Association of Frailty Indicators and Health Care Related Outcomes In Severe Chronic Obstructive Pulmonary Disease.

Background: COPD is a chronic disease that not only has a high prevalence but is associated with a significant reduced health- related quality of life (HRQoL). Frailty is a prevalent health problem of older people with adverse outcomes. The purpose of this study was to examine demographic characteristics, clinical characteristics, physical frailty indicators, and psychological frailty indicators and their impact on health care outcomes (health related quality of life, death, and utilization of health care resources) in people with severe COPD over time. Methods: The research was a secondary data analysis of 610 severe COPD individuals. HRQol was assessed using the St. George’s Respiratory Questionnaire (SGRQ), death was all cause mortality, and health care utilization measured by a self- reported questionnaire. Results: Age, gender, education, endurance, balance, mobility, coping, and depression were significant (p = <.05) predictors in the models of HRQOL. The total variance explained by the baseline model (demographic, physical, and psychological frailty indicators) was 36%, F (16, 567) = 20.31, p = < .001. The mean survival time for lower frail individuals was 7.4 years compared to 4.7 years for higher frail individuals (p = <.001). Gender, income, education, smoking history, depression, PaO2 (RA), DLCO, TLC, RV, FEV1, endurance, nutrition, education, and balance were significant (p = <.05) predictors in the models of health care utilization. Conclusions: Mobility and coping were significant indicators (p = <.001) over time predicting quality of life. These indicators should be included in frailty models. Higher frailty was associated with higher mortality. Those with higher COPD disease severity required increased home visits from health professionals.PHDNursingUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/107320/1/cathymel_1.pd

Geophysical-geotechnical sensor networks for landslide monitoring

Landslides are often the result of complex, multi-phase processes where gradual deterioration of shear strength within the sub-surface precedes the appearance of surface features and slope failure. Moisture content increases and the build-up of associated pore water pressures are invariably associated with a loss of strength, and thus are a precursor to failure. Consequently, hydraulic processes typically play a major role in the development of landslides. Geoelectrical techniques, such as resistivity and self-potential are being increasingly applied to study landslide structure and the hydraulics of landslide processes. The great strengths of these techniques are that they provide spatial or volumetric information at the site scale, which, when calibrated with appropriate geotechnical and hydrogeological data, can be used to characterise lithological variability and monitor hydraulic changes in the subsurface. In this study we describe the development of an automated time-lapse electrical resistivity tomography (ALERT) and geotechnical monitoring system on an active inland landslide near Malton, North Yorkshire, UK. The overarching objective of the research is to develop a 4D landslide monitoring system that can characterise the subsurface structure of the landslide, and reveal the hydraulic precursors to movement. The site is a particularly import research facility as it is representative of many lowland UK situations in which weak mudrocks have failed on valley sides. Significant research efforts have already been expended at the site, and a number of baseline data sets have been collected, including ground and airborne LIDAR, geomorphologic and geological maps, and geophysical models. The monitoring network comprises an ALERT monitoring station connected to a 3D monitoring electrode array installed across an area of 5,500 m2, extending from above the back scarp to beyond the toe of the landslide. The ALERT instrument uses wireless telemetry (in this case GPRS) to communicate with an office based server, which runs control software and a database management system. The control software is used to schedule data acquisition, whilst the database management system stores, processes and inverts the remotely streamed ERT data. Once installed and configured, the system operates autonomously without manual intervention. Modifications to the ALERT system at this site have included the addition of environmental and geotechnical sensors to monitor rainfall, ground movement, ground and air temperature, and pore pressure changes within the landslide. The system is housed in a weatherproof enclosure and is powered by batteries charged by a wind turbine & solar panels. 3D ERT images generated from the landslide have been calibrated against resistivity information derived from laboratory testing of borehole core recovered from the landslide. The calibrated images revealed key aspects of the 3D landslide structure, including the lateral extent of slipped material and zones of depletion and accumulation; the surface of separation and the thickness of individual earth flow lobes; and the dipping in situ geological boundary between the bedrock formations. Time-lapse analysis of resistivity signatures has revealed artefacts within the images that are diagnostic of electrode movement. Analytical models have been developed to simulate the observed artefacts, from which predictions of electrode movement have been derived. This information has been used to correct the ERT data sets, and has provided a means of using ERT to monitor landslide movement across the entire ALERT imaging area. Initial assessment of seasonal changes in the resistivity signature has indicated that the system is sensitive to moisture content changes in the body of the landslide, thereby providing a basis for further development of the system with the aim of monitoring hydraulic precursors to failure

