Search

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.

785 Background: Socioeconomic deprivation has been described as a barrier to cancer clinical trial participation. However, few studies have examined socioeconomic deprivation using patient-level or granular geocoded designations. To overcome this challenge, the Area Deprivation Index (ADI) was used to assess neighborhood socioeconomic deprivation in a cohort of gastrointestinal cancer clinical trial patients at an NCI-Designated Comprehensive Cancer Center. Methods: Patients enrolled in a gastrointestinal cancer clinical trial from 2008 to 2019 with an identifiable ADI national rank were identified. Socioeconomic deprivation was assessed using the ADI, a publicly available, validated dataset that ranks census block groups into percentiles using variables such as income, education, employment, and housing characteristics. For this study, ADI was categorized as quintiles listed in the table. Statistical analyses included Chi-square and Kruskal-Wallis tests. Results: The median age of the cohort (N=1,334) was 62.0 years. Most patients were male (54.3%). Race included White (88.2%), African American (6.8%), and Asian (1.5%) patients. Hispanic/Latinx patients made up 6.7% of the cohort. The median ADI was 46. The proportion of enrollees from lowest to highest ADI quintile was 11.2%, 29.3%, 27.3%, 19.1%, and 13.1%. Trial enrollment differed by ADI and age (p=0.019), gender (p=0.042), race (p

Tivozanib is a potent and selective inhibitor of the VEGF receptor. In an open-label, randomized phase 3 trial, we compared tivozanib to sorafenib in patients with metastatic renal cell carcinoma (mRCC) who had received two or three prior therapies. We have previously reported that the study met its primary endpoint, demonstrating an improvement in progression-free survival with tivozanib versus sorafenib (5.6 mo vs 3.9 mo; hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.56-0.94; p=0.016). The current report reflects the final assessment of overall survival, showing no difference between treatment with tivozanib and sorafenib (HR 0.97, 95% CI 0.75-1.24). Given its activity and distinct tolerability profile, tivozanib represents a treatment option for patients with previously treated mRCC. PATIENT SUMMARY: We show that tivozanib, a targeted therapy, can delay tumor growth relative to an already approved targeted therapy (sorafenib) in patients with kidney cancer who have received two or three prior treatments. No difference in survival was observed.

Rolapitant, a selective and long-acting neurokinin-1 receptor antagonist, is approved in an oral formulation for the prevention of delayed chemotherapy-induced nausea and vomiting in adults. The objective of this pivotal study was to assess the bioequivalence of a single intravenous infusion of rolapitant versus a single oral dose of rolapitant. In this randomized, open-label phase 1 study, healthy volunteers were administered rolapitant as a 180-mg oral dose or a 30-minute 166.5-mg intravenous infusion. Blood samples for pharmacokinetic analysis were collected predose and at points up to 912 hours postdose. Criteria for bioequivalence of the intravenous dose versus the oral dose were met if the 90% confidence intervals (CIs) for the ratios of the geometric least-squares means (GLSMs) for the area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC0-t ) and AUC from time 0 extrapolated to infinity (AUC0-∞ ) for rolapitant were within 0.80-1.25. Mean rolapitant systemic exposure and half-lives were similar in the oral (n = 62) and intravenous (n = 61) rolapitant groups. The 90%CIs of the ratio of GLSMs were within the 0.80-1.25 range for AUC0-t (0.94-1.09) and AUC0-∞ (0.93-1.10). The incidence of treatment-emergent adverse events, all mild or moderate in severity, was similar in the intravenous and oral groups. A 166.5-mg intravenous infusion of rolapitant met the bioequivalence criteria based on AUC to a 180-mg oral dose and was well tolerated.

