Fabry in the older patient: Clinical consequences and possibilities for treatment.

Baseline demographic and phenotypic characteristics of patients aged ≥50years in the Fabry Outcome Survey (Shire; data extracted June 2014) were compared with younger adults to investigate potential factors influencing treatment decisions in later life. Age groups were defined using age at treatment initiation or at FOS entry for untreated patients: 18-49 (n=1344; 49.5% male; 64.6% received agalsidase alfa enzyme replacement therapy [ERT]); 50-64 (n=537; 35.4% male; 74.3% treated); 65-74 (n=137; 32.1% male; 68.6% treated); and ≥75years (n=26; 26.9% male; 50.0% treated). Successive age groups showed higher median age at first symptom and diagnosis. Median alpha-galactosidase A activity, measured as percentage activity of the midpoint of the normal range, was much greater in females than males of all groups except ≥75years (33.4% in females; 27.8% in males). Patients aged ≥75years showed greater values than patients aged 18-49years for median left ventricular mass indexed to height (62.7 vs 42.4g/m(2.7)), mean ventricular wall thickness (15.0 vs 10.0mm) and prevalence of hypertension (57.7% vs 21.8%), and lower median estimated glomerular filtration rate (Modification of Diet in Renal Disease: 65.6 vs 98.5mL/min/1.73m(2)). Larger proportions in the groups aged ≥50 exhibited cardiac and/or cerebrovascular manifestations compared with patients aged 18-49years. The smaller proportion of patients receiving ERT aged ≥75years compared with the younger groups might reflect relatively milder disease burden or physician/patient reluctance to initiate/continue ERT at this age. Further studies are needed to increase knowledge of Fabry disease and ERT in later life

Cognitive and Neural Architecture of Decision Making Competence

Although cognitive neuroscience has made remarkable progress in understanding the neural foundations of goal-directed behavior and decision making, neuroscience research on decision making competence, the capacity to resist biases in human judgment and decision making, remain to be established. Here, we investigated the cognitive and neural mechanisms of decision making competence in 283 healthy young adults. We administered the Adult Decision Making Competence battery to assess the respondent’s capacity to resist standard biases in decision making, including: (1) resistance to framing, (2) recognizing social norms, (3) over/under confidence, (4) applying decision rules, (5) consistency in risk perception, and (6) resistance to sunk costs. Decision making competence was assessed in relation to core facets of intelligence, including measures of crystallized intelligence (Shipley Vocabulary), fluid intelligence (Figure Series), and logical reasoning (LSAT). Structural equation modeling was applied to examine the relationship(s) between each cognitive domain, followed by an investigation of their association with individual differences in cortical thickness, cortical surface area, and cortical gray matter volume as measured by high-resolution structural MRI. The results suggest that: (i) decision making competence is associated with cognitive operations for logical reasoning, and (ii) these convergent processes are associated with individual differences within cortical regions that are widely implicated in cognitive control (left dACC) and social decision making (right superior temporal sulcus; STS). Our findings motivate an integrative framework for understanding the neural mechanisms of decision making competence, suggesting that individual differences in the cortical surface area of left dACC and right STS are associated with the capacity to overcome decision biases and exhibit competence in decision makingThe work was supported by the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA), through Contract 2014-13121700004 with the University of Illinois at Urbana-Champaign (PI: Barbey). Francisco J. Román and Roberto Colom are also supported by Grant PSI2017-82218-P (Ministry of Economy, Industry and Competitiveness, Spain

Unconvincing statistical and functional inferences : reply to Catmur

A commentary on Unconvincing support for role of mirror neurons in “action understanding”: com-mentary on Michael et al. (2014) by Catmur, C. (2014). Front. Hum

2D and 3D Polar Plume Analysis from the Three Vantage Positions of STEREO/EUVI A, B, and SOHO/EIT

Polar plumes are seen as elongated objects starting at the solar polar regions. Here, we analyze these objects from a sequence of images taken simultaneously by the three spacecraft telescopes STEREO/EUVI A and B, and SOHO/EIT. We establish a method capable of automatically identifying plumes in solar EUV images close to the limb at 1.01 - 1.39 R in order to study their temporal evolution. This plume-identification method is based on a multiscale Hough-wavelet analysis. Then two methods to determined their 3D localization and structure are discussed: First, tomography using the filtered back-projection and including the differential rotation of the Sun and, secondly, conventional stereoscopic triangulation. We show that tomography and stereoscopy are complementary to study polar plumes. We also show that this systematic 2D identification and the proposed methods of 3D reconstruction are well suited, on one hand, to identify plumes individually and on the other hand, to analyze the distribution of plumes and inter-plume regions. Finally, the results are discussed focusing on the plume position with their cross-section area.Comment: 22 pages, 10 figures, Solar Physics articl

BRAIN Α-TOCOPHEROL CONCENTRATION IS INVERSELY ASSOCIATED WITH NEUROFIBRILLARY TANGLE COUNTS IN BRAIN REGIONS AFFECTED IN EARLIER BRAAK STAGES: A CROSS-SECTIONAL FINDING IN THE OLDEST OLD

