Acoustic and vibration isolation for a gravity gradiometer.

Vibration in the audio frequency band affects the performance of rotating gravity gradiometers used for airborne mineral exploration. This is probably due to translation to rotation coupling inside the gradiometer platform. It was found that the DC gravity gradient signal was proportional to the square of the third time derivative of position, or jerk squared. The demanding airborne environment for such instrumentation demands a light weight broadband acoustic shield and vibration isolator. This paper presents the design principles for such an isolator, based on vibration isolated spherical shell structures. Performance data are presented as well as flight test data that demonstrated a 14% gravity gradient noise reduction compared with an unshielded instrument.

Asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) longitudinal profiling study.

BACKGROUND: Asthma is a heterogeneous disease and development of novel therapeutics requires an understanding of pathophysiologic phenotypes. The purpose of the ADEPT study was to correlate clinical features and biomarkers with molecular characteristics, by profiling asthma (NCT01274507). This report presents for the first time the study design, and characteristics of the recruited subjects. METHODS: Patients with a range of asthma severity and healthy non-atopic controls were enrolled. The asthmatic subjects were followed for 12 months. Assessments included history, patient questionnaires, spirometry, airway hyper-responsiveness to methacholine, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum, blood, and bronchoscopy samples. All subjects underwent sputum induction and 30 subjects/cohort had bronchoscopy. RESULTS: Mild (n = 52), moderate (n = 55), severe (n = 51) asthma cohorts and 30 healthy controls were enrolled from North America and Western Europe. Airflow obstruction, bronchodilator response and airways hyperresponsiveness increased with asthma severity, and severe asthma subjects had reduced forced vital capacity. Asthma control questionnaire-7 (ACQ7) scores worsened with asthma severity. In the asthmatics, mean values for all clinical and biomarker characteristics were stable over 12 months although individual variability was evident. FENO and blood eosinophils did not differ by asthma severity. Induced sputum eosinophils but not neutrophils were lower in mild compared to the moderate and severe asthma cohorts. CONCLUSIONS: The ADEPT study successfully enrolled asthmatics across a spectrum of severity and non-atopic controls. Clinical characteristics were related to asthma severity and in general asthma characteristics e.g. lung function, were stable over 12 months. Use of the ADEPT data should prove useful in defining biological phenotypes to facilitate personalized therapeutic approaches.

Computed tomographic measures of airway morphology in smokers and never-smoking normals.

Bronchial wall area percent (WA% = 100 × wall area/total bronchial cross sectional area) is a standard computed tomographic (CT) measure of central airway morphology utilized in smokers with chronic obstructive pulmonary disease (COPD). Although it provides significant clinical correlations, the range of reported WA% is narrow. This suggests limited macroscopic change in response to smoking or that remodeling proportionally affects the airway wall and lumen dimensions such that their ratio is preserved. The objective of this study is to assess central airway wall area (WA), lumen area (Ai), and total bronchial area (Ao) from CT scans of 5,179 smokers and 92 never smoking normal subjects. In smokers, WA, Ai, and Ao were positively correlated with forced expiratory volume in 1 s (FEV1) expressed as a percent of predicted (FEV1%), and the WA% was negatively correlated with FEV1% (P < 0.0001 for all comparisons). Importantly, smokers with lower FEV1% tended to have airways of smaller cross-sectional area with lower WA. The increases in the WA% across GOLD stages of chronic obstructive pulmonary disease (COPD) can therefore not be due to increases in WA. The data suggest two possible origins for the WA% increases: 1) central airway remodeling resulting in overall reductions in airway caliber in excess of the decreased WA or 2) those with COPD had smaller native airways before they began smoking. In both cases, these observations provide an explanation for the limited range of values of WA% across stages of COPD.

Biologic lung volume reduction therapy for advanced homogeneous emphysema.

This report summarises phase 2 trial results of biologic lung volume reduction (BioLVR) for treatment of advanced homogeneous emphysema. BioLVR therapy was administered bronchoscopically to 25 patients with homogeneous emphysema in an open-labelled study. Eight patients received low dose (LD) treatment with 10 mL per site at eight subsegments; 17 received high dose (HD) treatment with 20 mL per site at eight subsegments. Safety was assessed in terms of medical complications during 6-month follow-up. Efficacy was assessed in terms of change from baseline in gas trapping, spirometry, diffusing capacity, exercise capacity, dyspnoea and health-related quality of life. There were no deaths or serious medical complications during the study. A statistically significant reduction in gas trapping was observed at 3-month follow-up among HD patients, but not LD patients. At 6 months, changes from baseline in forced expiratory volume in 1 s (-8.0+/-13.93% versus +13.8+/-20.26%), forced vital capacity (-3.9+/-9.41% versus +9.0+/-13.01%), residual volume/total lung capacity ratio (-1.4+/-13.82% versus -5.4+/-12.14%), dyspnoea scores (-0.4+/-1.27 versus -0.8+/-0.73 units) and St George's Respiratory Questionnaire total domain scores (-4.9+/-8.3 U versus -12.2+/-12.38 units) were better with HD than with LD therapy. BioLVR therapy with 20 mL per site at eight subsegmental sites may be a safe and effective therapy in patients with advanced homogeneous emphysema.

Use of beta blockers and the risk of death in hospitalised patients with acute exacerbations of COPD.

