Fatal bleeding is a serious consequence of anticoagulant therapy, but factors associated with fatal bleeding during the first 3 months of treatment of venous thromboembolism (VTE) are uncertain.
...Using data from RIETE, an ongoing registry of consecutive patients with acute VTE, we assessed risk factors for fatal bleeding among all patients. We then used this information to derive a clinical model that would stratify a patient's risk of fatal bleeding during the first 3 months of treatment.
Of 24 395 patients, 546 (2.24%) had a major bleed and 135 (0.55%) had a fatal bleed. The gastrointestinal tract was the most common site (40% of fatal bleeds), followed by intracranial bleeding (25%). Fatal bleeding was independently associated with the following factors at the time of VTE diagnosis: age >75 years (OR, 2.16), metastatic cancer (OR, 3.80), immobility > or = 4 days (OR, 1.99), a major bleed within the past 30 days (OR, 2.64), an abnormal prothrombin time (OR, 2.09), a platelet count < 100 x 10(9) L(-1) (OR, 2.23), creatinine clearance < 30 mL min(-1) (OR, 2.27), anemia (OR, 1.54), and distal deep vein thrombosis (OR, 0.39). INR at the time of bleeding is not known. A clinical prediction rule for risk of fatal bleeding that included nine baseline factors was derived. Fatal bleeding occurred in 0.16% (95% CI, 0.11-0.23) of the low-risk, 1.06% (95% CI, 0.85-1.30) of the moderate-risk, and 4.24% (95% CI, 2.76-6.27) of the high-risk category.
Patient characteristics and laboratory variables can identify patients at high risk for fatal bleeding during treatment of VTE.
The metabolic syndrome (MetS) encompasses a constellation of metabolic abnormalities that are thought to place patients at higher risk for the development of diabetes and cardiovascular (CV) disease. ...The underlying pathophysiology is still a point of contention among various professional organizations leading to inconsistencies in the manner in which MetS is defined. Each definition has its advantages and disadvantages. Nonetheless, there is an agreement that insulin resistance and obesity are likely the central contributing factors. Because the prevalence of obesity has been increasing at a frightening rate in the past few decades, MetS represents a major public health problem that should be identified clinically in individual patients. This review describes the changing epidemiology of obesity and of MetS and discusses its importance in CV disease. We outline the existing controversies that surround MetS and discuss the role of lifestyle, pharmacological, surgical, and novel approaches in its management.
Clinical Pharmacology & Therapeutics (2007) 82, 509–524; doi:10.1038/sj.clpt.6100355; published online 12 September 2007
Comfort has traditionally been assessed as a single deterministic index that can be assigned to each railway vehicle type (at a given speed on a given track quality level). However, it is now well ...established that passengers influence vibration and, as a consequence, occupancy level and seating arrangement influence comfort, thus turning it into a stochastic variable. The concept of Compound Comfort, presented in Palomares et al. Is the standard ride comfort index an actual estimation of railway passenger comfort? Veh Syst Dyn. 2022;1-14. doi:
10.1080/00423114.2022.2148543
, is used in this paper to evaluate several train types. Simplified models are used as a first approximation for vibration analysis. Despite model simplicity, since the number of possible seating arrangements is intractable, a Monte Carlo procedure is used to obtain compound comfort probability density distributions from a randomised subset of cases. The results from the work presented here will show that the information provided by stochastic distributions is much richer than a single deterministic index. Nevertheless, obtaining distributions from Monte Carlo tests (numerical or experimental) is impractical for any commercial assessment of comfort. Therefore, an inference procedure is called for and has been devised in order to obtain probability density function parameters from just one tare test, along with ten runs of a half laden test. This recipe has been adapted from one presented previously to be able to accommodate the skewed distributions that emerge when a wide range of train configurations is considered.
