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Search Results: 1 - 10 of 199211 matches for " Steven D. Shirk "
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A web-based normative calculator for the uniform data set (UDS) neuropsychological test battery
Steven D Shirk, Meghan B Mitchell, Lynn W Shaughnessy, Janet C Sherman, Joseph J Locascio, Sandra Weintraub, Alireza Atri
Alzheimer's Research & Therapy , 2011, DOI: 10.1186/alzrt94
Abstract: Data from 3,268 clinically cognitively-normal older UDS subjects from a cohort reported by Weintraub and colleagues (2009) were included. For all neuropsychological tests, z-scores were estimated by subtracting the raw score from the predicted mean and then dividing this difference score by the root mean squared error term (RMSE) for a given linear regression model.For each neuropsychological test, an estimated z-score was calculated for any raw score based on five different models that adjust for the demographic predictors of SEX, AGE and EDUCATION, either concurrently, individually or without covariates. The interactive online calculator allows the entry of a raw score and provides five corresponding estimated z-scores based on predictions from each corresponding linear regression model. The calculator produces percentile ranks and graphical output.An interactive, regression-based, normative score online calculator was created to serve as an additional resource for UDS clinical researchers, especially in guiding interpretation of individual performances that appear to fall in borderline realms and may be of particular utility for operationalizing subtle cognitive impairment present according to the newly proposed criteria for Stage 3 preclinical Alzheimer's disease.The Uniform Data Set (UDS) neuropsychological test battery is administered to research participants at all contributing Alzheimer's Disease Centers (ADCs) and Alzheimer's Disease Research Centers (ADRCs) [1]. However, because the subjects are not reflective of the national population and the tests within the UDS battery were modified for pragmatic use, reliable normative data are not available for the battery. Weintraub and colleagues [2] provided descriptive information from initial neuropsychological data of over 3,000 clinically cognitively normal, older adults and developed linear regression models to estimate the impact of age, sex, and education on test performance. The report by Weintraub et al.
Social Activity and Cognitive Functioning Over Time: A Coordinated Analysis of Four Longitudinal Studies
Cassandra L. Brown,Laura E. Gibbons,Robert F. Kennison,Annie Robitaille,Magnus Lindwall,Meghan B. Mitchell,Steven D. Shirk,Alireza Atri,Cynthia R. Cimino,Andreana Benitez,Stuart W. S. MacDonald,Elizabeth M. Zelinski,Sherry L. Willis,K. Warner Schaie,Boo Johansson,Roger A. Dixon,Dan M. Mungas,Scott M. Hofer,Andrea M. Piccinin
Journal of Aging Research , 2012, DOI: 10.1155/2012/287438
Abstract: Social activity is typically viewed as part of an engaged lifestyle that may help mitigate the deleterious effects of advanced age on cognitive function. As such, social activity has been examined in relation to cognitive abilities later in life. However, longitudinal evidence for this hypothesis thus far remains inconclusive. The current study sought to clarify the relationship between social activity and cognitive function over time using a coordinated data analysis approach across four longitudinal studies. A series of multilevel growth models with social activity included as a covariate is presented. Four domains of cognitive function were assessed: reasoning, memory, fluency, and semantic knowledge. Results suggest that baseline social activity is related to some, but not all, cognitive functions. Baseline social activity levels failed to predict rate of decline in most cognitive abilities. Changes in social activity were not consistently associated with cognitive functioning. Our findings do not provide consistent evidence that changes in social activity correspond to immediate benefits in cognitive functioning, except perhaps for verbal fluency. 