Digital Commons Network^™

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease, David W. Fardo, Laura E. Gibbons, Shubhabrata Mukherjee, M. Maria Glymour, Wayne Mccormick, Susan M. Mccurry, James D. Bowen, Eric B. Larson, Paul K. Crane

Biostatistics Faculty Publications

INTRODUCTION—Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS—We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS …

Consequences Of Severe Habitat Fragmentation On Density, Genetics, And Spatial Capture-Recapture Analysis Of A Small Bear Population, Sean Mccarthy Murphy, Ben C. Augustine, Wade Allen Ulrey, Joseph Maddox Guthrie, Brian K Scheick, J. Walter Mccown, John J. Cox

Forestry and Natural Resources Faculty Publications

Loss and fragmentation of natural habitats caused by human land uses have subdivided several formerly contiguous large carnivore populations into multiple small and often isolated subpopulations, which can reduce genetic variation and lead to precipitous population declines. Substantial habitat loss and fragmentation from urban development and agriculture expansion relegated the Highlands-Glades subpopulation (HGS) of Florida, USA, black bears (Ursus americanus floridanus) to prolonged isolation; increasing human land development is projected to cause ≥ 50% loss of remaining natural habitats occupied by the HGS in coming decades. We conducted a noninvasive genetic spatial capture-recapture study to quantitatively describe the …

Peripheral Inflammation, Apolipoprotein E4, And Amyloid-Β Interact To Induce Cognitive And Cerebrovascular Dysfunction, Felecia M. Marottoli, Yuriko Katsumata, Kevin P. Koster, Riya Thomas, David W. Fardo, Leon M. Tai

Biostatistics Faculty Publications

Cerebrovascular dysfunction is rapidly reemerging as a major process of Alzheimer’s disease (AD). It is, therefore, crucial to delineate the roles of AD risk factors in cerebrovascular dysfunction. While apolipoprotein E4 (APOE4), Amyloid-β (Aβ), and peripheral inflammation independently induce cerebrovascular damage, their collective effects remain to be elucidated. The goal of this study was to determine the interactive effect of APOE4, Aβ, and chronic repeated peripheral inflammation on cerebrovascular and cognitive dysfunction in vivo. EFAD mice are a well-characterized mouse model that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce human Aβ42 via expression of …

Normal Breast Tissue Dna Methylation Differences At Regulatory Elements Are Associated With The Cancer Risk Factor Age., Kevin C Johnson, E Andres Houseman, Jessica E King, Brock C Christensen

Faculty Research 2017

BACKGROUND: The underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies.

METHODS: Here we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450 K array) in cancer-free women from the Susan G. Komen Tissue Bank (n = 100). We tested the relation of established breast cancer risk factors, age, body mass index, parity, and …

A Phase Iii, Randomized, Multi-Center, Double Blind, Placebo Controlled Study Of Safety And Efficacy Of Lofexidine For Relief Of Symptoms In Individuals Undergoing Inpatient Opioid Withdrawal, Charles W. Gorodetzky, Sharon L. Walsh, Peter R. Martin, Andrew J. Saxon, Kristen L. Gullo, Kousick Biswas

Center on Drug and Alcohol Research Faculty Publications

Background: Lofexidine is an alpha-2-adrenergic receptor agonist approved in the United Kingdom (UK) for the treatment of opioid withdrawal symptoms. Lofexidine has demonstrated better efficacy than placebo for reducing opioid withdrawal symptoms in patients undergoing opioid withdrawal with less reported hypotension than clonidine.

Methods: Designed as an FDA registration trial, this 8-day, randomized, double-blind, placebo-controlled, parallel-group study in 264 patients dependent on short-acting opioids evaluated the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid withdrawal. The primary efficacy measures were SOWS-Gossop on Day 3 and time-to-dropout. Secondary endpoints included the proportion of participants who were completers; …

Comparing Adult Cannabis Treatment-Seekers Enrolled In A Clinical Trial With National Samples Of Cannabis Users In The United States, Erin A. Mcclure, Jacqueline S. King, Aimee Wahle, Abigail G. Matthews, Susan C. Sonne, Michelle R. Lofwall, Aimee L. Mcrae-Clark, Udi E. Ghitza, Melissa Martinez, Kasie Cloud, Harvir S. Virk, Kevin M. Gray

