Cardiopulmonary Exercise Testing as a Longitudinal Clinical Tool in Interstitial Lung Disease Management

This is an abstract from International Conference of the American-Thoracic-Society Location: Dallas, TX Date: MAY 17-22, 2019Royal 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

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

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

Study protocol for the translating research in elder care (TREC): building context – an organizational monitoring program in long-term care project (project one)

<p>Abstract</p> <p>Background</p> <p>While there is a growing awareness of the importance of organizational context (or the work environment/setting) to successful knowledge translation, and successful knowledge translation to better patient, provider (staff), and system outcomes, little empirical evidence supports these assumptions. Further, little is known about the factors that enhance knowledge translation and better outcomes in residential long-term care facilities, where care has been shown to be suboptimal. The project described in this protocol is one of the two main projects of the larger five-year Translating Research in Elder Care (TREC) program.</p> <p>Aims</p> <p>The purpose of this project is to establish the magnitude of the effect of organizational context on knowledge translation, and subsequently on resident, staff (unregulated, regulated, and managerial) and system outcomes in long-term care facilities in the three Canadian Prairie Provinces (Alberta, Saskatchewan, Manitoba).</p> <p>Methods/Design</p> <p>This study protocol describes the details of a multi-level – including provinces, regions, facilities, units within facilities, and individuals who receive care (residents) or work (staff) in facilities – and longitudinal (five-year) research project. A stratified random sample of 36 residential long-term care facilities (30 urban and 6 rural) from the Canadian Prairie Provinces will comprise the sample. Caregivers and care managers within these facilities will be asked to complete the TREC survey – a suite of survey instruments designed to assess organizational context and related factors hypothesized to be important to successful knowledge translation and to achieving better resident, staff, and system outcomes. Facility and unit level data will be collected using standardized data collection forms, and resident outcomes using the Resident Assessment Instrument-Minimum Data Set version 2.0 instrument. A variety of analytic techniques will be employed including descriptive analyses, psychometric analyses, multi-level modeling, and mixed-method analyses.</p> <p>Discussion</p> <p>Three key challenging areas associated with conducting this project are discussed: sampling, participant recruitment, and sample retention; survey administration (with unregulated caregivers); and the provision of a stable set of study definitions to guide the project.</p

Optimal free descriptions of many-body theories

Interacting bosons or fermions give rise to some of the most fascinating phases of matter, including high-temperature superconductivity, the fractional quantum Hall effect, quantum spin liquids and Mott insulators. Although these systems are promising for technological applications, they also present conceptual challenges, as they require approaches beyond mean-field and perturbation theory. Here we develop a general framework for identifying the free theory that is closest to a given interacting model in terms of their ground-state correlations. Moreover, we quantify the distance between them using the entanglement spectrum. When this interaction distance is small, the optimal free theory provides an effective description of the low-energy physics of the interacting model. Our construction of the optimal free model is non-perturbative in nature; thus, it offers a theoretical framework for investigating strongly correlated systems

Antibodies Targeted to the Brain with Image-Guided Focused Ultrasound Reduces Amyloid-β Plaque Load in the TgCRND8 Mouse Model of Alzheimer's Disease

Immunotherapy for Alzheimer's disease (AD) relies on antibodies directed against toxic amyloid-beta peptide (Aβ), which circulate in the bloodstream and remove Aβ from the brain [1], [2]. In mouse models of AD, the administration of anti-Aβ antibodies directly into the brain, in comparison to the bloodstream, was shown to be more efficient at reducing Aβ plaque pathology [3], [4]. Therefore, delivering anti-Aβ antibodies to the brain of AD patients may also improve treatment efficiency. Transcranial focused ultrasound (FUS) is known to transiently-enhance the permeability of the blood-brain barrier (BBB) [5], allowing intravenously administered therapeutics to enter the brain [6]–[8]. Our goal was to establish that anti-Aβ antibodies delivered to the brain using magnetic resonance imaging-guided FUS (MRIgFUS) [9] can reduce plaque pathology. To test this, TgCRND8 mice [10] received intravenous injections of MRI and FUS contrast agents, as well as anti-Aβ antibody, BAM-10. MRIgFUS was then applied transcranially. Within minutes, the MRI contrast agent entered the brain, and BAM-10 was later found bound to Aβ plaques in targeted cortical areas. Four days post-treatment, Aβ pathology was significantly reduced in TgCRND8 mice. In conclusion, this is the first report to demonstrate that MRIgFUS delivery of anti-Aβ antibodies provides the combined advantages of using a low dose of antibody and rapidly reducing plaque pathology

Maximum expected accuracy structural neighbors of an RNA secondary structure

International audienceBACKGROUND: Since RNA molecules regulate genes and control alternative splicing by allostery, it is important to develop algorithms to predict RNA conformational switches. Some tools, such as paRNAss, RNAshapes and RNAbor, can be used to predict potential conformational switches; nevertheless, no existent tool can detect general (i.e., not family specific) entire riboswitches (both aptamer and expression platform) with accuracy. Thus, the development of additional algorithms to detect conformational switches seems important, especially since the difference in free energy between the two metastable secondary structures may be as large as 15-20 kcal/mol. It has recently emerged that RNA secondary structure can be more accurately predicted by computing the maximum expected accuracy (MEA) structure, rather than the minimum free energy (MFE) structure. RESULTS: Given an arbitrary RNA secondary structure S₀ for an RNA nucleotide sequence a = a₁,..., a(n), we say that another secondary structure S of a is a k-neighbor of S₀, if the base pair distance between S₀ and S is k. In this paper, we prove that the Boltzmann probability of all k-neighbors of the minimum free energy structure S₀ can be approximated with accuracy ε and confidence 1 - p, simultaneously for all 0 ≤ k N(ε,p,K)=Φ⁻¹(p/2K)²/4ε², where Φ(z) is the cumulative distribution function (CDF) for the standard normal distribution. We go on to describe the algorithm RNAborMEA, which for an arbitrary initial structure S₀ and for all values 0 ≤ k < K, computes the secondary structure MEA(k), having maximum expected accuracy over all k-neighbors of S₀. Computation time is O(n³ * K²), and memory requirements are O(n² * K). We analyze a sample TPP riboswitch, and apply our algorithm to the class of purine riboswitches. CONCLUSIONS: The approximation of RNAbor by sampling, with rigorous bound on accuracy, together with the computation of maximum expected accuracy k-neighbors by RNAborMEA, provide additional tools toward conformational switch detection. Results from RNAborMEA are quite distinct from other tools, such as RNAbor, RNAshapes and paRNAss, hence may provide orthogonal information when looking for suboptimal structures or conformational switches. Source code for RNAborMEA can be downloaded from http://sourceforge.net/projects/rnabormea/ or http://bioinformatics.bc.edu/clotelab/RNAborMEA/