The frequency of asthma exacerbations and healthcare utilization in patients with asthma from the UK and USA

Asthma exacerbations are frequent in patients with severe disease. This report describes results from two retrospective cohort studies describing exacerbation frequency and risk, emergency department (ED)/hospital re-admissions, and asthma-related costs by asthma severity in the US and UK

eosinophil derived neurotoxin and clinical outcomes with mepolizumab in severe eosinophilic asthma

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Thermal Stabilization of the HCP Phase in Titanium

We have used a tight-binding model that is fit to first-principles electronic-structure calculations for titanium to calculate quasi-harmonic phonons and the Gibbs free energy of the hexagonal close-packed (hcp) and omega crystal structures. We show that the true zero-temperature ground-state is the omega structure, although this has never been observed experimentally at normal pressure, and that it is the entropy from the thermal population of phonon states which stabilizes the hcp structure at room temperature. We present the first completely theoretical prediction of the temperature- and pressure-dependence of the hcp-omega phase transformation and show that it is in good agreement with experiment. The quasi-harmonic approximation fails to adequately treat the bcc phase because the zero-temperature phonons of this structure are not all stable

Nucleon-nucleon elastic scattering analysis to 2.5 GeV

A partial-wave analysis of NN elastic scattering data has been completed. This analysis covers an expanded energy range, from threshold to a laboratory kinetic energy of 2.5 GeV, in order to include recent elastic pp scattering data from the EDDA collaboration. The results of both single-energy and energy-dependent analyses are described.Comment: 23 pages of text. Postscript files for the figures are available from ftp://clsaid.phys.vt.edu/pub/said/n

EpiDiP/NanoDiP: a versatile unsupervised machine learning edge computing platform for epigenomic tumour diagnostics.

DNA methylation analysis based on supervised machine learning algorithms with static reference data, allowing diagnostic tumour typing with unprecedented precision, has quickly become a new standard of care. Whereas genome-wide diagnostic methylation profiling is mostly performed on microarrays, an increasing number of institutions additionally employ nanopore sequencing as a faster alternative. In addition, methylation-specific parallel sequencing can generate methylation and genomic copy number data. Given these diverse approaches to methylation profiling, to date, there is no single tool that allows (1) classification and interpretation of microarray, nanopore and parallel sequencing data, (2) direct control of nanopore sequencers, and (3) the integration of microarray-based methylation reference data. Furthermore, no software capable of entirely running in routine diagnostic laboratory environments lacking high-performance computing and network infrastructure exists. To overcome these shortcomings, we present EpiDiP/NanoDiP as an open-source DNA methylation and copy number profiling suite, which has been benchmarked against an established supervised machine learning approach using in-house routine diagnostics data obtained between 2019 and 2021. Running locally on portable, cost- and energy-saving system-on-chip as well as gpGPU-augmented edge computing devices, NanoDiP works in offline mode, ensuring data privacy. It does not require the rigid training data annotation of supervised approaches. Furthermore, NanoDiP is the core of our public, free-of-charge EpiDiP web service which enables comparative methylation data analysis against an extensive reference data collection. We envision this versatile platform as a useful resource not only for neuropathologists and surgical pathologists but also for the tumour epigenetics research community. In daily diagnostic routine, analysis of native, unfixed biopsies by NanoDiP delivers molecular tumour classification in an intraoperative time frame

Detection of air trapping in chronic obstructive pulmonary disease by low frequency ultrasound

<p>Abstract</p> <p>Background</p> <p>Spirometry is regarded as the gold standard for the diagnosis of COPD, yet the condition is widely underdiagnosed. Therefore, additional screening methods that are easy to perform and to interpret are needed. Recently, we demonstrated that low frequency ultrasound (LFU) may be helpful for monitoring lung diseases. The objective of this study was to evaluate whether LFU can be used to detect air trapping in COPD. In addition, we evaluated the ability of LFU to detect the effects of short-acting bronchodilator medication.</p> <p>Methods</p> <p>Seventeen patients with COPD and 9 healthy subjects were examined by body plethysmography and LFU. Ultrasound frequencies ranging from 1 to 40 kHz were transmitted to the sternum and received at the back during inspiration and expiration. The high pass frequency was determined from the inspiratory and the expiratory signals and their difference termed ΔF. Measurements were repeated after inhalation of salbutamol.</p> <p>Results</p> <p>We found significant differences in ΔF between COPD subjects and healthy subjects. These differences were already significant at GOLD stage 1 and increased with the severity of COPD. Sensitivity for detection of GOLD stage 1 was 83% and for GOLD stages worse than 1 it was 91%. Bronchodilator effects could not be detected reliably.</p> <p>Conclusions</p> <p>We conclude that low frequency ultrasound is cost-effective, easy to perform and suitable for detecting air trapping. It might be useful in screening for COPD.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01080924">NCT01080924</a></p

Incidence, risk factors and re-exacerbation rate of severe asthma exacerbations in a multinational, multidatabase pediatric cohort study