Natural hybridization and its role in evolution and specifically in generating new diversity is an old and yet endlessly revitalized topic (Lotsy, 1916; Anderson, 1949; Stebbins, 1959; Rieseberg et ...al., 2003;Mallet, 2007; Soltis and Soltis, 2009; Larsen et al., 2010; Arnold et al., 2012b; Pereira et al., 2014; Grant and Grant, 2015; Abbott et al., 2016; Pennisi, 2016). Homoploid hybrid specification (HHS) is the formation of a new-hybridspecies, independent from its parents, via hybridization with no whole-genome duplication and thus no increase in ploidy.Beyond this basic definition, complete agreement is lacking on key aspects of the process, such as the relative proportions of each parental genome present in a hybrid species, the mechanisms leading to reproductive isolation (RI), the degree of RI or the role played by hybridization in the process (Rieseberg, 1997; Abbott et al., 2010).While our understanding of HHS has been improved by detailed evolutionary case studies documented by recent reviews (Abbott et al., 2013; Yakimowski and Rieseberg, 2014; Payseur and Rieseberg, 2016) and empirical studies focused on mechanisms leading to HHS (Renaut et al., 2014; Selz et al., 2014; Lukhtanov et al., 2015), there is controversy concerning the criteria to identify and demonstrate HHS, and even the range of situations that HHS might encompass.
The presence of muons in air-showers initiated by cosmic ray protons and nuclei is well established as a powerful tool to separate such showers from those initiated by gamma rays. However, so far ...this approach has been fully exploited only for ground level particle detecting arrays. We explore the feasibility of using Cherenkov light from muons as a background rejection tool for imaging atmospheric Cherenkov telescope arrays at the highest energies. We adopt an analytical model of the Cherenkov light from individual muons to allow rapid simulation of a large number of showers in a hybrid mode. This allows us to explore the very high background rejection power regime at acceptable cost in terms of computing time. We show that for very large (
≳
20
m mirror diameter) telescopes, efficient identification of muon light can potentially lead to background rejection levels up to 10
-
5
whilst retaining high efficiency for gamma rays. While many challenges remain in the effective exploitation of the muon Cherenkov light in the data analysis for imaging Cherenkov telescope arrays, our study indicates that for arrays containing at least one large telescope, this is a very worthwhile endeavor.
•Finite element calculations of collapsing thick-walled cylinders with actual porous microstructure.•Microstructural porosity favors shear banding in temperature softening materials.•Microstructural ...porosity alone does not trigger shear bands in temperature independent materials.•Increasing the maximum voids diameter favors shear localization and decreases the number of shear bands.•For a given void volume fraction, increasing the number of pores increases the number of shear bands.
This paper provides new insights into the role of porous microstructure on dynamic shear localization. For that purpose, we have performed 3D finite element calculations of electro-magnetically collapsing thick-walled cylinders. The geometry and dimensions of the cylindrical specimens are taken from the experiments of Lovinger et al. (2015), and the loading and boundary conditions from the 2D simulations performed by Lovinger et al. (2018). The mechanical behavior of the material is modeled as elastic-plastic, with yielding described by the von Mises criterion, an associated flow rule and isotropic hardening/softening, being the flow stress dependent on strain, strain rate and temperature. Moreover, plastic deformation is considered to be the only source of heat, and the analysis accounts for the thermal conductivity of the material. The distinctive feature of this work is that we have followed the methodology developed by Marvi-Mashhadi et al. (2021) to incorporate into the finite element calculations the actual porous microstructure of 4 different additively manufactured materials –aluminium alloy AlSi10Mg, stainless steel 316L, titanium alloy Ti6Al4V and Inconel 718– for which the initial void volume fraction varies between 0.001% and 2%, and the pores size ranges from ≈6 µm to ≈110 µm. The numerical simulations have been performed using the Coupled Eulerian-Lagrangian approach available in ABAQUS/Explicit (2016), which allows to capture the shape evolution, coalescence and collapse of the voids at large strains. To the authors’ knowledge, this paper contains the first finite element simulations with explicit representation of the material porosity which demonstrate that voids promote dynamic shear localization, acting as preferential sites for the nucleation of the shear bands, speeding up their development, and tailoring their direction of propagation. In addition, the numerical calculations bring out that for a given void volume fraction more shear bands are nucleated as the number of voids increases, while the shear bands are incepted earlier and develop faster as the size of the pores increases.
