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Search Results: 1 - 10 of 191327 matches for " D. Rountree "
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Persistent treatment with cholinesterase inhibitors and/or memantine slows clinical progression of Alzheimer disease
Susan D Rountree, Wenyaw Chan, Valory N Pavlik, Eveleen J Darby, Samina Siddiqui, Rachelle S Doody
Alzheimer's Research & Therapy , 2009, DOI: 10.1186/alzrt7
Abstract: Six hundred forty-one probable AD patients were followed prospectively at an academic center over 20 years. Cumulative drug exposure was expressed as a persistency index (PI) reflecting total years of drug use divided by total years of disease symptoms. Baseline and annual testing consisted of Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Baylor Profound Mental Status Examination (BPMSE), Clinical Dementia Rating-Sum of Boxes (CDR-SB), Physical Self-Maintenance Scale (PSMS), and Instrumental Activities of Daily Living (IADL). Annual change in slope of neuropsychological and functional tests as predicted by follow-up time, PI, and the interaction of these two variables was evaluated.PI was associated with significantly slower rates of decline (with, without adjustment for covariates) on MMSE (P < 0.0001), PSMS (P < 0.05), IADL (P < 0.0001), and CDR-SB (P < 0.001). There was an insignificant trend (P = 0.053) for the PI to be associated with slower rate of decline on BPMSE. The association of PI with ADAS-Cog followed a quadratic trend (P < 0.01). Analysis including both linear and quadratic terms suggests that PI slowed ADAS-Cog decline temporarily. The magnitude of the favorable effect of a rate change in PI was: MMSE 1 point per year, PSMS 0.4 points per year, IADL 1.4 points per year, and CDR-SB 0.6 points per year. The change in mean test scores is additive over the follow-up period (3 ± 1.94 years).Persistent drug treatment had a positive impact on AD progression assessed by multiple cognitive, functional, and global outcome measures. The magnitude of the treatment effect was clinically significant. Positive treatment effects were even found in those with advanced disease.Since 1993, five drugs have been marketed for the treatment of Alzheimer disease (AD). These treatments are sometimes regarded as having only 'symptomatic' rather than 'disease-modifying' effects, although the utility of this distincti
Factors that influence survival in a probable Alzheimer disease cohort
Susan D Rountree, Wenyaw Chan, Valory N Pavlik, Eveleen J Darby, Rachelle S Doody
Alzheimer's Research & Therapy , 2012, DOI: 10.1186/alzrt119
Abstract: Time to death after symptom onset was determined in 641 probable AD patients who were evaluated annually until death or loss to follow-up, and information was entered into a longitudinal database. Date of death was available for everyone including those eventually lost. Baseline variables included age, sex, race, disease severity, a calculated index of rate of initial cognitive decline from symptom onset to cohort entry (pre-progression rate or PPR), years of education, and medical comorbidities (diabetes, hypertension, hyperlipidemia, coronary disease, cerebrovascular disease). Multivariable Cox proportional hazard regression analysis was used to analyze the baseline and/or time dependent association in Mini-mental Status Exam (MMSE) severity, Physical Self Maintenance Scale (PSMS), Persistency Index (PI) of exposure to antipsychotic and antidementia drugs, and psychotic symptoms (hallucinations, delusions) with mortality.Baseline covariates significantly associated with increased survival were younger age (p = .0016), female sex (p = .0001), and a slower PPR (p < .0001). Overall disease severity at baseline, medical comorbidities, and education did not influence time to death. Time-dependent changes in antipsychotic drug use, development of psychotic symptoms, antidementia drug use, and observed MMSE change were not predictive. In the final model the only time-dependent covariate that significantly decreased survival was worsening of functional ability on the PSMS (hazard ratio = 1.10; CI: 1.07-1.11).In this large AD cohort survival is influenced by age, sex, and the development of functional disability during follow-up. The most important predictor of mortality was a faster rate of cognitive decline at the initial patient visit (PPR). The currently available antidementia drugs do not prolong survival in Alzheimer patients.Life expectancy in people with Alzheimer's disease (AD) is, overall, shorter than what is expected in age-matched, cognitively normal seniors a
LENS as a Probe of Sterile Neutrino Mediated Oscillations
C. Grieb,J. M. Link,M. L. Pitt,R. S. Raghavan,D. Rountree,R. B. Vogelaar
Physics , 2007,
Abstract: Sterile neutrino ($\nu_s$) conversion in meter scale baselines can be sensitively probed using mono-energetic, sub-MeV, flavor pure $\nu_e$'s from an artificial MCi source and the unique technology of the LENS low energy solar $\nu_e$ detector. Active-sterile {\em oscillations} can be directly observed in the granular LENS detector itself to critically test and extend results of short baseline accelerator and reactor experiments.
