Study of the polycarbonate-urethane/metal contact in different positions during gait cycle

Nowadays, a growing number of young andmore active patients receive hip replacement.More strenuous activities in such patients involve higher friction and wear rates, with friction on the bearing surface being crucial to ensure arthroplasty survival in the long term. Over the last years, the polycarbonate-urethane has offered a feasible alternative to conventional bearings. A finite element model of a healthy hip joint was developed and adjusted to three gait phases (heel strike, mid-stance, and toe-off), serving as a benchmark for the assessment of the results of joint replacement model. Three equivalent models were made with the polycarbonate-urethane Tribofit system implanted, one for each of the three gait phases, after reproducing a virtual surgery over the respective healthy models. Standard body-weight loads were considered: 230% body-weight toe-off, 275% body-weight mid-stance, and 350% body-weight heel strike. Contact pressures were obtained for the different models. When comparing the results corresponding to the healthy model to polycarbonate-urethane joint, contact areas are similar and so contact pressures are within a narrower value range. In conclusion, polycarbonate-urethane characteristics are similar to those of the joint cartilage. So, it is a favorable alternative to traditional bearing surfaces in total hip arthroplasty, especially in young patients

Anisotropic magnetoconductance and Coulomb blockade in defect engineered Cr2Ge2Te6 van der Waals heterostructures

This is the final version. Available from the American Physical Society via the DOI in this record.We demonstrate anisotropic tunnel magnetoconductance by controllably engineering charging islands inthe layered semiconducting ferromagnet Cr2Ge2Te6. This is achieved by assembling vertical van der Waalsheterostructures comprised of graphene electrodes separated by crystals of Cr2Ge2Te6. Carefully applyingvertical electric fields in the region of (E∼25–50 mV/nm) across the Cr2Ge2Te6causes its dielectric breakdownat cryogenic temperatures. This breakdown process has the effect of introducing subgap defect states withinthe otherwise semiconducting ferromagnetic material. Low-temperature electron transport through chargingislands reveals Coulomb blockade behavior with a strongly gate-tuneable anisotropic magnetoconductance,which persists up toT∼60 K. We report average tunnel magnetoresistance values of 100%. This work opensnew avenues and material systems for the development of nanometer-scale electrically controlled spintronicdevices.Royal Academy of Engineering (RAE)Royal SocietyEngineering and Physical Sciences Research Council (EPSRC

Cementless hydroxyapatite coated hip prostheses

More than twenty years ago, hydroxyapatite (HA), calcium phosphate ceramics, was introduced as a coating for cementless hip prostheses. The choice of this ceramic is due to its composition being similar to organic apatite bone crystals. This ceramic is biocompatible, bioactive, and osteoconductive. These qualities facilitate the primary stability and osseointegration of implants Our surgical experience includes the implantation of more than 4,000 cementless hydroxyapatite coated hip prostheses since 1990 The models implanted are coated with HA in the acetabulum and in the metaphyseal area of the stem.The results corresponding to survival and stability of implants were very satisfactory in the long-term. From our experience, HA-coated hip implants are a reliable alternative which can achieve long termsurvival, provided that certain requirements aremet: good design selection, sound choice of bearing surfaces based on patient life expectancy,meticulous surgical technique, and indications based on adequate bone quality

Persistent Homology Over Directed Acyclic Graphs

We define persistent homology groups over any set of spaces which have inclusions defined so that the corresponding directed graph between the spaces is acyclic, as well as along any subgraph of this directed graph. This method simultaneously generalizes standard persistent homology, zigzag persistence and multidimensional persistence to arbitrary directed acyclic graphs, and it also allows the study of more general families of topological spaces or point-cloud data. We give an algorithm to compute the persistent homology groups simultaneously for all subgraphs which contain a single source and a single sink in $O(n^4)$ arithmetic operations, where $n$ is the number of vertices in the graph. We then demonstrate as an application of these tools a method to overlay two distinct filtrations of the same underlying space, which allows us to detect the most significant barcodes using considerably fewer points than standard persistence.Comment: Revised versio

Gender differences in the incidence of and risk factors for hip fracture: A 16-year longitudinal study in a southern European population