Lung CD8+ T cells in COPD have increased expression of bacterial TLRs

Abstract Background Toll-like receptors (TLRs) on T cells can modulate their responses, however, the extent and significance of TLR expression by lung T cells, NK cells, or NKT cells in chronic obstructive pulmonary disease (COPD) is unknown. Methods Lung tissue collected from clinically-indicated resections (n = 34) was used either: (a) to compare the expression of TLR1, TLR2, TLR2/1, TLR3, TLR4, TLR5, TLR6 and TLR9 on lung CD8+ T cells, CD4+ T cells, NK cells and NKT cells from smokers with or without COPD; or (b) to isolate CD8+ T cells for culture with anti-CD3ε without or with various TLR ligands. We measured protein expression of IFN-γ, TNF-α, IL-13, perforin, granzyme A, granzyme B, soluble FasL, CCL2, CCL3, CCL4, CCL5, CCL11, and CXCL9 in supernatants. Results All the lung subsets analyzed demonstrated low levels of specific TLR expression, but the percentage of CD8+ T cells expressing TLR1, TLR2, TLR4, TLR6 and TLR2/1 was significantly increased in COPD subjects relative to those without COPD. In contrast, from the same subjects, only TLR2/1 and TLR2 on lung CD4+ T cells and CD8+ NKT cells, respectively, showed a significant increase in COPD and there was no difference in TLR expression on lung CD56+ NK cells. Production of the Tc1 cytokines IFN-γ and TNF-α by lung CD8+ T cells were significantly increased via co-stimulation by Pam3CSK4, a specific TLR2/1 ligand, but not by other agonists. Furthermore, this increase in cytokine production was specific to lung CD8+ T cells from patients with COPD as compared to lung CD8+ T cells from smokers without COPD. Conclusions These data suggest that as lung function worsens in COPD, the auto-aggressive behavior of lung CD8+ T cells could increase in response to microbial TLR ligands, specifically ligands against TLR2/1.http://deepblue.lib.umich.edu/bitstream/2027.42/112427/1/12931_2012_Article_1320.pd

Basal Gene Expression by Lung CD4+ T Cells in Chronic Obstructive Pulmonary Disease Identifies Independent Molecular Correlates of Airflow Obstruction and Emphysema Extent

Lung CD4+ T cells accumulate as chronic obstructive pulmonary disease (COPD) progresses, but their role in pathogenesis remains controversial. To address this controversy, we studied lung tissue from 53 subjects undergoing clinically-indicated resections, lung volume reduction, or transplant. Viable single-cell suspensions were analyzed by flow cytometry or underwent CD4+ T cell isolation, followed either by stimulation with anti-CD3 and cytokine/chemokine measurement, or by real-time PCR analysis. In lung CD4+ T cells of most COPD subjects, relative to lung CD4+ T cells in smokers with normal spirometry: (a) stimulation induced minimal IFN-γ or other inflammatory mediators, but many subjects produced more CCL2; (b) the T effector memory subset was less uniformly predominant, without correlation with decreased IFN-γ production. Analysis of unstimulated lung CD4+ T cells of all subjects identified a molecular phenotype, mainly in COPD, characterized by markedly reduced mRNA transcripts for the transcription factors controlling TH1, TH2, TH17 and FOXP3+ T regulatory subsets and their signature cytokines. This mRNA-defined CD4+ T cell phenotype did not result from global inability to elaborate mRNA; increased transcripts for inhibitory CD28 family members or markers of anergy; or reduced telomerase length. As a group, these subjects had significantly worse spirometry, but not DLCO, relative to subjects whose lung CD4+ T cells expressed a variety of transcripts. Analysis of mRNA transcripts of unstimulated lung CD4+ T cell among all subjects identified two distinct molecular correlates of classical COPD clinical phenotypes: basal IL-10 transcripts correlated independently and inversely with emphysema extent (but not spirometry); by contrast, unstimulated IFN-γ transcripts correlated independently and inversely with reduced spirometry (but not reduced DLCO or emphysema extent). Aberrant lung CD4+ T cells polarization appears to be common in advanced COPD, but also exists in some smokers with normal spirometry, and may contribute to development and progression of specific COPD phenotypes. Trial Registration ClinicalTrials.gov as NCT0028122

