Neuropsychological Decline Stratifies Dementia Risk in Cognitively Unimpaired and Impaired Older Adults

ObjectiveValidation and widespread use of markers indicating decline in serial neuropsychological exams has remained elusive despite potential value in prognostic and treatment decision-making. This study aimed to operationalize neuropsychological decline, termed “neuropsychological (NP) decline,” in older adults followed over 12 months in order to aid in the stratification of dementia risk along the cognitively unimpaired-to-mild cognitive impairment (MCI) spectrum.MethodsA prospective cohort study utilized 6,794 older adults from the National Alzheimer’s Coordinating Center (NACC) database with a baseline diagnosis of normal cognition, impaired without MCI or with MCI. Operationalization of NP decline over 12-month follow-up used regression-based norms developed in a robustly normal reference sample. The extent to which each participant’s 12-month follow-up score deviated from norm-referenced expectations was quantified and standardized to an NP decline z-score. Cox regression evaluated whether the NP decline metric predicted future dementia.ResultsParticipant’s NP decline scores predicted future all-cause dementia in the total sample, χ2 = 110.71, hazard ratio (HR) = 1.989, p < 0.001, and in the subset diagnosed with normal cognition, χ2 = 40.84, HR = 2.006, p < 0.001, impaired without MCI diagnosis, χ2 = 14.89, HR = 2.465, p < 0.001, and impaired with MCI diagnosis, χ2 = 55.78, HR = 1.916, p < 0.001.ConclusionOperationalizing NP decline over 12 months with a regression-based norming method allows for further stratification of dementia risk along the cognitively unimpaired-to-MCI spectrum. The use of NP decline as an adjunctive marker of risk beyond standard cognitive diagnostic practices may aid in prognosis and clinical decision-making

The prognosis of allocentric and egocentric neglect : evidence from clinical scans

We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome

Heterosubtype Neutralizing Responses to Influenza A (H5N1) Viruses Are Mediated by Antibodies to Virus Haemagglutinin

Background: It is increasingly clear that influenza A infection induces cross-subtype neutralizing antibodies that may potentially confer protection against zoonotic infections. It is unclear whether this is mediated by antibodies to the neuraminidase (NA) or haemagglutinin (HA). We use pseudoviral particles (H5pp) coated with H5 haemagglutinin but not N1 neuraminidase to address this question. In this study, we investigate whether cross-neutralizing antibodies in persons unexposed to H5N1 is reactive to the H5 haemagglutinin. Methodology/Principal Findings: We measured H5-neutralization antibody titers pre- and post-vaccination using the H5N1 micro-neutralization test (MN) and H5pp tests in subjects given seasonal vaccines and in selected sera from European elderly volunteers in a H5N1 vaccine trial who had detectable pre-vaccination H5N1 MN antibody titers. We found detectable (titer ≥20) H5N1 neutralizing antibodies in a minority of pre-seasonal vaccine sera and evidence of a serological response to H5N1 in others after seasonal influenza vaccination. There was excellent correlation in the antibody titers between the H5N1 MN and H5pp tests. Similar correlations were found between MN and H5pp in the pre-vaccine sera from the cohort of H5N1 vaccine trial recipients. Conclusions/Significance: Heterosubtype neutralizing antibody to H5N1 in healthy volunteers unexposed to H5N1 is mediated by cross-reaction to the H5 haemagglutinin. Copyright: © 2009 Garcia et al.published_or_final_versio

Credibility and adjustment: gold standards versus currency boards

It is often maintained that currency boards (CBs) and gold standards (GSs) are alike in that they are stringent monetary rules, the two basic features of which are high credibility of monetary authorities and the existence of automatic adjustment (non discretionary) mechanism. This article includes a comparative analysis of these two types of regimes both from the perspective of the sources and mechanisms of generating confidence and credibility, and the elements of operation of the automatic adjustment mechanism. Confidence under the GS is endogenously driven, whereas it is exogenously determined under the CB. CB is a much more asymmetric regime than GS (the adjustment is much to the detriment of peripheral countries) although asymmetry is a typical feature of any monetary regime. The lack of credibility is typical for peripheral countries and cannot be overcome completely even by “hard” monetary regimes.http://deepblue.lib.umich.edu/bitstream/2027.42/40078/3/wp692.pd

