Progress in Absorber R&D for Muon Cooling

A stored-muon-beam neutrino factory may require transverse ionization cooling of the muon beam. We describe recent progress in research and development on energy absorbers for muon-beam cooling carried out by a collaboration of university and laboratory groups.Comment: 7 pages, 1 figure, presented at the 3rd International Workshop on Neutrino Factory Based on Muon Storage Rings (NuFACT'01), May 24-30, 2001, Tsukuba, Japa

Probing the Nature of Short Swift Bursts via Deep INTEGRAL Monitoring of GRB 050925

We present results from Swift, XMM-Newton, and deep INTEGRAL monitoring in the region of GRB 050925. This short Swift burst is a candidate for a newly discovered soft gamma-ray repeater (SGR) with the following observational burst properties: 1) galactic plane (b=-0.1 deg) localization, 2) 150 msec duration, and 3) a blackbody rather than a simple power-law spectral shape (with a significance level of 97%). We found two possible X-ray counterparts of GRB 050925 by comparing the X-ray images from Swift XRT and XMM-Newton. Both X-ray sources show the transient behavior with a power-law decay index shallower than -1. We found no hard X-ray emission nor any additional burst from the location of GRB 050925 in ~5 Ms of INTEGRAL data. We discuss about the three BATSE short bursts which might be associated with GRB 050925, based on their location and the duration. Assuming GRB 050925 is associated with the H II regions (W 58) at the galactic longitude of l=70 deg, we also discuss the source frame properties of GRB 050925.Comment: 13 pages, 13 figures, accepted for publication in ASR special issue on Neutron Stars and Gamma Ray Bursts, full resolution of Fig 5 is available at http://asd.gsfc.nasa.gov/Takanori.Sakamoto/GRB050925/integral_ibis_images.ep

Dysfunctional Dopaminergic Neurones in Mouse Models of Huntington's Disease: A Role for SK3 Channels

Background: Huntington's disease (HD) is a late-onset fatal neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the gene coding for the protein huntingtin and is characterised by progressive motor, psychiatric and cognitive decline. We previously demonstrated that normal synaptic function in HD could be restored by application of dopamine receptor agonists, suggesting that changes in the release or bioavailability of dopamine may be a contributing factor to the disease process. Objective: In the present study, we examined the properties of midbrain dopaminergic neurones and dopamine release in presymptomatic and symptomatic transgenic HD mice. Methods and Results:Using intracellular sharp recordings and immunohistochemistry, we found that neuronal excitability was increased due to a loss of slow afterhyperpolarisation and that these changes were related to an apparent functional loss and abnormal distribution of SK3 channels (KCa2.3 encoded by the KCNN3 gene), a class of small-conductance calcium-activated potassium channels. Electrochemical detection of dopamine showed that this observation was associated with an enhanced dopamine release in presymptomatic transgenic mice and a drastic reduction in symptomatic animals. These changes occurred in the context of a progressive expansion in the CAG repeat number and nuclear localisation of mutant protein within the substantia nigra pars compacta. Conclusions: Dopaminergic neuronal dysfunction is a key early event in HD disease progression. The initial increase in dopamine release appears to be related to a loss of SK3 channel function, a protein containing a polyglutamine tract. Implications for polyglutamine-mediated sequestration of SK3 channels, dopamine-associated DNA damage and CAG expansion are discussed in the context of HD.</br

Associations between subjective social status and physical and mental health functioning among patients with hypertension

We examine the cross-sectional association between subjective social status and self-rated physical and mental health functioning in 518 Black and White patients enrolled in a community-based hypertension control research study. We found that (1) subjective social status, measured using both a proximal and distal referent group, was positively associated with physical and mental health functioning scores independent of educational level, household income, or both; (2) the effect of subjective social status on physical and mental health functioning differed significantly by race when using the distal, not the proximal, referent group. When the associations differed, they were stronger for Whites than Blacks

Practice level costs of office-based hypertension performance improvement: The Heart Healthy Lenoir study

