Prominent effects and neural correlates of visual crowding in a neurodegenerative disease population.

Crowding is a breakdown in the ability to identify objects in clutter, and is a major constraint on object recognition. Crowding particularly impairs object perception in peripheral, amblyopic and possibly developing vision. Here we argue that crowding is also a critical factor limiting object perception in central vision of individuals with neurodegeneration of the occipital cortices. In the current study, individuals with posterior cortical atrophy (n=26), typical Alzheimer's disease (n=17) and healthy control subjects (n=14) completed centrally-presented tests of letter identification under six different flanking conditions (unflanked, and with letter, shape, number, same polarity and reverse polarity flankers) with two different target-flanker spacings (condensed, spaced). Patients with posterior cortical atrophy were significantly less accurate and slower to identify targets in the condensed than spaced condition even when the target letters were surrounded by flankers of a different category. Importantly, this spacing effect was observed for same, but not reverse, polarity flankers. The difference in accuracy between spaced and condensed stimuli was significantly associated with lower grey matter volume in the right collateral sulcus, in a region lying between the fusiform and lingual gyri. Detailed error analysis also revealed that similarity between the error response and the averaged target and flanker stimuli (but not individual target or flanker stimuli) was a significant predictor of error rate, more consistent with averaging than substitution accounts of crowding. Our findings suggest that crowding in posterior cortical atrophy can be regarded as a pre-attentive process that uses averaging to regularize the pathologically noisy representation of letter feature position in central vision. These results also help to clarify the cortical localization of feature integration components of crowding. More broadly, we suggest that posterior cortical atrophy provides a neurodegenerative disease model for exploring the basis of crowding. These data have significant implications for patients with, or who will go on to develop, dementia-related visual impairment, in whom acquired excessive crowding likely contributes to deficits in word, object, face and scene perception

Advanced Technology Large-Aperture Space Telescope (ATLAST): A Technology Roadmap for the Next Decade

The Advanced Technology Large-Aperture Space Telescope (ATLAST) is a set of mission concepts for the next generation of UVOIR space observatory with a primary aperture diameter in the 8-m to 16-m range that will allow us to perform some of the most challenging observations to answer some of our most compelling questions, including "Is there life elsewhere in the Galaxy?" We have identified two different telescope architectures, but with similar optical designs, that span the range in viable technologies. The architectures are a telescope with a monolithic primary mirror and two variations of a telescope with a large segmented primary mirror. This approach provides us with several pathways to realizing the mission, which will be narrowed to one as our technology development progresses. The concepts invoke heritage from HST and JWST design, but also take significant departures from these designs to minimize complexity, mass, or both. Our report provides details on the mission concepts, shows the extraordinary scientific progress they would enable, and describes the most important technology development items. These are the mirrors, the detectors, and the high-contrast imaging technologies, whether internal to the observatory, or using an external occulter. Experience with JWST has shown that determined competitors, motivated by the development contracts and flight opportunities of the new observatory, are capable of achieving huge advances in technical and operational performance while keeping construction costs on the same scale as prior great observatories.Comment: 22 pages, RFI submitted to Astro2010 Decadal Committe

Intellectual enrichment and genetic modifiers of cognition and brain volume in Huntington's disease

An important step towards the development of treatments for cognitive impairment in ageing and neurodegenerative diseases is to identify genetic and environmental modifiers of cognitive function and understand the mechanism by which they exert an effect. In Huntington’s disease, the most common autosomal dominant dementia, a small number of studies have identified intellectual enrichment, i.e. a cognitively stimulating lifestyle and genetic polymorphisms as potential modifiers of cognitive function. The aim of our study was to further investigate the relationship and interaction between genetic factors and intellectual enrichment on cognitive function and brain atrophy in Huntington’s disease. For this purpose, we analysed data from Track-HD, a multi-centre longitudinal study in Huntington’s disease gene carriers and focused on the role of intellectual enrichment (estimated at baseline) and the genes FAN1, MSH3, BDNF, COMT and MAPT in predicting cognitive decline and brain atrophy. We found that carrying the 3a allele in the MSH3 gene had a positive effect on global cognitive function and brain atrophy in multiple cortical regions, such that 3a allele carriers had a slower rate of cognitive decline and atrophy compared with non-carriers, in agreement with its role in somatic instability. No other genetic predictor had a significant effect on cognitive function and the effect of MSH3 was independent of intellectual enrichment. Intellectual enrichment also had a positive effect on cognitive function; participants with higher intellectual enrichment, i.e. those who were better educated, had higher verbal intelligence and performed an occupation that was intellectually engaging, had better cognitive function overall, in agreement with previous studies in Huntington’s disease and other dementias. We also found that intellectual enrichment interacted with the BDNF gene, such that the positive effect of intellectual enrichment was greater in Met66 allele carriers than non-carriers. A similar relationship was also identified for changes in whole brain and caudate volume; the positive effect of intellectual enrichment was greater for Met66 allele carriers, rather than for non-carriers. In summary, our study provides additional evidence for the beneficial role of intellectual enrichment and carrying the 3a allele in MSH3 in cognitive function in Huntington’s disease and their effect on brain structure

Toll-like receptors in inflammatory bowel diseases: A decade later

Differential alteration of Toll-like receptor (TLR) expression in inflammatory bowel disease (IBD) was first described 10 years ago. Since then, studies from many groups have led to the current concept that TLRs represent key mediators of innate host defense in the intestine, involved in maintaining mucosal as well as commensal homeostasis. Recent findings in diverse murine models of colitis have helped to reveal the mechanistic importance of TLR dysfunction in IBD pathogenesis. It has become evident that environment, genetics, and host immunity form a multidimensional and highly interactive regulatory triad that controls TLR function in the intestinal mucosa. Imbalanced relationships within this triad may promote aberrant TLR signaling, critically contributing to acute and chronic intestinal inflammatory processes in IBD colitis and associated cancer. (Inflamm Bowel Dis 2010

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Donald Trump and Institutional Change Strategies

This article integrates three fields of study: the “regime politics” paradigm in law and courts, the “institutional change” approach in public policy, and the “unilateral presidency” literature. In doing so, we show how law, politics, and public policy are inextricably linked, and that researchers can borrow assumptions, methods, and theories from a variety of fields. We use Donald Trump’s early presidency to show how political actors (especially presidents) can use four different change strategies. In the case of Trump, we highlight: shifting of decision-making authority via insurrectionary displacement; the elimination of the individual mandate via subversive layering; a change in drone use policy via opportunistic conversion; and a gradual desensitization and change in school choice education policy via symbiotic drift. We conclude by offering lessons for all three literatures we incorporate, as well as a way forward for studying a presidential administration that many find difficult to analyze

Un soir chez Dave Cash / Dave CASH, avec l'orch. de C. BELLEST

Comprend : DER WOILER JING / D. CASH, L. MERCIER - DAVE SPOUTNIK / D. CASH, L. MERCIER - CURES MIT HOULA HOP / D. CASH, L. MERCIER - DAVE CASH IS LEARNING ENGLISH / CASH, MERCIER - OI MASEL / CASH, MERCIER - ARAN AROIS / CASH, MERCIER - KOURTEN SPIELER / CASH, MERCIER - NARESHKEITEN / CASH, MERCIER - VERDREHTE MISCHPOCHE / CASH, MERCIERBnF-Partenariats, Collection sonore - BelieveContient une table des matière