1. Introduction Cognitive decline in older adulthood remains an area of great concern as the population ages. Some changes in cognitive function, such as decreased processing speed, are considered normative aspects of the aging process [1]. However, the impact of even mild cognitive impairment on functional capacity highlights the importance of maintaining cognitive function for as long as possible [2]. Substantial evidence suggests that lifestyle factors and cognitive function in older adulthood are related [3]. Sometimes summarized by the adage “use it or lose it,” current evidence suggests that leading an active lifestyle “using it” may buffer the effects of age-related cognitive decline “losing it” [3–5]. The mechanisms by which an active and engaged lifestyle may be related to better or preserved cognitive function in older adulthood remain to be fully elucidated. However, the cognitive reserve hypothesis predicts that some individuals are better able to withstand the physiological insults to the brain without measurable cognitive deficits because they had greater capacity to begin with [6]. Individuals may be able to actively increase their “reserve” through engaging in cognitively stimulating activities [3]. Social activities are considered part of what constitutes an active and engaged lifestyle, alongside cognitive and physical activities [3, 4, 7–9]. However, the evidence for a relationship
Cognitively Stimulating Activities: Effects on Cognition across Four Studies with up to 21 Years of Longitudinal Data
Meghan B. Mitchell,Cynthia R. Cimino,Andreana Benitez,Cassandra L. Brown,Laura E. Gibbons,Robert F. Kennison,Steven D. Shirk,Alireza Atri,Annie Robitaille,Stuart W. S. MacDonald,Magnus Lindwall,Elizabeth M. Zelinski,Sherry L. Willis,K. Warner Schaie,Boo Johansson,Roger A. Dixon,Dan M. Mungas,Scott M. Hofer,Andrea M. Piccinin
Journal of Aging Research , 2012, DOI: 10.1155/2012/461592
Abstract: Engagement in cognitively stimulating activities has been considered to maintain or strengthen cognitive skills, thereby minimizing age-related cognitive decline. While the idea that there may be a modifiable behavior that could lower risk for cognitive decline is appealing and potentially empowering for older adults, research findings have not consistently supported the beneficial effects of engaging in cognitively stimulating tasks. Using observational studies of naturalistic cognitive activities, we report a series of mixed effects models that include baseline and change in cognitive activity predicting cognitive outcomes over up to 21 years in four longitudinal studies of aging. Consistent evidence was found for cross-sectional relationships between level of cognitive activity and cognitive test performance. Baseline activity at an earlier age did not, however, predict rate of decline later in life, thus not supporting the concept that engaging in cognitive activity at an earlier point in time increases one's ability to mitigate future age-related cognitive decline. In contrast, change in activity was associated with relative change in cognitive performance. Results therefore suggest that change in cognitive activity from one's previous level has at least a transitory association with cognitive performance measured at the same point in time. 1. Introduction With the rising proportion of older adults and increases in life expectancy [1], there has been increased interest in maintaining and promoting cognitive health in later life. Although declines in some domains of cognition are part of the natural course of aging [2, 3], sufficient evidence from prospective and observational studies indicates that the trajectories and outcomes of cognitive decline may be mitigated by participating in cognitively stimulating activities [4, 5]. Recent reviews of cognitive interventions suggest some potential benefits that may improve functioning in healthy older adults or slow decline in individuals with mild cognitive impairment (MCI) and those already affected with dementia [6–9]. Results from a meta-analysis of randomized controlled trials in healthy aging revealed a strong positive effect on cognition at immediate, medium-, and long-term followup after cognitive training [10]. Compelling results from large longitudinal studies have also shown that engagement in everyday cognitive activities predicts preserved cognition [11, 12] and decreases in incident Alzheimer’s disease [13]. It is therefore not surprising that the market for “brain fitness” technologies,
Dynamic Associations of Change in Physical Activity and Change in Cognitive Function: Coordinated Analyses of Four Longitudinal Studies
Magnus Lindwall,Cynthia R. Cimino,Laura E. Gibbons,Meghan B. Mitchell,Andreana Benitez,Cassandra L. Brown,Robert F. Kennison,Steven D. Shirk,Alireza Atri,Annie Robitaille,Stuart W. S. MacDonald,Elizabeth M. Zelinski,Sherry L. Willis,K. Warner Schaie,Boo Johansson,Marcus Praetorius,Roger A. Dixon,Dan M. Mungas,Scott M. Hofer,Andrea M. Piccinin
Journal of Aging Research , 2012, DOI: 10.1155/2012/493598