Primary care practice leaderswho consider engaging in quality improvement (QI) need to understand the practice level costs incurred when asking staff to take on new tasks. The HeartHealthy Lenoir study is a prospective cohort trial in whichQImethods were used to enhance hypertension (HTN) care and reduce racial disparities in blood pressure control in small rural primary care practices inNorth Carolina. As part of this effort, we performed an activity-based costing analysis to describe the costs incurred to develop, implement, and maintain key tasks. We interviewed 20 practice stakeholders and phone-based health coaches during 2012-2014. We calculated the time invested by individuals to perform each task within each study phase and applied national hourly wages to generate cost estimates. Our descriptive analyses focus on four of themost widely used practices. Activities included time to abstract HTN control data, participate in project meetings, identify patients with uncontrolled HTN, create standardized work, and provide additional health coaching for patients with uncontrolled HTN. Despite practice and staffing differences, the developmental phase costs were similar, ranging from $879 to$1, 417. Implementation costs varied more widely as practices took different approaches to identifying patients with uncontrolled HTN. Practice-specific phone health coaching costs ranged from $19, 508 to more than$38, 000. This study adds to the growing literature regarding practice level costs of engaging in systems change. Understanding these costs and balancing them against practice incentives may be helpful as stakeholders make decisions regarding HTN QI

Perceived Social Standing, Medication Nonadherence, and Systolic Blood Pressure in the Rural South

Purpose: Little is known about how perceived social standing versus traditional socioeconomic characteristics influence medication adherence and blood pressure (BP) among African American and white patients with hypertension in the rural southeastern United States. Methods: Perceived social standing, socioeconomic characteristics, self-reported antihypertensive medication adherence, and BP were measured at baseline in a cohort of rural African American and white patients (n = 495) with uncontrolled hypertension attending primary care practices. Multivariate models examined the relationship of perceived social standing and socioeconomic indicators with medication adherence and systolic BP. Findings: Medication nonadherence was reported by 40% of patients. Younger age [β = 0.20; P = .001], African American race [β = -0.30; P = .03], and lower perceived social standing [β = 0.08; P = .002] but not sex or traditional socioeconomic characteristics including education and household income, were significantly associated with lower medication adherence. Race-specific analyses revealed that this pattern was limited to African Americans and not observed in whites. In stepwise modeling, older age [β = 0.57, P = .001], African American race [β = 4.4; P = .03], and lower medication adherence [β = -1.7, P = .01] but not gender, education, or household income, were significantly associated with higher systolic BP. Conclusions: Lower perceived social standing and age, but not traditional socioeconomic characteristics, were significantly associated with lower medication adherence in African Americans. Lower medication adherence was associated with higher systolic BP. These findings suggest the need for tailored, culturally relevant medication adherence interventions in rural communities

Race-Specific Patterns of Treatment Intensification Among Hypertensive Patients Using Home Blood Pressure Monitoring: Analysis Using Defined Daily Doses in the Heart Healthy Lenoir Study

Background: Racial disparities in blood pressure (BP) control persist, but whether differences by race in antihypertensive medication intensification (AMI) contribute is unknown. Objective: To compare AMI by race for patients with elevated home BP readings. Methods: This prospective cohort study followed adult patients from 6 rural primary care practices who used home BP monitoring (HBPM) and recorded/reported values. For providers, AMI was encouraged when mean HBPM systolic blood pressure (SBP) values were ⩾135 mm Hg; patients received phone-based coaching on HBPM technique and sharing HBPM findings. AMI was assessed between baseline and 12 months using defined daily dose (DDD) and summed to create a total antihypertensive DDD value. Results: A total of 217 patients (mean age = 61.4 ± 10.2 years; 66% female; 57% black) provided usable HBPM data. Among 90 (41%) intensification-eligible hypertensive patients (ie, mean HBPM SBP values for 6-months ⩾135 mm Hg), mean total antihypertensive DDD was increased in 61% at 12 months. Blacks had significantly higher mean DDD at baseline and 12 months, but intensification (+0.72 vs +0.65; P = 0.83) was similar by race. However, intensification was greater in males than females (+1.1 vs +0.39; P = 0.031). Reduction in mean SBP following intensification was greater in white versus black patients (−8.2 vs −3.9 mm Hg; P = 0.14). Conclusion/Relevance: Treatment intensification in HBPM users was similar by race, differed significantly by gender, and may produce a greater response in white patients. Differential AMI in HBPM users does not appear to contribute to persistent racial disparities in BP control