Center on Drug and Alcohol Research Faculty Publications

Background—Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased prevalence of cannabis use disorder and the need for more clinical trials to evaluate efficacious treatment strategies. Clinical trials are the gold standard for evaluating treatment, yet study samples are rarely representative of the target population. This finding has not yet been established for cannabis treatment trials. This study compared demographic and cannabis use characteristics of a cannabis cessation clinical trial sample (run through National Drug Abuse Treatment Clinical Trials Network) with three nationally …

Ketamine Use For Successful Resolution Of Post-Ercp Acute Pancreatitis Abdominal Pain, S Agerwala, D Sundarapandiyan, Garret Weber

NYMC Faculty Publications

We report a case in which a patient with intractable pain secondary to post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis is successfully treated with a subanesthetic ketamine infusion. Shortly after ERCP, the patient reported severe stabbing epigastric pain. She exhibited voluntary guarding and tenderness without distension. Amylase and lipase levels were elevated. Pain persisted for hours despite hydromorphone PCA, hydromorphone boluses, fentanyl boluses, and postprocedure anxiolytics. Pain management was consulted and a ketamine infusion was trialed, leading to a dramatic reduction in pain. This case suggests that ketamine may be a promising option in treating intractable pain associated with ERCP acute …

Treatment Pathway Of Bone Sarcoma In Children, Adolescents, And Young Adults, Damon R. Reed, Masanori Hayashi, Lars M. Wagner, Odion Binitie, Diana A. Steppan, Andrew S. Brohl, Eric T. Shinohara, Julia A. Bridge, David M. Loeb, Scott C. Borinstein, Michael S. Isakoff

Pediatrics Faculty Publications

When pediatric, adolescent, and young adult patients present with a bone sarcoma, treatment decisions, especially after relapse, are complex and require a multidisciplinary approach. This review presents scenarios commonly encountered in the therapy of bone sarcomas with the goal of objectively presenting a consensus, multidisciplinary management approach. Little variation was found in the authors' group with respect to local control or systemic therapy. Clinical trials were universally prioritized in all settings. Decisions regarding relapse therapies in the absence of a clinical trial had very minor variations initially, but a consensus was reached after a literature review and discussion. This review …

A Mathematical Formula For Institutional Gme Program Support, Kimberly Baker-Genaw, Crystal Gyiraszin

Graduate Medical Education Articles

No abstract provided.

Risk Of Incident Clinical Diagnosis Of Alzheimer's Disease-Type Dementia Attributable To Pathology-Confirmed Vascular Disease, Hiroko H. Dodge, Jian Zhu, Randy Woltjer, Peter T. Nelson, David A. Bennett, Nigel J. Cairns, David W. Fardo, Jeffrey A. Kaye, Deniz-Erten Lyons, Nora Mattek, Julie A. Schneider, Lisa C. Silbert, Chengjie Xiong, Lei Yu, Frederick A. Schmitt, Richard J. Kryscio, Erin L. Abner, Smart Data Consortium

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: The presence of cerebrovascular pathology may increase the risk of clinical diagnosis of Alzheimer's disease (AD).

METHODS: We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modeling of Aging and Risk of Transition study, a consortium of longitudinal cohort studies with more than 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate, or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with …

Lisinopril Or Coreg Cr In Reducing Cardiotoxicity In Women With Breast Cancer Receiving Trastuzumab: A Rationale And Design Of A Randomized Clinical Trial, Maya Guglin, Pamela Munster, Angelina Fink, Jeffrey Krischer

Internal Medicine Faculty Publications

Background—Trastuzumab (TZB) is an established therapy for HER2 positive breast cancer. The use of TZB is commonly associated with cardiotoxicity manifesting as asymptomatic decrease in left ventricular ejection fraction (LVEF) or overt heart failure. Several studies demonstrated favorable effects of angiotensin converting enzyme (ACE) inhibitors and beta blockers (BB) in the prevention of chemotherapy-induced cardiotoxicity. We hypothesize that patients, randomized to receive an ACE inhibitor or a beta-blocker during trastuzumab therapy for breast cancer, will maintain a higher LVEF than patients randomized to placebo.

