Feasibility of cardiopulmonary exercise testing in idiopathic pulmonary fibrosis

This is the author accepted manuscript. The final version is available from BMJ Publishing Group via the DOI in this recordBritish Thoracic Society Winter Meeting 2018, London, UK, 5-7 December 2018Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of irreversible declining lung function. Reductions in forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) are the common clinical endpoints for prognostic monitoring and assessing treatment outcomes. The use of cardiopulmonary exercise testing (CPET) in IPF remains largely unexplored. Objectives To explore the feasibility of CPET as a clinical measure in IPF and identify associations with established clinical variables. Methods Seventeen patients with IPF were approached, and fifteen (88%) were recruited (13 male, 68.1±7.5 years). Incremental exercise testing to exhaustion was undertaken via electronically braked cycle ergometer. Variables included: peak oxygen consumption (VO2peak), peak work rate (WRpeak), nadir SpO2, ventilatory drive (VE/VCO2), alongside standard clinical pulmonary function tests of FVC and DLCO. Pearson’s correlation coefficients established relationships between variables. Results One participant was excluded (high baseline systolic blood pressure). Eight out of fourteen (57%) participants reached volitional exhaustion. Five CPETs were terminated early due to desaturation (SpO2 <88%) and one to an exercise-induced right bundle branch block (recovery within minutes of ceasing exercise). Mean (±SD) pulmonary and exercise results were: FVC, 84.9%±17.0%; DLCO, 56.5%±11.4%; VO2peak, 1.4±0.4 L.min-1, 16.5±5.5 mL.kg-1.min-1; WRpeak, 104±42 W; SpO2, 90±3%; VE/VCO2, 27.1±6.4. Significant correlations were identified between: FVC and SpO2 (r=0.58, p=0.032), DLCO and VE/VCO2 (r=0.81, p<0.001) and WRpeak (r=0.58, p=0.03). Body-mass relative VO2peak held moderate, but not significant relationships with FVC (r=0.44, p=0.11) and DLCO (r=0.53, p=0.51). Conclusions Initial findings from this study have found CPET to be acceptable to patients with IPF and potentially feasible as a testing measure. Preliminary results identified common exercise desaturation, suggesting less conservative SpO2 termination criteria (e.g. 80% cut-off) could be considered. Although exercise parameters held limited relationships with FVC and DLCO, results from VO2peak identifies potential additional and dynamic prognostic information and warrants further investigation.Royal Devon & Exeter Hospita

Ventilatory dynamics and clinical status during cardiopulmonary exercise testing in patients with interstitial lung disease

This is the author accepted manuscript. The final version is available from Building a circular supply chain. Achieving resilient operations with the circular economy via the DOI in this recordPoster P98 presented at the British Thoracic Society Winter Meeting 2023, London, UK, 22 - 24 November 202

Validity and repeatability of cardiopulmonary exercise testing in interstitial lung disease

This is the final version. Available from BMC via the DOI in this record. Availability of data and materials: Data cannot be deposited in open access repositories for ethical reasons. Please contact the corresponding author (CAW) to discuss data access.Background: Cardiopulmonary exercise testing (CPET), and its primary outcome of peak oxygen uptake (VO2peak), are acknowledged as biomarkers in the diagnostic and prognostic management of interstitial lung disease (ILD). However, the validity and repeatability of CPET in those with ILD has yet to be fully characterised, and this study flls this evidence gap. Methods: Twenty-six people with ILD were recruited, and 21 successfully completed three CPETs. Of these, 17 completed two valid CPETs within a 3-month window, and 11 completed two valid CPETs within a 6-month window. Technical standards from the European Respiratory Society established validity, and repeatability was determined using mean change, intraclass correlation coefcient and typical error. Results: Every participant (100%) who successfully exercised to volitional exhaustion produced a maximal, and therefore valid, CPET. Approximately 20% of participants presented with a plateau in VO2, the primary criteria for establishing a maximal efort. The majority of participants otherwise presented with secondary criteria of respiratory exchange ratios in excess of 1.05, and maximal heart rates in excess of their predicted values. Repeatability analyses identifed that the typical error (expressed as percent of coefcient of variation) was 20% over 3-months in those reaching volitional exhaustion. Conclusion: This work has, for the frst time, fully characterised how patients with ILD respond to CPET in terms of primary and secondary verifcation criteria, and generated novel repeatability data that will prove useful in the assessment of disease progression, and future evaluation of therapeutic regimens where VO2peak is used as an outcome measure.Royal Devon and Exeter NHS Foundation Trust HospitalNational Institute for Health Research (NIHR)GW4 BioMed Medical Research Counci

The utility of the oxygen uptake efficiency plateau as a submaximal exercise biomarker in interstitial lung disease

This is the author accepted manuscript. The final version is available from BMJ Publishing Group via the DOI in this recordPaper S14 presented at the British Thoracic Society Winter Meeting, 17 - 19 February 202

