Use of flucinolone acetonide for patients with diabetic macular oedema:patient selection criteria and early outcomes in real world setting

Introduction: Fluocinolone acetonide slow release implant (Iluvien®) was approved in December 2013 in UK for treatment of eyes which are pseudophakic with DMO that is unresponsive to other available therapies. This approval was based on evidence from FAME trials which were conducted at a time when ranibizumab was not available. There is a paucity of data on implementation of guidance on selecting patients for this treatment modality and also on the real world outcome of fluocinolone therapy especially in those patients that have been unresponsive to ranibizumab therapy. Method: Retrospective study of consecutive patients treated with fluocinolone between January and August 2014 at three sites were included to evaluate selection criteria used, baseline characteristics and clinical outcomes at 3-month time point. Results: Twenty two pseudophakic eyes of 22 consecutive patients were included. Majority of patients had prior therapy with multiple intravitreal anti-VEGF injections. Four eyes had controlled glaucoma. At baseline mean VA and CRT were 50.7 letters and 631 μm respectively. After 3 months, 18 patients had improved CRT of which 15 of them also had improved VA. No adverse effects were noted. One additional patient required IOP lowering medication. Despite being unresponsive to multiple prior therapies including laser and anti-VEGF injections, switching to fluocinolone achieved treatment benefit. Conclusion: The patient level selection criteria proposed by NICE guidance on fluocinolone appeared to be implemented. This data from this study provides new evidence on early outcomes following fluocinolone therapy in eyes with DMO which had not responded to laser and other intravitreal agents

POSIWID and determinism in design for behaviour change

Copyright @ 2012 Social Services Research GroupWhen designing to influence behaviour for social or environmental benefit, does designers' intent matter? Or are the effects on behaviour more important, regardless of the intent involved? This brief paper explores -- in the context of design for behaviour change -- some treatments of design, intentionality, purpose and responsibility from a variety of fields, including Stafford Beer's "The purpose of a system is what it does" and Maurice Broady's perspective on determinism. The paper attempts to extract useful implications for designers working on behaviour-related problems, in terms of analytical or reflective questions to ask during the design process

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

Nkx2.7 and Nkx2.5 Function Redundantly and Are Required for Cardiac Morphogenesis of Zebrafish Embryos

Nkx2.7 is the tinman-related gene, as well as orthologs of Nkx2.5 and Nkx-2.3. Nkx2.7 and Nkx2.5 express in zebrafish heart fields of lateral plate mesoderm. The temporal and spatial expression patterns of Nkx2.7 are similar to those of Nkx2.5, but their functions during cardiogenesis remain unclear.Here, Nkx2.7 is demonstrated to compensate for Nkx2.5 loss of function and play a predominant role in the lateral development of the heart, including normal cardiac looping and chamber formation. Knocking down Nkx2.5 showed that heart development was normal from 24 to 72 hpf. However, when knocking down either Nkx2.7 or Nkx2.5 together with Nkx2.7, it appeared that the heart failed to undergo looping and showed defective chambers, although embryos developed normally before the early heart tube stage. Decreased ventricular myocardium proliferation and defective myocardial differentiation appeared to result from late-stage up-regulation of bmp4, versican, tbx5 and tbx20, which were all expressed normally in hearts at an early stage. We also found that tbx5 and tbx20 were modulated by Nkx2.7 through the heart maturation stage because an inducible overexpression of Nkx2.7 in the heart caused down-regulation of tbx5 and tbx20. Although heart defects were induced by overexpression of an injection of 150-pg Nkx2.5 or 5-pg Nkx2.7 mRNA, either Nkx2.5 or Nkx2.7 mRNA rescued the defects induced by Nkx2.7-morpholino(MO) and Nkx2.5-MO with Nkx2.7-MO.Therefore, we conclude that redundant activities of Nkx2.5 and Nkx2.7 are required for cardiac morphogenesis, but that Nkx2.7 plays a more critical function, specifically indicated by the gain-of-function and loss-of- function experiments where Nkx2.7 is observed to regulate the expressions of tbx5 and tbx20 through the maturation stage

The mediating role of self/everyday creativity and depression on the relationship between creative personality traits and problematic social media use among emerging adults

Personality is one of the important contributory factors in the development of problematic technology use. The purpose of the present study was to investigate the direct and indirect associations of creative personality traits with problematic social media use via self/everyday creativity, depression, and loneliness. A total of 460 Turkish emerging adults aged between 18 and 26 years (61% female) were surveyed. Findings indicated that (i) task-orientedness was indirectly associated with problematic social media use via self/everyday creativity, (ii) self-confidence was directly and indirectly associated with problematic social media use via self/everyday creativity and depression, (iii) risk-taking was indirectly associated with problematic social media use via depression, and (iv) self/everyday creativity and depression were directly associated with problematic social media use. The present study is the first to suggest that creative personality traits (i.e., task-orientedness, self-confidence, and risk-taking) and self/everyday creativity are associated with problematic social media use and that these factors should be taken into account when considering the etiology of problematic social media use

Toll-like receptor 9 polymorphisms are associated with severity variables in a cohort of meningococcal meningitis survivors