Methods and Results—We designed a prospective, multicenter, randomized, phase II placebo-controlled clinical trial to …

Simulating Within-Vector Generation Of The Malaria Parasite Diversity, Lauren M. Childs, Olivia F. Prosper

Mathematics Faculty Publications

Plasmodium falciparum, the most virulent human malaria parasite, undergoes asexual reproduction within the human host, but reproduces sexually within its vector host, the Anopheles mosquito. Consequently, the mosquito stage of the parasite life cycle provides an opportunity to create genetically novel parasites in multiply-infected mosquitoes, potentially increasing parasite population diversity. Despite the important implications for disease transmission and malaria control, a quantitative mapping of how parasite diversity entering a mosquito relates to diversity of the parasite exiting, has not been undertaken. To examine the role that vector biology plays in modulating parasite diversity, we develop a two-part model framework …

A Lung Cancer Risk Classifier Comprising Genome Maintenance Genes Measured In Normal Bronchial Epithelial Cells, Jiyoun Yeo, Erin L. Crawford, Xiaolu Zhang, Sadik Khuder, Tian Chen, Albert M. Levin, Thomas M. Blomquist, James C. Willey

Public Health Sciences Articles

BACKGROUND: Annual low dose CT (LDCT) screening of individuals at high demographic risk reduces lung cancer mortality by more than 20%. However, subjects selected for screening based on demographic criteria typically have less than a 10% lifetime risk for lung cancer. Thus, there is need for a biomarker that better stratifies subjects for LDCT screening. Toward this goal, we previously reported a lung cancer risk test (LCRT) biomarker comprising 14 genome-maintenance (GM) pathway genes measured in normal bronchial epithelial cells (NBEC) that accurately classified cancer (CA) from non-cancer (NC) subjects. The primary goal of the studies reported here was to …

Optimal Nutrition And The Ever-Changing Dietary Landscape: A Conference Report., A Shao, A Drewnowski, D C Willcox, L Krämer, Christopher G Lausted, M Eggersdorfer, J Mathers, J D Bell, R K Randolph, R Witkamp, J C Griffiths

Articles, Abstracts, and Reports

The field of nutrition has evolved rapidly over the past century. Nutrition scientists and policy makers in the developed world have shifted the focus of their efforts from dealing with diseases of overt nutrient deficiency to a new paradigm aimed at coping with conditions of excess-calories, sedentary lifestyles and stress. Advances in nutrition science, technology and manufacturing have largely eradicated nutrient deficiency diseases, while simultaneously facing the growing challenges of obesity, non-communicable diseases and aging. Nutrition research has gone through a necessary evolution, starting with a reductionist approach, driven by an ambition to understand the mechanisms responsible for the effects …

Perspectives And Expectations In Structural Bioinformatics Of Metalloproteins, Sen Yao, Robert M. Flight, Eric C. Rouchka, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Recent papers highlight the presence of large numbers of compressed angles in metal ion coordination geometries for metalloprotein entries in the worldwide Protein Data Bank, due mainly to multidentate coordination. The prevalence of these compressed angles has raised the controversial idea that significantly populated aberrant or even novel coordination geometries may exist. Some of these papers have undergone severe criticism, apparently due to views held that only canonical coordination geometries exist in significant numbers. While criticism of controversial ideas is warranted and to be expected, we believe that a line was crossed where unfair criticism was put forth to discredit …

Prophylactic Hemodialysis For Protection Against Gadolinium-Induced Nephrogenic Systemic Fibrosis: A Doll's House, Jerry Yee

Nephrology Articles

No abstract provided.

Restriction Spectrum Imaging Improves Risk Stratification In Patients With Glioblastoma., A P Krishnan, R Karunamuni, K M Leyden, T M Seibert, R L Delfanti, J M Kuperman, H Bartsch, P Elbe, A Srikant, A M Dale, Santosh Kesari, D E Piccioni, J A Hattangadi-Gluth, N Farid, C R Mcdonald, N S White

Articles, Abstracts, and Reports

BACKGROUND AND PURPOSE: ADC as a marker of tumor cellularity has been promising for evaluating the response to therapy in patients with glioblastoma but does not successfully stratify patients according to outcomes, especially in the upfront setting. Here we investigate whether restriction spectrum imaging, an advanced diffusion imaging model, performed after an operation but before radiation therapy, could improve risk stratification in patients with newly diagnosed glioblastoma relative to ADC.