BACKGROUND: Cardiovascular disease is a major cause of death in patients with chronic obstructive pulmonary disease (COPD) and predicts hospitalisation for acute exacerbation, in-hospital death and post-discharge mortality. Although beta blockers improve cardiovascular outcomes, patients with COPD often do not receive them owing to concerns about possible adverse pulmonary effects. There are no published data about beta blocker use among inpatients with COPD exacerbations. A study was undertaken to identify factors associated with beta blocker use in this setting and to determine whether their use is associated with decreased in-hospital mortality. METHODS: Administrative data from the University of Alabama Hospital were reviewed and patients admitted between October 1999 and September 2006 with an acute exacerbation of COPD as a primary diagnosis or as a secondary diagnosis with a primary diagnosis of acute respiratory failure were identified. Demographic data, co-morbidities and medication use were recorded and subjects receiving beta blockers were compared with those who did not. Multivariate regression analysis was performed to determine predictors of in-hospital death after controlling for known covariates and the propensity to receive beta blockers. RESULTS: 825 patients met the inclusion criteria. In-hospital mortality was 5.2%. Those receiving beta blockers (n = 142) were older and more frequently had cardiovascular disease than those who did not. In multivariate analysis adjusting for potential confounders including the propensity score, beta blocker use was associated with reduced mortality (OR = 0.39; 95% CI 0.14 to 0.99). Age, length of stay, number of prior exacerbations, the presence of respiratory failure, congestive heart failure, cerebrovascular disease or liver disease also predicted in-hospital mortality (p<0.05). CONCLUSIONS: The use of beta blockers by inpatients with exacerbations of COPD is well tolerated and may be associated with reduced mortality. The potential protective effect of beta blockers in this population warrants further study.

Automated electronic systems for the detection of oestrus and timing of AI in cattle.

For the majority of dairy herds where artificial insemination (AI) is practiced, the limiting factor toward obtaining efficient reproductive performance is the failure to detect oestrus in a timely and accurate manner. Periodic visual observation has been the dominant method used to identify cows in oestrus. New approaches are being developed to provide automated systems of detection of oestrus using electronic technology. The goal of an oestrus detection program should be to identify oestrus positively and accurately in all cycling animals and consequently to identify animals not cycling. The ultimate goal should be to predict the time of ovulation, thus allowing for insemination that will maximize the opportunity for conception. Unfortunately, most studies designed to evaluate the optimal time of AI generally contained two technical deficiencies: inadequate numbers of cows for valid statistical comparisons and inaccurate knowledge of the onset of oestrus because of low frequency of visual observations and/or efficiency of methods used for the detection of oestrus. Studies using pedometry and a pressure sensing radiotelemetric system will be reviewed as each have independently obtained an optimal time of AI of 5 to 17 h after either the increase in locomotive activity or following the first standing event associated with the onset of oestrus.

Differential control of autoantibodies and lymphoproliferation by Fas ligand expression on CD4+ and CD8+ T cells in vivo.

We have previously shown that the gld autoimmune syndrome is suppressed in lethally irradiated gld mice reconstituted with a mixture of normal and gld bone marrow (BM). Furthermore, in vivo depletion of normal Thy-1+ cells restores lymphoproliferation and autoantibody production in such chimeras, suggesting that T cells bearing Fas ligand are responsible for correcting the gld defect. In this study, mixed-BM chimeras lacking either normal CD4+ (B6CD4KO-B6gld) or normal CD8+ T cells (B6CD8KO-B6gld) were generated to determine the contribution of the normal T cell subsets to disease suppression. Lymphoproliferation was completely suppressed in B6CD4KO-B6gld chimeras but only modestly in B6CD8KO-B6gld chimeras. On the other hand, both types of mixed-BM chimeras had incomplete effects on the suppression of serum autoantibodies when compared with B6gld reconstituted with isologous BM. These results suggest that both T cell subsets provide Fas ligand to suppress immune cells responsible for autoantibody production; however, CD8+ T cells are mainly responsible for preventing lymphoproliferation.

Timing of insemination for dairy cows identified in estrus by a radiotelemetric estrus detection system.

The optimal time of artificial insemination (AI) was determined from data for 2661 AI in 17 herds utilizing a radiotelemetric system for estrus detection that has the potential for continuous 24-h surveillance to monitor behavioral events associated with estrus. The system consisted of pressure-sensitive radio frequency transmitters affixed over the sacrum region of cows. The activation of the sensor sent a radiotelemetric signal to a microcomputer via a fixed antenna. Cow identification, date, time, and duration of each standing event were recorded in the software program provided with the system. Each farm selected a 3-h interval to AI for cows that were identified in estrus during the previous 24 h. Pregnancy status was determined from data for return to estrus and palpation of the uterus 35 to 75 d following AI. Standing events during estrus averaged (+/- SD) 8.5 +/- 6.6 per cow, and the number of events per estrus across herds averaged from 6.2 +/- 5.1 to 12.8 +/- 9.9 per cow. The duration of estrus ranged from 5.1 +/- 3.8 to 10.6 +/- 6.8 h across herds; the mean was 7.1 +/- 5.4 h. The interval from the first standing event to AI affected the probability of pregnancy; the highest conception rates for AI occurred between 4 and 12 h after the onset of standing activity. The probability of pregnancy was higher for cows > 100 d in milk, exhibiting > 2 standing events during estrus, and inseminated during March, April or May.