A Multi-Compartment, Single and Multiple Dose Pharmacokinetic Study of the Vaginal Candidate Microbicide 1% Tenofovir Gel
Jill L. Schwartz, Wes Rountree, Angela D. M. Kashuba, Vivian Brache, Mitchell D. Creinin, Alfred Poindexter, Brian P. Kearney
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025974
Abstract: Background Tenofovir (TFV) gel is being evaluated as a microbicide with pericoital and daily regimens. To inhibit viral replication locally, an adequate concentration in the genital tract is critical. Methods and Findings Forty-nine participants entered a two-phase study: single-dose (SD) and multi-dose (MD), were randomized to collection of genital tract samples (endocervical cells [ECC], cervicovaginal aspirate and vaginal biopsies) at one of seven time points [0.5, 1, 2, 4, 6, 8, or 24 hr(s)] post-dose following SD exposure of 4 mL 1% TFV gel and received a single dose. Forty-seven were randomized to once (QD) or twice daily (BID) dosing for 2 weeks and to collection of genital tract samples at 4, 8 or 24 hrs after the final dose, but two discontinued prior to gel application. Blood was collected during both phases at the seven times post-dose. TFV exposure was low in blood plasma for SD and MD; median Cmax was 4.0 and 3.4 ng/mL, respectively (C≤29 ng/mL). TFV concentrations were high in aspirates and tissue after SD and MD, ranging from 1.2×104 to 9.9×106 ng/mL and 2.1×102 to 1.4×106 ng/mL, respectively, and did not noticeably differ between proximal and distal tissue. TFV diphosphate (TFV-DP), the intracellular active metabolite, was high in ECC, ranging from 7.1×103 to 8.8×106 ng/mL. TFV-DP was detectable in approximately 40% of the tissue samples, ranging from 1.8×102 to 3.5×104 ng/mL. AUC for tissue TFV-DP was two logs higher after MD compared to SD, with no noticeable differences when comparing QD and BID. Conclusions Single-dose and multiple-dose TFV gel exposure resulted in high genital tract concentrations for at least 24 hours post-dose with minimal systemic absorption. These results support further study of TFV gel for HIV prevention. Trial registration ClinicalTrials.gov NCT00561496
Stem cells in drug discovery, regenerative medicine and cancer
C Bart Rountree
Genome Medicine , 2011, DOI: 10.1186/gm229
Abstract: The Stem Cell World Congress brought together scholars and experts from a wide array of stem cell research. Discussions covered a range of issues and topics, including basic science discoveries related to the use of neural progenitors and mesenchymal stem cells (MSCs) for the treatment of neurodegenerative disease, the legal aspects related to patent protection of stem-cell-based discoveries, the best practices for biobanking of cord blood, and the ethical considerations related to stem cell research. This report focuses on major themes of the meeting, with a focus on the stem cell topics related specifically to medical genomics.One of the primary focuses of the meeting was the use of stem-cell-based therapy in regenerative medicine, which aims to regenerate damaged tissues. Keynote presentations discussed research in the field of neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Jan Nolta (University of California Davis, Sacramento, USA) suggested that stem cell therapy for neurodegenerative diseases represents a potential cure, compared with small-molecule-based therapy, which can ameliorate symptoms but not correct underlying genetic or structural problems. Nolta focused on Huntington's disease, an autosomal dominant disease that is linked to increased CAG repeats in the Huntington gene (HTT) on chromosome 4. Nolta is using a catheter-based approach to deliver bone-marrow-derived MSCs, which are programmed to secrete a small interfering RNA to downregulate mutant Htt protein. She has found that MSCs home to sites of injury within the brain, have a 'neuro-protective effect', and can reverse injury through Htt downregulation. The MSCs do not form tumors, even 8 months after transplant into immune-deficient animals. Risk of tumor is one of the concerns in using human embryonic stem (hES) cells for regenerative medicine.Larry Goldstein (University of California San Diego, USA) discussed the idea of using