MATERIALS AND METHODS: Pre-radiation therapy diffusion-weighted and structural imaging of 40 patients with glioblastoma were examined retrospectively. Restriction spectrum imaging and ADC-based hypercellularity volume fraction (restriction spectrum imaging-FLAIR volume fraction, …

Tuberculosis And Risk Of Acute Myocardial Infarction: A Propensity Score-Matched Analysis, Moises A. Huaman, Richard J. Kryscio, Carl J. Fichtenbaum, David Henson, Elizabeth G. Salt, Timothy R. Sterling, Beth A. Garvy

Biostatistics Faculty Publications

Several pathogens have been associated with increased cardiovascular disease (CVD) risk. Whether this occurs with Mycobacterium tuberculosis infection is unclear. We assessed if tuberculosis disease increased the risk of acute myocardial infarction (AMI). We identified patients with tuberculosis index claims from a large de-identified database of ~15 million adults enrolled in a U.S. commercial insurance policy between 2008 and 2010. Tuberculosis patients were 1:1 matched to patients without tuberculosis claims using propensity scores. We compared the occurrence of index AMI claims between the tuberculosis and non-tuberculosis cohorts using Kaplan–Meier curves and Cox Proportional Hazard models. Data on 2026 patients with …

Demographics, Patterns Of Care, And Survival In Pediatric Medulloblastoma, Emily V. Dressler, Therese A. Dolecek, Meng Liu, John L. Villano

Internal Medicine Faculty Publications

We evaluated the American College of Surgeon’s National Cancer Data Base (NCDB) to describe current hospital-based epidemiologic frequency, survival, and patterns of care of pediatric medulloblastoma. We analyzed NCDB 1998–2011 data on medulloblastoma for children ages 0–19 years using logistic and poisson regression, Kaplan–Meier survival estimates, and Cox proportional hazards models. 3647 cases of medulloblastoma in those aged 0–19 years were identified. Chemotherapy was received by 79 and 74% received radiation, with 65% receiving both therapies. Those who received radiation were more likely to be older than four, while those who received chemotherapy were more likely to be age four …

Role Of Biomechanical Forces In Hyperfiltration-Mediated Glomerular Injury In Congenital Anomalies Of The Kidney And Urinary Tract., Tarak Srivastava, Ganesh Thiagarajan, Uri S. Alon, Ram Sharma, Ashraf El-Meanawy, Ellen T. Mccarthy, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Congenital anomalies of the kidney and urinary tract (CAKUT) including solitary kidney constitute the main cause of progressive chronic kidney disease (CKD) in children. Children born with CAKUT develop signs of CKD only during adolescence and do not respond to renin-angiotensin-aldosterone system blockers. Early cellular changes underlying CKD progression to end-stage renal disease by early adulthood are not well understood. The mechanism of maladaptive hyperfiltration that occurs from loss of functional nephrons, including solitary kidney, is not clear. We re-examine the phenomenon of hyperfiltration in the context of biomechanical forces with special reference to glomerular podocytes. Capillary stretch exerts tensile …

Sonoelastography Of The Common Flexor Tendon Of The Elbow With Histologic Agreement: A Cadaveric Study., Andrea S Klauser, Mathias J Pamminger, Ethan J. Halpern, Mohamed M H Abd Ellah, Bernhard Moriggl, Mihra S Taljanovic, Christian Deml, Judith Sztankay, Guenter Klima, Leonhard Gruber, Werner R Jaschke

Department of Radiology Faculty Papers

Purpose To determine the correlation of the results of conventional B-mode ultrasonography (US) and compression sonoelastography with histologic results in common flexor tendons of the elbow in human cadavers. Materials and Methods Twenty-five common flexor tendons were evaluated in 16 fresh, unembalmed cadavers of 11 women with a median age of 85 years (range, 71-101 years) and five men with a median age of 78 years (range, 70-88 years). Informed consent was provided according to the last will of the donors. B-mode US results were classified as grade 1, normal tendon with homogeneous fibrillar pattern; grade 2, tendon thickening or …