Post-acute Ambulatory Care Service Use among Patients Discharged Home after Stroke or TIA: The Cluster-randomized COMPASS Study

Background and Objectives: We examined transitional care management within 90 days and 1 year following discharge home among acute stroke and transient ischemic attack patients from the Comprehensive Post-Acute Stroke Services (COMPASS) Study, a cluster-randomized pragmatic trial of early supported discharge conducted in 41 hospitals (40 hospital units) in North Carolina, United States. Methods: Data for 2262 of the total 6024 (37.6%; 1069 intervention and 1193 usual care) COMPASS patients were linked with the Centers for Medicare and Medicaid Services fee-for-service Medicare claims. Time to the first ambulatory care visit was examined using Cox proportional hazard models adjusted for patient characteristics not included in the randomization protocol. Results: Only 6% of the patients [mean (SD) age 74.9 (10.2) years, 52.1% women, 80.3% White)] did not have an ambulatory care visit within 90 days postdischarge. Mean time (SD) to first ambulatory care visit was 12.0 (26.0) and 16.3 (35.1) days in intervention and usual care arms, respectively, with the majority of visits in both study arms to primary care providers. The COMPASS intervention resulted in a 27% greater use of ambulatory care services within 1 year postdischarge, relative to usual care [HR=1.27 (95% CI: 1.14-1.41)]. The use of transitional care billing codes was significantly greater in the intervention arm as compared with usual care [OR=1.87 (95% CI: 1.54-2.27)]. Discussion: The COMPASS intervention, which was aimed at improving stroke post-acute care, was associated with an increase in the use of ambulatory care services by stroke and transient ischemic attack patients discharged home and an increased use of transitional care billing codes by ambulatory providers

The role of emotion, values, and beliefs in the construction of innovative work realities

Traditional approaches to requirements elicitation stress systematic and rational analysis and representation of organizational context and system requirements. This paper argues that (1) for an organization, a software system implements a shared vision of a future work reality and that (2) understanding the emotions, feelings, values, beliefs, and interests that drive organizational human action is needed in order to invent the requirements of such a software system. This paper debunks some myths about how organizations transform themselves through the adoption of Information and Communication Technology; describes the concepts of emotion, feeling, value, and belief; and presents some constructionist guidelines for the process of eliciting requirements for a software system that helps an organization to fundamentally change its work patterns.(undefined

A COMBINED MEASURE OF COGNITION AND FUNCTION FOR CLINICAL TRIALS: THE INTEGRATED ALZHEIMER’S DISEASE RATING SCALE (IADRS)

It is generally recognized that more sensitive instruments for the earliest stages of Alzheimer’s disease (AD) are needed. The integrated Alzheimer’s Disease Rating Scale (iADRS) combines scores from 2 widely accepted measures, the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Alzheimer’s Disease Cooperative Study – instrumental Activities of Daily Living (ADCS-iADL). Disease progression and treatment differences as measured by the iADRS were analyzed using data from solanezumab EXPEDITION, EXPEDITION2, and EXPEDITION-EXT Studies; semagacestat IDENTITY Study; and donepezil ADCS – mild cognitive impairment (ADCS-MCI) Study. Psychometric properties of the iADRS were established through principal component analysis (PCA) and estimation of contributions of subscores and individual item scores to the iADRS total score. The iADRS performed better than most composites and scales in detecting disease progression and comparably or better than individual scales in detecting treatment differences. PCA demonstrated the iADRS can be divided into two principal components primarily representing cognitive items and instrumental ADLs. Dynamic ranges of the subscales were similar across all studies, reflecting approximately equal contributions from both subscales to the iADRS total score. In item analyses, every item contributed to the total score, with varying strength of contributions by item and across data sets. The iADRS demonstrated acceptable psychometric properties and was effective in capturing disease progression from MCI through moderate AD and treatment effects across the early disease spectrum. These findings suggest the iADRS can be used in studies of mixed populations, ensuring sensitivity to treatment effects as subjects progress during studies of putative disease-modifying agents