Incremental value of biomarker combinations to predict progression of mild cognitive impairment to Alzheimer’s dementia

Background The progression of mild cognitive impairment (MCI) to Alzheimer’s disease (AD) dementia can be predicted by cognitive, neuroimaging, and cerebrospinal fluid (CSF) markers. Since most biomarkers reveal complementary information, a combination of biomarkers may increase the predictive power. We investigated which combination of the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR)-sum-of-boxes, the word list delayed free recall from the Consortium to Establish a Registry of Dementia (CERAD) test battery, hippocampal volume (HCV), amyloid-beta1–42 (Aβ42), amyloid-beta1–40 (Aβ40) levels, the ratio of Aβ42/Aβ40, phosphorylated tau, and total tau (t-Tau) levels in the CSF best predicted a short-term conversion from MCI to AD dementia. Methods We used 115 complete datasets from MCI patients of the “Dementia Competence Network”, a German multicenter cohort study with annual follow-up up to 3 years. MCI was broadly defined to include amnestic and nonamnestic syndromes. Variables known to predict progression in MCI patients were selected a priori. Nine individual predictors were compared by receiver operating characteristic (ROC) curve analysis. ROC curves of the five best two-, three-, and four-parameter combinations were analyzed for significant superiority by a bootstrapping wrapper around a support vector machine with linear kernel. The incremental value of combinations was tested for statistical significance by comparing the specificities of the different classifiers at a given sensitivity of 85%. Results Out of 115 subjects, 28 (24.3%) with MCI progressed to AD dementia within a mean follow-up period of 25.5 months. At baseline, MCI-AD patients were no different from stable MCI in age and gender distribution, but had lower educational attainment. All single biomarkers were significantly different between the two groups at baseline. ROC curves of the individual predictors gave areas under the curve (AUC) between 0.66 and 0.77, and all single predictors were statistically superior to Aβ40. The AUC of the two-parameter combinations ranged from 0.77 to 0.81. The three-parameter combinations ranged from AUC 0.80–0.83, and the four- parameter combination from AUC 0.81–0.82. None of the predictor combinations was significantly superior to the two best single predictors (HCV and t-Tau). When maximizing the AUC differences by fixing sensitivity at 85%, the two- to four-parameter combinations were superior to HCV alone. Conclusion A combination of two biomarkers of neurodegeneration (e.g., HCV and t-Tau) is not superior over the single parameters in identifying patients with MCI who are most likely to progress to AD dementia, although there is a gradual increase in the statistical measures across increasing biomarker combinations. This may have implications for clinical diagnosis and for selecting subjects for participation in clinical trials

Synchrotron Cooling in Energetic Gamma-Ray Bursts Observed by the Fermi Gamma-Ray Burst Monitor

We study the time-resolved spectra of eight GRBs observed by Fermi GBM in its first five years of mission, with 1 keV - 1 MeV fluence $f>1.0\times10^{-4}$ erg cm$^{-2}$ and signal-to-noise level $\text{S/N}\geq10.0$ above 900 keV. We aim to constrain in detail the spectral properties of GRB prompt emission on a time-resolved basis and to discuss the theoretical implications of the fitting results in the context of various prompt emission models. We perform time-resolved spectral analysis using a variable temporal binning technique according to optimal S/N criteria, resulting in a total of 299 time-resolved spectra. We fit the Band function to all spectra and obtain the distributions for the low-energy power-law index $\alpha$, the high-energy power-law index $\beta$, the peak energy in the observed $\nu F_\nu$ spectrum $E_\text{p}$, and the difference between the low- and high-energy power-law indices $\Delta s=\alpha-\beta$. Using the distributions of $\Delta s$ and $\beta$, the electron population index $p$ is found to be consistent with the "moderately fast" scenario which fast- and slow-cooling scenarios cannot be distinguished. We also apply a physically motivated synchrotron model, which is a triple power-law with constrained power-law indices and a blackbody component, to test for consistency with a synchrotron origin for the prompt emission and obtain the distributions for the two break energies $E_\text{b,1}$ and $E_\text{b,2}$, the middle segment power-law index $\beta$, and the Planck function temperature $kT$. A synchrotron model is found consistent with the majority of time-resolved spectra for these eight energetic Fermi GBM bursts with good high-energy photon statistics, as long as both the cooling and injection break are included and the leftmost spectral slope is lifted either by inclusion of a thermal component or when an evolving magnetic field is accounted for.Comment: 20 pages, 7 figures, 8 tables, accepted for publication in A&