A Longitudinal Cline Characterizes The Genetic Structure Of Human Populations In The Tibetan Plateau, Choongwon Jeong, Benjamin M. Peter, Buddha Basnyat, Maniraj Neupane, Geoff Childs, Sienna Craig, John Novembre, Anna Di Rienzo

Dartmouth Scholarship

Indigenous populations of the Tibetan plateau have attracted much attention for their good performance at extreme high altitude. Most genetic studies of Tibetan adaptations have used genetic variation data at the genome scale, while genetic inferences about their de- mography and population structure are largely based on uniparental markers. To provide genome-wide information on population structure, we analyzed new and published data of 338 individuals from indigenous populations across the plateau in conjunction with world- wide genetic variation data. We found a clear signal of genetic stratification across the east- west axis within Tibetan samples. Samples from more eastern locations …

Functional Human Grin2b Promoter Polymorphism And Variation Of Mental Processing Speed In Older Adults, Yang Jiang, Ming Kuan Lin, Gregory A. Jicha, Xiuhua Ding, Sabrina L. Mcilwrath, David W. Fardo, Lucas S. Broster, Frederick A. Schmitt, Richard J. Kryscio, Robert H. Lipsky

Behavioral Science Faculty Publications

We investigated the role of a single nucleotide polymorphism rs3764030 (G > A) within the human GRIN2B promoter in mental processing speed in healthy, cognitively intact, older adults. In vitro DNA-binding and reporter gene assays of different allele combinations in transfected cells showed that the A allele was a gain-of-function variant associated with increasing GRIN2B mRNA levels. We tested the hypothesis that individuals with A allele will have better memory performance (i.e. faster reaction times) in older age. Twenty-eight older adults (ages 65-86) from a well-characterized longitudinal cohort were recruited and performed a modified delayed match-to-sample task. The rs3764030 polymorphism was …

Seasonality Of Auricular Amputations In Rabbits, Kathleen Yaremchuk, Vigen Darian, Amy M. Williams

Otolaryngology Articles

This retrospective observational analysis hypothesizes that an increase occurs in online reports and images of auricular amputations of confectionary rabbits during the spring. Using the online search engine Google, online content and visual portrayals of confectionary rabbit auricular amputations from 2012 to 2017 were identified and trended against seasonal variations. To determine incidence, commercial availability of chocolate rabbits in retail facilities were assayed. A statistically significant increase in mention of rabbit auricular amputations occurred during the spring. Mapping techniques showed the annual peak incidence for 2012 to 2017 to be near Easter for each year studied. Human adults and children …

Outcomes After Diagnosis Of Mild Cognitive Impairment In A Large Autopsy Series, Erin L. Abner, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Daniela C. Moga, Eseosa T. Ighodaro, Gregory A. Jicha, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Randall L. Woltjer, Julie A. Schneider, Nigel J. Cairns, David A. Bennett, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).

METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

RESULTS: Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical …

Intraindividual Variability In Cortisol: Approaches, Illustrations, And Recommendations, Suzanne C. Segerstrom, Sandra E. Sephton, Philip M. Westgate

Psychology Faculty Publications

Most of the variance in diurnal cortisol is attributable to intraindividual variability (IIV), defined as relatively short-term, reversible changes. Multiple methods for measuring IIV have been proposed, and some have already been applied to cortisol IIV. In the present review, measurement methods are described and applied to simulated cortisol data with known underlying differences in IIV and to real cortisol data from first-year law students. More slope variance and more residual or net variance were well captured by their individual standard deviations. Explorations of reliability suggested that 10 slopes and 50 residuals result in reliable and stable estimates of the …

Evaluating Parents' Self-Efficacy For Diabetes Management In Pediatric Type 1 Diabetes., Amy E. Noser, Susana R. Patton, Jason Van Allen, Michael B. Nelson, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

Objective: To examine the factor structure and construct validity of the Maternal Self-Efficacy for Diabetes Management Scale (MSED) in 135 youth ( Mage  = 13.50  ±  1.83 years), with type 1 diabetes mellitus.

