Meta-analysis of RNA-seq expression data across species, tissues and studies.

BackgroundDifferences in gene expression drive phenotypic differences between species, yet major organs and tissues generally have conserved gene expression programs. Several comparative transcriptomic studies have observed greater similarity in gene expression between homologous tissues from different vertebrate species than between diverse tissues of the same species. However, a recent study by Lin and colleagues reached the opposite conclusion. These studies differed in the species and tissues analyzed, and in technical details of library preparation, sequencing, read mapping, normalization, gene sets, and clustering methods.ResultsTo better understand gene expression evolution we reanalyzed data from four studies, including that of Lin, encompassing 6-13 tissues each from 11 vertebrate species using standardized mapping, normalization, and clustering methods. An analysis of independent data showed that the set of tissues chosen by Lin et al. were more similar to each other than those analyzed by previous studies. Comparing expression in five common tissues from the four studies, we observed that samples clustered exclusively by tissue rather than by species or study, supporting conservation of organ physiology in mammals. Furthermore, inter-study distances between homologous tissues were generally less than intra-study distances among different tissues, enabling informative meta-analyses. Notably, when comparing expression divergence of tissues over time to expression variation across 51 human GTEx tissues, we could accurately predict the clustering of expression for arbitrary pairs of tissues and species.ConclusionsThese results provide a framework for the design of future evolutionary studies of gene expression and demonstrate the utility of comparing RNA-seq data across studies

Randomised positive control trial of NSAID and antimicrobial treatment for calf fever caused by pneumonia

One hundred and fifty-four preweaning calves were followed between May and October 2015. Calves were fitted with continuous monitoring temperature probes (TempVerified FeverTag), programmed so a flashing light emitting diode (LED) light was triggered following six hours of a sustained ear canal temperature of ≥39.7°C. A total of 83 calves (61.9 per cent) developed undifferentiated fever, with a presumptive diagnosis of pneumonia through exclusion of other calf diseases. Once fever was detected, calves were randomly allocated to treatment groups. Calves in group 1 (NSAID) received 2 mg/kg flunixin meglumine (Allevinix, Merial) for three consecutive days and group 2 (antimicrobial) received 6 mg/kg gamithromycin (Zactran, Merial). If fever persisted for 72 hours after the initial treatment, calves were given further treatment (group 1 received antimicrobial and group 2 received NSAID). Calves in group 1 (NSAID) were five times more likely (P=0.002) to require a second treatment (the antimicrobial) after 72 hours to resolve the fever compared with the need to give group 2 (antimicrobial) calves a second treatment (NSAID). This demonstrates the importance of ongoing monitoring and follow-up of calves with respiratory disease. However, of calves with fever in group 1 (NSAID), 25.7 per cent showed resolution following NSAID-only treatment with no detrimental effect on the development of repeated fever or daily live weight gain. This suggests that NSAID alone may be a useful first-line treatment, provided adequate attention is given to ongoing monitoring to identify those cases that require additional antimicrobial treatment

Estimating the cost-effectiveness of fluticasone propionate for treating chronic obstructive pulmonary disease in the presence of missing data

