Numerical modelling of silicon melt purification in induction directional solidification system

Solar grade silicon production is an energy intensive and harmful to the environment process. Yet 40% of this valuable product material is lost into sawdust (kerf loss) during wafering. The kerf waste from Fixed Abrasive Sawing of PV silicon wafers is pelletized and then remelted in an induction furnace. The furnace has a square cross-section quartz crucible, surrounded by graphite susceptors and heated by an induction coil that enables directional solidification of the new ingot. Top and bottom 'pancake' coils provide additional temperature control. Once melted, silicon becomes electrically conductive and subject to stirring by induction. To recycle the silicon, particulate impurities (due to the sawing, condensed silicon oxides or carbides) need to be removed. Flow control and the electromagnetic Leenov-Kolin force are used to expel particulates, through a novel dual frequency induction scheme. Three-dimensional, multi-physics numerical modelling captures the electromagnetic, fluid-flow and heat-transfer effects in this process. The presented results show it is possible to retain the impurity particles on the sides of the solidified ingot where they can be sliced off and removed

Prostate cancer and the influence of dietary factors and supplements: a systematic review

Background Prostate cancer is the second most common cause of cancer worldwide after lung cancer. There is increasing evidence that diet and lifestyle plays a crucial role in prostate cancer biology and tumourigenesis. Prostate cancer itself represents a good model of cancer in which to look for chemopreventive agents due to the high disease prevalence, slowly progressive nature, and long latency period. Dietary agents have gained considerable attention, often receiving much publicity in the media. Aim To review the key evidence available for potential chemopreventive nutrients. Methods The methodology for this review involved a PubMed search from 1990 to 2013 using the key-words “diet and prostate cancer”, “nutrition and prostate cancer”, “dietary factors and prostate cancer”, “prostate cancer epidemiology”, “prostate cancer prevention”, “prostate cancer progression”. Results Red meat, dietary fat and milk intake should be minimised as they appear to increase the risk of prostate cancer. Fruit and vegetables and polyphenols may be preventive in prostate cancer, but further studies are needed to draw more solid conclusions and to clarify their role in patients with an established diagnosis of prostate cancer. Selenium and vitamin supplements cannot be advocated for the prevention of prostate cancer and indeed higher doses may be associated with a worse prognosis. There is no specific evidence regarding benefits of probiotics or prebiotics in prostate cancer. Conclusions From the wealth of evidence available, many recommendations can be made although more randomised control trials are required. These need to be carefully designed due to the many confounding factors and heterogeneity of the population

Experimental and numerical study of the cold crucible melting process

The cold crucible, or induction skull melting process as is otherwise known, has the potential to produce high purity melts of a range of difficult to melt materials, including Ti–Al and Ti6Al4V alloys for Aerospace, Ti–Ta and other biocompatible materials for surgical implants, silicon for photovoltaic and electronic applications, etc. A water cooled AC coil surrounds the crucible causing induction currents to melt the alloy and partially suspend it against gravity away from water-cooled surfaces. Strong stirring takes place in the melt due to the induced electromagnetic Lorentz forces and very high temperatures are attainable under the right conditions (i.e., provided contact with water cooled walls is minimised). In a joint numerical and experimental research programme, various aspects of the design and operation of this process are investigated to increase our understanding of the physical mechanisms involved and to maximise process efficiency. A combination of FV and Spectral CFD techniques are used at Greenwich to tackle this problem numerically, with the experimental work taking place at Birmingham University. Results of this study, presented here, highlight the influence of turbulence and free surface behaviour on attained superheat and also discuss coil design variations and dual frequency options that may lead to winning crucible designs

Anti-protein C antibodies and acquired protein C resistance in SLE: novel markers for thromboembolic events and disease activity?

OBJECTIVES: Risk factors for thromboembolism in SLE are poorly understood. We hypothesized a possible role for protein C, based on its dual activity in inflammation and haemostasis and on the evidence of an association between acquired activated protein C (APC) resistance (APCR) and high-avidity anti-protein C antibodies (anti-PC) with a severe thrombotic phenotype in venous thrombosis APS patients. METHODS: In a cross-sectional study of 156 SLE patients, the presence and avidity of IgG anti-PC was established by in house-ELISA, and APCR to exogenous recombinant human APC (rhAPC) and Protac (which activates endogenous protein C) was assessed by thrombin generation-based assays. Associations with aPL profile, thrombotic history and disease activity (BILAG and SLEDAI-2K) were also established. RESULTS: Anti-PC were detected in 54.5% of patients and APCR in 59%. Anti-PC positivity was associated with APCR to both rhAPC (P <0.0001) and Protac (P =0.0001). High-avidity anti-PC, detected in 26.3% of SLE patients, were associated with APCR in patients with thrombosis only (P <0.05), and with the development of thrombosis over time (range: 0-52 years; P =0.014). High-avidity anti-PC levels correlated with SLEDAI-2K (P =0.033) and total BILAG (P =0.019); SLEDAI-2K correlated inversely with APCR to Protac (P =0.004). CONCLUSION: Anti-PC occur in patients with SLE, independently of aPL profile, and are associated with APCR. High-avidity anti-PC are associated with thrombosis and with active disease and might prove a novel marker to monitor the risk of thrombosis and disease progression in SLE

