XRISE-M: X-radiography facility for solidification and diffusion studies of alloys aboard sounding rockets.

A compact fully protected microfocus X-radiography facility (XRISE-M) is presented for the study of microstructure evolution during the solidification of thin liquid alloy samples and chemical diffusion in liquid binary alloys in situ and in real-time aboard a sounding rocket. XRISE-M presently enables the simultaneous processing of either two near-isothermal solidification furnaces or a combination of a linear-shear cell diffusion furnace and a near-isothermal solidification furnace. For optimal detector calibration shortly before flight, the furnaces can be rotated around the central beam axis and calibration images can be recorded. The facility allows preheating the samples into the liquid state prior to lift-off without leakage during the ascent phase at accelerations of up to 27 g. Macrosegregation on remelting of thin metal samples for microstructure evolution investigations is prevented by an inclinable furnace metric. The use of ion-getter pumps for vacuum generation enables us to exploit the entire available time of reduced gravity for image recording and data acquisition. With the device and currently available sample environments, microstructure formation upon solidification and chemical diffusion under purely diffusive conditions in alloys can be investigated. The facility can be used equally for other investigations such as granular matter dynamics or metal foaming, provided that suitable experiment inserts are developed in the future.

ARTEC-A furnace module for directional solidification and quenching experiments in microgravity.

A new experimental design for directional solidification experiments with high cooling rates under microgravity conditions is presented. The aerogel-based furnace module ARTEC (AeRogel TEchnology for Cast alloys) developed at DLR extends the earlier presented sounding rocket facility ARTEX by enabling a transition from low to high solidification velocities and a simultaneous operation of five independent furnaces in the same sounding rocket module. The furnaces for directional solidification are equipped with thermally insulating aerogels as a crucible material. Their optical transparency allows the control of the solidification parameters (velocity and temperature gradient) with optical methods in the lab. In ARTEC, a drastically increased solidification velocity is achieved by contacting the sample with a movable cooling-rod during processing. Therefore, a better theoretical understanding of the influence of a sudden change in solidification velocity on microstructure formation is obtained. Carrying out experiments in microgravity gives access to purely diffusive solidification conditions. Hence, convection free-growth can be compared with growth subject to natural (earth) and/or forced-convection (earth and space). Furthermore, alloys with high density differences in their alloy components and, hence, also between the primary solidifying phase and the surrounding liquid can be studied without the negative influence of fluid-flow or macrosegregation being present.

Automated end-to-end blood testing at the point-of-care: Integration of robotic phlebotomy with downstream sample processing.

Diagnostic blood testing is the most commonly performed clinical procedure in the world, and influences the majority of medical decisions made in hospital and laboratory settings. However, manual blood draw success rates are dependent on clinician skill and patient physiology, and results are generated almost exclusively in centralized labs from large-volume samples using labor-intensive analytical techniques. This paper presents a medical device that enables end-to-end blood testing by performing blood draws and providing diagnostic results in a fully automated fashion at the point-of-care. The system couples an image-guided venipuncture robot, developed to address the challenges of routine venous access, with a centrifuge-based blood analyzer to obtain quantitative measurements of hematology. We first demonstrate a white blood cell assay on the analyzer, using a blood mimicking fluid spiked with fluorescent microbeads, where the area of the packed bead layer is correlated with the bead concentration. Next we perform experiments to evaluate the pumping efficiency of the sample handling module. Finally, studies are conducted on the integrated device - from blood draw to analysis - using blood vessel phantoms to assess the accuracy and repeatability of the resulting white blood cell assay.

Alpha-1 antitrypsin deficiency targeted testing and augmentation therapy: a Canadian Thoracic Society clinical practice guideline.

