Diffuse large B-cell lymphoma of the central nervous system in mycophenolate mofetil-treated patients with systemic lupus erythematosus

We report the third case of primary lymphoma of the central nervous system (PCNSL) in a patient with systemic lupus erythematosus (SLE) given long-term mycophenolate mofetil (MMF). Our 43-year-old patient has a history of lupus nephritis and has been treated with MMF 500 mg/day in addition to azathioprine (AZA) for 8 years. She presented with subacute left-sided weakness. Magnetic resonance imaging revealed a gadoliniumenhancing mass in the right parietal region which was isointense on T2-weighted imaging. Brain biopsy revealed diffuse sheets of large lymphoid cells which demonstrated strong membranous expression of CD20 by immunohistochemistry and positive signal for Epstein Bar virus (EBV)–encoded RNA by in-situ hybridization study. Complete remission of PCNSL was achieved after discontinuation of MMF and administration of rituximab and whole brain radiotherapy. Patients with SLE are predisposed to development of lymphoma regardless of immunosuppressive use. One meta-analysis found that non-Hodgkin’s lymphoma was more common in SLE patients with a standardized incidence rate ranging from 5.2 to 44.4. However, the development of PCNSL secondary to immunosuppressive use is being increasingly recognised especially in MMF-treated renal transplant recipients with onset of PCNSL after a median of 14 months. It has also been described in some MMF-treated autoimmune conditions such as myasthenia gravis, dermatomyositis and relapsing polychondritis. Although AZA in combination with corticosteroids has been shown to predispose post-renal transplant patients to lymphoproliferative disease with a relative risk of 12.7, the association of AZA and EBV-related lymphoma is rare. The approach to management of this condition includes withdrawal of MMF and judicious use of future immunosuppressive agents.published_or_final_versionThe 15th Medical Research Conference (15th MRC), Department of Medicine, University of Hong Kong, Hong Kong, 16 January 2010. In Hong Kong Medical Journal, 2010, v. 16 n. 1, suppl. 1, p. 54, abstract no. 9

Stability analysis and quasinormal modes of Reissner Nordstr{\o}m Space-time via Lyapunov exponent

We explicitly derive the proper time $(\tau)$ principal Lyapunov exponent ($\lambda_{p}$) and coordinate time ($t$) principal Lyapunov exponent ($\lambda_{c}$) for Reissner Nordstr{\o}m (RN) black hole (BH) . We also compute their ratio. For RN space-time, it is shown that the ratio is $\frac{\lambda_{p}}{\lambda_{c}}=\frac{r_{0}}{\sqrt{r_{0}^2-3Mr_{0}+2Q^2}}$ for time-like circular geodesics and for Schwarzschild BH it is $\frac{\lambda_{p}}{\lambda_{c}}=\frac{\sqrt{r_{0}}}{\sqrt{r_{0}-3M}}$. We further show that their ratio $\frac{\lambda_{p}}{\lambda_{c}}$ may vary from orbit to orbit. For instance, Schwarzschild BH at innermost stable circular orbit(ISCO), the ratio is $\frac{\lambda_{p}}{\lambda_{c}}\mid_{r_{ISCO}=6M}=\sqrt{2}$ and at marginally bound circular orbit (MBCO) the ratio is calculated to be $\frac{\lambda_{p}}{\lambda_{c}}\mid_{r_{mb}=4M}=2$. Similarly, for extremal RN BH the ratio at ISCO is $\frac{\lambda_{p}}{\lambda_{c}}\mid_{r_{ISCO}=4M}=\frac{2\sqrt{2}}{\sqrt{3}}$. We also further analyse the geodesic stability via this exponent. By evaluating the Lyapunov exponent, it is shown that in the eikonal limit , the real and imaginary parts of the quasi-normal modes of RN BH is given by the frequency and instability time scale of the unstable null circular geodesics.Comment: Accepted in Pramana, 07/09/201

Freeze-Fracture Replica Immunolabelling Reveals Urothelial Plaques in Cultured Urothelial Cells

The primary function of the urothelium is to provide the tightest and most impermeable barrier in the body, i.e. the blood-urine barrier. Urothelial plaques are formed and inserted into the apical plasma membrane during advanced stages of urothelial cell differentiation. Currently, it is supposed that differentiation with the final formation of urothelial plaques is hindered in cultured urothelial cells. With the aid of the high-resolution imaging technique of freeze-fracture replica immunolabelling, we here provide evidence that urothelial cells in vitro form uroplakin-positive urothelial plaques, localized in fusiform-shaped vesicles and apical plasma membranes. With the establishment of such an in vitro model of urothelial cells with fully developed urothelial plaques and functional properties equivalent to normal bladder urothelium, new perspectives have emerged which challenge prevailing concepts of apical plasma membrane biogenesis and blood-urine barrier development. This may hopefully provide a timely impulse for many ongoing studies and open up new questions for future research

Spin-orbit-enhanced robustness of supercurrent in graphene/WS2Josephson junctions

We demonstrate the enhanced robustness of the supercurrent through graphene-based Josephson junctions in which strong spin-orbit interactions (SOIs) are induced. We compare the persistence of a supercurrent at high out-of-plane magnetic fields between Josephson junctions with graphene on hexagonal boron-nitride and graphene on WS2, where strong SOIs are induced via the proximity effect. We find that in the shortest junctions both systems display signatures of induced superconductivity, characterized by a suppressed differential resistance at a low current, in magnetic fields up to 1 T. In longer junctions, however, only graphene on WS2 exhibits induced superconductivity features in such high magnetic fields, and they even persist up to 7 T. We argue that these robust superconducting signatures arise from quasiballistic edge states stabilized by the strong SOIs induced in graphene by WS2

Can We “Hedge” against the Development of Antiviral Resistance among Pandemic Influenza Viruses?

