A Cpu-Instruction-Based Asymmetric Signing/Decryption Mechanism For Secure Handling Of Asymmetric Keys

A method and system are disclosed for allowing a central processing unit (CPU) to perform signing/decryption operations securely. The system includes the CPU, which embeds an asymmetric private decryption key called CPU Decryption Key (CDK). A public key corresponding to the CDK, known as CPU Encryption Key (CEK) is published by the CPU vendor, and comes with a vendor-signed certificate. The CPU exposes two instructions - IMPORT_KEY and USE_KEY, which point to memory locations for storing decrypted keys, wrapped keys, and data. The disclosed mechanism provides a high level of security in cloud environments by providing a secure key delivery to the signer and protecting the signer. In addition, it involves low cost when compared to hardware security modules(HSM)

Differentiable VQ-VAE's for Robust White Matter Streamline Encodings

Given the complex geometry of white matter streamlines, Autoencoders have been proposed as a dimension-reduction tool to simplify the analysis streamlines in a low-dimensional latent spaces. However, despite these recent successes, the majority of encoder architectures only perform dimension reduction on single streamlines as opposed to a full bundle of streamlines. This is a severe limitation of the encoder architecture that completely disregards the global geometric structure of streamlines at the expense of individual fibers. Moreover, the latent space may not be well structured which leads to doubt into their interpretability. In this paper we propose a novel Differentiable Vector Quantized Variational Autoencoder, which are engineered to ingest entire bundles of streamlines as single data-point and provides reliable trustworthy encodings that can then be later used to analyze streamlines in the latent space. Comparisons with several state of the art Autoencoders demonstrate superior performance in both encoding and synthesis.Comment: 5 pages, 4 figures, 1 tabl

Lewy Body Dementia Association\u27s Research Centers of Excellence Program: Inaugural Meeting Proceedings.

The first Lewy Body Dementia Association (LBDA) Research Centers of Excellence (RCOE) Investigator\u27s meeting was held on December 14, 2017, in New Orleans. The program was established to increase patient access to clinical experts on Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson\u27s disease dementia (PDD), and to create a clinical trials-ready network. Four working groups (WG) were created to pursue the LBDA RCOE aims: (1) increase access to high-quality clinical care, (2) increase access to support for people living with LBD and their caregivers, (3) increase knowledge of LBD among medical and allied (or other) professionals, and (4) create infrastructure for a clinical trials-ready network as well as resources to advance the study of new therapeutics

Healthcare costs in women with metastatic breast cancer receiving chemotherapy as their principal treatment modality

<p>Abstract</p> <p>Background</p> <p>The economic costs of treating patients with metastatic breast cancer have been examined in several studies, but available estimates of economic burden are at least a decade old. In this study, we characterize healthcare utilization and costs in the US among women with metastatic breast cancer receiving chemotherapy as their principal treatment modality.</p> <p>Methods</p> <p>Using a large private health insurance claims database (2000-2006), we identified all women initiating chemotherapy for metastatic breast cancer with no evidence of receipt of concomitant or subsequent hormonal therapy, or receipt of trastuzumab at anytime. Healthcare utilization and costs (inpatient, outpatient, medication) were estimated on a cumulative basis from date of chemotherapy initiation ("index date") to date of disenrollment from the health plan or the end of the study period, whichever occurred first. Study measures were cumulated over time using the Kaplan-Meier Sample Average (KMSA) method; 95% CIs were generated using nonparametric bootstrapping. Findings also were examined among the subgroup of patients with uncensored data.</p> <p>Results</p> <p>The study population consisted of 1444 women; mean (SD) age was 59.1 (12.1) years. Over a mean follow-up of 532 days (range: 3 to 2412), study subjects averaged 1.7 hospital admissions, 10.7 inpatient days, and 83.6 physician office and hospital outpatient visits. Mean (95% CI) cumulative total healthcare costs were $128,556 ($118,409, $137,644) per patient. Outpatient services accounted for 29% of total costs, followed by medication other than chemotherapy (26%), chemotherapy (25%), and inpatient care (20%).</p> <p>Conclusions</p> <p>Healthcare costs-especially in the outpatient setting--are substantial among women with metastatic breast cancer for whom treatment options other than chemotherapy are limited.</p

Ocean acidification alters morphology of all otolith types in Clark’s anemonefish (Amphiprion clarkii)

