Zusammenfassung
Hintergrund
Da kognitive Defizite im Rahmen einer demenziellen Entwicklung vom Betroffenen häufig nicht berichtet werden, kommt der Auskunft einer engen Bezugsperson in der ...Früherkennung von Demenzen eine wichtige Bedeutung zu. Ein international verbreitetes und gut evaluiertes Fremdbeurteilungs-Screeningverfahren des kognitiven Abbaus ist der Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Er besitzt den Vorteil, kognitive Veränderungen direkt zu erfassen. Für den deutschen Sprachraum fehlen für den IQCODE bisher Vergleichswerte und psychometrische Untersuchungen.
Methodik
Es wurden Vergleichsdaten für die deutsche Version der IQCODE-Langform an 46 normal gesunden älteren Ehepaaren erhoben. Diese wurden hinsichtlich der konkurrenten und diskriminanten Validität mit Patientengruppen mit leichter kognitiver Störung (LKS, n=25), Alzheimer-Demenz bzw. Mischdemenz (AD, n=59) und frontotemporalen Lobärdegenerationen (FTLD, n=15) verglichen.
Ergebnisse
Der deutsche IQCODE zeigte gute psychometrische Eigenschaften und trennte am besten kognitiv unauffällige Probanden von AD-Patienten. Der mittels Receiver-operating-characteristic-Analyse errechnete Cut-off-Wert von 3,38 entsprach den Ergebnissen internationaler Studien. Auch wurden Patienten mit LKS und FTLD reliabel von normal-gesunden Probanden abgegrenzt, jedoch gelang mittels IQCODE keine überzufällige Unterscheidung zwischen Patienten mit AD und FTLD.
Schlussfolgerungen
Die deutsche Version des IQCODE trennt zuverlässig zwischen kognitiv unauffälligen Probanden und Patienten mit LKS bzw. kortikalen Demenzen, jedoch nicht zwischen verschiedenen kortikalen Demenzen wie AD und FTLD. Der IQCODE kann als ökonomisches Fremdbeurteilungs-Screening zur Früherkennung demenzieller Entwicklungen beitragen.
•Neural oscillations sample the acoustic environment at multiple timescales.•Delta-band oscillations encode temporal regularities and predict tone onsets.•Beta-band oscillations parse auditory ...sequences by superimposing accentuation patterns.•Delta-beta oscillations provide a neural code for dynamic attending environmental rhythms.
When sensory input conveys rhythmic regularity, we can form predictions about the timing of upcoming events. Although rhythm processing capacities differ considerably between individuals, these differences are often obscured by participant- and trial-level data averaging procedures in M/EEG research. Here, we systematically assessed neurophysiological variability displayed by individuals listening to isochronous (1.54 Hz) equitone sequences interspersed with unexpected (amplitude-attenuated) deviant tones. Our approach aimed at revealing time-varying adaptive neural mechanisms for sampling the acoustic environment at multiple timescales. Rhythm tracking analyses confirmed that individuals encode temporal regularities and form temporal expectations, as indicated in delta-band (1.54 Hz) power and its anticipatory phase alignment to expected tone onsets. Zooming into tone- and participant-level data, we further characterized intra- and inter-individual variabilities in phase-alignment across auditory sequences. Further, individual modeling of beta-band tone-locked responses showed that a subset of auditory sequences was sampled rhythmically by superimposing binary (strong-weak; S-w), ternary (S-w-w) and mixed accentuation patterns. In these sequences, neural responses to standard and deviant tones were modulated by a binary accentuation pattern, thus pointing towards a mechanism of dynamic attending. Altogether, the current results point toward complementary roles of delta- and beta-band activity in rhythm processing and further highlight diverse and adaptive mechanisms to track and sample the acoustic environment at multiple timescales, even in the absence of task-specific instructions.
