Systematic Multi-Domain Alzheimer's Risk Reduction Trial (SMARRT): Study Protocol.

This article describes the protocol for the Systematic Multi-domain Alzheimer's Risk Reduction Trial (SMARRT), a single-blind randomized pilot trial to test a personalized, pragmatic, multi-domain Alzheimer's disease (AD) risk reduction intervention in a US integrated healthcare delivery system. Study participants will be 200 higher-risk older adults (age 70-89 years with subjective cognitive complaints, low normal performance on cognitive screen, and ≥ two modifiable risk factors targeted by our intervention) who will be recruited from selected primary care clinics of Kaiser Permanente Washington, oversampling people with non-white race or Hispanic ethnicity. Study participants will be randomly assigned to a two-year Alzheimer's risk reduction intervention (SMARRT) or a Health Education (HE) control. Randomization will be stratified by clinic, race/ethnicity (non-Hispanic white versus non-white or Hispanic), and age (70-79, 80-89). Participants randomized to the SMARRT group will work with a behavioral coach and nurse to develop a personalized plan related to their risk factors (poorly controlled hypertension, diabetes with evidence of hyper or hypoglycemia, depressive symptoms, poor sleep quality, contraindicated medications, physical inactivity, low cognitive stimulation, social isolation, poor diet, smoking). Participants in the HE control group will be mailed general health education information about these risk factors for AD. The primary outcome is two-year cognitive change on a cognitive test composite score. Secondary outcomes include: 1) improvement in targeted risk factors, 2) individual cognitive domain composite scores, 3) physical performance, 4) functional ability, 5) quality of life, and 6) incidence of mild cognitive impairment, AD, and dementia. Primary and secondary outcomes will be assessed in both groups at baseline and 6, 12, 18, and 24 months

The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 weeks from a multicenter study.

IntroductionDuchenne muscular dystrophy (DMD) subjects ≥5 years with nonsense mutations were followed for 48 weeks in a multicenter, randomized, double-blind, placebo-controlled trial of ataluren. Placebo arm data (N = 57) provided insight into the natural history of the 6-minute walk test (6MWT) and other endpoints.MethodsEvaluations performed every 6 weeks included the 6-minute walk distance (6MWD), timed function tests (TFTs), and quantitative strength using hand-held myometry.ResultsBaseline age (≥7 years), 6MWD, and selected TFT performance are strong predictors of decline in ambulation (Δ6MWD) and time to 10% worsening in 6MWD. A baseline 6MWD of <350 meters was associated with greater functional decline, and loss of ambulation was only seen in those with baseline 6MWD <325 meters. Only 1 of 42 (2.3%) subjects able to stand from supine lost ambulation.ConclusionFindings confirm the clinical meaningfulness of the 6MWD as the most accepted primary clinical endpoint in ambulatory DMD trials

Evolution of dopant-induced helium nanoplasmas

Two-component nanoplasmas generated by strong-field ionization of doped helium nanodroplets are studied in a pump-probe experiment using few-cycle laser pulses in combination with molecular dynamics simulations. High yields of helium ions and a pronounced, droplet size-dependent resonance structure in the pump-probe transients reveal the evolution of the dopant-induced helium nanoplasma. The pump-probe dynamics is interpreted in terms of strong inner ionization by the pump pulse and resonant heating by the probe pulse which controls the final charge states detected via the frustration of electron-ion recombination

Investigating the Feasibility of Utilizing Carbon Nanotube Fibers for Spacesuit Dust Mitigation

Historical data from the Apollo missions has compelled NASA to identify dust mitigation of spacesuits and other components as a critical path prior to sending humans on potential future lunar exploration missions. Several studies thus far have proposed passive and active countermeasures to address this challenge. However, these technologies have been primarily developed and proven for rigid surfaces such as solar cells and thermal radiators. Integration of these technologies for spacesuit dust mitigation has remained an open challenge due to the complexity of suit design. Current research investigates novel methods to enhance integration of the Electrodynamic Dust Shield (EDS) concept for spacesuits. We leverage previously proven EDS concept developed by NASA for rigid surfaces and apply new techniques to integrate the technology into spacesuits to mitigate dust contamination. The study specifically examines the feasibility of utilizing Carbon Nanotube (CNT) yarns manufactured by Rice University as electrodes in spacesuit material. Proof of concept testing was conducted at NASA Kennedy Space Center using lunar regolith simulant to understand the feasibility of the proposed techniques for spacesuit application. Results from the experiments are detailed in this paper. Potential challenges of applying this technology for spacesuits are also identified

Orchestrating Tuple-based Languages

The World Wide Web can be thought of as a global computing architecture supporting the deployment of distributed networked applications. Currently, such applications can be programmed by resorting mainly to two distinct paradigms: one devised for orchestrating distributed services, and the other designed for coordinating distributed (possibly mobile) agents. In this paper, the issue of designing a pro- gramming language aiming at reconciling orchestration and coordination is investigated. Taking as starting point the orchestration calculus Orc and the tuple-based coordination language Klaim, a new formalism is introduced combining concepts and primitives of the original calculi. To demonstrate feasibility and effectiveness of the proposed approach, a prototype implementation of the new formalism is described and it is then used to tackle a case study dealing with a simplified but realistic electronic marketplace, where a number of on-line stores allow client applications to access information about their goods and to place orders

Proteomic profiling of the mesenteric lymph after hemorrhagic shock: Differential gel electrophoresis and mass spectrometry analysis

Experiments show that upon traumatic injury the composition of mesenteric lymph changes such that it initiates an immune response that can ultimately result in multiple organ dysfunction syndrome (MODS). To identify candidate protein mediators of this process we carried out a quantitative proteomic study on mesenteric lymph from a well characterized rat shock model. We analyzed three animals using analytical 2D differential gel electrophoresis. Intra-animal variation for the majority of protein spots was minor. Functional clustering of proteins revealed changes arising from several global classes that give novel insight into fundamental mechanisms of MODS. Mass spectrometry based proteomic analysis of proteins in mesenteric lymph can effectively be used to identify candidate mediators and loss of protective agents in shock models

Genetic Differences in Dorsal Hippocampus Acetylcholinesterase Activity Predict Contextual Fear Learning Across Inbred Mouse Strains.

Learning is a critical behavioral process that is influenced by many neurobiological systems. We and others have reported that acetylcholinergic signaling plays a vital role in learning capabilities, and it is especially important for contextual fear learning. Since cholinergic signaling is affected by genetic background, we examined the genetic relationship between activity levels of acetylcholinesterase (AChE), the primary enzyme involved in the acetylcholine metabolism, and learning using a panel of 20 inbred mouse strains. We measured conditioned fear behavior and AChE activity in the dorsal hippocampus, ventral hippocampus, and cerebellum. Acetylcholinesterase activity varied among inbred mouse strains in all three brain regions, and there were significant inter-strain differences in contextual and cued fear conditioning. There was an inverse correlation between fear conditioning outcomes and AChE levels in the dorsal hippocampus. In contrast, the ventral hippocampus and cerebellum AChE levels were not correlated with fear conditioning outcomes. These findings strengthen the link between acetylcholine activity in the dorsal hippocampus and learning, and they also support the premise that the dorsal hippocampus and ventral hippocampus are functionally discrete