Cost-effectiveness of intravitreal therapy with both anti-VEGF and Dexamethasone implant in patients with Diabetic Macular Edema

Purpose: The aim of this study was to evaluate the cost-effectiveness of intravitreal therapy (IVT) with both anti-VEGF and Dexamethasone implant in patients with Diabetic Macular Edema (DME) during two years’ follow-up. Methods: A retrospective review of 191 patients (382 eyes) with type I and II diabetes and DME was performed. Pre-IVT and final best correct visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP), number and type of IVT,number of examinations, and fluorescein angiography were assessed. Based on surgery procedure other than IVT, patients were divided into 5 groups. To avoid bias, we analysed only patients who had undergone cataract surgery before (group 1) or during enrolment (group 2). Results: 41 eyes from Group 1 and 48 eyes from group 2 were evaluated. Median BCVA ranged between 20/80 and 20/63 Snellen (P = 0.008) in Group 1 and from 20/63 to 20/40 Snellen (P = 0.0035) in Group 2, while improvement up to 1 Snellen line was observed in 58.5 and 68.75% of eyes in Group 1 and 2, respectively.In terms of median CMT, a statistically reduction (P = 0.0007) was found in Group 2 (-85 μm), whereas no statistical differences were found in Group 1. The two groups showed no statistically significant difference in median IOP. The estimated cost per eye was €7803 in Group 1 and €8988 Group 2, whereas the mean cost per patient was €15190 and €16580 in Group 1 and 2, respectively. Analysis between groups did not show any statistical difference in the considered parameters. Conclusions: In this study, despite the high treatment cost, vision improvement in DME patients undergoing IVT was disappointing. Our results emphasise the need for a better understanding of the cost-effectiveness of DME treatmen

Arc Statistics in Clusters: Galaxy Contribution

The frequency with which background galaxies appear as long arcs as a result of gravitational lensing by foreground clusters of galaxies has recently been found to be a very sensitive probe of cosmological models by Bartelmann et al. (1998). They have found that such arcs would be expected far less frequently than observed (by an order of magnitude) in the currently favored model for the universe, with a large cosmological constant $\Omega_\Lambda \sim 0.7$. Here we analyze whether including the effect of cluster galaxies on the likelihood of clusters to generate long-arc images of background galaxies can change the statistics. Taking into account a variety of constraints on the properties of cluster galaxies, we find that there are not enough sufficiently massive galaxies in a cluster for them to significantly enhance the cross section of clusters to generate long arcs. We find that cluster galaxies typically enhance the cross section by only $\lesssim 15$.Comment: 19 pages, 1 figure, uses aasms4.sty, submitted to Ap

A Recurrent Silent Mutation Implicates fecA in Ethanol Tolerance by Escherichia coli.

BACKGROUND: An issue associated with efficient bioethanol production is the fact that the desired product is toxic to the biocatalyst. Among other effects, ethanol has previously been found to influence the membrane of E. coli in a dose-dependent manner and induce changes in the lipid composition of the plasma membrane. We describe here the characterization of a collection of ethanol-tolerant strains derived from the ethanologenic Escherichia coli strain FBR5. RESULTS: Membrane permeability assays indicate that many of the strains in the collection have alterations in membrane permeability and/or responsiveness of the membrane to environmental changes such as temperature shifts or ethanol exposure. However, analysis of the strains by gas chromatography and mass spectrometry revealed no qualitative changes in the acyl chain composition of membrane lipids in response to ethanol or temperature. To determine whether these strains contain any mutations that might contribute to ethanol tolerance or changes in membrane permeability, we sequenced the entire genome of each strain. Unexpectedly, none of the strains displayed mutations in genes known to control membrane lipid synthesis, and a few strains carried no mutations at all. Interestingly, we found that four independently-isolated strains acquired an identical C → A (V244 V) silent mutation in the ferric citrate transporter gene fecA. Further, we demonstrated that either a deletion of fecA or over-expression of fecA can confer increased ethanol survival, suggesting that any misregulation of fecA expression affects the cellular response to ethanol. CONCLUSIONS: The fact that no mutations were observed in several ethanol-tolerant strains suggested that epigenetic mechanisms play a role in E. coli ethanol tolerance and membrane permeability. Our data also represent the first direct phenotypic evidence that the fecA gene plays a role in ethanol tolerance. We propose that the recurring silent mutation may exert an effect on phenotype by altering RNA-mediated regulation of fecA expression

Regulation of S1PR2 by the EBV oncogene LMP1 in aggressive ABC subtype diffuse large B cell lymphoma.