Inhaled corticosteroids reduce senescence in endothelial progenitor cells from COPD patients

Cellular senescence contributes to the pathophysiology of chronic obstructive pulmonary disease (COPD) and cardiovascular disease. Using endothelial-colony-forming-cells (ECFC), we have demonstrated accelerated senescence in smokers and COPD patients compared to non-smokers. Subgroup analysis suggests that ECFC from COPD patients on inhaledcorticosteroids (ICS) (n=14; 8 on ICS) exhibited significantly reduced senescence (Senescence-associated-beta galactosidase activity, p21CIP1), markers of DNA damage response (DDR) and IFN-γ-inducible-protein-10 compared to COPD patients not on ICS. In vitro studies using human-umbilical-vein-endothelial-cells showed a protective effect of ICS on the DDR, senescence and apoptosis caused by oxidative-stress, suggesting a protective molecular mechanism of action of corticosteroids on endothelium

The association between IgG and IgM antibodies against cardiolipin, β2-glycoprotein I and Domain I of β2-glycoprotein I with disease profile in patients with multiple sclerosis

Antiphospholipid antibodies (aPL) occur in patients with multiple sclerosis (MS) with a number of studies reporting elevated levels; their exact prevalence and pathogenic role remain unclear. Epidemiological studies associate MS with an increased risk of deep venous thromboembolism and stroke; overlapping clinical features with APS. Antibodies against the first domain – Domain I (DI) – of β2glycoprotein I (β2GPI), show the most clinical significance and evidence for pathogenicity in the antiphospholipid syndrome (APS), but have not yet been investigated in MS. Serum from a well-defined cohort of 127 MS patients and 92 healthy controls were tested for IgM and IgG antibodies against cardiolipin (CL), β2GPI and DI. Higher frequency of IgM and IgG anti-CL were found in MS patients (18.1% and 21.3%), compared to controls (1.1% in both cases, p < 0.0001). We report that anti-DI antibodies were associated with MS patients, with 6.3% and 7.1% positive for IgM and IgG, respectively, compared to controls, 1.1% (p < 0.05). IgM anti-CL antibodies were elevated in secondary progressive MS and primary progressive MS compared to relapse-remitting MS, (p < 0.005). This study enrolled the largest number of patients with definite MS for studying the association with aPL. Although we confirmed IgM and IgG anti-CL antibodies occur in patients with MS, this is the first study that identified anti-DI antibodies in MS patients. This new finding may prove valuable and future studies are required to evaluate its role as a potential risk factor of thromboembolic phenomena in MS

Identification of a Novel HIF-1α-α_{M}β_{2} Integrin-NET Axis in Fibrotic Interstitial Lung Disease

Neutrophilic inflammation correlates with mortality in fibrotic interstitial lung disease (ILD) particularly in the most severe form, idiopathic pulmonary fibrosis (IPF), although the underlying mechanisms remain unclear. Neutrophil function is modulated by numerous factors, including integrin activation, inflammatory cytokines and hypoxia. Hypoxia has an important role in inflammation and may also contribute to pulmonary disease. We aimed to determine how neutrophil activation occurs in ILD and the relative importance of hypoxia. Using lung biopsies and bronchoalveolar lavage (BAL) fluid from ILD patients we investigated the extent of hypoxia and neutrophil activation in ILD lungs. Then we used ex vivo neutrophils isolated from healthy volunteers and BAL from patients with ILD and non-ILD controls to further investigate aberrant neutrophil activation in hypoxia and ILD. We demonstrate for the first time using intracellular staining, HIF-1α stabilization in neutrophils and endothelial cells in ILD lung biopsies. Hypoxia enhanced both spontaneous (+1.31-fold, p < 0.05) and phorbol 12-myristate 13-acetate (PMA)-induced (+1.65-fold, p < 0.001) neutrophil extracellular trap (NET) release, neutrophil adhesion (+8.8-fold, <0.05), and trans-endothelial migration (+1.9-fold, p < 0.05). Hypoxia also increased neutrophil expression of the αM (+3.1-fold, p < 0.001) and αX (+1.6-fold, p < 0.01) integrin subunits. Interestingly, NET formation was induced by αMβ2 integrin activation and prevented by cation chelation. Finally, we observed NET-like structures in IPF lung sections and in the BAL from ILD patients, and quantification showed increased cell-free DNA content (+5.5-fold, p < 0.01) and MPO-citrullinated histone H3 complexes (+21.9-fold, p < 0.01) in BAL from ILD patients compared to non-ILD controls. In conclusion, HIF-1α upregulation may augment neutrophil recruitment and activation within the lung interstitium through activation of β2 integrins. Our results identify a novel HIF-1α- αMβ2 integrin axis in NET formation for future exploration in therapeutic approaches to fibrotic ILD