Objectives: Higher vitamin E status has been associated with lower risk of Alzheimer’s disease (AD). However, evidence of the association of vitamin E concentration in neural tissue with AD pathologies is limited. Design: The cross-sectional relationship between the human brain concentrations of α- and γ-tocopherol and the severity of AD pathologies – neurofibrillary tangle (NFT) and neuritic plaque (NP) – was investigated. Setting & Participants: Brains from 43 centenarians (≥ 98 years at death) enrolled in the Phase III of the Georgia Centenarian Study were collected at autopsy. Measurements: Brain α- and γ-tocopherol concentrations (previously reported) were averaged from frontal, temporal, and occipital cortices. NP and NFT counts (previously reported) were assessed in frontal, temporal, parietal, entorhinal cortices, amygdala, hippocampus, and subiculum. NFT topological progression was assessed using Braak staging. Multiple linear regression was performed to assess the relationship between tocopherol concentrations and NP or NFT counts, with and without adjustment for covariates. Results: Brain α-tocopherol concentrations were inversely associated with NFT but not NP counts in amygdala (β = -2.67, 95% CI [-4.57, -0.79]), entorhinal cortex (β = -2.01, 95% CI [-3.72, -0.30]), hippocampus (β = -2.23, 95% CI [-3.82, -0.64]), and subiculum (β = -2.52, 95% CI [-4.42, -0.62]) where NFT present earlier in its topological progression, but not in neocortices. Subjects with Braak III-IV had lower α-tocopherol (median = 69,622 pmol/g, IQR = 54,389-72,155 pmol/g) than those with Braak I-II (median = 72,108 pmol/g, IQR = 64,056-82,430 pmol/g), but the difference was of borderline significance (p = 0.063). γ-Tocopherol concentrations were not associated with either NFT or NP counts in any brain regions assessed. Conclusions: Higher brain α-tocopherol level is specifically associated with lower NFT counts in brain structures affected in earlier Braak stages. Our findings emphasize the possible importance of α-tocopherol intervention timing in tauopathy progression and warrant future clinical trials

On peak phenomena for non-commutative H∞H^\infty

A non-commutative extension of Amar and Lederer's peak set result is given. As its simple applications it is shown that any non-commutative $H^\infty$-algebra $H^\infty(M,\tau)$ has unique predual,and moreover some restriction in some of the results of Blecher and Labuschagne are removed, making them hold in full generality.Comment: final version (the presentation of some part is revised and one reference added

Clinico-Neuropathological Findings in the Oldest Old from the Georgia Centenarian Study

Background: Centenarian studies are important sources for understanding of factors that contribute to longevity and healthy aging. Clinico-neuropathological finding is a key in identifying pathology and factors contributing to age-related cognitive decline and dementia in the oldest old. Objective: To characterize the cross-sectional relationship between neuropathologies and measures of premortem cognitive performance in centenarians. Methods: Data were acquired from 49 centenarians (≥98 years) from the Georgia Centenarian Study. Cognitive assessment from the time point closest to mortality was used (\u3c1 year for all subjects) and scores for cognitive domains were established. Neuropathologies [cerebral atrophy, ventricular dilation, atherosclerosis, cerebral amyloid angiopathy (CAA), Lewy bodies, hippocampal sclerosis (HS), hippocampal TDP-43 proteinopathy, neuritic plaque (NP) and neurofibrillary tangle (NFT) counts, Braak staging, and National Institute on Aging-Reagan Institute (NIARI) criteria for the neuropathological diagnosis of Alzheimer’s disease (AD)] were compared among subjects with different ratings of dementia. Linear regression was applied to evaluate the association between cognitive domain scores and neuropathologies. Results: Wide ranges of AD-type neuropathological changes were observed in both non-demented and demented subjects. Neocortical NFT and Braak staging were related to clinical dementia rating. Neocortical NFT and NP, Braak and NIARI staging, cerebral and ventricular atrophy, HS, CAA, and TDP-43 proteinopathy were differentially associated with poor performance in multiple cognitive domains and activities of daily living. Conclusion: AD-type pathology was associated with severe dementia and poor cognition but was not the only variable that explained cognitive impairment, indicating the complexity and heterogeneity of pathophysiology of dementia in the oldest old

A roadmap for research in octoploid strawberry

The cultivated strawberry (Fragaria × ananassa) is an allo-octoploid species, originating nearly 300 years ago from wild progenitors from the Americas. Since that time the strawberry has become the most widely cultivated fruit crop in the world, universally appealing due to its sensory qualities and health benefits. The recent publication of the first high-quality chromosome-scale octoploid strawberry genome (cv. Camarosa) is enabling rapid advances in genetics, stimulating scientific debate and provoking new research questions. In this forward-looking review we propose avenues of research toward new biological insights and applications to agriculture. Among these are the origins of the genome, characterization of genetic variants, and big data approaches to breeding. Key areas of research in molecular biology will include the control of flowering, fruit development, fruit quality, and plant–pathogen interactions. In order to realize this potential as a global community, investments in genome resources must be continually augmented.Peer reviewe