Spatially Resolved Chemistry in Nearby Galaxies I. The Center of IC 342

We have imaged emission from the millimeter lines of eight molecules--C2H, C34S, N2H+, CH3OH, HNCO, HNC, HC3N, and SO--in the central half kpc of the nearby spiral galaxy IC 342. The 5" (~50 pc) resolution images were made with OVRO. Using these maps we obtain a picture of the chemistry within the nuclear region on the sizescales of individual GMCs. Bright emission is detected from all but SO. There are marked differences in morphology for the different molecules. A principal component analysis is performed to quantify similarities and differences among the images. This analysis reveals that while all molecules are to zeroth order correlated, that is, they are all found in dense molecular clouds, there are three distinct groups of molecules distinguished by the location of their emission within the nuclear region. N2H+, C18O, HNC and HCN are widespread and bright, good overall tracers of dense molecular gas. C2H and C34S, tracers of PDR chemistry, originate exclusively from the central 50-100 pc region, where radiation fields are high. The third group of molecules, CH3OH and HNCO, correlates well with the expected locations of bar-induced orbital shocks. The good correlation of HNCO with the established shock tracer molecule CH3OH is evidence that this molecule, whose chemistry has been uncertain, is indeed produced by processing of grains. HC3N is observed to correlate tightly with 3mm continuum emission, demonstrating that the young starbursts are the sites of the warmest and densest molecular gas. We compare our HNC images with the HCN images of Downes et al. (1992) to produce the first high resolution, extragalactic HCN/HNC map: the HNC/HCN ratio is near unity across the nucleus and the correlation of both of these gas tracers with the star formation is excellent. (Abridged).Comment: 54 pages including 10 figures and 8 tables. Accepted for publication in Ap

Two-dimensional limit of exchange-correlation energy functional approximations in density functional theory

We investigate the behavior of three-dimensional (3D) exchange-correlation energy functional approximations of density functional theory in anisotropic systems with two-dimensional (2D) character. Using two simple models, quasi-2D electron gas and two-electron quantum dot, we show a {\it fundamental limitation} of the local density approximation (LDA), and its semi-local extensions, generalized gradient approximation (GGA) and meta-GGA (MGGA), the most widely used forms of which are worse than the LDA in the strong 2D limit. The origin of these shortcomings is in the inability of the local (LDA) and semi-local (GGA/MGGA) approximations to describe systems with 2D character in which the nature of the exchange-correlation hole is very nonlocal. Nonlocal functionals provide an alternative approach, and explicitly the average density approximation (ADA) is shown to be remarkably accurate for the quasi-2D electron gas system. Our study is not only relevant for understanding of the functionals but also practical applications to semiconductor quantum structures and materials such as graphite and metal surfaces. We also comment on the implication of our findings to the practical device simulations based on the (semi-)local density functional method.Comment: 21 pages including 9 figures, to be published in Phys. Rev.

Complete Sequencing of pNDM-HK Encoding NDM-1 Carbapenemase from a Multidrug-Resistant Escherichia coli Strain Isolated in Hong Kong

BACKGROUND: The emergence of plasmid-mediated carbapenemases, such as NDM-1 in Enterobacteriaceae is a major public health issue. Since they mediate resistance to virtually all β-lactam antibiotics and there is often co-resistance to other antibiotic classes, the therapeutic options for infections caused by these organisms are very limited. METHODOLOGY: We characterized the first NDM-1 producing E. coli isolate recovered in Hong Kong. The plasmid encoding the metallo-β-lactamase gene was sequenced. PRINCIPAL FINDINGS: The plasmid, pNDM-HK readily transferred to E. coli J53 at high frequencies. It belongs to the broad host range IncL/M incompatibility group and is 88803 bp in size. Sequence alignment showed that pNDM-HK has a 55 kb backbone which shared 97% homology with pEL60 originating from the plant pathogen, Erwina amylovora in Lebanon and a 28.9 kb variable region. The plasmid backbone includes the mucAB genes mediating ultraviolet light resistance. The 28.9 kb region has a composite transposon-like structure which includes intact or truncated genes associated with resistance to β-lactams (bla(TEM-1), bla(NDM-1), Δbla(DHA-1)), aminoglycosides (aacC2, armA), sulphonamides (sul1) and macrolides (mel, mph2). It also harbors the following mobile elements: IS26, ISCR1, tnpU, tnpAcp2, tnpD, ΔtnpATn1 and insL. Certain blocks within the 28.9 kb variable region had homology with the corresponding sequences in the widely disseminated plasmids, pCTX-M3, pMUR050 and pKP048 originating from bacteria in Poland in 1996, in Spain in 2002 and in China in 2006, respectively. SIGNIFICANCE: The genetic support of NDM-1 gene suggests that it has evolved through complex pathways. The association with broad host range plasmid and multiple mobile genetic elements explain its observed horizontal mobility in multiple bacterial taxa

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: Baryon Acoustic Oscillations in the Data Release 9 Spectroscopic Galaxy Sample