Alpha-1 antitrypsin (A1AT) functions primarily to inhibit neutrophil elastase, and deficiency predisposes individuals to the development of chronic obstructive pulmonary disease (COPD). Severe A1AT deficiency occurs in one in 5000 to one in 5500 of the North American population. While the exact prevalence of A1AT deficiency in patients with diagnosed COPD is not known, results from small studies provide estimates of 1% to 5%. The present document updates a previous Canadian Thoracic Society position statement from 2001, and was initiated because of lack of consensus and understanding of appropriate patients suitable for targeted testing for A1AT deficiency, and for the use of A1AT augmentation therapy. Using revised guideline development methodology, the present clinical practice guideline document systematically reviews the published literature and provides an evidence-based update. The evidence supports the practice that targeted testing for A1AT deficiency be considered in individuals with COPD diagnosed before 65 years of age or with a smoking history of <20 pack years. The evidence also supports consideration of A1AT augmentation therapy in nonsmoking or exsmoking patients with COPD (forced expiratory volume in 1 s of 25% to 80% predicted) attributable to emphysema and documented A1AT deficiency (level ≤11 µmol/L) who are receiving optimal pharmacological and nonpharmacological therapies (including comprehensive case management and pulmonary rehabilitation) because of benefits in computed tomography scan lung density and mortality.

Defining the clinical outcome status (COS) in sarcoidosis: results of WASOG Task Force.

The clinical outcome of sarcoidosis is quite variable. Several scoring systems have been used to assess the level of disease and clinical outcome. The definition of clinical phenotypes has become an important goal as genetic studies have identified distinct genotypes associated with different clinical phenotypes. In addition, treatment strategies have been developed for patients with resolving versus non resolving disease. A task force was established by the World Association of Sarcoidosis and Other Granulomatous diseases (WASOG) to define clinical phenotypes of the disease based on the clinical outcome status (COS). The committee chose to examine patients five years after diagnosis to determine the COS. Several features of the disease were incorporated into the final nine categories of the disease. These included the current or past need for systemic therapy, the resolution of the disease, and current status of the condition. Sarcoidosis patients who were African American or older were likely to have a higher COS, indicating more chronic disease. The COS may be useful in future studies of sarcoidosis.

Counting, analysing and reporting exacerbations of COPD in randomised controlled trials.

BACKGROUND: Clinical trials measure exacerbations of chronic obstructive pulmonary disease (COPD) inconsistently. A study was undertaken to determine if different methods for ascertaining and analysing COPD exacerbations lead to biased estimates of treatment effects. METHODS: Information on the methods used to count, analyse and report COPD exacerbation rates was abstracted from clinical trials of long-acting bronchodilators or long-acting bronchodilator/inhaled steroid combination products published between 2000 and 2006. Data from the Canadian Optimal Therapy of COPD Trial was used to illustrate how different analytical approaches can affect the estimate of exacerbation rates and their confidence intervals. RESULTS: 22 trials (17,156 patients) met the inclusion criteria and were reviewed. None of the trials adjudicated exacerbations or determined independence of events. 14/22 studies (64%) introduced selection bias by not analysing outcome data for subjects who prematurely stopped study medications. Only 31% of trials used time-weighted analyses to calculate the mean number of exacerbations/patient-year and only 15% accounted for between-subject variation. In the Canadian Optimal Therapy of COPD Trial the rate ratio for exacerbations/patient-year was 0.85 when all data were included in a time-weighted analysis, but was overestimated as 0.79 when data for those who prematurely stopped study medications were excluded and was further overestimated as 0.46 when a time-weighted analysis was not conducted; p values ranged from 0.03 to 0.24 depending on how exacerbations were determined and analysed. CONCLUSIONS: Clinical trials have used widely different methods to define and analyse COPD exacerbations and this can lead to biased estimates of treatment effects. Future trials should strive to include blinded adjudication and assessment of the independence of exacerbation events, and trials should report time-weighted intention-to-treat analyses with adjustments for between-subject variation in COPD exacerbations.

Treating acute exacerbations of chronic bronchitis and community-acquired pneumonia: how effective are respiratory fluoroquinolones?