Objectives To analyze independently in men and women the incidence rate of and risk factors for hip fracture in a southern European population. Illiteracy, dementia, clinically significant depression and disability were factors to receive special emphasis. Study design A community sample of 4803 individuals aged over 55 years was assessed in a two-phase case-finding study in Zaragoza, Spain, and was followed up for 16 years. Medical history and psychiatric history were collected with standardized instruments, including the History and Aetiology Schedule, the Geriatric Mental State (GMS) scale, and a Risk Factors Questionnaire. Operational criteria were used to define covariates, including diagnostic criteria for both dementia and depression. The statistical analysis included calculations of incidence rate, IR; women/men incidence rate ratio (IRR); and Hazard Ratios (HR) in multivariate Cox proportional hazards regression models. Main outcome measures Cases of hip fracture (International Classification of Diseases, WHO) identified in the treating hospitals, validated by blinded researchers. Results Hip fractures were more frequent among women than men (IRR = 3.1). Illiteracy (HR = 1.55) and depression (HR = 1.44) increased the risk in women, and smoking (HR = 2.13) and disability in basic activities of daily living (HR = 3.14) increased the risk in men. Dementia was associated with an increased risk in an univariate analysis, but the association disappeared (power = 85% in men, 95% in women) when disability was included in the multivariate models. Conclusions The IR of hip fractures was three times higher among women. Illiteracy and clinically significant depression among women and active smoking and disability (HR = 3.14) among men independently increased the risk, but dementia did not

Up-regulation of HDACs, a harbinger of uraemic endothelial dysfunction, is prevented by defibrotide

Altres ajuts: This work was supported by Jazz Pharmaceuticals Plc (IST-16-10355 to MDR. and EC); German José Carreras Leukaemia Foundation (Grant 11R/2016 and 03R/2019 to MDR. and EC); [...]. We would like to thank the Proteomics unit staff (CCIT, University of Barcelona) for their support in the proteomic assay performance and analysis, and to the Primary Hemostasis laboratory group for their technical support. We also acknowledge the collaboration of Dr Josep Maria Cruzado of Institut d'Hemodiàlisi Barcelona who collaborated in obtaining the blood samples, the staff of the Maternitat Hospital, in Barcelona, for providing the umbilical cords that made possible some of the current results and to Shook Studio for the visual abstract design.Endothelial dysfunction is an earlier contributor to the development of atherosclerosis in chronic kidney disease (CKD), in which the role of epigenetic triggers cannot be ruled out. Endothelial protective strategies, such as defibrotide (DF), may be useful in this scenario. We evaluated changes induced by CKD on endothelial cell proteome and explored the effect of DF and the mechanisms involved. Human umbilical cord vein endothelial cells were exposed to sera from healthy donors (n = 20) and patients with end-stage renal disease on haemodialysis (n = 20). Differential protein expression was investigated by using a proteomic approach, Western blot and immunofluorescence. HDAC1 and HDAC2 overexpression was detected. Increased HDAC1 expression occurred at both cytoplasm and nucleus. These effects were dose-dependently inhibited by DF. Both the HDACs inhibitor trichostatin A and DF prevented the up-regulation of the endothelial dysfunction markers induced by the uraemic milieu: intercellular adhesion molecule-1, surface Toll-like receptor-4, von Willebrand Factor and reactive oxygen species. Moreover, DF down-regulated HDACs expression through the PI3/AKT signalling pathway. HDACs appear as key modulators of the CKD-induced endothelial dysfunction as specific blockade by trichostatin A or by DF prevents endothelial dysfunction responses to the CKD insult. Moreover, DF exerts its endothelial protective effect by inhibiting HDAC up-regulation likely through PI3K/AKT

