Partition of the contact force network obtained in discrete element simulations of element tests

The transmission of stress within a granular material composed of rigid spheres is explored using the discrete element method. The contribution of contacts to both deviatoric stress and structural anisotropy is investigated. The influences of five factors are considered: inter-particle friction coefficient, loading regime, packing density, contact model, and boundary conditions. The data generated indicate that using the above-average normal contact force criterion to decompose the contact force network into two subsets with distinct contributions to stress transmission and structural anisotropy is not robust. The characteristic normal contact forces marking the transition from negative to positive contribution to the overall deviatoric stress and structural anisotropy are not unique values but vary during shearing. Once the critical state is attained (i.e., once shearing continues at a constant deviator stress and solid fraction), the characteristic normal contact force remains approximately constant and this critical state characteristic normal force is observed to decrease with increasing inter-particle friction. The characteristic normal contact force considering the contribution to deviatoric stress has a power-law relationship with the mean effective stress at the critical state

Role of enzymic antioxidants in mediating oxidative stress and contrasting wound healing capabilities in oral mucosal/skin fibroblasts and tissues

Unlike skin, oral mucosal wounds are characterized by rapid healing and minimal scarring, attributable to the “enhanced” healing properties of oral mucosal fibroblasts (OMFs). As oxidative stress is increasingly implicated in regulating wound healing outcomes, this study compared oxidative stress biomarker and enzymic antioxidant profiles between patient-matched oral mucosal/skin tissues and OMFs/skin fibroblasts (SFs) to determine whether superior oral mucosal antioxidant capabilities and reduced oxidative stress contributed to these preferential healing properties. Oral mucosa and skin exhibited similar patterns of oxidative protein damage and lipid peroxidation, localized within the lamina propria/dermis and oral/skin epithelia, respectively. SOD1, SOD2, SOD3 and catalase were primarily localized within epithelial tissues overall. However, SOD3 was also widespread within the lamina propria localized to OMFs, vasculature and the extracellular matrix. OMFs were further identified as being more resistant to reactive oxygen species (ROS) generation and oxidative DNA/protein damage than SFs. Despite histological evaluation suggesting that oral mucosa possessed higher SOD3 expression, this was not fully substantiated for all OMFs examined due to inter-patient donor variability. Such findings suggest that enzymic antioxidants have limited roles in mediating privileged wound healing responses in OMFs, implying that other non-enzymic antioxidants could be involved in protecting OMFs from oxidative stress overall

Hand osteoarthritis: clinical phenotypes, molecular mechanisms and disease management

Osteoarthritis (OA) is a highly prevalent condition and the hand is the most commonly affected site. Patients with hand OA frequently report symptoms of pain, functional limitations, and frustration in undertaking everyday activities. The condition presents clinically with changes to the bone, ligaments, cartilage and synovial tissue, which can be observed using radiography, ultrasonography or MRI. Hand OA is a heterogeneous disorder and is considered to be multifactorial in aetiology. This review provides an overview of the epidemiology, presentation and burden of hand OA, including an update on hand OA imaging (including the development of novel techniques), disease mechanisms and management. In particular, areas for which new evidence has substantially changed the way we understand, consider and treat hand OA are highlighted. For example, genetic studies, clinical trials and careful prospective imaging studies from the past 5 years are beginning to provide insights into the pathogenesis of hand OA that might uncover new therapeutic targets in disease

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Discrete element modelling of grain size segregation in bi-disperse granular flows down chute

ABSTRACT Grain size segregation in dense granular chute flows is generally explained by the mechanisms of kinetic sieving and squeeze expulsion (after In this paper, three-dimensional DEM simulations are presented. Different cubic bi-disperse samples are generated in pluviation, on the rough base formed by randomly located particles. Periodic boundaries are applied to the flow direction, while two different types of boundary conditions are imposed on the sides, i.e. periodic boundaries and rigid walls. Parametrical studies, involving slope, width, volume fraction, and coefficient of friction, are systemically performed. In all presented cases, steady, fully developed (SFD) flows are achieved, that the kinetic energy and fractional volume distribution keep constant. Segregations are completed with slightly different extents, in the sense that a thick layer of pure coarse grains appears on the top of the flow. From the macroscopic view, the profiles of volume fraction, mean velocity and shear stress are calculated and interpreted by performing averaging in space. The rheology of binary granular system is presented. On the other hand, one of the major objectives is to provide microscopic evidences for the reviewed mechanisms (i.e., kinetic sieving and squeeze expulsion), since the discrete element modelling produce more detailed information on the individual particles. The trajectory of each particle is tracked and analysed, showing clearly the contact conditions and shear history that one single particle has experienced. It has been found that the connectivity of small particles are at a lower level than that of the large ones, indicating that the probability of their dropping into voids under gravity is higher. The large particles see a significant increase of connectivity when they are migrating through the layer of small particles. The upward forces exerting on the coarse grains become dominant at the same time with the highest rate of segregation of the entire flow. For the periodic side-boundary cases, when the width of the sample is increased, diffusion and re-mixing are observed in the minor direction (i.e. the transverse dimension). The percolations of small particles occur in either directions, instead of just in the direction normal to the base. Velocity fluctuations with slightly higher probability towards the top lead to the upward movement of the coarse layer. When the sample is narrow, or is confined by sidewalls, pure upward/downward movements are observed and the shear stress plays an important role in the process of segregation

Co-expression of SNAIL and TWIST determines prognosis in estrogen receptor–positive early breast cancer patients

Epithelial mesenchymal transition (EMT) plays an important role in the development of metastases. One of the hallmarks of EMT is loss of E-cadherin and gain of N-cadherin expression, which are regulated by transcription factors, such as SNAIL, SLUG, and TWIST. We examined the prognostic value of these factors as well as E-cadherin and N-cadherin, in a well-described large cohort of breast cancer patients treated with primary surgery. Analyses were stratified by estrogen receptor (ER) status, because of its crucial role in the regulation of these transcription factors. SNAIL, SLUG, and TWIST expression were examined on a TMA containing 575 breast tumors using immunohistochemistry. Nuclear expression was quantified using a weighted histoscore and classified as high versus low expression, based on the median histoscore. High expression of SNAIL, SLUG, and TWIST was seen in 54, 50, and 50% of tumors, respectively. The level of SNAIL (P = 0.014) and TWIST (P = 0.006) expression was associated with a worse patient relapse-free period, specifically in patients with ER-positive tumors (interaction Cox proportional hazards P = 0.039). Combining both factors resulted in an independent prognostic factor with high discriminative power (both low versus either high: HR 1.15; both low versus both high HR 1.84; P = 0.010). Co-expression of SNAIL-TWIST was associated with low-E-cadherin and high-N-cadherin expression, especially in ER-positive tumors (P = 0.009), suggesting that, through interactions with ER, SNAIL and TWIST may regulate E- and N-cadherin expression, thereby inducing EMT. Our results are indicative that SNAIL and TWIST play a crucial role in EMT through regulation of E- and N-cadherin expression, exclusively in ER-positive breast cancer patients.Molecular tumour pathology - and tumour genetic