Ocean acidification, the ongoing decline of surface ocean pH and [CO ${}_{3}^{2-}$ 3 2 − ] due to absorption of surplus atmospheric CO2, has far-reaching consequences for marine biota, especially calcifiers. Among these are teleost fishes, which internally calcify otoliths, critical elements of the inner ear and vestibular system. There is evidence in the literature that ocean acidification increases otolith size and alters shape, perhaps impacting otic mechanics and thus sensory perception. Here, larval Clark’s anemonefish, Amphiprion clarkii (Bennett, 1830), were reared in various seawater pCO2/pH treatments analogous to future ocean scenarios. At the onset of metamorphosis, all otoliths were removed from each individual fish and analyzed for treatment effects on morphometrics including area, perimeter, and circularity; scanning electron microscopy was used to screen for evidence of treatment effects on lateral development, surface roughness, and vaterite replacement. The results corroborate those of other experiments with other taxa that observed otolith growth with elevated pCO2, and provide evidence that lateral development and surface roughness increased as well. Both sagittae exhibited increasing area, perimeter, lateral development, and roughness; left lapilli exhibited increasing area and perimeter while right lapilli exhibited increasing lateral development and roughness; and left asterisci exhibited increasing perimeter, roughness, and ellipticity with increasing pCO2. Right lapilli and left asterisci were only impacted by the most extreme pCO2 treatment, suggesting they are resilient to any conditions short of aragonite undersaturation, while all other impacted otoliths responded to lower concentrations. Finally, fish settlement competency at 10 dph was dramatically reduced, and fish standard length marginally reduced with increasing pCO2. Increasing abnormality and asymmetry of otoliths may impact inner ear function by altering otolith-maculae interactions

Avoid or Embrace? Practice Effects in Alzheimer's Disease Prevention Trials

Demonstrating a slowing in the rate of cognitive decline is a common outcome measure in clinical trials in Alzheimer’s disease (AD). Selection of cognitive endpoints typically includes modeling candidate outcome measures in the many, richly phenotyped observational cohort studies available. An important part of choosing cognitive endpoints is a consideration of improvements in performance due to repeated cognitive testing (termed “practice effects”). As primary and secondary AD prevention trials are comprised predominantly of cognitively unimpaired participants, practice effects may be substantial and may have considerable impact on detecting cognitive change. The extent to which practice effects in AD prevention trials are similar to those from observational studies and how these potential differences impact trials is unknown. In the current study, we analyzed data from the recently completed DIAN-TU-001 clinical trial (TU) and the associated DIAN-Observational (OBS) study. Results indicated that asymptomatic mutation carriers in the TU exhibited persistent practice effects on several key outcomes spanning the entire trial duration. Critically, these practice related improvements were larger on certain tests in the TU relative to matched participants from the OBS study. Our results suggest that the magnitude of practice effects may not be captured by modeling potential endpoints in observational studies where assessments are typically less frequent and drug expectancy effects are absent. Using alternate instrument forms (represented in our study by computerized tasks) may partly mitigate practice effects in clinical trials but incorporating practice effects as outcomes may also be viable. Thus, investigators must carefully consider practice effects (either by minimizing them or modeling them directly) when designing cognitive endpoint AD prevention trials by utilizing trial data with similar assessment frequencies

P1‐349: Advancing Clinical And Biomarker Research In Ad: The Lead Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152716/1/alzjjalz201906904.pd

Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is a clinically heterogeneous disorder with a substantial burden on healthcare. Despite this, the genetic basis of the disorder is not well defined and its boundaries with other neurodegenerative diseases are unclear. Here, we performed whole exome sequencing of a cohort of 1118 Caucasian DLB patients, and focused on genes causative of monogenic neurodegenerative diseases. We analyzed variants in 60 genes implicated in DLB, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and atypical parkinsonian or dementia disorders, in order to determine their frequency in DLB. We focused on variants that have previously been reported as pathogenic, and also describe variants reported as pathogenic which remain of unknown clinical significance, as well as variants associated with strong risk. Rare missense variants of unknown significance were found in APP, CHCHD2, DCTN1, GRN, MAPT, NOTCH3, SQSTM1, TBK1 and TIA1. Additionally, we identified a pathogenic GRN p.Arg493* mutation, potentially adding to the diversity of phenotypes associated with this mutation. The rarity of previously reported pathogenic mutations in this cohort suggests that the genetic overlap of other neurodegenerative diseases with DLB is not substantial. Since it is now clear that genetics plays a role in DLB, these data suggest that other genetic loci play a role in this disease.Peer reviewe

Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory

Non-fibrillar soluble oligomeric forms of amyloid-\u3b2 peptide (oA\u3b2) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oA\u3b2 initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of A\u3b2, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oA\u3b2 levels. The impairment is immediate as it raises as soon as 20\u2009min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oA\u3b2 to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and A\u3b2 on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with A\u3b2 and tau pathology

Lewy Body Dementia Association’s Research Centers of Excellence Program: Inaugural Meeting Proceedings

Abstract The first Lewy Body Dementia Association (LBDA) Research Centers of Excellence (RCOE) Investigator’s meeting was held on December 14, 2017, in New Orleans. The program was established to increase patient access to clinical experts on Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), and to create a clinical trials-ready network. Four working groups (WG) were created to pursue the LBDA RCOE aims: (1) increase access to high-quality clinical care, (2) increase access to support for people living with LBD and their caregivers, (3) increase knowledge of LBD among medical and allied (or other) professionals, and (4) create infrastructure for a clinical trials-ready network as well as resources to advance the study of new therapeutics.https://deepblue.lib.umich.edu/bitstream/2027.42/148286/1/13195_2019_Article_476.pd