Comment on “The extent of forest in dryland biomes”

This is the author accepted manuscript. The final version is available from American Association for the Advancement of Science via the DOI in this record.Bastin et al. (Reports, 12 May 2017, p. 635) infer forest as more globally extensive than previously estimated using tree cover data. However, their forest definition does not reflect ecosystem function or biotic composition. These structural and climatic definitions inflate forest estimates across the tropics and undermine conservation goals, leading to inappropriate management policies and practices in tropical grassy ecosystems

The Reform of Employee Compensation in China’s Industrial Enterprises

Although employee compensation reform in Chinese industrial sector has been discussed in the literature, the real changes in compensation system and pay practices have received insufficient attention and warrant further examination. This paper briefly reviews the pre- and post-reform compensation system, and reports the results of a survey of pay practices in the four major types of industrial enterprises in China. The research findings indicate that the type of enterprise ownership has little influence on general compensation practices, adoption of profit-sharing plans, and subsidy and allowance packages. In general, pay is linked more to individual performance and has become an important incentive to Chinese employees. However, differences are found across the enterprise types with regard to performance-related pay. Current pay practices are positively correlated to overall effectiveness of the enterprise

Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD

Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel

Computational identification of ubiquitylation sites from protein sequences

<p>Abstract</p> <p>Background</p> <p>Ubiquitylation plays an important role in regulating protein functions. Recently, experimental methods were developed toward effective identification of ubiquitylation sites. To efficiently explore more undiscovered ubiquitylation sites, this study aims to develop an accurate sequence-based prediction method to identify promising ubiquitylation sites.</p> <p>Results</p> <p>We established an ubiquitylation dataset consisting of 157 ubiquitylation sites and 3676 putative non-ubiquitylation sites extracted from 105 proteins in the UbiProt database. This study first evaluates promising sequence-based features and classifiers for the prediction of ubiquitylation sites by assessing three kinds of features (amino acid identity, evolutionary information, and physicochemical property) and three classifiers (support vector machine, <it>k</it>-nearest neighbor, and NaïveBayes). Results show that the set of used 531 physicochemical properties and support vector machine (SVM) are the best kind of features and classifier respectively that their combination has a prediction accuracy of 72.19% using leave-one-out cross-validation.</p> <p>Consequently, an informative physicochemical property mining algorithm (IPMA) is proposed to select an informative subset of 531 physicochemical properties. A prediction system UbiPred was implemented by using an SVM with the feature set of 31 informative physicochemical properties selected by IPMA, which can improve the accuracy from 72.19% to 84.44%. To further analyze the informative physicochemical properties, a decision tree method C5.0 was used to acquire if-then rule-based knowledge of predicting ubiquitylation sites. UbiPred can screen promising ubiquitylation sites from putative non-ubiquitylation sites using prediction scores. By applying UbiPred, 23 promising ubiquitylation sites were identified from an independent dataset of 3424 putative non-ubiquitylation sites, which were also validated by using the obtained prediction rules.</p> <p>Conclusion</p> <p>We have proposed an algorithm IPMA for mining informative physicochemical properties from protein sequences to build an SVM-based prediction system UbiPred. UbiPred can predict ubiquitylation sites accompanied with a prediction score each to help biologists in identifying promising sites for experimental verification. UbiPred has been implemented as a web server and is available at <url>http://iclab.life.nctu.edu.tw/ubipred</url>.</p

PIK3CA dependence and sensitivity to therapeutic targeting in urothelial carcinoma

Background Many urothelial carcinomas (UC) contain activating PIK3CA mutations. In telomerase-immortalized normal urothelial cells (TERT-NHUC), ectopic expression of mutant PIK3CA induces PI3K pathway activation, cell proliferation and cell migration. However, it is not clear whether advanced UC tumors are PIK3CA-dependent and whether PI3K pathway inhibition is a good therapeutic option in such cases. Methods We used retrovirus-mediated delivery of shRNA to knock down mutant PIK3CA in UC cell lines and assessed effects on pathway activation, cell proliferation, migration and tumorigenicity. The effect of the class I PI3K inhibitor GDC-0941 was assessed in a panel of UC cell lines with a range of known molecular alterations in the PI3K pathway. Results Specific knockdown of PIK3CA inhibited proliferation, migration, anchorage-independent growth and in vivo tumor growth of cells with PIK3CA mutations. Sensitivity to GDC-0941 was dependent on hotspot PIK3CA mutation status. Cells with rare PIK3CA mutations and co-occurring TSC1 or PTEN mutations were less sensitive. Furthermore, downstream PI3K pathway alterations in TSC1 or PTEN or co-occurring AKT1 and RAS gene mutations were associated with GDC-0941 resistance. Conclusions Mutant PIK3CA is a potent oncogenic driver in many UC cell lines and may represent a valuable therapeutic target in advanced bladder cancer