Weinsteinpovlsen9778

Irregular sleep-wake rhythm disorder (ISWRD) is a common sleep disorder in individuals with Alzheimer's disease dementia (AD-D).

This exploratory phase 2 proof-of-concept and dose-finding clinical trial evaluated the effects of lemborexant compared with placebo on circadian rhythm parameters, nighttime sleep, daytime wakefulness and other clinical measures of ISWRD in individuals with ISWRD and mild to moderate AD-D.

Multicenter, randomized, double-blind, placebo-controlled, parallel-group study.

Sites in the United States, Japan and the United Kingdom.

Men and women 60 to 90 years of age with documentation of diagnosis with AD-D and Mini-Mental State Exam (MMSE) score 10 to 26.

Subjects were randomized to placebo or one of four lemborexant treatment arms (2.5 mg, 5 mg, 10 mg or 15 mg) once nightly at bedtime for 4 weeks.

An actigraph was used to collect subject rest-activity data, which were used to calculate sleep-related, wake-related and circadian rhythm-related parameters. These parameters ine to week 4 in MDSB during the daytime indicated a numerical decrease in duration for LEM5, LEM10 and LEM15, which was significantly different from placebo for LEM5 and LEM15 (p < 0.01 and p = 0.002, respectively). There were no serious treatment-emergent adverse events or worsening of cognitive function, as assessed by the MMSE and ADAS-Cog. Lemborexant was well tolerated. No subjects discontinued treatment.

This study provides preliminary evidence of the potential utility of lemborexant as a treatment to address both nighttime and daytime symptoms in patients with ISWRD and AD-D.

This study provides preliminary evidence of the potential utility of lemborexant as a treatment to address both nighttime and daytime symptoms in patients with ISWRD and AD-D.Previous findings from the positron emission tomography (PET) substudy of the SCarlet RoAD and Marguerite RoAD open-label extension (OLE) showed gantenerumab doses up to 1200 mg every 4 weeks administered subcutaneously resulted in robust beta-amyloid (Aβ) plaque removal over 24 months in people with prodromal-to-moderate Alzheimer's disease (AD). In this 36-month update, we demonstrate continued reduction, with mean (standard error) centiloid values at 36 months of -4.3 (7.5), 0.8 (6.7), and 4.7 (8.0) in the SCarlet RoAD (double-blind pooled placebo and active groups), Marguerite RoAD double-blind placebo, and Marguerite RoAD double-blind active groups respectively, representing a change of -57.0 (10.3), -90.3 (9.0), and -74.9 (10.5) centiloids respectively. These results demonstrate that prolonged gantenerumab treatment, at doses up to 1200 mg, reduces amyloid plaque levels below the amyloid positivity threshold. The ongoing GRADUATE Phase III trials will evaluate potential clinical benefits associated with gantenerumab-induced amyloid-lowering in people with early (prodromal-to-mild) AD.The terahertz (THz) spectrum of dl-alanine has been measured for the first time at cryogenic temperatures and with a pure sample. Several sharp absorptions are observed, over a wide frequency range (0.8-4.8 THz), at 8 K. The sample structure and purity were confirmed with both Raman spectroscopy and X-ray diffraction. Temperature dependent spectra revealed redshifting, with increasing temperature, for all modes except one at 2.70 THz. This mode exhibits blueshifting until ≈120 K, where it starts to redshift. A Bose-Einstein distribution has been used to model the frequency shift with temperature for the four lowest energy modes. Strong correlations between the fits and data indicate that these modes are caused by phonon excitation in an anharmonic potential. Density functional theory has also been used to identify the origin of these low frequency modes. They are attributed to large scale molecular vibrations.

Several candidate vaccines to prevent COVID-19 disease have entered large-scale phase 3 placebo-controlled randomized clinical trials and some have demonstrated substantial short-term efficacy. Efficacious vaccines should, at some point, be offered to placebo participants, which will occur before long-term efficacy and safety are known.

Following vaccination of the placebo group, we show that placebo-controlled vaccine efficacy can be derived by assuming the benefit of vaccination over time has the same profile for the original vaccine recipients and the placebo crossovers. Bcl-2 activation This reconstruction allows estimation of both vaccine durability and potential vaccine-associated enhanced disease.

Post-crossover estimates of vaccine efficacy can provide insights about durability, identify waning efficacy, and identify late enhancement of disease, but are less reliable estimates than those obtained by a standard trial where the placebo cohort is maintained. As vaccine efficacy estimates for post-crossover periods acebo, yet still allows important insights about immunological and clinical effectiveness over time.Radiology reports contain important clinical information about patients which are often tied through spatial expressions. Spatial expressions (or triggers) are mainly used to describe the positioning of radiographic findings or medical devices with respect to some anatomical structures. As the expressions result from the mental visualization of the radiologist's interpretations, they are varied and complex. The focus of this work is to automatically identify the spatial expression terms from three different radiology sub-domains. We propose a hybrid deep learning-based NLP method that includes - 1) generating a set of candidate spatial triggers by exact match with the known trigger terms from the training data, 2) applying domain-specific constraints to filter the candidate triggers, and 3) utilizing a BERT-based classifier to predict whether a candidate trigger is a true spatial trigger or not. The results are promising, with an improvement of 24 points in the average F1 measure compared to a standard BERT-based sequence labeler.We present a novel method for global diffeomorphic phase alignment of time-series data from resting-state functional magnetic resonance imaging (rsfMRI) signals. Additionally, we propose a multidimensional, continuous, invariant functional representation of brain time-series data and solve a general global cost function that brings both the temporal rotations and phase reparameterizations in alignment. We define a family of cost functions for spatiotemporal warping and compare time-series warps across them. This method achieves direct alignment of time-series, allows population analysis by aligning time-series activity across subjects and shows improved global correlation maps, as well as z-scores from independent component analysis (ICA), while showing new information exploited by phase alignment that was not previously recoverable.