Lung function in our aging population

<p>Abstract</p> <p>Aims of investigation</p> <p>The chronological age of the Caucasian population and their anthropometrical data have significantly changed within the last five decades. Therefore the question arises whether or not the commonly used reference values of the European Community (ECCS) for lung function may still be accepted today. Since these values were obtained in the 1960s from subjects in a limited age range. For the elderly, the measured values are deduced by extrapolation beyond the range of reference equations which had been obtained in a different population. Therefore decisions concerning elderly and smaller subjects concerning remuneration due to impaired lung function after industrial exposure on the basis of EGKS values are questionable.</p> <p>Methods</p> <p>Lung function tests were performed by pneumotachography, recording static lung volumes and flow-volume-curves in 262 asymptomatic non smoking males, aged 20 to 90 years. Measurements were performed with the MasterLab, or Pneumo-Screen systems (CareFusion, Höchberg). Results were compared to the reference values of ECCS, SAPALDIA and LuftiBus.</p> <p>Results</p> <p>For simplicity analysis of age and height dependence of investigated respiratory parameters (VC, FVC, FEV₁, FEV₁%FVC, PEF, MEF_75,50,25) can be described by linear functions (y = a * height - b * age + c). The forced expiratory vital capacity, FVC, was calculated by FVC = 0.0615*H - 0.0308*A - 4.673; r = 0.78. Mean FVC for younger subjects was found to be 104.7 ± 10.7% of the ECCS reference values and 96.5 ± 11.8% in older subjects. For most parameters investigated linear regressions on age were steeper than described by the ECCS reference values. The regression of lung function to height largely follows the ECCS prescriptions.</p> <p>Summary</p> <p>Bochum lung function values of younger healthy subjects were higher compared to the reference values of the ECCS and showed a steeper age descent. The alternatively discussed reference values of the SAPALDIA-, or LuftiBus-Study are higher, but do not cover all necessary parameters and/or the age range. A multi centre study for contemporary reference values is recommended.</p

Learning Moore Machines from Input-Output Traces

The problem of learning automata from example traces (but no equivalence or membership queries) is fundamental in automata learning theory and practice. In this paper we study this problem for finite state machines with inputs and outputs, and in particular for Moore machines. We develop three algorithms for solving this problem: (1) the PTAP algorithm, which transforms a set of input-output traces into an incomplete Moore machine and then completes the machine with self-loops; (2) the PRPNI algorithm, which uses the well-known RPNI algorithm for automata learning to learn a product of automata encoding a Moore machine; and (3) the MooreMI algorithm, which directly learns a Moore machine using PTAP extended with state merging. We prove that MooreMI has the fundamental identification in the limit property. We also compare the algorithms experimentally in terms of the size of the learned machine and several notions of accuracy, introduced in this paper. Finally, we compare with OSTIA, an algorithm that learns a more general class of transducers, and find that OSTIA generally does not learn a Moore machine, even when fed with a characteristic sample

Sharper and Simpler Nonlinear Interpolants for Program Verification

Interpolation of jointly infeasible predicates plays important roles in various program verification techniques such as invariant synthesis and CEGAR. Intrigued by the recent result by Dai et al.\ that combines real algebraic geometry and SDP optimization in synthesis of polynomial interpolants, the current paper contributes its enhancement that yields sharper and simpler interpolants. The enhancement is made possible by: theoretical observations in real algebraic geometry; and our continued fraction-based algorithm that rounds off (potentially erroneous) numerical solutions of SDP solvers. Experiment results support our tool's effectiveness; we also demonstrate the benefit of sharp and simple interpolants in program verification examples

Stressor reflections, sleep, and psychological well-being: A pre-registered experimental test of self-distanced versus self-immersed reflections

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: All data and analysis code are publicly available via our OSF project (https://osf.io/ue9jm/). We pre-registered the design and analysis plan for this experiment via the OSF (https://osf.io/jyf69). Deviations from our registered protocol are reported in the manuscript in the section ‘Deviations from Pre-Registered Protocol’.Evidence supports the effectiveness of cuing people to analyse negative autobiographical experiences from self-distanced rather than self-immersed perspectives. However, the evidence on which this expectation resides is limited largely to static snapshots of mean levels of cognitive and emotional factors. Via a pre-registered, randomised controlled trial (N = 257), we examined the differential effectiveness of self-distanced relative to self-immersed reflections on mean levels and within-person variability of sleep duration and quality as well as psychological well-being over a 5-day working week. Except for sleep quality, we found that reflecting from a psychologically distanced perspective, overall, was no more effective for mean levels and within-person variability of sleep duration, well-being, and stress-related factors than when the current self is fully immersed in the experiential reality of the event. We consider several substantive and methodological considerations (e.g., dosage, salience of stressor event) that require interrogation in future research via experimental and longitudinal observational methods

Complete larval development of the hermit crabs Clibanarius aequabilis and Clibanarius erythropus (Decapoda : Anomura : Diogenidae), under laboratory conditions, with a revision of the larval features of genus Clibanarius

The complete larval development (four zoeae and one megalopa) of Clibanarius aequabilis and C. erythropus, reared under laboratory conditions, is described and illustrated. The larval stages of the two northeastern Atlantic Clibanarius species cannot be easily differentiated. Their morphological characters are compared with those of other known Clibanarius larvae. The genus Clibanarius is very homogeneous with respect to larval characters. All Clibanarius zoeae display a broad and blunt rostrum, smooth abdominal segments and an antennal scale without a terminal spine. Beyond the second zoeal stage, the fourth telson process is present as a fused spine, and the uropods are biramous. In the fourth larval stage all species display a mandibular palp. The Clibanarius megalopa presents weakly developed or no ocular scales, symmetrical chelipeds, apically curved corneous dactylus in the second and third pereiopods, and 5-11 setae on the posterior margin of the telson. Apart from the number of zoeal stages, Clibanarius species may be separated, beyond the second zoeal stage, by the telson formula and the morphology of the fourth telson process.info:eu-repo/semantics/publishedVersio

