616 research outputs found

    Minimum Information Disclosure with Efficiently Verifiable Credentials

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    Public-key based certificates provide a standard way to prove one's identity, as certified by some certificate authority (CA). However, standard certificates provide a binary identification: either the whole identity of the subject is known, or nothing is known. We propose using a Merkle hash tree structure, whereby it is possible for a single certificate to certify many separate claims or attributes, each of which may be proved independently, without revealing the others. Additionally, we demonstrate how trees from multiple sources can be combined together by modifying the tree structure slightly. This allows claims by different authorities, such as an employer or professional organization, to be combined under a single certificate, without the CA needing to know (let alone verify) all of the claims. In addition to describing the hash tree structure and protocols for constructing and verifying our proposed credential, we formally prove that it provides unforgeability and privacy and we present initial performance results demonstrating its efficiency

    Patient experience with NER1006 as a bowel preparation for colonoscopy: a prospective, multicenter US survey

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    BACKGROUND: NER1006 (Plenvu METHODS: Adults were recruited from 444 US community gastrointestinal practices and provided a kit number for enrollment into an online survey to be completed within 2 weeks. Survey questions evaluated colonoscopy history and prior bowel preparation(s) prescribed, patient experience during NER1006 administration, and patient satisfaction with the bowel preparation process. A 9-point predefined grading scale was used to evaluate ease of NER1006 preparation and consumption (range, 1 very difficult to 9 very easy ); the perceived importance of volume requirement and clear liquid options (range, 1 not important at all to 9 very important ); and patient satisfaction (range, 1 not satisfied at all to 9 very satisfied ). RESULTS: 1630 patients were enrolled, 1606 underwent colonoscopy, and 1598 completed the survey between September 15, 2018 and February 28, 2019. Among 1606 patients who had a colonoscopy, 62.5% were female, and the mean patient age was 54.4 years (range 18-89 years). Most patients (74.7%) did not report a family history of colon cancer, 62.6% had undergone prior colonoscopy, and 64.8% were undergoing colonoscopy for routine colorectal cancer screening. A majority (76.1%) of patients who completed the survey reported that NER1006 was very easy to prepare and take, and 89.9% were very or moderately satisfied with NER1006 overall. Most (97.6%) patients reported consuming all or most of the bowel preparation. Among 1005 patients with previous bowel preparation use, 84.7% indicated that their experience with NER1006 was much better or better (65.3%) or about the same (19.4%) compared with previously used bowel preparations, while only 15.3% rated NER1006 as worse or much worse. CONCLUSIONS: In this first real-world, US multicenter survey, patient-reported experience with NER1006 as a bowel preparation for colonoscopy was favorable and adherence was high. The majority of patients were very or moderately satisfied with the overall experience and found it much better/better than previously used bowel preparations. TRIAL REGISTRATION: Not applicable

    Targeted Screening for Alzheimer's Disease Clinical Trials Using Data-Driven Disease Progression Models

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    Heterogeneity in Alzheimer's disease progression contributes to the ongoing failure to demonstrate efficacy of putative disease-modifying therapeutics that have been trialed over the past two decades. Any treatment effect present in a subgroup of trial participants (responders) can be diluted by non-responders who ideally should have been screened out of the trial. How to identify (screen-in) the most likely potential responders is an important question that is still without an answer. Here, we pilot a computational screening tool that leverages recent advances in data-driven disease progression modeling to improve stratification. This aims to increase the sensitivity to treatment effect by screening out non-responders, which will ultimately reduce the size, duration, and cost of a clinical trial. We demonstrate the concept of such a computational screening tool by retrospectively analyzing a completed double-blind clinical trial of donepezil in people with amnestic mild cognitive impairment (clinicaltrials.gov: NCT00000173), identifying a data-driven subgroup having more severe cognitive impairment who showed clearer treatment response than observed for the full cohort

    What Else is Revealed by Order-Revealing Encryption?