Objectives: To explore the cost-effectiveness of fluticasone propionate (FP) for the treatment of chronic obstructive pulmonary disease (COPD), we estimated costs and qualityadjusted life-years (QALYs) over 3 years, based on an economic appraisal of a previously reported clinical trial (Inhaled Steroids in Obstructive Lung Disease in Europe [ISOLDE]). Methods: Seven hundred forty-two patients enrolled in the ISOLDE trial who received either FP or placebo had data available on health-care costs and quality of life over the period of the study. The SF-36-based utility scores for quality of life were used to calculate QALYs. A combined imputation and bootstrapping procedure was employed to handle missing data and to estimate statistical uncertainty in the estimated cumulative costs and QALYs over the study period. The imputation approach was based on propensity scoring and nesting this approach within the bootstrap ensured that multiple imputations were performed such that statistical estimates included imputation uncertainty. Results: Complete data were available on mortality within the follow-up period of the study and a nonsignificant trend toward improved survival of 0.06 (95% confidence interval [CI] –0.01 to 0.15) life-years was observed. In an analysis based on a propensity scoring approach to missing data we estimated the incremental costs of FP versus placebo to be £1021 (95% CI £619–1338) with an additional effect of 0.11 QALYs (CI 0.04–0.20). Cost-effectiveness estimates for the within-trial period of £17,700 per life-year gained (£6900 to ∞) and £9500 per QALY gained (CI £4300–26,500) were generated that include uncertainty due to the imputation process. An alternative imputation approach did not materially affect these estimates. Conclusions: Previous analyses of the ISOLDE study showed significant improvement on disease-specific health status measures and a trend toward a survival advantage for treatment with FP. This analysis shows that joint considerations of quality of life and survival result in a substantial increase in QALYs favoring treatment with FP. Based on these data, the inhaled corticosteroid FP appears costeffective for the treatment of COPD. Confirmation or refutation of this result may be achieved once the Towards a Revolution in COPD Health (TORCH) study reports, a large randomized controlled trial powered to detect mortality changes associated with the use of FP alone, or in combination with salmeterol, which is also collecting resource use and utility data suitable for estimating cost-effectiveness

Focus error estimation in images

Estimating focus error in an image involves a training phase and an application phase. In the training phase, an optical system is represented by a point-spread function. An image sensor array is represented by one or more wavelength sensitivity functions, one or more noise functions, and one or more spatial sampling functions. The point-spread function is applied to image patches for each of multiple defocus levels within a specified range to produce training data. Each of the images for each defocus level (i.e. focus error) is sampled using the wavelength sensitivity and spatial sampling functions. Noise is added using the noise functions. The responses from the sensor array to the training data are used to generate defocus filters for estimating focus error within the specified range. The defocus filters are then applied to the image patches of the training data and joint probability distributions of filter responses to each defocus level are characterized. In the application phase, the filter responses to arbitrary image patches are obtained and combined to derive continuous, signed estimates of the focus error of each arbitrary image patch.Board of Regents, University of Texas Syste

Clinical investigation of an outbreak of alveolitis and asthma in a car engine manufacturing plant

Background Exposure to metal working fluid (MWF) has been associated with outbreaks of EAA in the US, with bacterial contamination of MWF being a possible cause, but was uncommon in the UK. Twelve workers developed extrinsic allergic alveolitis (EAA) in a car engine manufacturing plant in the UK, presenting clinically between December 2003 and May 2004. This paper reports the subsequent epidemiological investigation of the whole workforce. This had three aims:- • To measure the extent of the outbreak by identifying other workers who may have developed EAA or other work-related respiratory diseases. • To provide case-detection so that those affected can be treated. • To provide epidemiological data to identify the cause of the outbreak. Methods The outbreak was investigated in a three-phase cross-sectional survey of the workforce. Phase I A respiratory screening questionnaire was completed by 808/836 workers (96.7%) in May 2004. Phase II 481 employees with at least one respiratory symptom on screening and 50 asymptomatic controls were invited for investigation at the factory in June 2004. This included a questionnaire, spirometry and clinical opinion. 454/481(94.4%) responded along with 48/50(96%) controls. Workers were identified who needed further investigation and serial measurements of peak expiratory flow (PEF). Phase III 162 employees were seen at the Birmingham Occupational Lung Disease clinic. 198 employees returned PEF records, including 141 of the 162 who attended for clinical investigation. Case definitions for diagnoses were agreed. Results 87 workers (10.4% of workforce) met case definitions for occupational lung disease, comprising EAA(19), occupational asthma(74) and humidifier fever(7). 12 workers had more than one diagnosis. The peak onset of work-related breathlessness was Spring 2003. The proportion of workers affected was higher for those using metal working fluid (MWF) from a large sump(27.3%) compared with working all over the manufacturing area (7.9%) (OR=4.39,p<0.001). Two workers had positive specific provocation tests to the used but not the unused MWF solution. Conclusions Extensive investigation of the outbreak of EAA detected a large number of affected workers, not only with EAA but also occupational asthma. This is the largest reported outbreak in Europe. Mist from used MWF is the likely cause. In workplaces using MWF, there is a need to carry out risk assessments, to monitor and maintain fluid quality, to control mist and to carry out respiratory health surveillance

