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Neuroimaging visualizes and quantifies age-related changes in brain structure, function, cerebral blood flow, and cerebral metabolic health. MRI studies show reductions in both overall and regional brain volumes, but to a lesser extent than in Alzheimer’s disease. Those aging non-pathologically tend to have relative preservation of mesial temporal and enthorhinal brain areas. White matter changes are also common as shown by hyperintensities on fluid attenuated inversion recovery and other T2 MRI images, presumably as a result of co-morbities that increasingly occur with age. Diffusion tensor imaging shows reductions in white matter integrity, including white matter fiber counts and overall white matter volume, beginning in mid- to late life. The neural response during both rest and task performance also shows reduced activation of core task-related networks but expansion to include other region activation. Reduced cerebral blood volume and flow also occur, likely reflecting alterations in hemodynamic function due to cerebrovascular and cardiovascular changes. Cerebral metabolic changes on MR spectroscopy occur with reduced concentrations of GABA and other neurotransmitters, as well as markers of neuronal integrity. Myoinositol, a marker of glial activation, may be elevated, indicating neuroinflammation, though this effect is likely not ubiquitous in successful aging.
The Lower Meuse Valley crosses the Roer Valley Rift System and provides an outstanding example of well-preserved late glacial and Holocene river terraces. The formation, preservation, and morphology of these terraces vary due to reach-specific conditions, a phenomenon that has been underappreciated in past studies. A detailed palaeogeographic reconstruction of the terrace series over the full length of the Lower Meuse Valley has been performed. This reconstruction provides improved insight into successive morphological responses to combined climatic and tectonic external forcing, as expressed and preserved in different ways along the river. New field data and data obtained from past studies were integrated using a digital mapping method in GIS. Results show that late glacial river terraces with diverse fluvial styles are best preserved in the Lower Meuse Valley downstream sub-reaches (traversing the Venlo Block and Peel Block), while Holocene terrace remnants are well-developed and preserved in the upstream sub-reaches (traversing the Campine Block and Roer Valley Graben). This reach-to-reach spatial variance in river terrace preservation and morphology can be ascribed to tectonically driven variations in river gradient and subsurface lithology, and to river-driven throughput of sediment supply.
OBJECTIVES/SPECIFIC AIMS: The study aimed to determine the effects of bilateral frontal active transcranial direct current stimulation (tDCS) at 2 mA for 12 minute Versus sham stimulation on functional connectivity of the working memory network during an fMRI N-Back task. METHODS/STUDY POPULATION: Stimulation was delivered over bilateral frontal dorsolateral prefrontal cortex via and MRI-compatible tDCS device during an fMRI working memory task in healthy older adults in a within-subject design. RESULTS/ANTICIPATED RESULTS: Active stimulation compared with sham resulted in significant increases in functional connectivity in working memory related brain regions during the N-Back task. DISCUSSION/SIGNIFICANCE OF IMPACT: Older adults typically have reduced functional connectivity compared with young adults. Our findings demonstrate that a single session of tDCS can increase functional connectivity of the working memory network in older adults. Based on this mechanism of effect, tDCS may serve as an adjunctive method for interventions aiming to enhance cognitive processes in older adults.
To develop a disaster triage tool for the evacuation of hospitalized neonatal and pediatric populations.
We expanded an existing neonatal disaster triage tool for the evacuation of a children’s hospital. We assessed inpatients using bedside visual assessments and chart review to categorize patients transport level based on local emergency medical services protocols and expert opinion. The tool was refined by using multiple Plan Do Study Act cycles. Primary outcome was the number of each level of transport required for hospital evacuation. Secondary outcome was improved efficiency of obtaining information about specific transport needs for evacuation.
We evaluated 1382 patients both visually and through electronic chart review over 10 random days. Accordance between visual assessment and electronic chart review reached 96.3%. During a 2 hour statewide disaster drill, no hospital units completed self-assessed transport needs for their patients; a single nurse used Triage by Resource Allocation in INpatients to determine transportation needs in less than 1 hour. (Disaster Med Public Health Preparedness. 2018;12:692-696)
Parametrized families of PDEs arise in various contexts such as inverse problems, control and optimization, risk assessment, and uncertainty quantification. In most of these applications, the number of parameters is large or perhaps even infinite. Thus, the development of numerical methods for these parametric problems is faced with the possible curse of dimensionality. This article is directed at (i) identifying and understanding which properties of parametric equations allow one to avoid this curse and (ii) developing and analysing effective numerical methods which fully exploit these properties and, in turn, are immune to the growth in dimensionality.
Part I of this article studies the smoothness and approximability of the solution map, that is, the map
is the parameter value and
is the corresponding solution to the PDE. It is shown that for many relevant parametric PDEs, the parametric smoothness of this map is typically holomorphic and also highly anisotropic, in that the relevant parameters are of widely varying importance in describing the solution. These two properties are then exploited to establish convergence rates of
-term approximations to the solution map, for which each term is separable in the parametric and physical variables. These results reveal that, at least on a theoretical level, the solution map can be well approximated by discretizations of moderate complexity, thereby showing how the curse of dimensionality is broken. This theoretical analysis is carried out through concepts of approximation theory such as best
-term approximation, sparsity, and
-widths. These notions determine a priori the best possible performance of numerical methods and thus serve as a benchmark for concrete algorithms.