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    The security of order-revealing encryption (ORE) has been unclear since its invention. Dataset characteristics for which ORE is especially insecure have been identified, such as small message spaces and low-entropy distributions. On the other hand, properties like one-wayness on uniformly-distributed datasets have been proved for ORE constructions. This work shows that more plaintext information can be extracted from ORE ciphertexts than was previously thought. We identify two issues: First, we show that when multiple columns of correlated data are encrypted with ORE, attacks can use the encrypted columns together to reveal more information than prior attacks could extract from the columns individually. Second, we apply known attacks, and develop new attacks, to show that the \emph{leakage} of concrete ORE schemes on non-uniform data leads to more accurate plaintext recovery than is suggested by the security theorems which only dealt with uniform inputs

    Live imaging of wound angiogenesis reveals macrophage orchestrated vessel sprouting and regression

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    © 2018 The Authors. Published under the terms of the CC BY 4.0 license Wound angiogenesis is an integral part of tissue repair and is impaired in many pathologies of healing. Here, we investigate the cellular interactions between innate immune cells and endothelial cells at wounds that drive neoangiogenic sprouting in real time and invivo. Our studies in mouse and zebrafish wounds indicate that macrophages are drawn to wound blood vessels soon after injury and are intimately associated throughout the repair process and that macrophage ablation results in impaired neoangiogenesis.Macrophages also positively influence wound angiogenesis by driving resolution of anti-angiogenic wound neutrophils. Experimental manipulation of the wound environment to specifically alter macrophage activation state dramatically influences subsequent blood vessel sprouting, with premature dampening of tumour necrosis factor-α expression leading to impaired neoangiogenesis. Complementary human tissue culture studies indicate that inflammatory macrophages associate with endothelial cells and are sufficient to drive vessel sprouting via vascular endothelial growth factor signalling. Subsequently, macrophages also play a role in blood vessel regression during the resolution phase of wound repair, and their absence, or shifted activation state, impairs appropriate vessel clearance

    Cortical tau is associated with microstructural imaging biomarkers of neurite density and dendritic complexity in Alzheimer's disease

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    INTRODUCTION: In Alzheimer's disease (AD), hyperphosphorylated tau is closely associated with focal neurodegeneration, but the mechanism remains uncertain. METHODS: We quantified cortical microstructure using neurite orientation dispersion and density imaging in 14 individuals with young onset AD. Diffusion tensor imaging measured mean diffusivity (MD). Amyloid beta and tau positron emission tomography were acquired and associations with microstructural measures were assessed. RESULTS: When regional volume was adjusted for, in the medial temporal lobe there was a significant negative association between neurite density and tau (partial R2  = 0.56, p = 0.008) and between orientation dispersion and tau (partial R2  = 0.66, p = 0.002), but not between MD and tau. In a wider cortical composite, there was an association between orientation dispersion and tau (partial R2  = 0.43, p = 0.030), but not between other measures and tau. DISCUSSION: Our findings are consistent with tau causing first dendritic pruning (reducing dispersion/complexity) followed by neuronal loss. Advanced magnetic resonance imaging (MRI) microstructural measures have the potential to provide information relating to underlying tau deposition

    Observations of the Gas Reservoir around a Star Forming Galaxy in the Early Universe