The Extragalactic IR Background

Current limits on the intensity of the extragalactic infrared background are consistent with the expected contribution from evolving galaxies. Depending on the behaviour of the star formation rate and of the initial mass function, we can expect that dust extinction during early evolutionary phases ranges from moderate to strong. An example of the latter case may be the ultraluminous galaxy IRAS F$10214 + 4724$. The remarkable lack of high redshift galaxies in faint optically selected samples may be indirect evidence that strong extinction is common during early phases. Testable implications of different scenarios are discussed; ISO can play a key role in this context. Estimates of possible contributions of galaxies to the background under different assumptions are presented. The COBE/FIRAS limits on deviations from a blackbody spectrum at sub-mm wavelengths already set important constraints on the evolution of the far-IR emission of galaxies and on the density of obscured (``Type 2'') AGNs. A major progress in the field is expected at the completion of the analysis of COBE/DIRBE data.Comment: 1994, invited review to be published in the Proc. of the Internatinal Conf. "Dust, Molecules and Backgrounds: from Laboratory to Space", Capri (NA), Italy, 12--15 September, 1994, in press. Tex file, 16 pages, 6 figures not included. ASTRPD-94-10-0

The seasonal cycle of ocean-atmosphere CO2 Flux in Ryder Bay, West Antarctic Peninsula

Approximately 15 million km2 of the Southern Ocean is seasonally ice covered, yet the processes affecting carbon cycling and gas exchange in this climatically important region remain inadequately understood. Here, 3 years of dissolved inorganic carbon (DIC) measurements and carbon dioxide (CO2) fluxes from Ryder Bay on the west Antarctic Peninsula (WAP) are presented. During spring and summer, primary production in the surface ocean promotes atmospheric CO2 uptake. In winter, higher DIC, caused by net heterotrophy and vertical mixing with Circumpolar Deep Water, results in outgassing of CO2 from the ocean. Ryder Bay is found to be a net sink of atmospheric CO2 of 0.59–0.94 mol C m−2 yr−1 (average of 3 years). Seasonal sea ice cover increases the net annual CO2 uptake, but its effect on gas exchange remains poorly constrained. A reduction in sea ice on the WAP shelf may reduce the strength of the oceanic CO2 sink in this region