Abstract Myocarditis and dilated cardiomyopathy (DCM) are inflammatory diseases of the myocardium, for which appropriate treatment remains a major clinical challenge. Oleanolic acid (OA), a natural ...triterpene widely distributed in food and medicinal plants, possesses a large range of biological effects with beneficial properties for health and disease prevention. Several experimental approaches have shown its cardioprotective actions, and OA has recently been proven effective for treating Th1 cell-mediated inflammatory diseases; however, its effect on inflammatory heart disorders, including myocarditis, has not yet been addressed. Therefore, the present study was undertaken to determine the effectiveness of OA in prevention and treatment of experimental autoimmune myocarditis (EAM). The utility of OA was evaluated in vivo through their administration to cardiac α-myosin (MyHc-α614–629 )-immunized BALB/c mice from day 0 or day 21 post-immunization to the end of the experiment, and in vitro through their addition to stimulated-cardiac cells. Prophylactic and therapeutic administration of OA dramatically decreased disease severity: the heart weight/body weight ratio as well as plasma levels of brain natriuretic peptide and myosin-specific autoantibodies production were significantly reduced in OA-treated EAM animals, compared with untreated ones. Histological heart analysis showed that OA-treatment diminished cell infiltration, fibrosis and dystrophic calcifications. OA also decreased proliferation of cardiac fibroblast in vitro and attenuated calcium and collagen deposition induced by relevant cytokines of active myocarditis. Furthermore, in OA-treated EAM mice the number of Treg cells and the production of IL-10 and IL-35 were markedly increased, while proinflammatory and profibrotic cytokines were significantly reduced. We demonstrate that OA ameliorates both developing and established EAM by promoting an antiinflammatory cytokine profile and by interfering with the generation of cardiac-specific autoantibodies, as well as through direct protective effects on cardiac cells. Therefore, we envision this natural product as novel helpful tool for intervention in inflammatory cardiomyopathies including myocarditis.
Abstract One hundred thirty-six isolates, 88 human and 48 environmental, that met the requirements to belong to the genus Paenibacillus were identified using a polyphasic taxonomic approach known as ...16S rRNA plus phenotypic traits. Thirty-seven Paenibacillus species were identified; some had not been previously reported from clinical samples. The main species were P. pabuli (13 isolates), P. provencensis (11), P. phoenicis (9) and P. lautus (8). P. pabuli (11/13) and P. provencensis (8/11) were mainly environmental isolates, while P. phoenicis (9/9) and P. lautus (6/8) were mainly human isolates. Despite the difficulties in assigning to human Paenibacillus isolates a role as a pathogen or contaminant, here 25% of the isolates were involved in true infections, especially in those cases that affected abscesses, wound exudates, ocular infections and diverse fluids. In addition, 15 isolates were identified as 11 ‘Candidatus’ to a new species, all of them from human specimens except one that was obtained from laboratory air. The antimicrobial susceptibility testing showed 95.6% of isolates were resistant to ampicillin, 44% were resistant to cotrimoxazole, 20 to 30% were resistant to cefotaxime and vancomycin and 13% were resistant to rifampicin and erythromycin.
The thermodynamic formalism of nonequilibrium systems together with the theory of complex systems and systems biology offer an appropriate theoretical framework to explain the complexity observed at ...the macroscopic level in physiological phenomena. In turn, they allow the establishment of an appropriate conceptual and operational framework to address the study of phenomena such as the emergence and evolution of cancer.This chapter is organized as follows: In Subheading 1, an integrated vision of these disciplines is offered for the characterization of the emergence and evolution of cancer, seen as a nonlinear dynamic system, temporally and spatially self-organized out of thermodynamic equilibrium. The development of the various mathematical models and different techniques and approaches used in the characterization of cancer metastasis is presented in Subheading 2. Subheading 3 is devoted to the time course of cancer metastasis, with particular emphasis on the epithelial-mesenchymal transition (EMT henceforth) as well as chronotherapeutic treatments. In Subheading 4, models of the spatial evolution of cancer metastasis are presented. Finally, in Subheading 5, some conclusions and remarks are presented.
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