Adherence and Tolerability of Alzheimer's Disease Medications: A Pragmatic Randomized Trial

BACKGROUND/OBJECTIVES: Post-marketing comparative trials describe medication use patterns in diverse, real-world populations. Our objective was to determine if differences in rates of adherence and tolerability exist among new users to acetylcholinesterase inhibitors (AChEI's). DESIGN: Pragmatic randomized, open label comparative trial of AChEI's currently available in the United States. SETTING: Four memory care practices within four healthcare systems in the greater Indianapolis area. PARTICIPANTS: Eligibility criteria included older adults with a diagnosis of possible or probable Alzheimer's disease (AD) who were initiating treatment with an AChEI. Participants were required to have a caregiver to complete assessments, access to a telephone, and be able to understand English. Exclusion criteria consisted of a prior severe adverse event from AChEIs. INTERVENTION: Participants were randomized to one of three AChEIs in a 1:1:1 ratio and followed for 18 weeks. MEASUREMENTS: Caregiver-reported adherence, defined as taking or not taking study medication, and caregiver-reported adverse events, defined as the presence of an adverse event. RESULTS: 196 participants were included with 74.0% female, 30.6% African Americans, and 72.9% who completed at least twelfth grade. Discontinuation rates after 18 weeks were 38.8% for donepezil, 53.0% for galantamine, and 58.7% for rivastigmine (P = .063) in the intent to treat analysis. Adverse events and cost explained 73.1% and 25.4% of discontinuation. No participants discontinued donepezil due to cost. Adverse events were reported by 81.2% of all participants; no between-group differences in total adverse events were statistically significant. CONCLUSIONS: This pragmatic comparative trial showed high rates of adverse events and cost-related non-adherence with AChEIs. Interventions improving adherence and persistence to AChEIs may improve AD management. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01362686 (https://clinicaltrials.gov/ct2/show/NCT01362686)

A Photometric Study of the Young Stellar Population Throughout the lambda Orionis Star-Forming Region

We present VRI photometry of 320,917 stars with 11 < R < 18 throughout the lambda Orionis star-forming region. We statistically remove the field stars and identify a representative PMS population throughout the interior of the molecular ring. The spatial distribution of this population shows a concentration of PMS stars around lambda Ori and in front of the B35 dark cloud. Few PMS stars are found outside these pockets of high stellar density, suggesting that star formation was concentrated in an elongated cloud extending from B35 through lambda Ori to the B30 cloud. We find a lower limit for the global stellar mass of about 500 Mo. We find that the global ratio of low- to high-mass stars is similar to that predicted by the field initial mass function, but this ratio varies strongly as a function of position in the star-forming region. Locally, the star-formation process does not produce a universal initial mass function. We construct a history of the star-forming complex. This history incorporates a recent supernova to explain the distribution of stars and gas today.Comment: 42 pages, 11 figures; to appear in the Astronomical Journa

Plakoglobin is required for maintenance of the cortical actin skeleton in early Xenopus embryos and for cdc42-mediated wound healing

Early Xenopus embryos are large, and during the egg to gastrula stages, when there is little extracellular matrix, the cytoskeletons of the individual blastomeres are thought to maintain their spherical architecture and provide scaffolding for the cellular movements of gastrulation. We showed previously that depletion of plakoglobin protein during the egg to gastrula stages caused collapse of embryonic architecture. Here, we show that this is due to loss of the cortical actin skeleton after depletion of plakoglobin, whereas the microtubule and cytokeratin skeletons are still present. As a functional assay for the actin skeleton, we show that wound healing, an actin-based behavior in embryos, is also abrogated by plakoglobin depletion. Both wound healing and the amount of cortical actin are enhanced by overexpression of plakoglobin. To begin to identify links between plakoglobin and the cortical actin polymerization machinery, we show here that the Rho family GTPase cdc42, is required for wound healing in the Xenopus blastula. Myc-tagged cdc42 colocalizes with actin in purse-strings surrounding wounds. Overexpression of cdc42 dramatically enhances wound healing, whereas depletion of maternal cdc42 mRNA blocks it. In combinatorial experiments we show that cdc42 cannot rescue the effects of plakoglobin depletion, showing that plakoglobin is required for cdc42-mediated cortical actin assembly during wound healing. However, plakoglobin does rescue the effect of cdc42 depletion, suggesting that cdc42 somehow mediates the distribution or function of plakoglobin. Depletion of α-catenin does not remove the cortical actin skeleton, showing that plakoglobin does not mediate its effect by its known linkage through α-catenin to the actin skeleton. We conclude that in Xenopus, the actin skeleton is a major determinant of cell shape and overall architecture in the early embryo, and that plakoglobin plays an essential role in the assembly, maintenance, or organization of this cortical actin