Rolapitant is a selective and long-acting neurokinin-1 receptor antagonist approved in an oral formulation in combination with other antiemetic agents for the prevention of delayed chemotherapy-induced nausea and vomiting in adults. Four open-label phase 1 studies evaluated the safety and drug-drug interactions of a single dose of rolapitant given intravenously (166.5 mg) or orally (180 mg) with oral digoxin (0.5 mg) or sulfasalazine (500 mg), probe substrates for the P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), respectively. Administration of intravenous rolapitant with the substrates did not result in clinically significant effects on digoxin and sulfasalazine pharmacokinetics. In contrast, peak concentration and area under the curve for last quantifiable plasma concentrations increased by 71% (geometric mean ratio [GMR], 1.71; 90% confidence interval [CI], 1.49-1.95) and 30% (GMR, 1.30; 90%CI, 1.19-1.42), respectively, when rolapitant was coadministered orally with digoxin compared with digoxin alone; they increased by 140% (GMR, 2.40; 90%CI, 2.02-2.86) and 127% (GMR, 2.27; 90%CI, 1.94-2.65), respectively, when rolapitant was given orally with sulfasalazine compared with sulfasalazine alone. Adverse events were mild to moderate in severity in the absence or presence of rolapitant. There were no abnormal clinical laboratory or electrocardiogram findings. Thus, whether administered orally or intravenously, rolapitant was safe and well tolerated. Patients taking oral rolapitant with P-gp and BCRP substrates with a narrow therapeutic index should be monitored for potential adverse events; although increased plasma concentrations of these substrates may raise the risk of toxicity, they are not contraindicated.

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.

Solid-state proton nuclear magnetic resonance (NMR) has been used to investigate the structure and dynamics of a thermoplastic polyurethane elastomer (TPE) filled with carbon nanofibers (CNF’s) for shape-memory applications. The TPE soft segments are above their glass transition temperature (Tg) at ambient temperature and give rise to relatively narrow (∼2 kHz) signals in the solid-state proton spectrum. The introduction of CNF’s leads to a concentration-dependent shifting and broadening of the signals, while the proton spin−lattice and spin−spin relaxation times are not significantly altered, showing that the broadening is inhomogeneous and related to the difference in magnetic susceptibility between the TPE and the CNF’s. Proton spin diffusion experiments reveal the onset of stress-induced crystallinity as the samples are stretched to 60%, and stretching to 1000% leads to crystallization at the CNF surface and increased separation between the CNF’s and the mobile amorphous phase of the TPE. The implicat...

Purpose: The surgical resident experience with trauma has changed. Many residents are exposed to predominantly nonoperative patient care experiences while on trauma rotations. Data from a large multicenter study were analyzed to estimate surgical resident exposure to trauma laparotomy, diagnostic peritoneal lavage (DPL), and focused abdominal sonography for trauma (U/S). Methods: Centers completed a self-report questionnaire on their institutional demographics, admissions, and procedure for a 2-year period (1998-1999). Results: A total of 82 trauma centers that provide resident teaching were included. The included centers represent over 247,000 trauma admissions. The majority of trauma centers (65.9%) had > 80% blunt injury. Although all centers performed laparotomies, other results were more variable. For U/S, 24.2% performed none at all and 47.0% performed fewer than two U/S examinations per month. For DPLs, 3.8% performed none and 66.7% performed fewer than two per month. Assuming 1 night of 4 on call, the average surgical resident training at a trauma center performing > 80% blunt trauma has the potential to participate in only 15 trauma laparotomies, 6 diagnostic peritoneal lavages, and 45 ultrasound examinations per year. In addition, the resident will care for an average of 500 blunt trauma patients before performing a splenectomy or liver repair. Conclusion: Surgical resident experience on most trauma services is heavily weighted to nonoperative management, with a relatively low number of procedures, little experience with DPL, and highly variable experience with ultrasound. These data have serious implications for resident training and recruitment into the specialty.

Over a 10-month period during 2013 and early 2014, development of the Neutron star Interior Composition Explorer (NICER) mission [1] proceeded through Phase B, Mission Definition. An external attached payload on the International Space Station (ISS), NICER is scheduled to launch in 2016 for an 18-month baseline mission. Its prime scientific focus is an in-depth investigation of neutron stars—objects that compress up to two Solar masses into a volume the size of a city—accomplished through observations in 0.2–12 keV X-rays, the electromagnetic band into which the stars radiate significant fractions of their thermal, magnetic, and rotational energy stores. Additionally, NICER enables the Station Explorer for X-ray Timing and Navigation Technology (SEXTANT) demonstration of spacecraft navigation using pulsars as beacons. During Phase B, substantive refinements were made to the mission-level requirements, concept of operations, and payload and instrument design. Fabrication and testing of engineering-model components improved the fidelity of the anticipated scientific performance of NICER’s X-ray Timing Instrument (XTI), as well as of the payload’s pointing system, which enables tracking of science targets from the ISS platform. We briefly summarize advances in the mission’s formulation that, together with strong programmatic performance in project management, culminated in NICER’s confirmation by NASA into Phase C, Design and Development, in March 2014.