Health care restructuring and family physician care for those who died of cancer

BACKGROUND: During the 1990s, health care restructuring in Nova Scotia resulted in downsized hospitals, reduced inpatient length of stay, capped physician incomes and restricted practice locations. Concurrently, the provincial homecare program was redeveloped and out-of-hospital cancer deaths increased from 20% (1992) to 30% (1998). These factors all pointed to a transfer of end-of-life inpatient hospital care to more community-based care. The purpose of this study was to describe the trends in the provision of Family Physician (FP) visits to advanced cancer patients in Nova Scotia (NS) during the years of health care restructuring. METHODS: Design Secondary multivariate analysis of linked population-based datafiles including the Queen Elizabeth II Health Sciences Centre Oncology Patient Information System (NS Cancer Registry, Vital Statistics), the NS Hospital Admissions/Separations file and the Medical Services Insurance Physician Services database. Setting Nova Scotia, an eastern Canadian province (population: 950,000). Subjects: All patients who died of lung, colorectal, breast or prostate cancer between April 1992 and March 1998 (N = 7,212). Outcome Measures Inpatient and ambulatory FP visits, ambulatory visits by location (office, home, long-term care facility, emergency department), time of day (regular hours, after hours), total length of inpatient hospital stay and number of hospital admissions during the last six months of life. RESULTS: In total, 139,641 visits were provided by family physicians: 15% of visits in the office, 10% in the home, 5% in the emergency department (ED), 5% in a long-term-care centre and 64% to hospital inpatients. There was no change in the rate of FP visits received for office, home and long-term care despite the fact that there were 13% fewer hospital admissions, and length of hospital stay declined by 21%. Age-sex adjusted estimates using negative binomial regression indicate a decline in hospital inpatient FP visits over time compared to 1992–93 levels (for 1997–98, adjusted RR = 0.88, 95%CI = 0.81–0.95) and an increase in FP ED visits (for 1997–98, adjusted RR = 1.18, 95%CI = 1.05–1.34). CONCLUSION: Despite hospital downsizing and fewer deaths occurring in hospitals, FP ambulatory visits (except for ED visits) did not rise correspondingly. Although such restructuring resulted in more people dying out of hospital, it does not appear FPs responded by providing more medical care to them in the community

Respiratory symptoms and lung function impairment in underground gold miners in Ghana

Background: This is the first study in Ghana in the Obuasi gold mines where the silica content of the respirable dust is 10%, less than in previously studied gold mines, with only 23% of the minershaving ever smoked. Objectives: The study was to assess the prevalence of respiratory impairment in the Ghanaian gold miner and to quantify the effects of the respirable dust on pulmonary functionDesign: A cross sectional epidemiological study Method: The study was carried out using MRC respiratory symptoms questionnaire, spirometry, and personal respirable dust measurements.Results: A total of 1236 miners were studied. The mean age was 39.7 ±5.8 (SD) years with a mean of 12.6 ± 6.7 (SD) years underground service and a mean total cumulative exposure to dust of 10.34±5.61 (SD) mg.m-3.years. The prevalence of chronic bronchitis was 21.2% and not clearly related to cumulative exposure. MRC breathlessness grade≥2 was 31.3%, significantly related to cumulativerespirable dust exposure after adjustment of age and smoking. There was however significant reduction in FEF25-75% with increasing dust exposure and an interaction with ever smoking. There was no correlation between cumulative exposure to respirable dust and FEV1 % predicted in any group, suggesting that exposure to respirable silicaat a mean level of 0.06 mg/m3 had no deleterious effect on FEV1 in a population with little tuberculosis, good housing and a low level of cigarette smoking. Conclusion: The prevalence of chronic bronchitisin the Ghanaian gold mine is related more to smoking than any occupational factor