Characteristics of Lightning Within Electrified Snowfall Events Using Total Lightning Measurements

No abstract availabl

Characteristics of Lightning Within Electrified Snowfall Events Using Lightning Mapping Arrays

This study examined 34 lightning flashes within four separate thundersnow events derived from lightning mapping arrays (LMAs) in northern Alabama, central Oklahoma, and Washington, DC. The goals were to characterize the in-cloud component of each lightning flash, as well as the correspondence between the LMA observations and lightning data taken from national lightning networks like the National Lightning Detection Network (NLDN). Individual flashes were examined in detail to highlight several observations within the dataset. The study results demonstrated that the structures of these flashes were primarily normal polarity. The mean area encompassed by this set of flashes is 375 square kilometers, with a maximum flash extent of 2300 square kilometers, a minimum of 3 square kilometers, and a median of 128 square kilometers. An average of 2.29 NLDN flashes were recorded per LMA-derived lightning flash. A maximum of 11 NLDN flashes were recorded in association with a single LMA-derived flash on 10 January 2011. Additionally, seven of the 34 flashes in the study contain zero NLDN identified flashes. Eleven of the 34 flashes initiated from tall human-made objects (e.g., communication towers). In at least six lightning flashes, the NLDN detected a return stroke from the cloud back to the tower and not the initial upward leader. This study also discusses lightning's interaction with the human built environment and provides an example of lightning within heavy snowfall observed by GOES-16's Geostationary Lightning Mapper

Routes To the Renaissance for Pittsfield, MA

The goal of the Master of Regional Planning Studio is to develop a student’s techniques for collecting, analyzing, and synthesizing spatial and non-spatial data and then presenting that collective data in a manner (i.e., report, video, presentation, and charettes) that is understandable to academics, professionals, and the public. Planning Studio allows students to integrate knowledge from coursework and research, and apply such knowledge to resolving representative planning problems. At UMASS Amherst, these problems are found in neighborhood, rural, urban, and/or regional settings. In the fall of 2015, the City of Pittsfield contracted the MRP Studio to create a vision plan to connect the goal’s of its Master Plan in 2009 to current development regulations that encourage development and redevelopment of an appropriate size, scale and design that meets the short term and long term vision of the community. The vision plan encompasses the following: Spatial and Physical Boundaries of Major Gateway Corridors: Analyze the major gateways and develop tools to make them more welcoming. Permitted Use Table and Definitions: Review, clarify, and consolidate the land-uses listed in the table to assess deficiencies and unclear definitions. Design Guidelines: Create a manual to guide architectural aesthetic standards for new retail developments. Sign Ordinance: Implement a streamlined regulation that improves sign quality. Site Plan Review: Develop thresholds to create clearer processes for review of development projects. Resolution for Split Parcels: Identify all properties that fall within two zoning districts and develop a mitigation tool. Pro Forma and Multi-Family Housing: Develop a financial model that will estimate the construction and maintenance cost of multi-family housing units and make projections for new development’s financial return

Genetic Influences on Educational Achievement in Cross-National Perspective

There is a growing interest in how social conditions moderate genetic influences on education [gene–environment interactions (GxE)]. Previous research has focused on the family, specifically parents’ social background, and has neglected the institutional environment. To assess the impact of macro-level influences, we compare genetic influences on educational achievement and their social stratification across Germany, Norway, Sweden, and the United States. We combine well-established GxE-conceptualizations with the comparative stratification literature and propose that educational systems and welfare-state regimes affect the realization of genetic potential. We analyse population-representative survey data on twins (Germany and the United States) and twin registers (Norway and Sweden), and estimate genetically sensitive variance decomposition models. Our comparative design yields three main findings. First, Germany stands out with comparatively weak genetic influences on educational achievement suggesting that early tracking limits the realization thereof. Second, in the United States genetic influences are comparatively strong and similar in size compared to the Nordic countries. Third, in Sweden genetic influences are stronger among disadvantaged families supporting the expectation that challenging and uncertain circumstances promote genetic expression. This ideosyncratic finding must be related to features of Swedish social institutions or welfare-state arrangements that are not found in otherwise similar countries

Solid Oxide Fuel Cell Seal Development at NASA Glenn Research Center

Researchers at NASA GRC are confronting the seal durability challenges of Solid Oxide Fuel Cells by pursuing an integrated and multidisciplinary development effort incorporating thermo-structural analyses, advanced materials, experimentation, and novel seal design concepts. The successful development of durable hermetic SOFC seals is essential to reliably producing the high power densities required for aerospace applications