Can CAPTURE Be Used to Identify Undiagnosed Patients with Mild-To-Moderate COPD Likely to Benefit from Treatment?

Background: COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE™) uses five questions and peak expiratory flow (PEF) thresholds (males ≤350 L/min; females ≤250 L/min) to identify patients with a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC)11 60%–80% predicted) who may also benefit from diagnosis and treatment. Methods: Data from the CAPTURE development study were used to test its sensitivity (SN) and specificity (SP) differentiating mild-to-moderate COPD (n=73) from no COPD (n=87). SN and SP for differentiating all COPD cases (mild to severe; n=259) from those without COPD (n=87) were also estimated. The modified Medical Research Council (mMRC) dyspnea scale and COPD Assessment Test (CAT™) were used to evaluate symptoms and health status. Clinical Trial Registration: NCT01880177, https://ClinicalTrials.gov/ct2/show/NCT01880177?term=NCT01880177&rank=1. Results: Mean age (+SD): 61 (+10.5) years; 41% male. COPD: FEV1/FVC=0.60 (+0.1), FEV1% predicted=74% (+12.4). SN and SP for differentiating mild-to-moderate and non-COPD patients (n=160): Questionnaire: 83.6%, 67.8%; PEF (≤450 L/min; ≤350 L/min): 83.6%, 66.7%; CAPTURE (Questionnaire+PEF): 71.2%, 83.9%. COPD patients whose CAPTURE results suggested that diagnostic evaluation was warranted (n=52) were more likely to be symptomatic than patients whose results did not (n=21) (mMRC \u3e2: 37% vs 5%, p10: 86% vs 57%, p Conclusion: CAPTURE (450/350) may be useful for identifying symptomatic patients with mild-to-moderate airflow obstruction in need of diagnostic evaluation for COPD

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

SAE clean snowmobile challenge 2003 summary of results

The Environmental Protection Agency (EPA) has published new emissions standards for snowmobiles, Federal Register 40 CFR, Control of Emissions from Non-road Large Spark Ignition Engines and Recreational Engines (Marine and Land Based) ; Final Rule, Volume 67., No.217, November 8, 2002. These rules require a phase in of lower snowmobile emissions over the period of 2006 to 2012. In addition, the International Snowmobile Manufacturers\u27 Association (ISMA) is developing new pass-by noise standards to replace the current wide-open throttle noise standard SAE J - 192 and J 1161. These new requirements set the stage for improvements in snowmobiles and form the basis for the Society of Automotive Engineers (SAE) Clean Snowmobile Challenge (CSC). SAE and Michigan Technological University (MTU) worked together, along with many other volunteers, to continue the SAE CSC, moving it from its original venue in Wyoming to Michigan. The goal of SAE CSC is to encourage development of a touring type snowmobile with improved emission and noise characteristics that does not sacrifice performance. Modifications are expected to be cost effective and practical. The participants in SAE CSC 2003 competed in a variety of events including emissions, noise, endurance/fuel economy, acceleration, handling, braking and design. Points were awarded to teams based on their performance in each of the events. The University of Idaho won SAE CSC 2003 with a snowmobile featuring a four-stroke engine with a custom built header, catalytic converter and a spiral silencer. The University of Idaho was also awarded Best Performance, Best Emissions, Best Fuel Economy, Quietest Snowmobile, and Best Value. It was successful at completing and passing all competition events and did so without any penalties

A randomised controlled trial of multimodal physiotherapy versus advice for recent onset, painful cervical radiculopathy - the PACeR trial protocol.

