Objectives

The purpose of this study was to test the hypothesis that in occlusions of the superficial femoral artery, removal of atherosclerotic plaque would result in a higher long-term patency rate compared to balloon dilatation alone. A secondary hypothesis was that long term patency would be proportional to the amount of plaque removed.

Methods

A randomized controlled study of patients with occluded superficial femoral arteries was performed comparing balloon dilatation alone versus a 2.7 mm or a larger (4.0 mm or 4.7 mm) transcutaneous extraction catheter (TEC) atherectomy device followed by balloon dilatation. The effect of these devices on plaque area was assessed directly by intravascular ultrasound imaging.

Results

The mean occlusion length was 19.4 cm +/- 11.7 cm. The mean lumen area increased from 4.7 mm2 to 15.1 mm2, primarily due to balloon dilatation, but the mean atheroma area of 19.8 mm2 did not change with either size of TEC device. Although the initial procedure success rate was high (79%), the 6 month patency was only 45%. There was no difference in 6 month patency between the 3 groups.

Conclusions

The data indicate that the TEC atherectomy devices do not remove a significant amount of atherosclerotic plaque in occluded superficial femoral arteries. The 6 month patency is no different with these atherectomy devices than with balloon dilatation alone. The larger (4.0 mm or 4.7 mm) TEC device does not remove any more tissue than the smaller (2.7 mm) device. The use of intravascular ultrasound to quantitate the effects of this atherectomy device provides important insights into the mechanism of action and lack of efficacy of the TEC atherectomy catheter.

Background

To assess the relationship between regional neocortical atrophy and psychotic symptoms in adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD).

Methods

Rates of change in regional neocortical atrophy as measured by longitudinal magnetic resonance imaging scans and the occurrence of psychotic symptoms and/or the long-term use of antipsychotic medications in 389 outpatients with MCI or AD in Alzheimer's Disease Neuroimaging Initiative.

Results

Atrophy rate of 3 specific neocortical regions, lateral frontal, lateral parietal, and anterior cingulate gyrus, was significantly associated with the onset of psychosis including delusions, agitation, wandering, and hallucinations and/or the need for chronic antipsychotic medications. Atrophy rate of the lateral frontal lobe correlated most significantly with onset of psychotic symptoms or need for chronic antipsychotic medications.

Conclusions

Psychosis was associated with volume loss in specific regions of the lateral frontal and parietal lobes as well as anterior cingulate gyrus.

In this paper we develop predictions from models of life-long demographic heterogeneity. These predictions are then compared to observations of mortality in large laboratory populations of Drosophila melanogaster. We find that the demographic heterogeneity models either require levels of variation that far exceed what would be considered biologically plausible, or they predict a much larger number of very old individuals than we actually observe. We conclude that the demographic heterogeneity models are not reasonable explanations of demographic patterns and are weakly motivated biological models.

We sought to develop and evaluate a composite memory score from the neuropsychological battery used in the Alzheimer's Disease (AD) Neuroimaging Initiative (ADNI). We used modern psychometric approaches to analyze longitudinal Rey Auditory Verbal Learning Test (RAVLT, 2 versions), AD Assessment Schedule - Cognition (ADAS-Cog, 3 versions), Mini-Mental State Examination (MMSE), and Logical Memory data to develop ADNI-Mem, a composite memory score. We compared RAVLT and ADAS-Cog versions, and compared ADNI-Mem to RAVLT recall sum scores, four ADAS-Cog-derived scores, the MMSE, and the Clinical Dementia Rating Sum of Boxes. We evaluated rates of decline in normal cognition, mild cognitive impairment (MCI), and AD, ability to predict conversion from MCI to AD, strength of association with selected imaging parameters, and ability to differentiate rates of decline between participants with and without AD cerebrospinal fluid (CSF) signatures. The second version of the RAVLT was harder than the first. The ADAS-Cog versions were of similar difficulty. ADNI-Mem was slightly better at detecting change than total RAVLT recall scores. It was as good as or better than all of the other scores at predicting conversion from MCI to AD. It was associated with all our selected imaging parameters for people with MCI and AD. Participants with MCI with an AD CSF signature had somewhat more rapid decline than did those without. This paper illustrates appropriate methods for addressing the different versions of word lists, and demonstrates the additional power to be gleaned with a psychometrically sound composite memory score.