224 Background: Nausea control remains an unmet need for patients receiving moderately or highly emetogenic chemotherapy (MEC, HEC). The objective of this analysis was to determine the effect of the neurokinin-1 (NK-1) receptor antagonist rolapitant (VARUBI) on the prevention of nausea in patients receiving either MEC or HEC. Methods: Post hoc analyses of nausea from three randomized, double-blind, active-controlled, phase 3 clinical trials were performed for carboplatin-based MEC (n = 401), non-carboplatin-based MEC (n = 228), total MEC (n = 629), anthracycline/cyclophosphamide (AC)-based chemotherapy (n = 703), and cisplatin-based HEC (n = 1070). Patients were randomized 1:1 to oral rolapitant 180 mg or placebo ~1–2 h before chemotherapy. All patients received active control: granisetron 2 mg oral or 10 mcg/kg IV and oral dexamethasone 20 mg. Granisetron was continued on days 2 and 3 for patients receiving MEC or AC-based therapy and dexamethasone 8 mg twice daily on days 2–4 for patients receiving HEC. Patients self-assessed nausea on days 1–6 using a 100-mm visual analog scale (VAS). Percentage of patients with no nausea (NN; maximum VAS < 5 mm) or no significant nausea (NSN; maximum VAS < 25 mm) was determined for overall, delayed, and acute phases of CINV in cycle 1. Results: Rates of NN in the carboplatin-based MEC and total MEC subgroups were significantly higher (P < 0.05) with rolapitant than active control in the delayed and overall phases. In the cisplatin-based HEC subgroup, rates of NN and NSN were significantly higher (P < 0.05) with rolapitant than active control in the delayed, acute, and overall phases. Conclusions: Rolapitant prevents nausea during all CINV phases in patients receiving cisplatin-based HEC, and during the delayed and overall phases in patients receiving carboplatin-based MEC. Clinical trial information: NCT01500226, NCT01499849, NCT01500213.

223 Background: Rolapitant, a long-acting neurokinin-1 receptor antagonist, protected against CINV in patients receiving highly or moderately emetogenic chemotherapy (HEC or MEC). Methods: In 3 double-blind phase 3 studies, patients were randomized to receive oral rolapitant 180 mg or placebo before administration of HEC or MEC. All patients received a 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone. In a post hoc analysis of 3 pooled studies (2 HEC and 1 MEC), we assessed the efficacy and safety of rolapitant in patients with gynecologic (ovarian, uterine, or cervical) cancer. Endpoints included complete response (CR; no emesis and no use of rescue medication), no emesis, no nausea (maximum visual analogue scale [VAS] < 5 mm), and complete protection (CP; no emesis, no use of rescue medication, and no significant nausea [maximum VAS < 25 mm]) in the overall (0–120 h), acute (≤ 24 h), and delayed (> 24–120 h) phases. Results: Of 201 patients with gynecologic cancer (60% ovarian, 28% uterine, and 12% cervical cancer), 55% received cisplatin-based HEC and 44% received MEC (99% of whom received carboplatin-based therapy). In the overall and delayed phases, improved rates of CR, no emesis, no nausea, and CP were observed with rolapitant compared with control (Table). The overall incidence of treatment-emergent adverse events was similar in the rolapitant and control groups (45% vs 54%). Conclusions: Rolapitant protected against overall and delayed CINV in patients with gynecologic cancer receiving HEC or MEC. Clinical trial information: NCT01500226, NCT01499849, NCT01500213. [Table: see text]

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.

10121Background: Addition of the neurokinin-1 receptor antagonist (RA) rolapitant to standard antiemetic therapy improved CINV control in a phase 3 trial of patients administered anthracycline/cycl...

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.

