A rate-(in)dependent constitutive model for porous single crystals with arbitrary crystal anisotropy (e.g., FCC, BCC, HCP, etc.) containing general ellipsoidal voids is developed. The proposed model, ...denoted as modified variational model (MVAR), is based on the nonlinear variational homogenization method, which makes use of a linear comparison porous material to estimate the response of the nonlinear porous single crystal. Periodic multi-void finite element simulations are used in order to validate the MVAR for a large number of parameters including cubic (FCC, BCC) and hexagonal (HCP) crystal anisotropy, various creep exponents (i.e., nonlinearity), several stress triaxiality ratios, general void shapes and orientations and various porosity levels. The MVAR model, which involves a priori no calibration parameters, is found to be in good agreement with the finite element results for all cases considered in the rate-dependent context. The model is then used in a predictive manner to investigate the complex response of porous single crystals in several cases with strong coupling between the anisotropy of the crystal and the (morphological) anisotropy induced by the shape and orientation of the voids. Finally, a simple way of calibrating the MVAR with just two adjustable parameters is depicted in the rate-independent context so that an excellent agreement with the FE simulation results is obtained. In this last case, this proposed model can be thought as a generalization of the Gurson model in the context of porous single crystals and general ellipsoidal void shapes and orientations.
Non‐technical summary Inter‐individual differences in regional GABA as assessed by magnetic resonance spectroscopy (MRS) relate to behavioural variation in humans. However, it is not clear what the ...relationship is between MRS measures of the concentration of neurotransmitters in a region and synaptic activity. Transcranial magnetic stimulation (TMS) techniques provide physiological measures of cortical excitation or inhibition. Here, we investigated the relationship between MRS and TMS measures of glutamatergic and GABAergic activity within the same individuals. We demonstrated a relationship between MRS‐assessed glutamate levels and a TMS measure of global cortical excitability, suggesting that MRS measures of glutamate do reflect glutamatergic activity. However, there was no clear relationship between MRS‐assessed GABA levels and TMS measures of synaptic GABAA or GABAB activity. A relationship was found between MRS‐assessed GABA and a TMS protocol with less clearly understood physiological underpinnings. We speculate that this protocol may therefore reflect extrasynaptic GABA tone.
Magnetic resonance spectroscopy (MRS) allows measurement of neurotransmitter concentrations within a region of interest in the brain. Inter‐individual variation in MRS‐measured GABA levels have been related to variation in task performance in a number of regions. However, it is not clear how MRS‐assessed measures of GABA relate to cortical excitability or GABAergic synaptic activity. We therefore performed two studies investigating the relationship between neurotransmitter levels as assessed by MRS and transcranial magnetic stimulation (TMS) measures of cortical excitability and GABA synaptic activity in the primary motor cortex. We present uncorrected correlations, where the P value should therefore be considered with caution. We demonstrated a correlation between cortical excitability, as assessed by the slope of the TMS input–output curve and MRS‐assessed glutamate levels (r = 0.803, P = 0.015) but no clear relationship between MRS‐assessed GABA levels and TMS‐assessed synaptic GABAA activity (2.5 ms inter‐stimulus interval (ISI) short‐interval intracortical inhibition (SICI); Experiment 1: r = 0.33, P = 0.31; Experiment 2: r =–0.23, P = 0.46) or GABAB activity (long‐interval intracortical inhibition (LICI); Experiment 1: r =–0.47, P = 0.51; Experiment 2: r = 0.23, P = 0.47). We demonstrated a significant correlation between MRS‐assessed GABA levels and an inhibitory TMS protocol (1 ms ISI SICI) with distinct physiological underpinnings from the 2.5 ms ISI SICI (r =–0.79, P = 0.018). Interpretation of this finding is challenging as the mechanisms of 1 ms ISI SICI are not well understood, but we speculate that our results support the possibility that 1 ms ISI SICI reflects a distinct GABAergic inhibitory process, possibly that of extrasynaptic GABA tone.
Dear Editor,
Patients receiving anticancer therapy usually suffer from side effects, such as loss of hair, epithelial barrier defects, and myelosuppression, which, however, are usually reversible ...when the therapy is discontinued. Although this clinical experience suggests that adult stem cells may survive such therapeutic interventions, the underlying molecular regulatory mechanisms are poorly understood. Such regulatory mechanisms also seem to protect adult stem cells from acquiring mutations, which could lead to additional tumorigenesis.