Antiphospholipid antibody positivity in early systemic lupus erythematosus is associated with subsequent vascular events

OBJECTIVE: Antiphospholipid antibodies (aPL) are found in the blood of 20-30% of patients with systemic lupus erythematosus (SLE). Although aPL cause vascular thrombosis in the antiphospholipid syndrome it is not clear whether positive aPL levels in early SLE increase risk of subsequent vascular events (VE). In a previous analysis of 276 patients with SLE, we found that early positivity for ≥2 of IgG anti-cardiolipin (anti-CL), IgG anti-beta2glycoprotein I (anti-β2GPI) and anti-Domain I of beta2glycoprotein I (anti-DI) showed a possible association with VE. Here we have extended that analysis. METHODS: Serum samples taken from 501 patients with SLE early in their disease had been tested for IgG anti-CL, anti-β2GPI and anti-DI by ELISA. Complete VE history was available for 423 patients of whom 23 were excluded because VE occurred before the diagnosis of SLE. For the remaining 400 patients we carried out Kaplan-Meier survival analysis to define groups at higher risk of VE. RESULTS: Of 400 patients, 154 (38.5%) were positive for one or more aPL; 27 (6.8%) were double/triple-positive and 127 (31.8%) were single-positive. There were 91 VE in 77 patients, of whom 42 were aPL-positive in early disease. VE were significantly increased in aPL-positive versus aPL-negative patients (p= 0.041) and in double/triple-positive versus single-positive versus aPL-negative patients (p= 0.0057).Omission of the IgG anti-DI assay would have missed 14 double/triple-positive patients of whom 6 had VE. CONCLUSION: Double/triple-positivity for IgG anti-CL, anti- anti-β2GPI and anti-DI in early SLE identifies a population at higher risk of subsequent VE

Improving uptake of hepatitis B and hepatitis C testing in South Asian migrants in community and faith settings using educational interventions - a prospective descriptive study

BACKGROUND: Chronic viral hepatitis (CVH) is a leading contributor to the UK liver disease epidemic, with global migration from high-prevalence areas (e.g. South Asia-SA). Despite international guidance for testing high-risk groups in line with elimination targets, there is no consensus on how to achieve this. OBJECTIVES: (i) Feasibility of recruiting SA migrants to view an educational film on CVH (ii) Effectiveness of the film in promoting testing, knowledge of CVH (iii) Methodological issues relevant to scale-up to randomized trial. METHODS: We recruited SA migrants to view the film (intervention) in community venues (primary care, religious, community), offering dried-blood spot CVH testing immediately afterwards. Pre/post-film questionnaires assessed the interventions effectiveness. RESULTS: Two hundred and nineteen first generation migrants >18yrs (53% female) were recruited to view the film;184 (84%) underwent CVH testing (HBc Ab or HCV Ab positive, demonstrating exposure in 8.5%) at the following sites: n = 112 (51%) religious, n = 98(45%) community, and primary care, n = 9 (4%). Pre (n = 173, 79%) and post (n = 154, 70%) intervention questionnaires were completed. CONCLUSIONS: We demonstrate the feasibility of recruiting first generation migrants to participate in a community-based educational film, promoting CVH testing in this higher-risk group, confirming value of developing interventions to facilitate global WHO plan for targeted case finding, elimination and future randomized controlled trial. We highlight the importance of culturally relevant interventions including faith, and culturally sensitive settings appearing to minimize logistical issues effective at engaging minority groups and allowing ease of access to individuals 'at risk'