Method: The study used exploratory factor analysis (EFA) to examine the factor structure and correlations to examine relationships among MSED factors and select parent and child diabetes-related health behaviors and outcomes.

Results: EFA identified an 11-item three-factor solution (χ 2 (25, n  = 133)  = 40.22, p  < .03, RMSEA = 0.07, CFI = 0.98, TLI = 0.97), with factors corresponding to parents' perceived ability to manage their child's diabetes (MSED-M), problem-solve issues surrounding glycemic control (MSED-P), and teach their child about diabetes care (MSED-T). Correlational analyses revealed significant associations between the MSED-M and MSED-T and parent-reported optimism and youth's diabetes-specific self-efficacy. The MSED-T was also associated with glycated hemoglobin and self-monitoring blood glucose.

Conclusions: Results provide preliminary evidence for the reliability and validity of a three-factor solution of the MSED.

Another Look At Pyrroloiminoquinone Alkaloids-Perspectives On Their Therapeutic Potential From Known Structures And Semisynthetic Analogues., Sheng Lin, Erin P. Mccauley, Nicholas Lorig-Roach, Karen Tenney, Cassandra N. Naphen, Ai-Mei Yang, Tyler A. Johnson, Thalia Hernadez, Ramandeep Rattan, Frederick A. Valeriote, Phillip Crews

Natural Sciences and Mathematics | Faculty Scholarship

This study began with the goal of identifying constituents from Zyzzya fuliginosa extracts that showed selectivity in our primary cytotoxicity screen against the PANC-1 tumor cell line. During the course of this project, which focused on six Z. fuliginosa samples collected from various regions of the Indo-Pacific, known compounds were obtained consisting of nine makaluvamine and three damirone analogues. Four new acetylated derivatives were also prepared. High-accuracy electrospray ionization mass spectrometry (HAESI-MS) m/z ions produced through MS² runs were obtained and interpreted to provide a rapid way for dereplicating isomers containing a pyrrolo[4,3,2-de]quinoline core. In vitro human pancreas/duct epithelioid …

A Statistical Method For The Conservative Adjustment Of False Discovery Rate (Q-Value)., Yinglei Lai

Epidemiology Faculty Publications

BACKGROUND: q-value is a widely used statistical method for estimating false discovery rate (FDR), which is a conventional significance measure in the analysis of genome-wide expression data. q-value is a random variable and it may underestimate FDR in practice. An underestimated FDR can lead to unexpected false discoveries in the follow-up validation experiments. This issue has not been well addressed in literature, especially in the situation when the permutation procedure is necessary for p-value calculation.

RESULTS: We proposed a statistical method for the conservative adjustment of q-value. In practice, it is usually necessary to calculate p-value by a permutation procedure. …

A Potent Antimalarial Benzoxaborole Targets A Plasmodium Falciparum Cleavage And Polyadenylation Specificity Factor Homologue., Ebere Sonoiki, Caroline L. Ng, Marcus C. S. Lee, Denghui Guo, Yong-Kang Zhang, Yasheen Zhou, M. R. K. Alley, Vida Ahyong, Laura M. Sanz, Maria Jose Lafuente-Monasterio, Chen Dong, Patrick G. Schupp, Jiri Gut, Jenny Legac, Roland A. Cooper, Francisco-Javier Gamo, Joseph Derisi, Yvonne R. Freund, David A. Fidock, Philip J. Rosenthal

Natural Sciences and Mathematics | Faculty Scholarship

Benzoxaboroles are effective against bacterial, fungal and protozoan pathogens. We report potent activity of the benzoxaborole AN3661 against Plasmodium falciparum laboratory-adapted strains (mean IC50 32 nM), Ugandan field isolates (mean ex vivo IC50 64 nM), and murine P. berghei and P. falciparum infections (day 4 ED90 0.34 and 0.57 mg kg-1, respectively). Multiple P. falciparum lines selected in vitro for resistance to AN3661 harboured point mutations in pfcpsf3, which encodes a homologue of mammalian cleavage and polyadenylation specificity factor subunit 3 (CPSF-73 or CPSF3). CRISPR-Cas9-mediated introduction of pfcpsf3 mutations into parental lines recapitulated AN3661 resistance. PfCPSF3 homology models placed these …