Part II of this article turns to the development of numerical algorithms based on the theoretically established sparse separable approximations. The numerical methods studied fall into two general categories. The first uses polynomial expansions in terms of the parameters to approximate the solution map. The second one searches for suitable low-dimensional spaces for simultaneously approximating all members of the parametric family. The numerical implementation of these approaches is carried out through adaptive and greedy algorithms. An a priori analysis of the performance of these algorithms establishes how well they meet the theoretical benchmarks.
The numerical approximation of parametric partial differential equations is a
computational challenge, in particular when the number of involved parameter is large.
This paper considers a model class of second order, linear, parametric, elliptic PDEs on a
bounded domain D with diffusion coefficients depending on the parameters
in an affine manner. For such models, it was shown in [9, 10] that under very weak assumptions
on the diffusion coefficients, the entire family of solutions to such equations can be
simultaneously approximated in the Hilbert space
V = H01(D) by multivariate sparse polynomials in the parameter
vector y with a controlled number N of terms. The
convergence rate in terms of N does not depend on the number of
parameters in V, which may be arbitrarily large or countably infinite,
thereby breaking the curse of dimensionality. However, these approximation results do not
describe the concrete construction of these polynomial expansions, and should therefore
rather be viewed as benchmark for the convergence analysis of numerical methods. The
present paper presents an adaptive numerical algorithm for constructing a sequence of
sparse polynomials that is proved to converge toward the solution with the optimal
benchmark rate. Numerical experiments are presented in large parameter dimension, which
confirm the effectiveness of the adaptive approach.
Both HIV infection and high levels of early life stress (ELS) have been related to abnormalities in frontal-subcortical structures, yet the combined effects of HIV and ELS on brain structure and function have not been previously investigated. In this study we assessed 49 non-demented HIV-seropositive (HIV+) and 47 age-matched HIV-seronegative healthy control (HC) adults. Levels of ELS exposure were quantified and used to define four HIV-ELS groups: HC Low-ELS (N = 20); HC High-ELS (N = 27); HIV+ Low-ELS (N = 24); HIV+ High-ELS (N = 25). An automated segmentation tool measured volumes of brain structures known to show HIV-related or ELS-related effects; a brief neurocognitive battery was administered. A significant HIV-ELS interaction was observed for amygdala volumes, which was driven by enlargements in HIV+ High-ELS participants. The HIV+ High-ELS group also demonstrated significant reductions in psychomotor/processing speed compared with HC Low-ELS. Regression analyses in the HIV+ group revealed that amygdala enlargements were associated with higher ELS, lower nadir CD4 counts, and reduced psychomotor/processing speed. Our results suggest that HIV infection and high ELS interact to increase amygdala volume, which is associated with neurocognitive dysfunction in HIV+ patients. These findings highlight the lasting neuropathological influence of ELS and suggest that high ELS may be a significant risk factor for neurocognitive impairment in HIV-infected individuals. (JINS, 2012, 19, 1–12)
HIV-associated neurocognitive dysfunction persists in the highly active antiretroviral therapy (HAART) era and may be exacerbated by comorbidities, including substance use and hepatitis C virus (HCV) infection. However, the neurocognitive impact of HIV, HCV, and substance use in the HAART era is still not well understood. In the current study, 115 HIV-infected and 72 HIV-seronegative individuals with significant rates of lifetime substance dependence and HCV infection received comprehensive neuropsychological assessment. We examined the effects of HIV serostatus, HCV infection, and substance use history on neurocognitive functioning. We also examined relationships between HIV disease measures (current and nadir CD4, HIV RNA, duration of infection) and cognitive functioning. Approximately half of HIV-infected participants exhibited neurocognitive impairment. Detectable HIV RNA but not HIV serostatus was significantly associated with cognitive functioning. HCV was among the factors most consistently associated with poorer neurocognitive performance across domains, while substance use was less strongly associated with cognitive performance. The results suggest that neurocognitive impairment continues to occur in HIV-infected individuals in association with poor virologic control and comorbid conditions, particularly HCV coinfection. (JINS, 2012, 18, 68–78)
The formal commissioning of the IRWG occurred at the 1991 Buenos Aires General Assembly, following a Joint Commission meeting at the IAU GA in Baltimore in 1988 that identified the problems with ground-based infrared photometry. The meeting justification, papers, and conclusions, can be found in Milone (1989). In summary, the challenges involved how to explain the failure to achieve the milli-magnitude precision expected of infrared photometry and an apparent 3% limit on system transformability. The proposed solution was to redefine the broadband Johnson system, the passbands of which had proven so unsatisfactory that over time effectively different systems proliferated, although bearing the same “JHKLMNQ” designations; the new system needed to be better positioned and centered in the spectral windows of the Earth's atmosphere, and the variable water vapour content of the atmosphere needed to be measured in real time to better correct for atmospheric extinction.