We present measurements of galaxy clustering from the Baryon Oscillation Spectroscopic Survey (BOSS), which is part of the Sloan Digital Sky Survey III (SDSS-III). These use the Data Release 9 (DR9) CMASS sample, which contains 264,283 massive galaxies covering 3275 square degrees with an effective redshift z=0.57 and redshift range 0.43 < z < 0.7. Assuming a concordance Lambda-CDM cosmological model, this sample covers an effective volume of 2.2 Gpc^3, and represents the largest sample of the Universe ever surveyed at this density, n = 3 x 10^-4 h^-3 Mpc^3. We measure the angle-averaged galaxy correlation function and power spectrum, including density-field reconstruction of the baryon acoustic oscillation (BAO) feature. The acoustic features are detected at a significance of 5\sigma in both the correlation function and power spectrum. Combining with the SDSS-II Luminous Red Galaxy Sample, the detection significance increases to 6.7\sigma. Fitting for the position of the acoustic features measures the distance to z=0.57 relative to the sound horizon DV /rs = 13.67 +/- 0.22 at z=0.57. Assuming a fiducial sound horizon of 153.19 Mpc, which matches cosmic microwave background constraints, this corresponds to a distance DV(z=0.57) = 2094 +/- 34 Mpc. At 1.7 per cent, this is the most precise distance constraint ever obtained from a galaxy survey. We place this result alongside previous BAO measurements in a cosmological distance ladder and find excellent agreement with the current supernova measurements. We use these distance measurements to constrain various cosmological models, finding continuing support for a flat Universe with a cosmological constant.Comment: 33 page

Heart Rate and Use of Beta-Blockers in Stable Outpatients with Coronary Artery Disease

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Heart rate (HR) is an emerging risk factor in coronary artery disease (CAD). However, there is little contemporary data regarding HR and the use of HR-lowering medications, particularly beta-blockers, among patients with stable CAD in routine clinical practice. The goal of the present analysis was to describe HR in such patients, overall and in relation to beta-blocker use, and to describe the determinants of HR.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and Findings:&lt;/b&gt; CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis of &#62;50%, or chest pain associated with proven myocardial ischemia. A total of 33,438 patients from 45 countries in Europe, the Americas, Africa, Middle East, and Asia/Pacific were enrolled between November 2009 and July 2010. Most of the 33,177 patients included in this analysis were men (77.5%). Mean (SD) age was 64.2 (10.5) years, HR by pulse was 68.3 (10.6) bpm, and by electrocardiogram was 67.2 (11.4) bpm. Overall, 44.0% had HR&#8805;70 bpm. Beta-blockers were used in 75.1% of patients and another 14.4% had intolerance or contraindications to beta-blocker therapy. Among 24,910 patients on beta-blockers, 41.1% had HR&#8805;70 bpm. HR&#8805;70 bpm was independently associated with higher prevalence and severity of angina, more frequent evidence of myocardial ischemia, and lack of use of HR-lowering agents.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Despite a high rate of use of beta-blockers, stable CAD patients often have resting HR&#8805;70 bpm, which was associated with an overall worse health status, more frequent angina and ischemia. Further HR lowering is possible in many patients with CAD. Whether it will improve symptoms and outcomes is being tested.&lt;/p&gt

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: Analysis of potential systematics

We analyze the density field of galaxies observed by the Sloan Digital Sky Survey (SDSS)-III Baryon Oscillation Spectroscopic Survey (BOSS) included in the SDSS Data Release Nine (DR9). DR9 includes spectroscopic redshifts for over 400,000 galaxies spread over a footprint of 3,275 deg^2. We identify, characterize, and mitigate the impact of sources of systematic uncertainty on large-scale clustering measurements, both for angular moments of the redshift-space correlation function and the spherically averaged power spectrum, P(k), in order to ensure that robust cosmological constraints will be obtained from these data. A correlation between the projected density of stars and the higher redshift (0.43 < z < 0.7) galaxy sample (the `CMASS' sample) due to imaging systematics imparts a systematic error that is larger than the statistical error of the clustering measurements at scales s > 120h^-1Mpc or k < 0.01hMpc^-1. We find that these errors can be ameliorated by weighting galaxies based on their surface brightness and the local stellar density. We use mock galaxy catalogs that simulate the CMASS selection function to determine that randomly selecting galaxy redshifts in order to simulate the radial selection function of a random sample imparts the least systematic error on correlation function measurements and that this systematic error is negligible for the spherically averaged correlation function. The methods we recommend for the calculation of clustering measurements using the CMASS sample are adopted in companion papers that locate the position of the baryon acoustic oscillation feature (Anderson et al. 2012), constrain cosmological models using the full shape of the correlation function (Sanchez et al. 2012), and measure the rate of structure growth (Reid et al. 2012). (abridged)Comment: Matches version accepted by MNRAS. Clarifications and references have been added. See companion papers that share the "The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey:" titl