey Potts, Diane C. Gooding, Benjamin J. Trachik, Chi C. Chan, Christopher C. Spencer

Psychology Faculty Publications

There is a need for a better understanding of transdiagnostic psychiatric symptoms that relate to neurophysiological abnormalities following rewarding and aversive feedback in order to inform development of novel targeted treatments. To address this need, we examined a transdiagnostic sample of 44 adults (mean age: 35.52; 57% female), which consisted of individuals with broadly-defined schizophrenia-spectrum disorders (n = 16), bipolar disorders (n = 10), other mood and anxiety disorders (n = 5), and no history of a psychiatric disorder (n = 13). Participants completed a Pavlovian monetary reward prediction task during 32-channel electroencephalogram recording. We assessed the event-related potentials (ERPs) …

Pulmonary Imaging Biomarkers Of Gas Trapping And Emphysema In Copd: (3)He Mr Imaging And Ct Parametric Response Maps, Dante P I Capaldi, Nanxi Zha, Fumin Guo, Damien Pike, David G Mccormack, Miranda Kirby, Grace Parraga

Medical Biophysics Publications

PURPOSE: To directly compare magnetic resonance (MR) imaging and computed tomography (CT) parametric response map (PRM) measurements of gas trapping and emphysema in ex-smokers both with and without chronic obstructive pulmonary disease (COPD).

MATERIALS AND METHODS: Participants provided written informed consent to a protocol that was approved by a local research ethics board and Health Canada and was compliant with the HIPAA (Institutional Review Board Reg. #00000940). The prospectively planned study was performed from March 2014 to December 2014 and included 58 ex-smokers (mean age, 73 years ± 9) with (n = 32; mean age, 74 years ± 7) and …

Serum Amyloid A Impairs The Antiinflammatory Properties Of Hdl, Chang Yeop Han, Chongren Tang, Myriam E. Guevara, Hao Wei, Tomasz Wietecha, Baohai Shao, Savitha Subramanian, Mohamed Omer, Shari Wang, Kevin D. O'Brien, Santica M. Marcovina, Thomas N. Wight, Tomas Vaisar, Maria C. De Beer, Frederick C. De Beer, William R. Osborne, Keith B. Elkon, Alan Chait

Physiology Faculty Publications

HDL from healthy humans and lean mice inhibits palmitate-induced adipocyte inflammation; however, the effect of the inflammatory state on the functional properties of HDL on adipocytes is unknown. Here, we found that HDL from mice injected with AgNO₃ fails to inhibit palmitate-induced inflammation and reduces cholesterol efflux from 3T3-L1 adipocytes. Moreover, HDL isolated from obese mice with moderate inflammation and humans with systemic lupus erythematosus had similar effects. Since serum amyloid A (SAA) concentrations in HDL increase with inflammation, we investigated whether elevated SAA is a causal factor in HDL dysfunction. HDL from AgNO₃-injected mice lacking Saa1.1 …

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 …