Real-space local polynomial basis for solid-state electronic-structure calculations: A finite-element approach

We present an approach to solid-state electronic-structure calculations based on the finite-element method. In this method, the basis functions are strictly local, piecewise polynomials. Because the basis is composed of polynomials, the method is completely general and its convergence can be controlled systematically. Because the basis functions are strictly local in real space, the method allows for variable resolution in real space; produces sparse, structured matrices, enabling the effective use of iterative solution methods; and is well suited to parallel implementation. The method thus combines the significant advantages of both real-space-grid and basis-oriented approaches and so promises to be particularly well suited for large, accurate ab initio calculations. We develop the theory of our approach in detail, discuss advantages and disadvantages, and report initial results, including the first fully three-dimensional electronic band structures calculated by the method.Comment: replacement: single spaced, included figures, added journal referenc

Amyloid-beta modulates the association between neurofilament light chain and brain atrophy in Alzheimer’s disease

Neurofilament light chain (NFL) measurement has been gaining strong support as a clinically useful neuronal injury biomarker for various neurodegenerative conditions. However, in Alzheimer’s disease (AD), its reflection on regional neuronal injury in the context of amyloid pathology remains unclear. This study included 83 cognitively normal (CN), 160 mild cognitive impairment (MCI), and 73 AD subjects who were further classified based on amyloid-beta (Aβ) status as positive or negative (Aβ+ vs Aβ−). In addition, 13 rats (5 wild type and 8 McGill-R-Thy1-APP transgenic (Tg)) were examined. In the clinical study, reduced precuneus/posterior cingulate cortex and hippocampal grey matter density were significantly associated with increased NFL concentrations in cerebrospinal fluid (CSF) or plasma in MCI Aβ+ and AD Aβ+. Moreover, AD Aβ+ showed a significant association between the reduced grey matter density in the AD-vulnerable regions and increased NFL concentrations in CSF or plasma. Congruently, Tg rats recapitulated and validated the association between CSF NFL and grey matter density in the parietotemporal cortex, entorhinal cortex, and hippocampus in the presence of amyloid pathology. In conclusion, reduced grey matter density and elevated NFL concentrations in CSF and plasma are associated in AD-vulnerable regions in the presence of amyloid positivity in the AD clinical spectrum and amyloid Tg rat model. These findings further support the NFL as a neuronal injury biomarker in the research framework of AD biomarker classification and for the evaluation of therapeutic efficacy in clinical trials

Worldwide Argus II implantation: recommendations to optimize patient outcomes

Abstract Background A position paper based on the collective experiences of Argus II Retinal Prosthesis System investigators to review strategies to optimize outcomes in patients with retinitis pigmentosa undergoing retinal prosthesis implantation. Methods Retinal surgeons, device programmers, and rehabilitation specialists from Europe, Canada, Middle East, and the United States were convened to the first international Argus II Investigator Meeting held in Ann Arbor, MI in March 2015. The recommendations from the collective experiences were collected. Factors associated with successful outcomes were determined. Results Factors leading to successful outcomes begin with appropriate patient selection, expectation counseling, and preoperative retinal assessment. Challenges to surgical implantation include presence of staphyloma and inadequate Tenon’s capsule or conjunctiva. Modified surgical technique may reduce risks of complications such as hypotony and conjunctival erosion. Rehabilitation efforts and correlation with validated outcome measures following implantation are critical. Conclusions Bringing together Argus II investigators allowed the identification of strategies to optimize patient outcomes. Establishing an on-line collaborative network will foster coordinated research efforts to advance outcome assessment and rehabilitation strategies.http://deepblue.lib.umich.edu/bitstream/2027.42/134581/1/12886_2016_Article_225.pd