Zusammenfassung
Hintergrund
Beginnende Alzheimer-Demenz (AD) ist bei Neurologen, Psychiatern und Nervenärzten eine häufige Verdachtsdiagnose, deren Bestätigung oder Ausschluss aufwändig ist. Es wird ...die Frage untersucht, inwieweit die von ärztlicher Seite gestellte Verdachtsdiagnose AD durch eine ausführliche neuropsychologische Differenzialdiagnostik bestätigt werden kann.
Methodik
Auf Basis der NINCDS-ADRDA-Diagnosekriterien für AD erfolgte eine deskriptive Datenauswertung einer Beobachtungsstudie von 47 ambulanten Patienten mit Verdacht auf AD.
Ergebnisse
Nur 38% der untersuchten Patienten erfüllten aus neuropsychologischer Sicht die NINCDS-ADRDA-Diagnosekriterien für AD oder Mischdemenz, bei weiteren 22% konnte eine andere Demenzdiagnose gestellt werden. Die übrigen Patienten wurden anderen Differenzialdiagnosen zugeordnet (23%) oder waren neuropsychologisch unauffällig (17%).
Schlussfolgerungen
Die Neuropsychologie ist ein notwendiger Bestandteil der differenzialdiagnostischen Beurteilung von leichten bis mittelschweren Demenzen. Sie kann zur Optimierung der Demenzbehandlung beitragen, indem sie Entscheidungshilfen zur Auswahl einer adäquaten Therapie gibt und nichtindizierte, kostenintensive Behandlungen vermeidet.
Pelagic marine predators face unprecedented challenges and uncertain futures. Overexploitation and climate variability impact the abundance and distribution of top predators in ocean ecosystems. ...Improved understanding of ecological patterns, evolutionary constraints and ecosystem function is critical for preventing extinctions, loss of biodiversity and disruption of ecosystem services. Recent advances in electronic tagging techniques have provided the capacity to observe the movements and long-distance migrations of animals in relation to ocean processes across a range of ecological scales. Tagging of Pacific Predators, a field programme of the Census of Marine Life, deployed 4,306 tags on 23 species in the North Pacific Ocean, resulting in a tracking data set of unprecedented scale and species diversity that covers 265,386 tracking days from 2000 to 2009. Here we report migration pathways, link ocean features to multispecies hotspots and illustrate niche partitioning within and among congener guilds. Our results indicate that the California Current large marine ecosystem and the North Pacific transition zone attract and retain a diverse assemblage of marine vertebrates. Within the California Current large marine ecosystem, several predator guilds seasonally undertake north-south migrations that may be driven by oceanic processes, species-specific thermal tolerances and shifts in prey distributions. We identify critical habitats across multinational boundaries and show that top predators exploit their environment in predictable ways, providing the foundation for spatial management of large marine ecosystems.
We report Hubble Space Telescope optical to near-infrared transmission spectroscopy of the hot-Jupiter WASP-6b, measured with the Space Telescope Imaging Spectrograph and Spitzer's InfraRed Array ...Camera. The resulting spectrum covers the range 0.29–4.5 μm. We find evidence for modest stellar activity of WASP-6 and take it into account in the transmission spectrum. The overall main characteristic of the spectrum is an increasing radius as a function of decreasing wavelength corresponding to a change of Δ (R
p / R
*) = 0.0071 from 0.33 to 4.5 μm. The spectrum suggests an effective extinction cross-section with a power law of index consistent with Rayleigh scattering, with temperatures of 973 ± 144 K at the planetary terminator. We compare the transmission spectrum with hot-Jupiter atmospheric models including condensate-free and aerosol-dominated models incorporating Mie theory. While none of the clear-atmosphere models is found to be in good agreement with the data, we find that the complete spectrum can be described by models that include significant opacity from aerosols including Fe-poor Mg2SiO4, MgSiO3, KCl and Na2S dust condensates. WASP-6b is the second planet after HD 189733b which has equilibrium temperatures near ∼1200 K and shows prominent atmospheric scattering in the optical.