Abstract: The present study used a coordinated analyses approach to examine the association of physical activity and cognitive change in four longitudinal studies. A series of multilevel growth models with physical activity included both as a fixed (between-person) and time-varying (within-person) predictor of four domains of cognitive function (reasoning, memory, fluency, and semantic knowledge) was used. Baseline physical activity predicted fluency, reasoning and memory in two studies. However, there was a consistent pattern of positive relationships between time-specific changes in physical activity and time-specific changes in cognition, controlling for expected linear trajectories over time, across all four studies. This pattern was most evident for the domains of reasoning and fluency. 1. Introduction Previous research has clearly demonstrated that cognitive change in old age does not occur in a homogenous manner for all individuals [1–3]. A number of predictors of cognitive change in old age have been identified, such as education, hypertension, objective indices of health and cardiovascular disease, and apolipoprotein E [4]. Regular engagement in different types of activities may also influence cognitive change. More specifically, according to the “use it or lose it” hypothesis [5], regular engagement in different activities may buffer age-related decline in cognitive functioning. A number of studies have found that general lifestyle activity engagement (often operationalized as the combination of intellectual, social, and physical activities) is associated with cognitive change [6–8] and that decline in activity in older age is associated with decline in cognitive functioning. In addition to general activity, other studies have specifically targeted the association of physical activity with cognitive change. Indeed, a growing body of the literature highlights the potential benefits of physical activity on the structure and function of the brain [9, 10]. The first line of evidence for the relationship between physical activity and cognition comes from a number of cross-sectional studies demonstrating that physically active older adults have higher cognitive performance and functioning compared with less active older adults [11, 12]. However, the evidence derived from these cross-sectional studies is limited, as it is not. possible to draw conclusions in terms of more complex associations of change. Stronger evidence may be found in longitudinal studies. Longitudinal studies may be viewed as the second line of evidence, offering valuable information on the
Epidermal growth factor mediates detachment from and invasion through collagen I and Matrigel in Capan-1 pancreatic cancer cells
Andrew J Shirk, Rahul Kuver
BMC Gastroenterology , 2005, DOI: 10.1186/1471-230x-5-12
Abstract: We tested this hypothesis by investigating the role of EGF in mediating adhesion to and invasion through collagen I and Matrigel in the metastatic pancreatic adenocarcinoma cell line Capan-1. Adhesion and invasion were measured using in vitro assays of fluorescently-labeled cells. Adhesion and invasion assays were also performed in the primary pancreatic adenocarcinoma cell line MIA PaCa-2.EGF inhibited adhesion to collagen I and Matrigel in Capan-1 cells. The loss of adhesion was reversed by AG825, an inhibitor of erbB2 receptor signalling and by wortmannin, a PI3K inhibitor, but not by the protein synthesis inhibitor cycloheximide. EGF stimulated invasion through collagen I and Matrigel at concentrations and time courses similar to those mediating detachment from these extracellular matrix components. Adhesion to collagen I was different in MIA PaCa-2 cells, with no significant change elicited following EGF treatment, whereas treatment with the EGF family member heregulin-alpha elicited a marked increase in adhesion. Invasion through Matrigel in response to EGF, however, was similar to that observed in Capan-1 cells.An inverse relationship exists between adhesion and invasion capabilities in Capan-1 cells but not in MIA PaCa-2 cells. EGF receptor signalling involving the erbB2 and PI3K pathways plays a role in mediating these events in Capan-1 cells.Pancreatic cancer carries a poor prognosis due to the advanced level of tumor invasion and metastasis often encountered at the time of diagnosis [1]. A clear understanding of the cellular processes involved in pancreatic cancer invasiveness and metastasis may be useful in the development of novel forms of therapy. The receptor tyrosine kinase epidermal growth factor receptor (EGF-R) and its ligands are over expressed in pancreatic cancer tissues and in pancreatic cancer cell lines [2,3], with coexpression of receptor and ligand correlating with tumor invasiveness [4]. The mitogenic effects of EGF-R stimulation in pancr