Summary
Short-term mechanical circulatory support (MCS) is increasingly used as a bridge to decision in patients with refractory cardiogenic shock. Subsequently, these patients might be bridged to ...durable MCS either as a bridge to candidacy/transplantation, or as destination therapy. The aim of this study was to review support duration and clinical outcome of short-term MCS in cardiogenic shock, and to analyse application of this technology as a bridge to long-term cardiac support (left ventricular assist device, LVAD) from 2006 till June 2016. Using Cochrane Register of Trials, Embase and Medline, a systematic review was performed on patients with cardiogenic shock from acute myocardial infarction, end-stage cardiomyopathy, or acute myocarditis, receiving short-term MCS. Studies on periprocedural, post-cardiotomy and cardiopulmonary resuscitation support were excluded. Thirty-nine studies, mainly registries of heterogeneous patient populations (n = 4151 patients), were identified. Depending on the device used (intra-aortic balloon pump, TandemHeart, Impella 2.5, Impella 5.0, CentriMag and peripheral veno-arterial extracorporeal membrane oxygenation), mean support duration was (range) 1.6–25 days and the mean proportion of short-term MCS patients discharged was (range) 45–66%. The mean proportion of bridge to durable LVAD was (range) 3–30%. Bridge to durable LVAD was most frequently performed in patients with end-stage cardiomyopathy (22 12–35%). We conclude that temporary MCS can be used to bridge patients with cardiogenic shock towards durable LVAD. Clinicians are encouraged to share their results in a large multicentre registry in order to investigate optimal device selection and best duration of support.
Purpose
Acute kidney injury
(
AKI) frequently occurs after heart transplantation (HTx), but its relation to preoperative right heart hemodynamic (RHH) parameters remains unknown. Therefore, we aimed ...to determine their predictive properties for postoperative AKI severity within 30 days after HTx.
Methods
From 1984 to 2016, all consecutive HTx recipients (
n
= 595) in our tertiary referral center were included and analyzed for the occurrence of postoperative AKI staged by the kidney disease improving global outcome criteria. The effects of preoperative RHH parameters on postoperative AKI were calculated using logistic regression, and predictive accuracy was assessed using integrated discrimination improvement (IDI), net reclassification improvement (NRI), and area under the receiver operating characteristic curves (AUC).
Results
Postoperative AKI occurred in 430 (72%) patients including 278 (47%) stage 1, 66 (11%) stage 2, and 86 (14%) stage 3 cases. Renal replacement therapy (RRT) was administered in 41 (7%) patients. Patients with higher AKI stages had also higher baseline right atrial pressure (RAP; median 7, 7, 8, and in RRT 11 mmHg,
p
trend = 0.021), RAP-to-pulmonary capillary wedge pressure ratio (median 0.37, 0.36, 0.40, 0.47,
p
trend = 0.009), and lower pulmonary artery pulsatility index (PAPi) values (median 2.83, 3.17, 2.54, 2.31,
p
trend = 0.012). Higher RAP and lower PAPi values independently predicted AKI severity adjusted odds ratio (OR) per doubling of RAP 1.16 (1.02–1.32),
p
= 0.029; of PAPi 0.85 (0.75–0.96),
p
= 0.008. Based on IDI, NRI, and delta AUC, inclusion of these parameters improved the models’ predictive accuracy.
Conclusions
Preoperative PAPi and RAP strongly predict the development of AKI early after HTx and can be used as early AKI predictors.
A thick endothelial glycocalyx provides the endothelial surface with a nonadherent shield. Oxidized LDL (Ox-LDL) degrades the endothelial glycocalyx. We hypothesized that glycocalyx degradation ...stimulates leukocyte-endothelial cell adhesion, whereas intravascular supplementation with sulfated polysaccharides reconstitutes the endothelial glycocalyx and attenuates Ox-LDL-induced leukocyte-endothelial cell adhesion.
Degradation of the endothelial glycocalyx by local microinjection of heparitinase (10 to 50 U/mL) into mouse cremaster venules dose-dependently increased the number of adherent leukocytes. Systemic administration of Ox-LDL (0.4 mg/100 g body weight) induced 10.1+/-0.9 adherent leukocytes/100 microm at 60 minutes. In the venules perfused with 500-kDa dextran sulfate (1 mg/mL), the number of adherent leukocytes at 60 minutes after Ox-LDL bolus application was not influenced (9.2+/-1.0 leukocytes/100 microm). However, the venules locally perfused with heparan sulfate (10 mg/mL) or heparin (1 mg/mL) displayed a significantly lower number of adherent leukocytes induced by Ox-LDL: 5.1+/-0.7 and 5.4+/-0.9 leukocytes/100 microm, respectively (P<0.05). Fluorescently labeled heparan sulfate and heparin, but not dextran sulfate, attached to the venule luminal surface after Ox-LDL administration.
Endothelial glycocalyx degradation stimulates leukocyte immobilization at the endothelial surface. Circulating heparan sulfate and heparin attach to the venule wall and attenuate Ox-LDL-induced leukocyte immobilization.