BACKGROUND: A research gap exists for optimal management of cervical radiculopathy in the first 12 weeks and short term natural history of the condition is somewhat unclear, although thought to be favourable. The primary aim of this assessor blinded, superiority, 2 parallel group randomised controlled trial is to investigate the effects of a 4 week physiotherapy programme (6-8 sessions) of manual therapy, exercise and upper limb neural unloading tape, compared to a control of weekly phone advice; on disability, pain and selected biopsychosocial measures, in acute and sub-acute cervical radiculopathy patients. A secondary aim is to identify whether any baseline variables, symptom duration or group allocation can predict outcome. METHODS: Participants are recruited from GP referrals in an urban setting, from a neurosurgery non-urgent waiting list and from self-referral through Facebook advertising. Eligible participants (n = 64) are diagnosed with radiculopathy based on a clinical prediction rule and must have symptoms of unilateral, single level, radiculopathy for between 2 and 12 weeks, without having yet received physiotherapy. Random 1:1 group allocation (using variable block sizes), allocation concealment, blinded assessment and intention to treat analysis are being employed. Treatment is provided by clinical specialist physiotherapists in primary and secondary care settings. Outcomes are measured at baseline, 4 (primary endpoint) and 12 weeks. Participants' report of pain, disability and their rating of recovery is also recorded by telephone interview at 6 months. Statistical analysis of between group differences will be performed with ANOVAs and MANOVAs, and multivariable regression analysis will be undertaken to explore predictor variables. Ethical approval for this study has been received from the Beaumont Hospital and Irish College of General Practitioners Research Ethics Committees. The trial is registered at ClinicalTrials.gov (NCT02449200). DISCUSSION: An internal pilot study to test retention and recruitment strategies led to trial expansion and this is now a multi centre trial involving 5 clinical sites. TRIAL REGISTRATION: NCT02449200 . Registered 20/05/15.</p

NETT Coordinators: Researchers, Caregivers, or Both?

The National Emphysema Treatment Trial (NETT) required the coordinated evaluation and treatment of thousands of patients with emphysema simultaneous with data collection to evaluate the safety and efficacy of surgery versus medical treatment for emphysema. These tasks were performed by a multidisciplinary team led by the clinic coordinator at each NETT center. The clinic coordinators functioned as members of the research team as well as communicators, managers, and members of the patient care team. The clinic coordinators' ability to balance these roles was instrumental to the successful completion of NETT, as evidenced by randomization of 1,218 subjects with only 10 subjects being lost to follow-up. Striving to achieve recruitment goals and working to retain study subjects was very labor intensive. The coordinator role was complicated by the study population's severity of illness combined with the complexity of the NETT protocol. Management of the study subjects' medical condition had to be balanced with the management of a multicenter, randomized clinical trial to ensure quality data collection and protocol adherence

Multidisciplinary Care of the Patient with Chronic Obstructive Pulmonary Disease

The National Emphysema Treatment Trial used a multidisciplinary team approach to implement the maximum medical care protocol, including adjustment of medications and outpatient pulmonary rehabilitation for all patients and nutritional and psychological counseling as needed. This article discusses the benefits of such an approach in the care of the patient with chronic obstructive pulmonary disease. Team member roles complement each other and contribute to the goal of providing the highest-quality medical care. The primary focus of the team is to reinforce the medical plan and to provide patient education and support. This article reviews the elements of the initial patient assessment and the functional and nutritional assessment. Patient education focuses on medication use, recognition and management of chronic obstructive pulmonary disease exacerbation symptoms, smoking cessation, advance directives, and travel