Multi-modal Biomarkers Quantify Recovery in Autoimmune Autonomic Ganglionopathy

Objective: To evaluate patients with ganglionic acetylcholine receptor antibody (gAChR‐Ab) positive autoimmune autonomic ganglionopathy using a multi‐modal testing protocol to characterise their full clinical phenotype and explore biomarkers to quantify immunotherapy response. Methods: Cohort study of thirteen individuals (seven female; 21–69 years) with autonomic failure and gAChR‐Ab>100pM identified between 2005–2019. From 2018, all patients were longitudinally assessed with cardiovascular, pupillary, urinary, sudomotor, lacrimal and salivary testing, and COMPASS‐31 autonomic symptom questionnaires. The orthostatic intolerance ratio was calculated by dividing change in systolic blood pressure over time tolerated on head‐up tilt. Eleven patients received immunotherapy. Results: At first assessment, all 13 patients had cardiovascular and pupillary impairments, 7/8 had post‐ganglionic sudomotor dysfunction, 9/11 had urinary retention and xeropthalmia, and 6/8 had xerostomia. After immunotherapy, there were significant improvements in orthostatic intolerance ratio (33.3[17.8–61.3] to 5.2[1.4–8.2], P = .007), heart rate response to deep breathing (1.5[0.0–3.3] to 4.5[3.0–6.3], P = .02), pupillary constriction to light (12.0[5.5–18.0] to 19.0[10.6–23.8]%, P = .02), saliva production (0.01[0.01–0.05] to 0.08[0.02–0.20]g/min, P = .03) and COMPASS‐31 scores (52 to 17, P = .03). Orthostatic intolerance ratio correlated with autonomic symptoms at baseline (r = 0.841, P = .01) and following immunotherapy (r = 0.889, P = .02). Immunofluorescence analyses of skin samples from a patient 32 years after disease onset showed loss of nerve fibres supplying the dermal autonomic adnexa and epidermis, with clear improvements following immunotherapy. Interpretation: Patients with autoimmune autonomic ganglionopathy demonstrated objective evidence of widespread sympathetic and parasympathetic autonomic failure, with significant improvements after immunotherapy. Quantitative autonomic biomarkers should be used to define initial deficits, guide therapeutic decisions, and document treatment response

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

Designed Azolopyridinium Salts Block Protective Antigen Pores In Vitro and Protect Cells from Anthrax Toxin

Background:Several intracellular acting bacterial protein toxins of the AB-type, which are known to enter cells by endocytosis, are shown to produce channels. This holds true for protective antigen (PA), the binding component of the tripartite anthrax-toxin of Bacillus anthracis. Evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric PA63 binding/translocation component are related phenomena. Chloroquine and some 4-aminoquinolones, known as potent drugs against Plasmodium falciparium infection of humans, block efficiently the PA63-channel in a dose dependent way.Methodology/Principal Findings:Here we demonstrate that related positively charged heterocyclic azolopyridinium salts block the PA63-channel in the μM range, when both, inhibitor and PA63 are added to the same side of the membrane, the cis-side, which corresponds to the lumen of acidified endosomal vesicles of target cells. Noise-analysis allowed the study of the kinetics of the plug formation by the heterocycles. In vivo experiments using J774A.1 macrophages demonstrated that the inhibitors of PA63-channel function also efficiently block intoxication of the cells by the combination lethal factor and PA63 in the same concentration range as they block the channels in vitro.Conclusions/Significance:These results strongly argue in favor of a transport of lethal factor through the PA63-channel and suggest that the heterocycles used in this study could represent attractive candidates for development of novel therapeutic strategies against anthrax. © 2013 Beitzinger et al

Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells

The mechanisms of Pb(II) toxicity have been studied in human red blood cells using confocal microscopy, immunolabeling, fluorescence-activated cell sorting and atomic force microscopy. The process follows a sequence of events, starting with calcium entry, followed by potassium release, morphological change, generation of ceramide, lipid flip-flop and finally cell lysis. Clotrimazole blocks potassium channels and the whole process is inhibited. Immunolabeling reveals the generation of ceramide-enriched domains linked to a cell morphological change, while the use of a neutral sphingomyelinase inhibitor greatly delays the process after the morphological change, and lipid flip-flop is significantly reduced. These facts point to three major checkpoints in the process: first the upstream exchange of calcium and potassium, then ceramide domain formation, and finally the downstream scramblase activation necessary for cell lysis. In addition, partial non-cytotoxic cholesterol depletion of red blood cells accelerates the process as the morphological change occurs faster. Cholesterol could have a role in modulating the properties of the ceramide-enriched domains. This work is relevant in the context of cell death, heavy metal toxicity and sphingolipid signaling.AGA was a predoctoral student supported by the Basque Government and later by the University of the Basque Country (UPV/EHU). This work was also supported in part by grants from the Spanish Government (FEDER/MINECO BFU 2015-66306-P to F.M.G. and A.A.) and the Basque Government (IT849-13 to F.M.G. and IT838-13 to A.A.), and by the Swiss National Science Foundation

Remarks on Andrew Lang's World Trade Law After Neo-Liberalism

No abstract available