209 Background: Rolapitant, a novel NK-1 receptor antagonist, showed efficacy in CINV prevention in patients (pts) receiving MEC (anthracycline/cyclophosphamide (AC) and other regimens) in a global phase 3 trial. Recent anti-emetic guidelines consider AC based regimens to be highly emetogenic. In this post hoc analysis, the efficacy and safety of rolapitant was assessed in Cycle 1 in pts receiving non-AC MEC, and in the subset of pts receiving carboplatin-based MEC. Methods: In a double-blind, active-controlled study, pts were randomized to oral rolapitant 180 mg or placebo 1–2 hours before MEC. All pts received granisetron 2 mg oral on days 1-3 and oral dexamethasone 20 mg on day 1. Complete response (CR = no emesis + no use of rescue medication), no emesis, and no nausea were assessed in overall (0-120 h), acute (0-24 h), and delayed ( > 24-120 h) phases. Results: CR was significantly (P < 0.01) higher with rolapitant than active control in overall and delayed phases in the carboplatin subset and in all 3 phases in the non-AC population (Table). No emesis rates were significantly (p < 0.05) higher with rolapitant in the carboplatin subset in the overall phase. No nausea rates were significantly (P < 0.05) higher with rolapitant in the overall and delayed phases in carboplatin-based MEC. Incidences of treatment-related AEs in Cycle 1 with rolapitant vs. active control were 11.3% vs. 6.7% in the carboplatin-based subset. Most common AEs with rolapitant and active control were constipation, fatigue, and headache. Conclusions: Rolapitant was superior to active control in preventing CINV in pts receiving non-AC MEC, including in the subgroup receiving carboplatin. Rolapitant was well tolerated with low incidence of AEs. Clinical trial information: NCT01500226. [Table: see text]

210 Background: The long-acting neurokinin-1 receptor antagonist (NK-1 RA) rolapitant has demonstrated efficacy for CINV prevention in patients receiving HEC and MEC during Cycle 1. The efficacy and safety of rolapitant was examined during subsequent cycles 2–6 in a pooled analysis. Methods: In 4 double-blind, active-controlled studies, patients were randomized to oral rolapitant 180 mg or placebo 1–2 hours before chemotherapy. All patients received active control: 5HT3 receptor antagonist + oral dexamethasone. Patients completing Cycle 1 could receive the same anti-emetic treatment in subsequent cycles. On Days 6-8 of subsequent cycles, patients self-reported the incidence of emesis, or of nausea interfering with normal daily life following Day 1 of chemotherapy. Results: A greater proportion of patients on rolapitant than on active control reported no emesis or interfering nausea separately for each subsequent cycle. Results of individual studies and pooled analysis are shown in the Table. During cycles 2-6, the incidence of treatment-related adverse events (AEs) was similar for rolapitant (5.5%) and control (6.8%). The most common treatment-related AEs were similar in both arms: constipation (rolapitant: 1.2%; control: 0.8%) and fatigue (rolapitant: 1.3%; control: 1.8%). Conclusions: Rolapitant was superior to active control in reducing CINV when administered over multiple cycles of moderately or highly emetogenic chemotherapy, with no increase in toxicity. Clinical trial information: NCT00394966 - NCT01500213 - NCT01500226 - NCT01499849. [Table: see text]

The Global Precipitation Measurement mission is a joint NASA/JAXA mission scheduled for launch in late 2013. The Preliminary Design Review was held in November 2008 and the Critical Design Review in December 2009. During that time and beyond, numerous design changes were implemented, some due to necessity and others due to the maturation of the design and requirements. This paper seeks to capture the lessons learned by discussing the design evolution and how it related to requirements and needs of the mission. The major design drivers and resultant design from before and through PDR will be discussed. The overall design required the avionics to be externally mounted to a spacecraft structure far from the center of gravity due to the required locations of the heavy nadir facing instruments. To conserve mass, a five-sided structure with the open side in the direction of deep space served as mounting structure for the avionics and radiated the waste heat out the cavity to space. An additional radiator was externally mounted and connected via heatpipes to this structure to supplement the cavity heat rejection. A Variable Conductance Heat Pipe (VCHP) system with isothermalizing CCHPs was also envisioned to maintain the stringent battery temperature and gradient requirements. Weaknesses of the PDR design were identified, as well as evolution of requirements; these weaknesses and requirements updates will be discussed along with the changes to the design that would eventually be presented at CDR. This design featured conventional radiators connected via heatpipes to the avionics and provided better margins for power growth. Lastly, post-CDR updates to specific subsystems will be described to fully determine the design that will be manufactured. Lessons learned through the design process are presented in hopes that future missions with similar requirements or needs can benefit from the challenges overcome by GPM.

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.