Multiple major increases and decreases in mitochondrial substitution rates in the plant family Geraniaceae
Christopher L Parkinson, Jeffrey P Mower, Yin-Long Qiu, Andrew J Shirk, Keming Song, Nelson D Young, Claude W dePamphilis, Jeffrey D Palmer
BMC Evolutionary Biology , 2005, DOI: 10.1186/1471-2148-5-73
Abstract: We explored a second potential case of highly accelerated mitochondrial sequence evolution in plants. This case was first suggested by relatively poor hybridization of mitochondrial gene probes to DNA of Pelargonium hortorum (the common geranium). We found that all eight mitochondrial genes sequenced from P. hortorum are exceptionally divergent, whereas chloroplast and nuclear divergence is unexceptional in P. hortorum. Two mitochondrial genes were sequenced from a broad range of taxa of variable relatedness to P. hortorum, and absolute rates of mitochondrial synonymous substitutions were calculated on each branch of a phylogenetic tree of these taxa. We infer one major, ~10-fold increase in the mitochondrial synonymous substitution rate at the base of the Pelargonium family Geraniaceae, and a subsequent ~10-fold rate increase early in the evolution of Pelargonium. We also infer several moderate to major rate decreases following these initial rate increases, such that the mitochondrial substitution rate has returned to normally low levels in many members of the Geraniaceae. Finally, we find unusually little RNA editing of Geraniaceae mitochondrial genes, suggesting high levels of retroprocessing in their history.The existence of major, mitochondrial-specific changes in rates of synonymous substitutions in the Geraniaceae implies major and reversible underlying changes in the mitochondrial mutation rate in this family. Together with the recent report of a similar pattern of rate heterogeneity in Plantago, these findings indicate that the mitochondrial mutation rate is a more plastic character in plants than previously realized. Many molecular factors could be responsible for these dramatic changes in the mitochondrial mutation rate, including nuclear gene mutations affecting the fidelity and efficacy of mitochondrial DNA replication and/or repair and – consistent with the lack of RNA editing – exceptionally high levels of "mutagenic" retroprocessing. That the mitocho
European Corn Borer (Ostrinia nubilalis) Induced Responses Enhance Susceptibility in Maize
Nicole J. Dafoe, James D. Thomas, Paul D. Shirk, Michelle E. Legaspi, Martha M. Vaughan, Alisa Huffaker, Peter E. Teal, Eric A. Schmelz
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0073394
Abstract: Herbivore-induced plant responses have been widely described following attack on leaves; however, less attention has been paid to analogous local processes that occur in stems. Early studies of maize (Zea mays) responses to stem boring by European corn borer (ECB, Ostrinia nubilalis) larvae revealed the presence of inducible acidic diterpenoid phytoalexins, termed kauralexins, and increases in the benzoxazinoid 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3?-one-glucose(HDMBOA-Glc) after 24 h of herbivory. Despite these rapidly activated defenses, larval growth was not altered in short-term feeding assays. Unexpectedly, ECB growth significantly improved in assays using stem tissue preconditioned by 48 h of larval tunneling. Correspondingly, measures of total soluble protein increased over 2.6-fold in these challenged tissues and were accompanied by elevated levels of sucrose and free linoleic acid. While microarray analyses revealed up-regulation of over 1100 transcripts, fewer individual protein increases were demonstrable. Consistent with induced endoreduplication, both wounding and ECB stem attack resulted in similar significant expansion of the nucleus, nucleolus and levels of extractable DNA from challenged tissues. While many of these responses are triggered by wounding alone, biochemical changes further enhanced in response to ECB may be due to larval secreted effectors. Unlike other Lepidoptera examined, ECB excrete exceedingly high levels of the auxin indole-3-acetic acid (IAA) in their frass which is likely to contact and contaminate the surrounding feeding tunnel. Stem exposure to a metabolically stable auxin, such as 2,4-dichlorophenoxyacetic acid (2,4-D), promoted significant protein accumulation above wounding alone. As a future testable hypothesis, we propose that ECB-associated IAA may function as a candidate herbivore effector promoting the increased nutritional content of maize stems.