Clinical application for the preservation of phospho-proteins through in-situ tissue stabilization
C Bart Rountree, Colleen A Van Kirk, Hanning You, Wei Ding, Hien Dang, Heather D VanGuilder, Willard M Freeman
Proteome Science , 2010, DOI: 10.1186/1477-5956-8-61
Abstract: In this report, we re-create laboratory and clinical scenarios for sample collection and test the utility of a new tissue stabilization technique in preserving proteins and protein modifications. In the laboratory setting, tissue stabilization with the Denator Stabilizor T1 resulted in a significantly higher yield of phospho-protein when compared to standard snap freeze preservation. Furthermore, in a clinical scenario, tissue stabilization at collection resulted in a higher yield of total phospho-protein, total phospho-tyrosine, pErkT202/Y204 and pAktS473 when compared to standard methods. Tissue stabilization did not have a significant effect on other post-translational modifications such as acetylation and glycosylation, which are more stable ex-vivo. Tissue stabilization did decrease total RNA quantity and quality.Stabilization at the time of collection offers the potential to better preserve tissue protein and protein modification levels, as well as reduce the variability related to tissue processing delays that are often associated with clinical samples.Recent advances in proteomic technologies have spurred a number of reports examining distinct alterations in protein expression [1,2] or modification [3-6] that are associated with, or can classify, disease states in human patients. Although these biomarker studies provide important analytical and diagnostic tools, a challenge for translational research is the transition of findings from the controlled laboratory environment to the clinical setting, where variation in tissue acquisition and handling practices can introduce significant data variability. This variation can confound data analysis and interpretation, and in turn, impact patient diagnosis and prognosis [7]. Combined with clinical heterogeneity resulting from genetic, physiological, and environmental factors, which are typically controlled for in animal models implemented in the laboratory setting, technical variance introduced during tissue collecti
First attempt to use a remotely operated vehicle to observe soniferous fish behavior in the Gulf of Maine, Western Atlantic Ocean
Rodney A. ROUNTREE, Francis JUANES
Current Zoology , 2010,
Abstract: Underwater sound and video observations were made at noon, sunset, and midnight in sand, gravel, and boulder habitat in the Stellwagen Bank National Marine Sanctuary, Gulf of Maine, USA in October 2001 using a remotely operated vehicle (ROV). Seventeen species of fish and squid were observed with clear habitat and time differences. Observations of feeding behavior, disturbance behavior, and both interspecific and intraspecific interactions provided numerous opportunities for potential sound production; however, sounds were recorded only during a single dive. Although high noise levels generated by the ROV and support ship may have masked some sounds, we conclude that fish sound production in the Gulf of Maine during the fall is uncommon. The recorded fish sounds are tentatively attributed to the cusk Brosme brosme. Cusk sounds consisted variously of isolated thumps, widely spaced thump trains, drumrolls, and their combinations. Frequency peaks were observed at 188, 539, and 1195 Hz. Use of a remotely operated vehicle (ROV) as a passive acoustic observation platform was problematic due to high ROV self-noise and the ROV’s inability to maintain a fixed position on the bottom without thruster power. Some fishes were clearly also disturbed by ROV noise, indicating a potential ROV sampling bias. Based on our observations, we suggest that new instruments incorporating both optic and passive acoustic technologies are needed to provide better tools for in situ behavioral studies of cusk and other fishes [Current Zoology 56 (1): 90–99 2010].