OBJECTIVE: To provide family physicians with a review of evidence supporting fluoroquinolone therapy for defined patient populations with acute exacerbations of chronic bronchitis (AECB) and community-acquired pneumonia (CAP). QUALITY OF EVIDENCE: A MEDLINE search found surveillance studies, randomized controlled trials, outcome studies, and expert consensus opinion. Descriptions of patient populations for which fluoroquinolone therapy is recommended are based on level I and level III evidence. MAIN MESSAGE: A growing body of evidence supports fluoroquinolones as first-choice agents for treatment of AECB or CAP patients with comorbidity or a recent history of antibiotic use. Judicious and targeted therapy using fluoroquinolones among patients at risk of infections of the lower respiratory tract should contribute to improved clinical outcomes and broader health care savings. CONCLUSION: Current data show clinical utility and cost-effectiveness of fluoroquinolones in lower respiratory tract infections. The most recently issued AECB and CAP guidelines now recommend these antimicrobial agents as first-choice agents for specific patient populations.

Diffuse panbronchiolitis in a Caucasian man in Canada.

Diffuse panbronchiolitis (DPB) is a rare, chronic bronchiolar disease in non-Asian populations and is therefore commonly overlooked in Western countries. It usually affects nonsmokers and manifests as persistent air flow obstruction, chronic cough and interstitial nodular opacities. Untreated, the prognosis is poor. In this report the authors describe a Caucasian man of Canadian descent who presented with progressive clinical and lung function impairment despite three years of bronchodilator and corticosteroid treatment with presumed asthma. His chest computed tomography scan showed diffuse centrilobular opacities. Lung biopsy revealed chronic bronchiolitis characterized by infiltration of lymphocytes, plasma cells and foam cells in respiratory and terminal bronchioles, compatible with a diagnosis of DPB. After two months of therapy with clarithromycin, the patient had already shown improvement. Physicians should be aware that DPB may occur in Western countries, and that DPB should be considered in the differential diagnosis of patients with persistent air flow obstruction and nodular shadows on chest radiograms.

Inhaled beclomethasone dipropionate improves acoustic measures of voice in patients with asthma.

BACKGROUND: Inhaled corticosteroids have the potential to produce upper-airway side effects such as hoarseness. As new compounds and delivery devices are developed and compared, it is difficult to quantify their adverse upper-airway effects. OBJECTIVE: We undertook the following study to test the ability of an acoustic analysis technique to quantify changes in vocal function in steroid-naive patients with asthma who receive inhaled beclomethasone dipropionate (BDP), 1,000 microg/d for 4 months. METHODS: Patients self-administered one of four regimens of inhaled BDP. Group 1 patients received one 250-microg puff qid via metered-dose inhaler (MDI); group 2 patients received one 250-microg puff qid via MDI with a holding chamber; group 3 patients received two 250-microg puffs bid via MDI; and group 4 patients received two 250-microg puffs bid via MDI with a holding chamber. A smaller cohort of nonsmoking asthmatic patients was managed without steroid intervention for 4 months. At baseline and again at 8 weeks and 16 weeks after the initiation of BDP treatment, patients underwent spirometry and methacholine challenge. At baseline and again at 2, 4, 8, 12, and 16 weeks, patients underwent voice recording for analysis of voice parameters. The recorded vowels were low-pass filtered (10 KHz), digitized (22 KHz), and analyzed by software to obtain two acoustic measures: (1) jitter, the cycle-to-cycle variation in the time period of the voice signal; and (2) shimmer, the cycle-to-cycle variation in voice signal amplitude. RESULTS: We recruited 77 patients for randomization to inhaled steroid therapy and 10 patients who continued to receive only occasional inhaled bronchodilator therapy. In all active treatment groups, FEV(1), FVC, and provocative concentration of methacholine causing a 20% fall in FEV(1) improved significantly after BDP treatment. Mean jitter scores, a measurement of variation in voice pitch, were not significantly influenced by BDP treatment. However, mean shimmer scores, a reflection of perturbation in vocal amplitude, fell significantly (p < 0.05) in the active treatment groups. These reductions in shimmer scores were not significantly different in the active treatment groups. Shimmer scores in the bronchodilator-treated group were unchanged during the 16 weeks of follow-up. CONCLUSIONS: Our data show that a simple and noninvasive acoustic analysis of voice is sensitive to subclinical changes associated with inhaled corticosteroid therapy. We have shown that 1,000 microg/d of inhaled BDP actually improves specific acoustic measures of voice in patients with inadequately controlled asthma. These improvements were uninfluenced by dosing schedule and whether a spacing chamber was used.