Laser writable high-K dielectric for van der Waals nano-electronics

This is the author accepted manuscript. The final version is available from American Association for the Advancement of Science via the DOI in this record.Like silicon-based semiconductor devices, van der Waals heterostructures will require integration with high-K oxides. This is needed to achieve suitable voltage scaling, improved performance as well as allowing for added functionalities. Unfortunately, commonly used high-k oxide deposition methods are not directly compatible with 2D materials. Here we demonstrate a method to embed a multi-functional few nm thick high-k oxide within van der Waals devices without degrading the properties of the neighbouring 2D materials. This is achieved by in-situ laser oxidation of embedded few layer HfS2 crystals. The resultant oxide is found to be in the amorphous phase with a dielectric constant of k~15 and break-down electric fields in the range of 0.5-0.6 V/nm. This transformation allows for the creation of a variety of fundamental nano-electronic and opto-electronic devices including, flexible Schottky barrier field effect transistors, dual gated graphene transistors as well as vertical light emitting and detecting tunnelling transistors. Furthermore, upon dielectric break-down, electrically conductive filaments are formed. This filamentation process can be used to electrically contact encapsulated conductive materials. Careful control of the filamentation process also allows for reversible switching between two resistance states. This allows for the creation of resistive switching random access memories (ReRAMs). We believe that this method of embedding a high-k oxide within complex van der Waals heterostructures could play an important role in future flexible multi-functional van der Waals devices.F.W acknowledges support from the Royal Academy of Engineering. J.D.M. acknowledges financial support from the Engineering and Physical Sciences Research Council (EPSRC) of the United Kingdom, via the EPSRC Centre for Doctoral Training in Metamaterials (Grant No. EP/L015331/1). S.R. and M.F.C. acknowledge financial support from EPSRC (Grant no. EP/K010050/1, EP/M001024/1, EP/M002438/1), from Royal Society international Exchanges Scheme 2016/R1, from The Leverhulme trust (grant title “Quantum Revolution” and "Quantum Drums"). A.P Rooney and S.J Haigh acknowledge support from the EPSRC postdoctoral fellowship and from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement ERC-2016-STG-EvoluTEM-715502) and the Defence Threat Reduction Agency (HDTRA1-12-1-0013). I.A. acknowledges financial support from The European Commission Marie Curie Individual Fellowships (Grant number 701704)

Endothelial damage, inflammation and immunity in chronic kidney disease

Chronic kidney disease (CKD) patients have an accelerated atherosclerosis, increased risk of thrombotic-ischemic complications, and excessive mortality rates when compared with the general population. There is also evidence of an endothelial damage in which the proinflammatory state, the enhanced oxidative stress, or the accumulation of toxins due to their reduced renal clearance in uremia play a role. Further, there is evidence that uremic endothelial cells are both involved in and victims of the activation of the innate immunity. Uremic endothelial cells produce danger associated molecular patterns (DAMPS), which by binding to specific pattern recognition receptors expressed in multiple cells, including endothelial cells, induce the expression of adhesion molecules, the production of proinflammatory cytokines and an enhanced production of reactive oxygen species in endothelial cells, which constitute a link between immunity and inflammation. The connection between endothelial damage, inflammation and defective immunity in uremia will be reviewed here

Acute Graft-vs.-Host Disease-Associated Endothelial Activation in vitro Is Prevented by Defibrotide

Altres ajuts: This study was supported in part by Jazz Pharmaceuticals Plc (IST-16-10355), German Jose Carreras Leukaemia Foundation (11R/2016 and 03R/2019).Angiogenesis and endothelial activation and dysfunction have been associated with acute graft-vs.-host disease (aGVHD), pointing to the endothelium as a potential target for pharmacological intervention. Defibrotide (DF) is a drug with an endothelium-protective effect that has been approved for the treatment of veno-occlusive disease/sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Clinical data suggest that DF also reduces the incidence of aGVHD; however, the mechanisms of DF-mediated aGVHD regulation have not been examined. To investigate possible DF-mediated prophylactic and therapeutic mechanisms in aGVHD, we performed in vitro studies using endothelial cell (EC) lines. We found that DF significantly and dose-dependently suppressed EC proliferation and notably reduced their ability to form vascular tubes in Matrigel. To explore whether DF administered prophylactically or therapeutically has a significant effect on aGVHD endothelial dysfunction, ECs were exposed to media containing sera from patients with aGVHD (n = 22) in the absence or presence of DF and from patients that did not develop aGVHD (n = 13). ECs upregulated adhesion molecules (vascular cell adhesion molecule 1, intercellular adhesion molecule 1), the adherence junction protein VE-cadherin, von Willebrand factor (VWF), and Akt phosphorylation in response to aGVHD sera. These responses were suppressed upon treatment with DF. In summary, DF inhibits vascular angiogenesis and endothelial activation induced by sera from aGVHD patients. Our results support the view that DF has notable positive effects on endothelial biology during aGVHD