Multiresolution analysis of electronic structure: semicardinal and wavelet bases

This article reviews recent developments in multiresolution analysis which make it a powerful tool for the systematic treatment of the multiple length-scales inherent in the electronic structure of matter. Although the article focuses on electronic structure, the advances described are useful for non-linear problems in the physical sciences in general. The new language and notations introduced are well- suited for both formal manipulations and the development of computer software using higher-level languages such as C++. The discussion is self-contained, and all needed algorithms are specified explicitly in terms of simple operators and illustrated with straightforward diagrams which show the flow of data. Among the reviewed developments is the construction of_exact_ multiresolution representations from extremely limited samples of physical fields in real space. This new and profound result is the critical advance in finally allowing systematic, all electron calculations to compete in efficiency with state-of-the-art electronic structure calculations which depend for their celerity upon freezing the core electronic degrees of freedom. This review presents the theory of wavelets from a physical perspective, provides a unified and self-contained treatment of non-linear couplings and physical operators and introduces a modern framework for effective single-particle theories of quantum mechanics.Comment: A "how-to from-scratch" book presently in press at Reviews of Modern Physics: 88 pages, 31 figures, 5 tables, 88 references. Significantly IMPROVED version, including (a) new diagrams illustrating algorithms; (b) careful proof-reading of equations and text; (c) expanded bibliography; (d) cosmetic changes including lists of figures and tables and a more reasonable font. Latest changes (Dec. 11, 1998): a more descriptive abstract, and minor lexicographical change

Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema : Subgroup analysis of the MEAD study

Background: Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Methods: Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34.68 Early Treatment Diabetic Retinopathy Study letters (20/200.20/50 Snellen equivalent), and central retinal thickness (CRT) 65300 \u3bcm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was 6515-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry. Results: Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n=261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had 6515-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was -126.1 \u3bcm with DEX 0.7 versus -39.0 \u3bcm with sham(P < 0.001). Cataract-related adverse events were reported in 70.3 % of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery. Conclusions: DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population

Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia

Data Availability Statement: The data that support the findings of this study are available on request via https://www.genfi.org/study/ or by emailing [email protected]. The data are not publicly available due to privacy or ethical restrictions.Supporting Information: available online at: https://onlinelibrary.wiley.com/doi/10.1002/hbm.26220#support-information-section .Copyright © 2023 The Authors. Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.Alzheimer Society of Canada; Weston Brain Institute; Fonds de Recherche du Québec - Santé; MRC UK GENFI, Grant/Award Number: MR/M023664/1; Italian Ministry of Health, Grant/Award Number: CoEN015; Canadian Institutes of Health Research; Alzheimer's Society grant, Grant/Award Number: AS-PG-16-007; Alzheimer's Society, Grant/Award Number: AS-JF-19a-004-517; NIHR Rare Diseases Translational Research Collaboration; Deutsche Forschungsgemeinschaft; NIHR Cambridge Biomedical Research Centre, Grant/Award Numbers: BRC-1215-20014, BRC149/NS/MH

Retinal arteriolar hemodynamic response to an acute hyperglycemic provocation in early and sight-threatening diabetic retinopathy

The aim was to quantify the magnitude of retinal arteriolar vascular reactivity to a hyperglycemic provocation in diabetic patients stratified by severity of retinopathy and in age-matched controls. The sample comprised 20 non-diabetic controls (Group 1), 19 patients with no clinically visible DR (Group 2), 18 patients with mild-to-moderate non-proliferative DR (Group 3) and 18 patients with diabetic macular edema (Group 4). Retinal hemodynamic measurements using the Canon Laser Blood Flowmeter (CLBF-100) were acquired before and 1 h after drinking a standardized oral glucose load drink. The magnitude of the retinal vascular response, as well as max:min velocity ratio and wall shear rate (WSR), was calculated and compared across groups. A significant change in blood glucose level was observed for all groups (p < 0.05). The change in blood glucose elevation was significantly less in Group 1 compared to the other groups. No significant change in arteriolar diameter, blood velocity, blood flow, max:min velocity ratio and WSR was found in patients with diabetes and in age-matched subjects without diabetes. The results of this study indicate that retinal arteriolar blood flow is unaffected by acute elevation of blood glucose using an oral glucose load drink in patients with diabetes and in age-matched controls. This lack of a blood flow response to acute hyperglycemia in patients with early sight-threatening DR may be explained by a loss of retinal vascular reactivity. © 2007 Elsevier Inc. All rights reserved.Link_to_subscribed_fulltex