Supracervical Lymph Node Biopsy under Local Anesthesia: A Cautionary Tale!  [PDF]
Steven D. Boggs, Elizabeth A. M. Frost
Open Journal of Anesthesiology (OJAnes) , 2015, DOI: 10.4236/ojanes.2015.53009
Abstract: A middle aged woman was scheduled for supracervical lymph node biopsy under local anesthesia. A scheduling conflict caused a significant operating room delay and she became very nervous. A surgical resident asked for anesthetic assistance in calming the patient. Assured that the case was under local anesthesia only, the anesthesiologist gave the patient soda to drink. In the operating room, the lady could not tolerate the procedure but as she now was at risk for aspiration, the anesthesiologist suggested the case be terminated and rescheduled. The surgeon disagreed and continued but was confronted with substantial bleeding. Emergency induction of general anesthesia was required. Postoperatively bleeding continued requiring re-exploration and intensive care unit admission. The patient developed a compressive left brachial plexopathy. The anatomy of the area indicated that general anesthesia was the preferred technique. The importance of team work and communication is underscored. Complications are more frequent when perioperative changes are made.
Dual Role of Novel Ingenol Derivatives from Euphorbia tirucalli in HIV Replication: Inhibition of De Novo Infection and Activation of Viral LTR
Celina M. Abreu, Sarah L. Price, Erin N. Shirk, Rodrigo D. Cunha, Luiz F. Pianowski, Janice E. Clements, Amilcar Tanuri, Lucio Gama
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0097257
Abstract: HIV infection is not cleared by antiretroviral drugs due to the presence of latently infected cells that are not eliminated with current therapies and persist in the blood and organs of infected patients. New compounds to activate these latent reservoirs have been evaluated so that, along with HAART, they can be used to activate latent virus and eliminate the latently infected cells resulting in eradication of viral infection. Here we describe three novel diterpenes isolated from the sap of Euphorbia tirucalli, a tropical shrub. These molecules, identified as ingenols, were modified at carbon 3 and termed ingenol synthetic derivatives (ISD). They activated the HIV-LTR in reporter cell lines and human PBMCs with latent virus in concentrations as low as 10 nM. ISDs were also able to inhibit the replication of HIV-1 subtype B and C in MT-4 cells and human PBMCs at concentrations of EC50 0.02 and 0.09 μM respectively, which are comparable to the EC50 of some antiretroviral currently used in AIDS treatment. Control of viral replication may be caused by downregulation of surface CD4, CCR5 and CXCR4 observed after ISD treatment in vitro. These compounds appear to be less cytotoxic than other diterpenes such as PMA and prostratin, with effective dose versus toxic dose TI>400. Although the mechanisms of action of the three ISDs are primarily attributed to the PKC pathway, downregulation of surface receptors and stimulation of the viral LTR might be differentially modulated by different PKC isoforms.
Spatially-explicit estimation of Wright's neighborhood size in continuous populations
Andrew J. Shirk,Samuel A. Cushman
Frontiers in Ecology and Evolution , 2014, DOI: 10.3389/fevo.2014.00062
Abstract: Effective population size (Ne) is an important parameter in conservation genetics because it quantifies a population's capacity to resist loss of genetic diversity due to inbreeding and drift. The classical approach to estimate Ne from genetic data involves grouping sampled individuals into discretely defined subpopulations assumed to be panmictic. Importantly, this assumption does not capture the continuous nature of populations genetically isolated by distance. Alternative approaches based on Wright's genetic neighborhood concept quantify the local number of breeding individuals (NS) in a continuous population (as opposed to the global Ne). However, they do not reflect the potential for NS to vary spatially nor do they account for the resistance of a heterogeneous landscape to gene flow (isolation by resistance). Here, we describe an application of Wright's neighborhood concept that provides spatially-explicit estimates of local NS from genetic data in continuous populations isolated by distance or resistance. We delineated local neighborhoods surrounding each sampled individual based on sigma (σ), a measure of the local extent of breeding. When σ was known, the linkage disequilibrium method applied to local neighborhoods produced unbiased estimates of NS that were highly variable across the landscape. NS near the periphery or areas surrounded by high resistance was as much as an order of magnitude lower compared to the center, raising the potential for a spatial component to extinction vortex dynamics in continuous populations. When σ is not known, it may be estimated from genetic data, but two methods we evaluated identified analysis extents that produced considerable bias or error in the estimate of NS. When σ is known or accurately estimated, and the assumptions of Wright's neighborhood are met, the method we describe provides spatially explicit information regarding short-term genetic processes that may inform conservation genetic analyses and management.
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