Background: There are sparse real-world data on severe asthma exacerbations (SAE) in children. This multinational cohort study assessed the incidence of and risk factors for SAE and the incidence of asthma-related rehospitalization in children with asthma. Methods: Asthma patients 5-17 years old with ≥1 year of follow-up were identified in six European electronic databases from the Netherlands, Italy, the UK, Denmark and Spain in 2008-2013. Asthma was defined as ≥1 asthma-specific disease code within 3 months of prescriptions/dispensing of asthma medication. Severe asthma was defined as high-dosed inhaled corticosteroids plus a second controller. SAE was defined by systemic corticosteroids, emergency department visit and/or hospitalization all for reason of asthma. Risk factors for SAE were estimated by Poisson regression analyses. Results: The cohort consisted of 212 060 paediatric asthma patients contributing to 678 625 patient-years (PY). SAE rates ranged between 17 and 198/1000 PY and were higher in severe asthma and highest in severe asthma patients with a history of exacerbations. Prior SAE (incidence rate ratio 3-45) and younger age increased the SAE risk in all countries, whereas obesity, atopy and GERD were a risk factor in some but not all countries. Rehospitalization rates were up to 79% within 1 year. Conclusions: In a real-world setting, SAE rates were highest in children with severe asthma with a history of exacerbations. Many severe asthma patients were rehospitalized within 1 year. Asthma management focusing on prevention of SAE is important to reduce the burden of asthma

Time to get personal? The impact of researchers choices on the selection of treatment targets using the experience sampling methodology:The impact of researchers choices on the selection of treatment targets using the experience sampling methodology

OBJECTIVE: One of the promises of the experience sampling methodology (ESM) is that a statistical analysis of an individual’s emotions, cognitions and behaviors in everyday-life could be used to identify relevant treatment targets. A requisite for clinical implementation is that outcomes of such person-specific time-series analyses are not wholly contingent on the researcher performing them. METHODS: To evaluate this, we crowdsourced the analysis of one individual patient’s ESM data to 12 prominent research teams, asking them what symptom(s) they would advise the treating clinician to target in subsequent treatment. RESULTS: Variation was evident at different stages of the analysis, from preprocessing steps (e.g., variable selection, clustering, handling of missing data) to the type of statistics and rationale for selecting targets. Most teams did include a type of vector autoregressive model, examining relations between symptoms over time. Although most teams were confident their selected targets would provide useful information to the clinician, not one recommendation was similar: both the number (0–16) and nature of selected targets varied widely. CONCLUSION: This study makes transparent that the selection of treatment targets based on personalized models using ESM data is currently highly conditional on subjective analytical choices and highlights key conceptual and methodological issues that need to be addressed in moving towards clinical implementation

Elevated Expression of Phospholipid Transfer Protein in Bone Marrow Derived Cells Causes Atherosclerosis

Background: Phospholipid transfer protein (PLTP) is expressed by various cell types. In plasma, it is associated with high density lipoproteins (HDL). Elevated levels of PLTP in transgenic mice result in decreased HDL and increased atherosclerosis. PLTP is present in human atherosclerosis lesions, where it seems to be macrophage derived. The aim of the present study is to evaluate the atherogenic potential of macrophage derived PLTP. Methods and Findings: Here we show that macrophages from human PLTP transgenic mice secrete active PLTP. Subsequently, we performed bone marrow transplantations using either wild type mice (PLTPwt/wt), hemizygous PLTP transgenic mice (huPLTPtg/wt) or homozygous PLTP transgenic mice (huPLTPtg/tg) as donors and low density lipoprotein receptor deficient mice (LDLR-/-) as acceptors, in order to establish the role of PLTP expressed by bone marrow derived cells in diet-induced atherogenesis. Atherosclerosis was increased in the huPLTPtg/wt → LDLR-/ - mice (2.3-fold) and even further in the huPLTPtg/tg→LDLR-/ - mice (4.5-fold) compared with the control PLTPwt/wt→LDLR-/- mice (both P<0.001). Plasma PLTP activity levels and non-HDL cholesterol were increased and HDL cholesterol decreased compared with controls (all P<0.01). PLTP was present in atherosclerotic plaques in the mice as demonstrated by immunohistochemistry and appears to co-localize with macrophages. Isolated macrophages from PLTP transgenic mice do not show differences in cholesterol efflux or in cytokine production. Lipopolysaccharide activation of macrophages results in increased production of PLTP. This effect was strongly amplified in PLTP transgenic macrophages. Conclusions: We conclude that PLTP expression by bone marrow derived cells results in atherogenic effects on plasma lipids, increased PLTP activity, high local PLTP protein levels in the atherosclerotic lesions and increased atherosclerotic lesion size

Myelin Proteomics: Molecular Anatomy of an Insulating Sheath

Fast-transmitting vertebrate axons are electrically insulated with multiple layers of nonconductive plasma membrane of glial cell origin, termed myelin. The myelin membrane is dominated by lipids, and its protein composition has historically been viewed to be of very low complexity. In this review, we discuss an updated reference compendium of 342 proteins associated with central nervous system myelin that represents a valuable resource for analyzing myelin biogenesis and white matter homeostasis. Cataloging the myelin proteome has been made possible by technical advances in the separation and mass spectrometric detection of proteins, also referred to as proteomics. This led to the identification of a large number of novel myelin-associated proteins, many of which represent low abundant components involved in catalytic activities, the cytoskeleton, vesicular trafficking, or cell adhesion. By mass spectrometry-based quantification, proteolipid protein and myelin basic protein constitute 17% and 8% of total myelin protein, respectively, suggesting that their abundance was previously overestimated. As the biochemical profile of myelin-associated proteins is highly reproducible, differential proteome analyses can be applied to material isolated from patients or animal models of myelin-related diseases such as multiple sclerosis and leukodystrophies