A Jungle in There: Bacteria in Belly Buttons are Highly Diverse, but Predictable
Jiri Hulcr, Andrew M. Latimer, Jessica B. Henley, Nina R. Rountree, Noah Fierer, Andrea Lucky, Margaret D. Lowman, Robert R. Dunn
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0047712
Abstract: The belly button is one of the habitats closest to us, and yet it remains relatively unexplored. We analyzed bacteria and arachaea from the belly buttons of humans from two different populations sampled within a nation-wide citizen science project. We examined bacterial and archaeal phylotypes present and their diversity using multiplex pyrosequencing of 16S rDNA libraries. We then tested the oligarchy hypothesis borrowed from tropical macroecology, namely that the frequency of phylotypes in one sample of humans predicts its frequency in another independent sample. We also tested the predictions that frequent phylotypes (the oligarchs) tend to be common when present, and tend to be more phylogenetically clustered than rare phylotypes. Once rarefied to four hundred reads per sample, bacterial communities from belly buttons proved to be at least as diverse as communities known from other skin studies (on average 67 bacterial phylotypes per belly button). However, the belly button communities were strongly dominated by a few taxa: only 6 phylotypes occurred on >80% humans. While these frequent bacterial phylotypes (the archaea were all rare) are a tiny part of the total diversity of bacteria in human navels (<0.3% of phylotypes), they constitute a major portion of individual reads (~1/3), and are predictable among independent samples of humans, in terms of both the occurrence and evolutionary relatedness (more closely related than randomly drawn equal sets of phylotypes). Thus, the hypothesis that “oligarchs” dominate diverse assemblages appears to be supported by human-associated bacteria. Although it remains difficult to predict which species of bacteria might be found on a particular human, predicting which species are most frequent (or rare) seems more straightforward, at least for those species living in belly buttons.
A search for cosmogenic production of $β$-neutron emitting radionuclides in water
S. Dazeley,M. Askins,M. Bergevin,A. Bernstein,N. S. Bowden,P. Jaffke,S. D. Rountree,T. M. Shokair,M. Sweany
Physics , 2015,
Abstract: Here we present the first results of WATCHBOY, a water Cherenkov detector designed to measure the yield of $\beta$-neutron emitting radionuclides produced by cosmic ray muons in water. In addition to the $\beta$-neutron measurement, we also provide a first look at isolating single-$\beta$ producing radionuclides following showering muons as a check of the detection capabilities of WATCHBOY. The data taken over $207$ live days indicates a $^{9}$Li production yield upper limit of $1.9\times10^{-7}\mu^{-1}g^{-1}\mathrm{cm}^2$ at $\sim400$ meters water equivalent (m.w.e.) overburden at the $90\%$ confidence level. In this work the $^{9}$Li signal in WATCHBOY was used as a proxy for the combined search for $^{9}$Li and $^{8}$He production. This result will provide a constraint on estimates of antineutrino-like backgrounds in future water-based antineutrino detectors.
A Study of the Residual 39Ar Content in Argon from Underground Sources
J. Xu,F. Calaprice,C. Galbiati,A. Goretti,G. Guray,T. Hohman,D. Holtz,A. Ianni,M. Laubenstein,B. Loer,C. Love,C. J. Martoff,D. Montanari,S. Mukhopadhyay,A. Nelson,S. D. Rountree,R. B. Vogelaar,A. Wright
Physics , 2012,
Abstract: The discovery of argon from underground sources with significantly less 39Ar than atmospheric argon was an important step in the development of direct-detection dark matter experiments using argon as the active target. We report on the design and operation of a low background detector with a single phase liquid argon target that was built to study the 39Ar content of the underground argon. Underground argon from the Kinder Morgan CO2 plant in Cortez, Colorado was determined to have less than 0.65% of the 39Ar activity in atmospheric argon.
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