•Development of a 3D cut cell algorithm, state redistribution (SRD), for finite volume methods on engineering geometries.•Generalization of the original SRD approach that is less dissipative at the ...embedded boundary and smoothly activates.•SRD is extended to PDEs with reaction and diffusion terms in both compressible and incompressible flows.•SRD has been included in the open-source exascale framework AMReX, which runs in parallel on hybrid CPU/GPU architectures.
State redistribution is an algorithm that stabilizes cut cells for embedded boundary grid methods. This work extends the earlier algorithm in several important ways. First, state redistribution is extended to three spatial dimensions. Second, we discuss several algorithmic changes and improvements motivated by the more complicated cut cell geometries that can occur in higher dimensions. In particular, we introduce a weighted version with less dissipation in an easily generalizable framework. Third, we demonstrate that state redistribution can also stabilize a solution update that includes both advective and diffusive contributions. The stabilization algorithm is shown to be effective for incompressible as well as compressible reacting flows. Finally, we discuss the implementation of the algorithm for several exascale-ready simulation codes based on AMReX, demonstrating ease of use in combination with domain decomposition, hybrid parallelism and complex physics.
PD-1/PD-L1 immune checkpoint inhibitors show potential for cervical cancer treatment. However, low response rates suggest that patient selection based on PD-L1 protein expression is not optimal. ...Here, we evaluated different PD-L1 detection methods and studied transcriptional regulation of PD-L1/PD-L2 expression by The Cancer Genome Atlas (TCGA) mRNAseq analysis. First, we determined the copy number of the PD-L1/PD-L2 locus by fluorescence
hybridization (FISH), PD-L1 mRNA expression by RNA
hybridization (RNAish), and PD-L1/PD-L2 protein expression by immunohistochemistry (IHC) on tissue microarrays containing a cohort of 60 patients. Additionally, distribution of PD-L1/PD-L2 was visualized based on flow cytometry analysis of single-cell suspensions (n = 10). PD-L1/PD-L2 locus amplification was rare (2%). PD-L1 mRNA expression in tumor cells was detected in 56% of cases, while 41% expressed PD-L1 protein. Discordant scores for PD-L1 protein expression on tumor cells between cores from one patient were observed in 27% of cases. Interestingly, with RNAish, PD-L1 heterogeneity was observed in only 11% of the cases. PD-L2 protein expression was found in 53%. PD-L1 mRNA and protein expression on tumor cells were strongly correlated (p < 0.001). PD-L1 and PD-L2 protein expression showed no correlation on tumor cells (p = 0.837), but a strong correlation on cells in stromal fields (p < 0.001). Co-expression of PD-L1 and PD-L2 on macrophage-like populations was also observed with flow cytometry analysis. Both PD-L1 and PD-L2 TCGA transcript levels strongly correlated in the TCGA data, and both PD-L1 and PD-L2 strongly correlated with interferon gamma (IFNG) expression/transcript levels (p < 0.0001). Importantly, patients with high PD-L1/PD-L2/IFNG transcript levels had a survival advantage over patients with high PD-L1/PD-L2 and low IFNG expression. Based on these findings, we conclude that PD-L1/PD-L2 expression in cervical cancer is mainly associated with interferon induction and not gene amplification, which makes FISH unsuitable as biomarker. The heterogeneous PD-L1 and PD-L2 expression patterns suggest IHC unreliable for patient selection. RNAish, in conjunction with interferon signaling evaluation, seems a promising technique for immune checkpoint detection. These results warrant further investigation into their prognostic and predictive potential.
Peptides are attracting increasing attention as therapeutic agents, as the technologies for peptide development and manufacture continue to mature. Concurrently, with booming research in ...nanotechnology for biomedical applications, peptides have been studied as an important class of components in nanomedicine, and they have been used either alone or in combination with nanomaterials of every reported composition. Peptides possess many advantages, such as smallness, ease of synthesis and modification, and good biocompatibility. Their functions in cancer nanomedicine, discussed in this review, include serving as drug carriers, as targeting ligands, and as protease-responsive substrates for drug delivery.
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