Subcortical hyperintensities (SH) on neuroimaging are a prominent feature of vascular dementia (VaD) and SH severity correlates with cognitive impairment in this population. Previous studies demonstrated that SH burden accounts for a degree of the cognitive burden among VaD patients, although it remains unclear if individual factors such as cognitive reserve influence cognitive status in VaD. To address this issue, we examined 36 individuals diagnosed with probable VaD (age = 77.56; education = 12). All individuals underwent MMSE evaluations and MRI brain scans. We predicted that individuals with higher educational attainment would exhibit less cognitive difficulty despite similar levels of SH volume, compared to individuals with less educational attainment. A regression analysis revealed that greater SH volume was associated with lower scores on the MMSE. Additionally, education moderated the relationship between SH volume and MMSE score, demonstrating that individuals with higher education had higher scores on the MMSE despite similar degrees of SH burden. These results suggest that educational attainment buffers the deleterious effects of SH burden on cognitive status among VaD patients. (JINS, 2011, 17, 531–536)
Characterized by frontostriatal dysfunction, human immunodeficiency virus (HIV) is associated with cognitive and psychiatric abnormalities. Several studies have noted impaired facial emotion recognition abilities in patient populations that demonstrate frontostriatal dysfunction; however, facial emotion recognition abilities have not been systematically examined in HIV patients. The current study investigated facial emotion recognition in 50 nondemented HIV-seropositive adults and 50 control participants relative to their performance on a nonemotional landscape categorization control task. We examined the relation of HIV-disease factors (nadir and current CD4 levels) to emotion recognition abilities and assessed the psychosocial impact of emotion recognition abnormalities. Compared to control participants, HIV patients performed normally on the control task but demonstrated significant impairments in facial emotion recognition, specifically for fear. HIV patients reported greater psychosocial impairments, which correlated with increased emotion recognition difficulties. Lower current CD4 counts were associated with poorer anger recognition. In summary, our results indicate that chronic HIV infection may contribute to emotion processing problems among HIV patients. We suggest that disruptions of frontostriatal structures and their connections with cortico-limbic networks may contribute to emotion recognition abnormalities in HIV. Our findings also highlight the significant psychosocial impact that emotion recognition abnormalities have on individuals with HIV. (JINS, 2010, 16, 1127–1137.)
The formal origin of the IRWG occured at the Buenos Aires General Assembly, following a Joint Commission meeting at the IAU GA in Baltimore in 1988 that identified the problems with ground-based infrared photometry. The situation is summarized in Milone (1989). In short, the challenges involved how to explain the failure to achieve the milli-magnitude precision expected of infrared photometry and an apparent 3% limit on system transformability. The proposed solution was to redefine the broadband Johnson system, the passbands of which had proven so unsatisfactory that over time effectively different systems proliferated, although bearing the same JHKLMNQ designations; the new system needed to be better positioned and centered in the atmospheric windows of the Earth's atmosphere, and the variable water vapour content of the atmosphere needed to be measured in real time to better correct for atmospheric extinction.
Autism is associated with intellectual disability. The strength and origin of this association is unclear.
To investigate the association between extreme autistic traits and intellectual disability in children from a community-based sample and to examine whether the association can be explained by genetic factors.
Children scoring in the extreme 5% on measures of autistic traits, IQ and academic achievement were selected from 7965 7/8-year-old and 3687 9-year-old twin pairs. Phenotypic associations between extreme autistic traits and intellectual disability were compared with associations among the full-range scores. Genetic correlations were estimated using bivariate DeFries–Fulker extremes analyses.
Extreme autistic traits were modestly related to intellectual disability; this association was driven by communication problems characteristic of autism. Although this association was largely explained by genetic factors, the genetic correlation between autistic traits and intellectual disability was only modest.
Extreme autistic traits are substantially genetically independent of intellectual disability.
As part of normal homeostasis, the pH of arterial blood is fairly tightly controlled by normal physiologic processes. Healthy adults maintain a reasonably stable pH, ranging from 7.35 to 7.45, and the initial pH after birth can range from 7.11 to 7.36. Acidosis (low pH) and alkalosis (high pH) occur commonly when there are disturbances of the body's normal physiology. This can result from either a pathologic process or medical interventions. When they are due to, or associated with, a pathologic process, the abnormal pH may be blamed for any long-term consequences of that event. Similarly, when a medication or treatment results in an abnormal pH, any long-term consequences may be assigned to that intervention. In both situations, it is not clear whether the underlying physiologic disturbance is responsible for the adverse long-term outcome, or whether the abnormal pH played a role, and if so, how important that role may have been.
Acidosis is known to accompany ischemia, and has been used as a marker for tissue hypoxia and damage. However, it is unclear whether or not acidosis per se is a cause of injury. To examine this issue, we need to separate the two clinical subtypes of acidosis – respiratory and metabolic.
Respiratory acidosis occurs when carbon dioxide (CO2), produced by metabolism, builds up in the body and dissolves in the bloodstream.