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In this paper we present time-dependent perturbations of second-order non-autonomous abstract Cauchy problems associated to a family of operators with constant domain. We make use of the equivalence to a first-order non-autonomous abstract Cauchy problem in a product space, which we elaborate in full detail. As an application we provide a perturbed non-autonomous wave equation. [ABSTRACT FROM AUTHOR]

Summary: Four machine learning models were developed and compared to predict the risk of a future major osteoporotic fracture (MOF), defined as hip, wrist, spine and humerus fractures, in patients with a prior fracture. We developed a user-friendly tool for risk calculation of subsequent MOF in osteopenia patients, using the best performing model. Introduction: Major osteoporotic fractures (MOFs), defined as hip, wrist, spine and humerus fractures, can have serious consequences regarding morbidity and mortality. Machine learning provides new opportunities for fracture prediction and may aid in targeting preventive interventions to patients at risk of MOF. The primary objective is to develop and compare several models, capable of predicting the risk of MOF as a function of time in patients seen at the fracture and osteoporosis outpatient clinic (FO-clinic) after sustaining a fracture. Methods: Patients aged > 50 years visiting an FO-clinic were included in this retrospective study. We compared discriminative ability (concordance index) for predicting the risk on MOF with a Cox regression, random survival forests (RSF) and an artificial neural network (ANN)-DeepSurv model. Missing data was imputed using multiple imputations by chained equations (MICE) or RSF's imputation function. Analyses were performed for the total cohort and a subset of osteopenia patients without vertebral fracture. Results: A total of 7578 patients were included, 805 (11%) patients sustained a subsequent MOF. The highest concordance-index in the total dataset was 0.697 (0.664–0.730) for Cox regression; no significant difference was determined between the models. In the osteopenia subset, Cox regression outperformed RSF (p = 0.043 and p = 0.023) and ANN-DeepSurv (p = 0.043) with a c-index of 0.625 (0.562–0.689). Cox regression was used to develop a MOF risk calculator on this subset. Conclusion: We show that predicting the risk of MOF in patients who already sustained a fracture can be done with adequate discriminative performance. We developed a user-friendly tool for risk calculation of subsequent MOF in patients with osteopenia. [ABSTRACT FROM AUTHOR]

Copyright of Manuelle Medizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Schmerz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Before and 7–12 days after an Himalayan expedition CO2 equilibration curves were determined in the blood plasma of 12 mountaineers by in vitro and in vivo CO2 titration; in vivo osmolality changes (ΔOsm · Δ PCO2 −1, ΔOsm · ΔpH−1, where PCO2 is the partial pressure of CO2) during the latter experiments yielded estimates of whole body CO2 storage. In vitro −Δ[HCO3 −] · ΔpH−1 [nonbicarbonate buffer capacity (β) of blood] was increased 7 days after descent [before 31.3 (SEM 0.4) mmol · kgH2O−1, after 38.3 (SEM 3.9) mmol · kgH2O−1; P<0.05] resulting from an increased proportion of young erythrocytes; in additional experiments an augmented β was found in young (low density cells) compared to old cells [<1.097 g · ml−1: 0.216 (SEM 0.028) mmol · gHb−1, >1.100 g · ml−1: 0.145 (SEM 0.013) mmol · gHb−1, where Hb is haemoglobin; P<0.02]. In spite of increased Hb mass in vivo Δ[CO2total] · Δ PCO2 −1 [0.192 (SEM 0.010) mmol · kgH2O−1 · mmHg−1] and −Δ[HCO3 −] · ΔpH−1 [17.9 (SEM 1.0) mmol · kgH2O−1] as indicators of extracellular β rose only slightly after altitude (7 days +16%, P<0.02; +7%, NS) because of haemodilution. The ΔOsm · Δ PCO2 −1 [0.230 (SEM 0.015) mosmol · kgH2O−1 · mmHg−1] remained unchanged. Prealtitude differences in ΔOsm · ΔpH−1 between hypercapnia [−41 (SEM 5) mosmol · kgH2O−1] and hypo-capnia [−20 (SEM 3) mosmol · kgH2O−1; P<0.01] disappeared temporarily after return since the former slope was reduced. The high value during hypercapnia before ascent probably resulted from mechanisms stabilizing intracellular pH during moderate hypercapnia which were attenuated after descent. [ABSTRACT FROM AUTHOR]

Modifications of drug-induced V inhibition by the combined treatment of the cardiac membrane with several class 1 antiarrhythmic agents were studied in guinea pig's ventricular myocardium taking the depression of upstroke velocity in fast action potentials as an indicator for I blockade. A novel analytical procedure, first beat phasic block determination, provided the opportunity to estimate phasic drug binding initiated by a single action potential. [ABSTRACT FROM AUTHOR]

In microelectrode experiments on isolated papillary muscles of guinea-pigs, the effect of propafenone (1×10 mol/l-1×10 mol/l) on the fast Na action potential was analyzed. Propafenone caused, without changing the resting potential, a concentration dependent decrease of $$\dot V_{\max } $$ . At continuous stimulation with a rate of 12/min, complete inhibition of $$\dot V_{\max } $$ appeared in response to 1×10 mol/l. Transformation of the concentration-response curve into the Hill form revealed a Hill coefficient of 1.8. Some minor changes of the action potential configuration occurred consisting of a plateau shift to less positive potentials and of an abbreviation of action potential duration. Propafenone did not alter the linear dependence of $$\dot V_{\max } $$ on the logarithm of external Na concentration. Propafenone shifted the curve relating $$\dot V_{\max } $$ to membrane potential ( h-curve) to more negative potentials suggesting an interference with the inactivation process of the fast Na system. This effect developed on the quiescent, non-stimulated preparation and leads to the occurrence of a resting-state block being, consequently, potential dependent. Repetitive stimulation enhanced the propafenone-induced inhibition indicating a use-dependent block. During a train of 5-7 (at 12/min) or 15-20 (at 120/min) action potentials, a continuous decline of $$\dot V_{\max } $$ occurred until a new steady-state was attained. The interstimulus interval determined strength and kinetics of development (τ) of the use-dependent block. It was 22% and 8.4s, respectively at 5000 ms, but 70% and 1.8 s, respectively, at 500 ms. A slight intensification could also be induced by a decrease of membrane potential whilst pH or temperature changes remained ineffective. After cessation of continuous stimulation, the use-dependent block disappeared with a time constant of 15.5 s. Neither an increase of pH from 7.4 to 8.4 nor a decrease to 6.4 had any influence on the action of propafenone ( pK=9.0). Resting-state and usedependent block were of an identical amount regardless of the pH in the medium. [ABSTRACT FROM AUTHOR]

Drug-induced depression of I was studied in microelectrode experiments on papillary muscles of guinea pigs by taking $$\dot V_{\max } $$ of the fast Na action potential as an estimate for g thereby systematically discriminating between tonic and phasic blockade. [ABSTRACT FROM AUTHOR]