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Substance misuse among older adults is a growing and complex problem with implications for society, aging adults, and their families. It is understudied in research and clinical practice. Limited and mixed evidence exists that suggests relationships between changes in older adults’ social environment and their drug use over time. This study addressed this gap by examining potential associations between social environment and drug use among community-dwelling older adults. Data were drawn from 3-waves of the national longitudinal survey of Midlife Development in the United States (MIDUS) (N= 2,020; age range=55-94 years; Mean=63.10, SD=5.66 at Wave 1). We estimated multilevel logistic growth models to assess the relationships between social environment indicators (social connectedness, social contribution, social engagement) and drug use, controlling for age, marital status, race/ethnicity, education level, household income, employment status, and number of chronic conditions. Our findings showed significant odds of drug use over the 20-year period of study, which were increased among older adults with multiple chronic conditions with a 59.5% risk of drug-related problems. Social contribution (feelings of being valued by society) negatively predicted older adults’ drug use whereas social connectedness and social engagement were not significant predictors over time. The models also indicated a moderating effect of social contribution on drug use, showing low changes in drug use over time with low social contribution. Our findings illuminate the differential roles of social environment indicators in drug use. Future research, policy, and practice may particularly focus on the role of social contribution in late-life drug use.

During 2014 and 2015, NASA's Neutron star Interior Composition Explorer (NICER) mission proceeded successfully through Phase C, Design and Development. An X-ray (0.2{12 keV) astrophysics payload destined for the International Space Station, NICER is manifested for launch in early 2017 on the Commercial Resupply Services SpaceX-11 flight. Its scientific objectives are to investigate the internal structure, dynamics, and energetics of neutron stars, the densest objects in the universe. During Phase C, flight components including optics, detectors, the optical bench, pointing actuators, electronics, and others were subjected to environmental testing and integrated to form the flight payload. A custom-built facility was used to co-align and integrate the X-ray \concentrator" optics and silicon-drift detectors. Ground calibration provided robust performance measures of the optical (at NASA's Goddard Space Flight Center) and detector (at the Massachusetts Institute of Technology) subsystems, while comprehensive functional tests prior to payload-level environmental testing met all instrument performance requirements. We describe here the implementation of NICER's major subsystems, summarize their performance and calibration, and outline the component-level testing that was successfully applied.

222 Background: Rolapitant (VARUBI) is a selective, long-acting neurokinin-1 receptor antagonist (RA) for the prevention of CINV. Rolapitant effectively prevented CINV in phase 3 trials of patients (pts) receiving highly or moderately emetogenic chemotherapy (HEC, MEC). While MEC and HEC regimens are commonly used to treat pts with gastrointestinal and colorectal cancers (GI/CRC), very few studies have evaluated the effectiveness of a neurokinin-1 RA regimen in these pts. We assessed the incidence of CINV and efficacy of rolapitant in a subset of pts with GI/CRC. Methods: This is a post hoc analysis of 3 similarly-designed, randomized, placebo-controlled trials. Pts with cancer of the esophagus, stomach, colon/rectum, or anus received a single oral dose of 180 mg oral rolapitant or placebo prior to HEC or MEC. All pts received a 5-hydroxytryptamine type 3 (5-HT3) RA and dexamethasone (active control). The HEC studies included cisplatin, and the MEC study carboplatin, oxaliplatin, irinotecan, epirubicin, and doxorubicin. Endpoints included complete response (CR; no emesis and no use of rescue medication), no emesis, no nausea (maximum visual analogue scale [VAS] < 5 mm), no significant nausea (maximum VAS < 25mm) and complete protection (CP; no emesis, no use of rescue medication, and no significant nausea) in the overall (0-120 h), acute (≤ 24 h), and delayed (> 24-120 h) phases. Results: Out of 188 GI/CRC pts, 101 pts received rolapitant and 87 received active control. Pts treated with rolapitant had significantly higher rates of CR, no nausea, no emesis, and CP in the overall phase (P < 0.05). Rolapitant was well-tolerated and overall incidence of treatment-emergent adverse events comparable in both groups. Conclusions: Addition of rolapitant to 5-HT3RA and dexamethasone therapy significantly improved CR, no nausea, no emesis, and CP in pts with GI/CRC receiving emetogenic chemotherapy. Clinical trial information: NCT01500226, NCT01499849, NCT01500213. [Table: see text]

Current theories propose that systemic lupus erythematosus develops when genetically predisposed individuals are exposed to certain environmental agents, although how these agents trigger lupus is uncertain. Some of these agents, such as procainamide, hydralazine, and UV-light inhibit T cell DNA methylation, increase lymphocyte function-associated antigen 1 (LFA-1) (CD11a/CD18) expression, and induce autoreactivity in vitro, and adoptive transfer of T cells that are made autoreactive by this mechanism causes a lupuslike disease. The mechanism by which these cells cause autoimmunity is unknown. In this report, we present evidence that LFA-1 overexpression is sufficient to induce autoimmunity. LFA-1 overexpression was induced on cloned murine Th2 cells by transfection, resulting in autoreactivity. Adoptive transfer of the transfected, autoreactive cells into syngeneic recipients caused a lupuslike disease with anti-DNA antibodies, an immune complex glomerulonephritis and pulmonary alveolitis, similar to that caused by cells treated with procainamide. These results indicate that agents or events which modify T cell DNA methylation may induce autoimmunity by causing T cell LFA-1 overexpression. Since T cells from patients with active lupus have hypomethylated DNA and overexpressed LFA-1, this mechanism could be important in the development of human autoimmunity.