In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.

Introduction

Comparative transcriptome analyses in Alzheimer's disease (AD) and other neurodegenerative proteinopathies can uncover both shared and distinct disease pathways.

Methods

We analyzed 940 brain transcriptomes including patients with AD, progressive supranuclear palsy (PSP; a primary tauopathy), and control subjects.

Results

We identified transcriptional coexpression networks implicated in myelination, which were lower in PSP temporal cortex (TCX) compared with AD. Some of these associations were retained even after adjustments for brain cell population changes. These TCX myelination network structures were preserved in cerebellum but they were not differentially expressed in cerebellum between AD and PSP. Myelination networks were downregulated in both AD and PSP, when compared with control TCX samples.

Discussion

Downregulation of myelination networks may underlie both PSP and AD pathophysiology, but may be more pronounced in PSP. These data also highlight conservation of transcriptional networks across brain regions and the influence of cell type changes on these networks.

Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.42 × 10(-12)), 8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472; P=3.41 × 10(-8)), and 2p22 at SOS1 (rs963731; P=1.76 × 10(-7)). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22; rs1768208; P=2.07 × 10(-7)) and MAPT H1c (17q21; rs242557; P=7.91 × 10(-6)). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein).

Physics at the Large Hadron Collider (LHC) and the International e+e- Linear Collider (ILC) will be complementary in many respects, as has been demonstrated at previous generations of hadron and lepton colliders. This report addresses the possible interplay between the LHC and ILC in testing the Standard Model and in discovering and determining the origin of new physics. Mutual benefits for the physics programme at both machines can occur both at the level of a combined interpretation of Hadron Collider and Linear Collider data and at the level of combined analyses of the data, where results obtained at one machine can directly influence the way analyses are carried out at the other machine. Topics under study comprise the physics of weak and strong electroweak symmetry breaking, supersymmetric models, new gauge theories, models with extra dimensions, and electroweak and QCD precision physics. The status of the work that has been carried out within the LHC/ILC Study Group so far is summarized in this report. Possible topics for future studies are outlined. © 2006 Elsevier B.V. All rights reserved.

Objective

Recent genome-wide association studies (GWAS) of late-onset Alzheimer disease (LOAD) identified 9 novel risk loci. Discovery of functional variants within genes at these loci is required to confirm their role in Alzheimer disease (AD). Single nucleotide polymorphisms that influence gene expression (eSNPs) constitute an important class of functional variants. We therefore investigated the influence of the novel LOAD risk loci on human brain gene expression.

Methods

We measured gene expression levels in the cerebellum and temporal cortex of autopsied AD subjects and those with other brain pathologies (∼400 total subjects). To determine whether any of the novel LOAD risk variants are eSNPs, we tested their cis-association with expression of 6 nearby LOAD candidate genes detectable in human brain (ABCA7, BIN1, CLU, MS4A4A, MS4A6A, PICALM) and an additional 13 genes ±100 kb of these SNPs. To identify additional eSNPs that influence brain gene expression levels of the novel candidate LOAD genes, we identified SNPs ±100 kb of their location and tested for cis-associations.

Results

CLU rs11136000 (p = 7.81 × 10(-4)) and MS4A4A rs2304933/rs2304935 (p = 1.48 × 10(-4)-1.86 × 10(-4)) significantly influence temporal cortex expression levels of these genes. The LOAD-protective CLU and risky MS4A4A locus alleles associate with higher brain levels of these genes. There are other cis-variants that significantly influence brain expression of CLU and ABCA7 (p = 4.01 × 10(-5)-9.09 × 10(-9)), some of which also associate with AD risk (p = 2.64 × 10(-2)-6.25 × 10(-5)).

Conclusions

CLU and MS4A4A eSNPs may at least partly explain the LOAD risk association at these loci. CLU and ABCA7 may harbor additional strong eSNPs. These results have implications in the search for functional variants at the novel LOAD risk loci.