From niche to mainstream

Migration, Integration und ethnische Diversität sind zu zentralen Konfliktthemen in zeitgenössischen westlichen Demokratien geworden. Politische Parteien agieren in diesem Zusammenhang sowohl als Vertreter wie auch als Initiatoren spezifischer Interessen und beteiligen sich an der öffentlichen Auseinandersetzung aus unterschiedlichen strategischen Erwägungen. Unter diesem Gesichtspunkt setzt sich die vorliegende Dissertation mit der Politisierung von Migration, Integration und Diversität innerhalb des österreichischen Parteienwettbewerbes auseinander und zielt dabei auf eine Integration der drei Forschungsbereiche Parteipolitik, Politische Kommunikation sowie Migrations-/Integrationsforschung ab. Auf Basis einer Inhaltsanalyse österreicher Nationalratswahlkämpfe von 1971 bis 2008 liefert die Dissertation drei wesentliche Beiträge: Sie entwickelt ein Konzept zur Analyse der Politisierung von Migration/Integration/ Diversität, aufbauend auf Salienz-, Themen- und Frame-Analyse des elektoralen Diskurses; sie schlägt ein Erklärungsframework für elektorale Politisierung vor, in dem sozio-strukturelle Rahmenbedingungen mit strategischen Wettbewerbserwägungen von Parteien verbunden werden; und sie vergleicht unterschiedliche Ebenen der Wahlkampfkommunikation hinsichtlich der Frage, ob und in welchem Maße politische Parteien zu konsistenter Kampagnenkommunikation in der Lage sind. Wie die empirischen Ergebnisse zu dem seit 1990 markant an Salienz gewinnenden Themenkomplex verdeutlichen, bilden sozio-strukturelle Bedingungen – etwa der Zuwanderung bzw. der Asylentwicklung – einen augenfälligen Impuls für die Politisierung dieser Themen durch Parteien im Querschnitt. Individuelles Parteiverhalten hingegen, so zeigt die Untersuchung, lässt sich über den Zeitverlauf nur in Verbindung mehrer erklärender Faktoren erfassen. Politische Konfliktlinien (Cleavages) und ideologischer Hintergrund prägen das Politisierungsverhalten durchgehend, insbesondere jenes von niche parties, die ihre Framing-Strategien relativ konstant halten und lediglich die Intensität ihrer Politisierung verändern. Mainstream parties hingegen verändern ihre Politisierungsstrategien merklich während der letzten beiden Dekaden (sowohl in puncto Intensität als auch Richtung), im Lichte wachsenden Drucks der politischen Rechten sowie sich verändernder Koalitions-perspektiven. Diese Politisierungsmuster variieren allerdings im Vergleich unterschiedlicher Kampagnenebenen, da programmatische Kommunikation strategische Parteierwägungen wesentlich deutlicher zum Vorschein bringt als tagespolitische Kommunikation, die in stärkerem Maße kurzfristigen Dynamiken innerhalb einzelner Wahlkämpfe unterworfen ist. In Summe vermag die Dissertation zu verdeutlichen, dass, wie und weshalb Migration, Integration und ethnische Diversität zu zentralen Bestandteilen parteipolitischer Konfliktlinien geworden sind, die den zeitgenössischen Parteienwettbewerb in Österreich strukturieren und dabei wechselnden Parteimotiven bei sich verändernden Mehrheits-verhältnissen unterworfen sind.Immigration, migrant integration and ethnic diversity have become major issues in contemporary Western democracies. Their increased public contention is both reflected as well as stimulated by political parties, who engage in the debate for different strategic reasons. The aim of the dissertation is to examine party politicization of immigration, migrant integration and ethnic diversity on a longitudinal basis by integrating three strands of literature on party politics, political communication and immigration research. Based on a content analysis of Austrian federal elections between 1971 and 2008, the study finally offers three main contributions: It develops an approach for the analysis of politicization of these contentious campaign issues, based on issue-salience, subtopics and policy frames; it suggests an explanatory framework for party politicization, integrating socio-structural conditions with strategic party competition factors; finally it compares different electoral campaign channels, in order to evaluate campaign consistency of party politicization in the electoral arena. As the empirical findings demonstrate, socio-structural conditions of immigration and asylum constitute a conspicuous context for party politicization, for they catalyze increasing issue-salience since the 1990ies. With regard to individual party behavior, though, only a synthesis of party competition factors is able to explain politicization over time: In the first place, party ideology and issue-ownership continuously structure parties’ strategies, especially those of Austrian niche parties, who retain their policy framing and only alter issue emphasis. Mainstream parties on the other hand remarkably shift their behavior in the light of far right success and changing coalition perspectives since the 1990ies – both in terms of emphasis and framing of immigration, migrant integration and ethnic diversity. Yet these patterns of politicization considerably differ between electoral campaign channels, since programmatic communication expresses party strategies more reliably, whereas daily campaign communication is subject to variant short-term dynamics of election campaign periods. In sum the dissertation documents, that immigration, migrant integration and ethnic diversity have established as major conflictive issues, structuring contemporary Austrian party competition and being subjected to changing party motives under shifting majority conditions