The Global Precipitation Measurement mission is a joint NASA/JAXA mission scheduled for launch in late 2013. The integration of thermal hardware onto the satellite began in the Fall of 2010 and will continue through the Summer of 2012. The thermal hardware on the mission included several constant conductance heat pipes, heaters, thermostats, thermocouples radiator coatings and blankets. During integration several problems arose and insights were gained that would help future satellite integrations. Also lessons learned from previous missions were implemented with varying degrees of success. These insights can be arranged into three categories. 1) the specification of flight hardware using analysis results and the available mechanical resources. 2) The integration of thermal flight hardware onto the spacecraft, 3) The preparation and implementation of testing the thermal flight via touch tests, resistance measurements and thermal vacuum testing.

Objective. Antigen-specific CD4+ T cells treated with DNA methylation inhibitors become autoreactive, suggesting a novel mechanism for autoimmunity. To test whether this mechanism might be involved in systemic lupus erythematosus (SLE), phenotypic markers for the autoreactive cells were sought. Methods. Cloned normal T cells were treated with the DNA methylation inhibitor 5-azacytidine (5-azaC) and studied for altered gene expression. T cells from patients with active SLE were then studied for a similar change in gene expression, and cells expressing the marker were tested for autoreactivity. Results. 5-azaC-treated normal T cells had increased CD11a (leukocyte function-associated antigen 1α) expression relative to other membrane molecules. A T cell subset with similar CD11a expression was found in patients with active SLE. This subset contained cells that spontaneously lysed autologous macrophages, with a specificity similar to that of 5-azaC-treated cells. Conclusion. The model of 5-azaC-induced autoreactivity may have relevance to SLE.

Objective. To determine if DNA methylation inhibitors make T cells autoreactive by inducing lymphocyte function—associated antigen type 1 (LFA–1) (CD11a/CD18) overexpression. Methods. T cell clones were treated with 3 distinct DNA methylation inhibitors or were stably transfected with a CD18 cDNA in a mammalian expression vector, and the effects on LFA–1 expression and activation requirements were examined. Results. LFA–1 overexpression, caused by DNA methylation inhibitors or by transfection, correlates with the development of autoreactivity. Conclusion. LFA–1 overexpression may contribute to T cell autoreactivity.

OBJECTIVE--Man made mineral fibres imitate asbestos and produce tumours of the pleura in animals. To answer the question, Does prolonged exposure to fibreglass adversely affect pulmonary function or produce radiographic abnormalities in human subjects? we studied workers in a midwestern appliance plant where refrigerator doors and previously entire cabinets were insulated with fibreglass sheeting and loose rotary spun fibreglass. METHODS--Spirometry and lung volumes were measured, respiratory and occupational questionnaires were administered, and chest x-ray films were read for pneumoconiosis using International Labour Office (ILO) 1980 criteria in 284 workers with exposure of 20 years or more. RESULTS--Expiratory flows were reduced including FEV1 (mean 90.3% of predicted (pr), FEF25-75 (85.5% pr), and FEF75-85 (76.2% pr). Forced vital capacity was significantly reduced (92.8% pr) and total lung capacity was significantly increased (109.2% pr). In white male smokers, a group large enough for comparisons, parameters of pulmonary function were reduced further in the presence of irregular opacities. Forty three workers (15.1%) had evidence of pneumoconiosis on chest radiographs: 26 of these (9.1%), had no known exposure to asbestos and 17 (6.0%) had some exposure. The best judgement was that in 36 (13.0%), pulmonary opacities or pleural abnormalities were due to fibreglass. CONCLUSION--Commercial rotary spun fibreglass used for insulating appliances appears to produce human disease that is similar to asbestosis.

Over the past three decades large amounts of information have been converted to image formats from paper documents. Though in digital form, extracting the information, usually textual, from these documents requires complex image processing and optical character recognition techniques. The processing pipeline from the image to information typically includes an orientation correction task, document identification task, and text analysis task. When there are many document variants the tasks become difficult requiring complex subanalysis for each variant and quickly exceeds human capability. In this work, we demonstrate a documentanalysis application with the orientation correction and document identification task carried out by supervised machine learning techniques for a large, international airline. The documents have been amassed over forty years with numerous variants and are mostly black and white, typically consist of text and lines, and somehave extensive noise. Low level symbols are extracted from the raw images and separated into partitions. The partitions are used to generate statistical features which are then used to train the classifiers. We compare the classifiers for each task (e.g. decision tree, support vector machine, and random forest) to choose the most appropriate. We also perform feature selection to reduce the complexity of the document type classifiers. These parsimonious models result in comparable accuracy with 80% or fewer features.