The Epstein-Barr virus (EBV) is found almost exclusively in the activated B cell (ABC) subtype of diffuse large B cell lymphoma (DLBCL), yet its contribution to this tumour remains poorly understood. We have focussed on the EBV-encoded latent membrane protein-1 (LMP1), a constitutively activated CD40 homologue expressed in almost all EBV-positive DLBCL and which can disrupt germinal centre (GC) formation and drive lymphomagenesis in mice. Comparison of the transcriptional changes that follow LMP1 expression with those that follow transient CD40 signalling in human GC B cells enabled us to define pathogenic targets of LMP1 aberrantly expressed in ABC-DLBCL. These included the down-regulation of S1PR2, a sphingosine-1-phosphate (S1P) receptor that is transcriptionally down-regulated in ABC-DLBCL, and when genetically ablated leads to DLBCL in mice. Consistent with this we found that LMP1-expressing primary ABC-DLBCL were significantly more likely to lack S1PR2 expression than were LMP1-negative tumours. Furthermore, we showed that the down-regulation of S1PR2 by LMP1 drives a signalling loop leading to constitutive activation of the phosphatidylinositol-3-kinase (PI3-K) pathway. Finally, core LMP1-PI3-K targets were enriched for lymphoma-related transcription factors and genes associated with shorter overall survival in patients with ABC-DLBCL. Our data identify a novel function for LMP1 in aggressive DLBCL

The Sunyaev-Zel'dovich effect in WMAP data

Using WMAP 5 year data, we look for the average Sunyaev-Zel'dovich effect (SZE) signal from clusters of galaxies by stacking the regions around hundreds of known X-ray clusters. We detect the average SZE at a very high significance level. The average cluster signal is spatially resolved in the W band. This mean signal is compared with the expected signal from the same clusters calculated on the basis of archival ROSAT data. From the comparison we conclude that the observed SZE seems to be less than the expected signal derived from X-ray measurements when a standard beta-model is assumed for the gas distribution. This conclusion is model dependent. Our predictions depend mostly on the assumptions made about the core radius of clusters and the slope of the gas density profile. Models with steeper profiles are able to simultaneously fit both X-ray and WMAP data better than a beta-model. However, the agreement is not perfect and we find that it is still difficult to make the X-ray and SZE results agree. A model assuming point source contamination in SZE clusters renders a better fit to the one-dimensional SZE profiles thus suggesting that contamination from point sources could be contributing to a diminution of the SZE signal. Selecting a model that better fits both X-ray and WMAP data away from the very central region, we estimate the level of contamination and find that on average, the point source contamination is on the level of 16 mJy (at 41 GHz), 26 mJy (at 61 GHz) and 18 mJy (at 94 GHz). These estimated fluxes are marginally consistent with the estimated contamination derived from radio and infrared surveys thus suggesting that the combination of a steeper gas profile and the contribution from point sources allows us to consistently explain the X-ray emission and SZE in galaxy clusters as measured by ROSAT and WMAP.Comment: 17 pages and 17 figures. Submited to MNRA

Sphingosine-1-phosphate signalling drives an angiogenic transcriptional programme in diffuse large B cell lymphoma

Although the over-expression of angiogenic factors is reported in diffuse large B-cell lymphoma (DLBCL), the poor response to anti-VEGF drugs observed in clinical trials suggests that angiogenesis in these tumours might be driven by VEGF-independent pathways. We show that sphingosine kinase-1 (SPHK1), which generates the potent bioactive sphingolipid sphingosine-1-phosphate (S1P), is over-expressed in DLBCL. A meta-analysis of over 2000 cases revealed that genes correlated with SPHK1 mRNA expression in DLBCL were significantly enriched for tumour angiogenesis meta-signature genes; an effect evident in both major cell of origin (COO) and stromal subtypes. Moreover, we found that S1P induces angiogenic signalling and a gene expression programme that is present within the tumour vasculature of SPHK1-expressing DLBCL. Importantly, S1PR1 functional antagonists, including Siponimod, and the S1P neutralising antibody, Sphingomab, inhibited S1P signalling in DLBCL cells in vitro. Furthermore, Siponimod, also reduced angiogenesis and tumour growth in an S1P-producing mouse model of angiogenic DLBCL. Our data define a potential role for S1P signalling in driving an angiogenic gene expression programme in the tumour vasculature of DLBCL and suggest novel opportunities to target S1P-mediated angiogenesis in patients with DLBCL

Simple procedure for nutrient analysis of coffee plant with energy dispersive X-ray fluorescence spectrometry (EDXRF)

Nutrient analysis is used to estimate nutrient content of crop plants to manage fertilizer application for sustained crop production. Direct solid analysis of agricultural and environmental samples by energy dispersive X-ray fluorescence spectrometry (EDXRF) was chosen as alternative technique to evaluate the simultaneous multielemental quantification of the most important essential elements in coffee (Coffea arabica L.) plants. Inductively coupled plasma atomic emission spectrometry and certified reference materials made from leaves were used to calibrate and check the trueness of EDXRF method for the determination of the concentration of several nutrients in coffee leaves and branches. Fluorescence spectrometry proved to be advantageous and presented low cost as loose powder samples could be used. Samples collected from a field experiment where coffee plants were treated with excess of Ni and Zn were used to verify the practical application of the method. Good relationships were achieved between certified values and data obtained by EDXRF, with recoveries ranging from 82 to 117 %

A randomized controlled trial of mesentericocaval shunt with autologous jugular vein

After a large uncontrolled experience, in April 1976, a randomized clinical trial between side-to-side portacaval anastomosis and a mesentericocaval shunt with internal jugular vein interposition was initiated. Up to April 1979, 23 patients were operated upon with a mesentericocaval shunt and 26 with a portacaval anastomosis. With a mean follow-up time of 23 months, no statistically significant differences in terms of operative mortality, hepatic encephalopathy and long term survival were found between the two operations. Therefore, a mesentericocaval shunt does not appear to offer effective advantages compared with the portacaval anastomosis, and it should be peformed in particular instances in which, for anatomic reasons, a portocaval anastomosis cannot be performed