Abstract Background Cystic fibrosis-related diabetes (CFRD) is correlated with a decline in lung function. Under certain circumstances, oral glucose tolerance test (OGTT) screening, used to diagnose ...CFRD, fails to reveal early glucose tolerance abnormalities. In this situation, continuous glucose monitoring (CGM) could be a useful tool for evaluating early abnormalities of glucose tolerance in CF patients. We aimed to study the CGM glucose profile in CF patients with normal OGTT screening results and to evaluate lung function and nutritional status according to the CGM glucose profile. Methods We assessed glycemic control, the CGM glucose profile, nutritional status, lung function antibiotic courses and colonization ( P. aeruginosa and S. aureus ) in CF patients, aged 10 years and over, with normal screening OGTT results (blood glucose at T120 min < 7.8 mmol/l). Two groups were identified according to the max CGM glucose value: Group 1 < 11 mmol/l and Group 2 ≥ 11 mmol/l. Results Among the 38 patients with normal OGTT, 12 (31.6%) were in Group 2. Compared to Group 1, Group 2 patients exhibited a significant impairment in lung function: FEV1 , 68.2 ± 25.6% vs. 87.3 ± 17%, p = 0.01 and FVC, 86.1% ± 19.4% vs. 99.3% ± 13.4%, p = 0.021, as well as a higher rate of colonization by P. aeruginosa : 83.3% vs. 44%, p = 0.024. Nevertheless, there were no differences in nutritional status (BMI standard deviation score: p = 0.079; prealbumin: p = 0.364). Conclusions CGM reveals early abnormalities of glucose tolerance that remain undiagnosed by OGTT screening and are associated with worse lung function and a higher prevalence of P. aeruginosa colonization in patients with CF. Clinical trial registration number: NCT00476281.
The great success of stents in treating cardiovascular disease is actually undermined by their long-term fatigue failure. The high variability of stent failure incidence suggests that it is due to ...several correlated aspects, such as loading conditions, material properties, component design, surgical procedure, and patient functional anatomy. Numerical and experimental non-clinical assessments are included in the recommendations and requirements of several regulatory bodies and they are thus exploited in the analysis of stent fatigue performance. Optimization-based simulation methodologies have been developed as well, to improve the fatigue endurance of novel designs. This paper presents a review on the fatigue issue in metallic stents, starting from a description of clinical evidence about stent fracture up to the analysis of computational approaches available from the literature. The reported discussion on both the experimental and numerical framework aims at providing a general insight into stent lifetime prediction as well as at understanding the factors which affect stent fatigue performance for the design of novel components.
•A probabilistic low cycle fatigue criterion is proposed for nodular cast-iron.•Largest Graphite nodules population are considered as micro-cracks initiation sites.•Gumbel extreme values distribution ...is introduced in a failure probability estimation.•Lifetime scattering is estimated by nodules distribution and micro-crack growth law.
This paper proposes an original method for characterising the Low Cycle Fatigue (LCF) lifetime using probability density functions. The protocol is based on statistics of microstructure heterogeneities taken as damage initiation sites, a qualitative mechanical analysis of the heterogeneities harmfulness and the definition of a micro-crack growth law. The technique is here established and the associated model identified for a nodular cast iron where the graphite nodules are assumed to be the damage initiation zones. The LCF lifetime is characterised from both a large set of experimental test between 300 and 600 °C and damage observations at the micro-scale. Experimental post-mortem observation combined with an expanded literature review first enable to assume the harmfulness of nodules according to their size and their probable role in the damage process A probability density function for the lifetime is then built from the following steps: (i) a quantitative analysis of the material micro-structure, which provides the probability density of nodules occurrence depending of their size (ii) an extreme value analysis using a Gumbel distribution and (iii) a micro-crack growth law associated with LCF conventional terms of energy densities. Its parameters are obtained using an optimisation process applied to laboratory fatigue experiment. The obtained probability function provides a good match for the lifetime and greatly improves results given by conventional criteria. It moreover provides a robust estimate of the lifetime scatter for different types of fatigue tests.
•A semi-analytical approach for the indentation of a multilayered solid is presented.•The method of solution is based on the Hankel transform and the transfer matrix.•The implementation is done with ...Mathematica under the form of a fast and efficient code.•The procedure is valid for a large wide material combinations and arbitrary layer’s thickness.•A series of results for flat, conical, spherical and blunted punches is given.
This paper is concerned with a semi-analytical approach to the solution of the axisymmetric indentation problem for a multilayered elastic half-space. The stress and displacement fields for each layer and the substrate are derived in closed form by using the Papkovich–Neuber potentials and the Hankel transform. The bonded or sliding interface conditions between the sub-layers are handled by the use of the appropriate transfer matrix, and then the mixed boundary value problem is reduced to a Fredholm integral equation. Symbolic and numerical computations of the solution are implemented in the symbolic software Mathematica in the form of a fast and efficient numerical algorithm, allowing rapid determination of the load–displacement curves and composite elastic properties for an arbitrary rigid indenter shape. A series of results for different indenters (flat, conical, spherical and blunted conical punch shapes) and different multilayered composites is presented and discussed.
The complete set of symbolic and numerical computations are provided as supplementary resources with the paper.
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