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.

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.

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 $a\mapsto u(a)$, where $a$ is the parameter value and $u(a)$ 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 $n$-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 $n$-term approximation, sparsity, and $n$-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.

Is human immunodeficiency virus still a terminal condition? Recent advances in treatment have significantly reduced both mortality and morbidity associated with HIV, but these treatments have not been successful in eradicating the virus itself. As such, HIV has evolved into a chronic condition that is complicated by neurocognitive factors. Cognitive difficulties associated with HIV are characterized by a subcortical pattern with primary deficits in information processing speed and psychomotor speed. These deficits interfere with the ability of patients to complete important instrumental activities of daily living even in the absence of dementia. Treatment of HIV improves neurocognitive functioning, but the regimens are complex and patient adherence is critical. Cognitive factors can negatively impact treatment adherence, which in turn results in poorer immunological, cognitive, and psychiatric outcome. This cycle emphasizes the important interrelationships between symptom expression and treatment outcome in patients with HIV. The nature of these relationships will change with further developments in treatment regimens such as once-daily dosing. Less complex treatment approaches should improve health outcome as well as provide additional opportunities to further understand the impact of HIV on brain function.

Given the fact that we are able to agree on a set of categories for the collection of material on early nationalist movements in Africa, it is necessary also to ask whether or not the form in which the material is gathered is important. Our answer would be: it is essential to the secondary analysis of the oral history material that it be put in such a form that “more than” and “less than” questions be answered by its use when material from one or more countries is compared with that from other areas. If in comparing data on early nationalism from one area with those of others we are not interested in saying area A has more of this or that than area B, then quantification serves no useful purpose. However, we would contend that such statements are crucial in several ways. First, they allow us to compare areas more precisely, and, secondly, such data allow us and others the privilege of utilizing them to test theoretical formulations already present in the literature. Thus, if African socialism, as many theorize, denies the usual Marxist statements that socialism originates from the alienation felt by political thinkers and the masses as a result of the industrialization of the society, then early nationalists, many of whom were socialists in orientation, should be compared so as to see whether they were in fact alienated from their society--who were more so, and where were the early natiionalist movements more and where were they less socialistic, and where were they more and less alienated. If the informants who can remember the early nationalist movements are available, then such questions can be answered when researchers are made aware that these data may have, eventually, to be coded into more than, and less than, categories.

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.