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    We present a high signal-to-noise spectrum of a bright galaxy at z = 4.9 in 14 h of integration on VLT FORS2. This galaxy is extremely bright, i_850 = 23.10 +/- 0.01, and is strongly-lensed by the foreground massive galaxy cluster Abell 1689 (z=0.18). Stellar continuum is seen longward of the Ly-alpha emission line at ~7100 \AA, while intergalactic H I produces strong absorption shortward of Ly-alpha. Two transmission spikes at ~6800 Angstroms (A) and ~7040 A are also visible, along with other structures at shorter wavelengths. Although fainter than a QSO, the absence of a strong central ultraviolet flux source in this star forming galaxy enables a measurement of the H I flux transmission in the intergalactic medium (IGM) in the vicinity of a high redshift object. We find that the effective H I optical depth of the IGM is remarkably high within a large 14 Mpc (physical) region surrounding the galaxy compared to that seen towards QSOs at similar redshifts. Evidently, this high-redshift galaxy is located in a region of space where the amount of H I is much larger than that seen at similar epochs in the diffuse IGM. We argue that observations of high-redshift galaxies like this one provide unique insights on the nascent stages of baryonic large-scale structures that evolve into the filamentary cosmic web of galaxies and clusters of galaxies observed in the present universe.Comment: Accepted for publication in ApJL (corrected typos

    In vivo hypothalamic regional volumetry across the frontotemporal dementia spectrum

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    BACKGROUND: Frontotemporal dementia (FTD) is a spectrum of diseases characterised by language, behavioural and motor symptoms. Among the different subcortical regions implicated in the FTD symptomatology, the hypothalamus regulates various bodily functions, including eating behaviours which are commonly present across the FTD spectrum. The pattern of specific hypothalamic involvement across the clinical, pathological, and genetic forms of FTD has yet to be fully investigated, and its possible associations with abnormal eating behaviours have yet to be fully explored. METHODS: Using an automated segmentation tool for volumetric T1-weighted MR images, we measured hypothalamic regional volumes in a cohort of 439 patients with FTD (197 behavioural variant FTD [bvFTD]; 7 FTD with associated motor neurone disease [FTD-MND]; 99 semantic variant primary progressive aphasia [svPPA]; 117 non-fluent variant PPA [nfvPPA]; 19 PPA not otherwise specified [PPA-NOS]) and 118 age-matched controls. We compared volumes across the clinical, genetic (29 MAPT, 32 C9orf72, 23 GRN), and pathological diagnoses (61 tauopathy, 40 TDP-43opathy, 4 FUSopathy). We correlated the volumes with presence of abnormal eating behaviours assessed with the revised version of the Cambridge Behavioural Inventory (CBI-R). RESULTS: On average, FTD patients showed 14% smaller hypothalamic volumes than controls. The groups with the smallest hypothalamic regions were FTD-MND (20%), MAPT (25%) and FUS (33%), with differences mainly localised in the anterior and posterior regions. The inferior tuberal region was only significantly smaller in tauopathies (MAPT and Pick’s disease) and in TDP-43 type C compared to controls and was the only regions that did not correlate with eating symptoms. PPA-NOS and nfvPPA were the groups with the least frequent eating behaviours and the least hypothalamic involvement. CONCLUSIONS: Abnormal hypothalamic volumes are present in all the FTD forms, but different hypothalamic regions might play a different role in the development of abnormal eating behavioural and metabolic symptoms. These findings might therefore help in the identification of different underlying pathological mechanisms, suggesting the potential use of hypothalamic imaging biomarkers and the research of potential therapeutic targets within the hypothalamic neuropeptides

    Measuring brain atrophy with a generalized formulation of the boundary shift integral

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    AbstractBrain atrophy measured using structural magnetic resonance imaging (MRI) has been widely used as an imaging biomarker for disease diagnosis and tracking of pathologic progression in neurodegenerative diseases. In this work, we present a generalized and extended formulation of the boundary shift integral (gBSI) using probabilistic segmentations to estimate anatomic changes between 2 time points. This method adaptively estimates a non-binary exclusive OR region of interest from probabilistic brain segmentations of the baseline and repeat scans to better localize and capture the brain atrophy. We evaluate the proposed method by comparing the sample size requirements for a hypothetical clinical trial of Alzheimer's disease to that needed for the current implementation of BSI as well as a fuzzy implementation of BSI. The gBSI method results in a modest but reduced sample size, providing increased sensitivity to disease changes through the use of the probabilistic exclusive OR region
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