David K. Shay and Benjamin Ridenhour discuss a modeling study predicting that stockpiling a secondary antiviral for use early in a flu pandemic can forestall resistance to the primary stockpiled drug

Preferential regulation of stably expressed genes in the human genome suggests a widespread expression buffering role of microRNAs

In this study, we comprehensively explored the stably expressed genes (SE genes) and fluctuant genes (FL genes) in the human genome by a meta-analysis of large scale microarray data. We found that these genes have distinct function distributions. miRNA targets are shown to be significantly enriched in SE genes by using propensity analysis of miRNA regulation, supporting the hypothesis that miRNAs can buffer whole genome expression fluctuation. The expression-buffering effect of miRNA is independent of the target site number within the 3'-untranslated region. In addition, we found that gene expression fluctuation is positively correlated with the number of transcription factor binding sites in the promoter region, which suggests that coordination between transcription factors and miRNAs leads to balanced responses to external perturbations

The Effect of wake Turbulence Intensity on Transition in a Compressor Cascade

Direct numerical simulations of separating flow along a section at midspan of a low-pressure V103 compressor cascade with periodically incoming wakes were performed. By varying the strength of the wake, its influence on both boundary layer separation and bypass transition were examined. Due to the presence of small-scale three-dimensional fluctuations in the wakes, the flow along the pressure surface undergoes bypass transition. Only in the weak-wake case, the boundary layer reaches a nearly-separated state between impinging wakes. In all simulations, the flow along the suction surface was found to separate. In the simulation with the strong wakes, separation is intermittently suppressed as the periodically passing wakes managed to trigger turbulent spots upstream of the location of separation. As these turbulent spots convect downstream, they locally suppress separation. © 2014 Springer Science+Business Media Dordrecht

Weather, day length and physical activity in older adults: Cross-sectional results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Norfolk Cohort

$\textbf{Background}$ A wide range of environmental factors have been related to active ageing, but few studies have explored the impact of weather and day length on physical activity in older adults. We investigate the cross-sectional association between weather conditions, day length and activity in older adults using a population-based cohort in England, the European Prospective Investigation into Cancer and Nutrition (EPIC) Norfolk study. $\textbf{Methods}$ Physical activity was measured objectively over 7 days using an accelerometer and this was used to calculate daily total physical activity (counts per minute), daily minutes of sedentary behaviour and light, moderate and vigorous physical activity (LMVPA). Day length and two types of weather conditions, precipitation and temperature, were obtained from a local weather station. The association between these variables and physical activity was examined by multilevel first-order autoregressive modelling. $\textbf{Results}$ After adjusting for individual factors, short day length and poor weather conditions, including high precipitation and low temperatures, were associated with up to 10% lower average physical activity (p<0.01) and 8 minutes less time spent in LMVPA but 15 minutes more sedentary time, compared to the best conditions. $\textbf{Conclusion}$ Day length and weather conditions appear to be an important factor related to active ageing. Future work should focus on developing potential interventions to reduce their impact on physical activity behaviours in older adults.This work was funded by the Medical Research Council (Grant Number: G0401527; URL: http://www.mrc.ac.uk/). The work was undertaken under the auspices of the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence which is funded by the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust

To compare the efficacy of two kinds of Zhizhu pills in the treatment of functional dyspepsia of spleen-deficiency and qi-stagnation syndrome:a randomized group sequential comparative trial

<p>Abstract</p> <p>Background</p> <p>In Traditional Chinese Medicine (TCM) theory, functional dyspepsia (FD) can be divided into different syndromes according to different clinical symptoms and signs, and the most common one is spleen-deficiency and qi-stagnation syndrome that can be treated by Chinese traditional patent medicine ---- two kinds of Zhizhu pills, between which the primary difference in ingredients is that one contains immature orange fruit of Citrus aurantium L.(IFCA) and the other contains that of Citrus sinensis Osbeck (IFCS). The trial's objective was to compare the efficacy of two kinds of Zhizhu pills on symptom changes in patients with FD of spleen-deficiency and qi-stagnation syndrome.</p> <p>Methods</p> <p>A randomized, group sequential, double-blinded, multicenter trial was conducted in patients with FD of spleen-deficiency and qi-stagnation syndrome at 3 hospitals in Beijing between June 2003 and May 2005. Participants were randomly allocated into two groups (IFCA group and IFCS group) in a 1:1 ratio, and respectively took one of the two kinds of Zhizhu pills orally, 6 g each time, 3 times a day, for 4 weeks. Statistical analysis was performed with use of a group sequential method, the triangular test (TT).</p> <p>Results</p> <p>A total of 163 patients were randomized, and 3 patients were excluded from analysis because of early dropouts, leaving 160 patients (IFCA group: n = 82; IFCS group: n = 78) for statistical analysis. Three interim analyses were done after 62, 116, and 160 patients had completed their 4-week treatment, respectively. At the third interim analysis, the sample path crossed the upper boundary and the trial was stopped, the cure-markedly effective rates were 45% for IFCS group and 67% for IFCA group, respectively, the one-sided <it>p</it>-value was 0.0036, the median unbiased estimate of the odds ratio (OR) for the benefit of IFCA relative to IFCS was 2.91 with 95%CI: 1.40 to 6.06.</p> <p>No adverse events were observed in the two groups.</p> <p>Conclusions</p> <p>Zhizhu pills containing IFCA was superior to Zhizhu pills containing IFCS in the treatment of FD of spleen-deficiency and qi-stagnation syndrome. The application of group sequential analysis in clinical trials of TCM may offer some financial and ethical benefits.</p> <p>Trial Registration</p> <p>Chinese Clinical Trial Registry (ChiCTR): ChiCTR-TRC-00000485</p