Tau and atrophy: domain-specific relationships with cognition.

BackgroundLate-onset Alzheimer's disease (AD) is characterized by primary memory impairment, which then progresses towards severe deficits across cognitive domains. Here, we report how performance in cognitive domains relates to patterns of tau deposition and cortical thickness.MethodsWe analyzed data from 131 amyloid-β positive participants (55 cognitively normal, 46 mild cognitive impairment, 30 AD) of the Alzheimer's Disease Neuroimaging Initiative who underwent magnetic resonance imaging (MRI), flortaucipir (FTP) positron emission tomography, and neuropsychological testing. Surface-based vertex-wise and region-of-interest analyses were conducted between FTP and cognitive test scores, and between cortical thickness and cognitive test scores.ResultsFTP and thickness were differentially related to cognitive performance in several domains. FTP-cognition associations were more widespread than thickness-cognition associations. Further, FTP-cognition patterns reflected cortical systems that underlie different aspects of cognition.ConclusionsOur findings indicate that AD-related decline in domain-specific cognitive performance reflects underlying progression of tau and atrophy into associated brain circuits. They also suggest that tau-PET may have better sensitivity to this decline than MRI-derived measures of cortical thickness

Parallel importance sampling in conditional linear Gaussian networks

In this paper we analyse the problem of probabilistic inference in CLG networks when evidence comes in streams. In such situations, fast and scalable algorithms, able to provide accurate responses in a short time are required. We consider the instantiation of variational inference and importance sampling, two well known tools for probabilistic inference, to the CLG case. The experimental results over synthetic networks show how a parallel version importance sampling, and more precisely evidence weighting, is a promising scheme, as it is accurate and scales up with respect to available computing resources

SorLA Controls Neurotrophic Activity by Sorting of GDNF and Its Receptors GFR alpha 1 and RET

Peer reviewe

Red blood cell transfusion in septic shock - clinical characteristics and outcome of unselected patients in a prospective, multicentre cohort

BACKGROUND: Treating anaemia with red blood cell (RBC) transfusion is frequent, but controversial, in patients with septic shock. Therefore we assessed characteristics and outcome associated with RBC transfusion in this group of high risk patients. METHODS: We did a prospective cohort study at 7 general intensive care units (ICUs) including all adult patients with septic shock in a 5-month period. RESULTS: Ninety-five of the 213 included patients (45%) received median 3 (interquartile range 2–5) RBC units during shock. The median pre-transfusion haemoglobin level was 8.1 (7.4–8.9) g/dl and independent of shock day and bleeding. Patients with cardiovascular disease were transfused at higher haemoglobin levels. Transfused patients had higher Simplified Acute Physiology Score (SAPS) II (56 (45-69) vs. 48 (37-61), p = 0.0005), more bleeding episodes, lower haemoglobin levels days 1 to 5, higher Sepsis-related Organ Failure Assessment (SOFA) scores (days 1 and 5), more days in shock (5 (3-10) vs. 2 (2-4), p = 0.0001), more days in ICU (10 (4-19) vs. 4 (2-8), p = 0.0001) and higher 90-day mortality (66 vs. 43%, p = 0.001). The latter association was lost after adjustment for admission category and SAPS II and SOFA-score on day 1. CONCLUSIONS: The decision to transfuse patients with septic shock was likely affected by disease severity and bleeding, but haemoglobin level was the only measure that consistently differed between transfused and non-transfused patients

Immune gene expression in the spleen of chickens experimentally infected with Ascaridia galli

Ascaridia galli is a gastrointestinal nematode infecting chickens. Chickens kept in alternative rearing systems or at free-range experience increased risk for infection with resulting high prevalences. A. gall infection causes reduced weight gain, decreased egg production and in severe cases increased mortality. More importantly, the parasitised chickens are more susceptible to secondary infections and their ability to develop vaccine-induced protective immunity against other diseases may be compromised. Detailed information about the immune response to the natural infection may be exploited to enable future vaccine development. In the present study, expression of immune genes in the chicken spleen during an experimental infection with A. galli was investigated using the Fluidigm (R) BioMark (TM) microfluidic qPCR platform which combines automatic high-throughput with attractive low sample and reagent consumption. Spleenic transcription of immunological genes was compared between infected chickens and non-infected controls at week 2, 6, and 9 p.i. corresponding to different stages of parasite development/maturation. At week 2 p.i. increased expression of IL-13 was observed in infected chickens. Increased expression of MBL, CRP, IFN-alpha, IL-1 beta, IL-8, IL-12 beta and IL-18 followed at week 6 p.i. and at both week 6 and 9 p.i. expression of DEF beta 1 was highly increased in infected chickens. In summary, apart from also earlier reported increased expression of the Th2 signature cytokine IL-13 we observed only few differentially expressed genes at week 2 p.i. which corresponds to the larvae histotrophic phase. In contrast, we observed increased expression of pro-inflammatory cytokines and acute phase proteins in infected chickens, by week 6 p.i. where the larvae re-enter the intestinal lumen. Increased expression of DEF beta 1 was observed in infected chickens at week 6 p.i. but also at week 9 p.i. which corresponds to a matured stage where adult worms are present in the intestinal lumen. (C) 2015 Elsevier B.V. All rights reserved

Scientific Opportunities with an X-ray Free-Electron Laser Oscillator

An X-ray free-electron laser oscillator (XFELO) is a new type of hard X-ray source that would produce fully coherent pulses with meV bandwidth and stable intensity. The XFELO complements existing sources based on self-amplified spontaneous emission (SASE) from high-gain X-ray free-electron lasers (XFEL) that produce ultra-short pulses with broad-band chaotic spectra. This report is based on discussions of scientific opportunities enabled by an XFELO during a workshop held at SLAC on June 29 - July 1, 2016Comment: 21 pages, 12 figure