BACKGROUND: Genetic variation in immune response genes is associated with susceptibility and severity of infectious diseases. Toll-like receptor (TLR) 9 polymorphisms are associated with susceptibility to develop meningococcal meningitis (MM). The aim of this study is to compare genotype distributions of two TLR9 polymorphisms between clinical severity variables in MM survivors. METHODS: We used DNA samples of a cohort of 390 children who survived MM. Next, we determined the genotype frequencies of TLR9 -1237 and TLR9 +2848 polymorphisms and compared these between thirteen clinical variables associated with prognostic factors predicting adverse outcome of bacterial meningitis in children. RESULTS: The TLR9 -1237 TC and CC genotypes were associated with a decreased incidence of a positive blood culture for Neisseria (N.) meningitidis (p = 0.014, odds ratio (OR) 0.5. 95% confidence interval (CI) 0.3 – 0.9). The TLR9 +2848 AA mutant was associated with a decreased incidence of a positive blood culture for N. meningitidis (p = 0.017, OR 0.6, 95% CI 0.3 – 0.9). Cerebrospinal fluid (CSF) leukocytes per μL were higher in patients carrying the TLR9 -1237 TC or CC genotypes compared to carriers of the TT wild type (WT) (p = 0.024, medians: 2117, interquartile range (IQR) 4987 versus 955, IQR 3938). CSF blood/glucose ratios were lower in TLR9 -1237 TC or CC carriers than in carriers of the TT WT (p = 0.017, medians: 0.20, IQR 0.4 versus 0.35, IQR 0.5). CSF leukocytes/μL were higher in patients carrying the TLR9 +2848 AA mutant compared to carriers of GG or GA (p = 0.0067, medians: 1907, IQR 5221 versus 891, IQR 3952). CONCLUSIONS: We identified TLR9 genotypes associated with protection against meningococcemia and enhanced local inflammatory responses inside the central nervous system, important steps in MM pathogenesis and defense

Visual Acuity Improvement When Switching From Ranibizumab To Aflibercept Is Not Sustained

PURPOSE: To assess whether visual benefits exist in switching to aflibercept in patients who have been chronically treated with ranibizumab for neovascular age-related macular degeneration. METHODS: A multicenter, national, electronic medical record database study was performed. Patients undergoing six continuous monthly ranibizumab injections and then switched to continuous aflibercept were matched to those on continuous ranibizumab therapy. Matching was performed in a 2:1 ratio and based on visual acuity 6 months before and at the time of the switch, and the number of previous ranibizumab injections. RESULTS: Patients who were switched to aflibercept demonstrated transiently significant improvement in visual acuity that peaked at an increase of 0.9 Early Treatment Diabetic Retinopathy Study letters 3 months after the switch, whereas control patients continued on ranibizumab treatment showed a steady decline in visual acuity. Visual acuity differences between the groups were significant (P < 0.05) at 2, 3, and 5 months after the switch. Beginning at 4 months after the switch, the switch group showed a visual acuity decline similar to the control group. CONCLUSION: Transient, nonsustained improvement in visual acuity occurs when switching between anti-vascular endothelial growth factor agents, which may have implications in treating patients on chronic maintenance therapy on one anti-vascular endothelial growth factor medication

Catalogue of far-infrared loops in the Galaxy

Aims: An all-sky survey of loop- and arc-like intensity enhancements has been performed in order to investigate the large-scale structure of the diffuse far-infrared emission. Methods: We used maps made of 60 and 100 micrometer processed IRAS data (Sky Survey Atlas and dust infrared emission maps) to identify large-scale structures: loops, arcs or cavities, in the far-infrared emission in the Galaxy. Distances were attributed to a subsample of loops using associated objects. Results: We identified 462 far-infrared loops, analyzed their individual FIR properties and their distribution. This data forms the Catalogue of Far-Infrared Loops in the Galaxy. We obtained observational estimates of f_in~30% and f_out~5% for the hot gas volume filling factor of the inward and outward Galactic neighbourhood of the Solar System. We obtained a slope of the power law size luminosity function {beta}=1.37 for low Galactic latitudes in the outer Milky Way. Conclusions: Deviations in the celestial distribution of far-infrared loops clearly indicate, that violent events frequently overwrite the structure of the interstellar matter in the inner Galaxy. Our objects trace out the spiral arm structure of the Galaxy in the neighbourhood of the Sun and their distribution clearly suggests that there is an efficient process that can generate loop-like features at high Galactic latitudes. Power law indices of size luminosity distributions suggest, that the structure of the ISM is ruled by supernovae and stellar winds at low Galactic latitudes while it is governed by supersonic turbulence above the Galactic plane.Comment: 11 pages - 10 figures (together with Appendix A), accepted for publication in Astronomy & Astrophysics. Appendix B, C and D are available at http://kisag.konkoly.hu/CFIRLG

Far-infrared loops in the 2nd Galactic Quadrant

We present the results of an investigation of the large scale structure of the diffuse interstellar medium in the 2nd Galactic Quadrant (90 <= l <= 180). 145 loops were identified on IRAS based far-infrared maps. Our catalogue lists their basic physical properties. The distribution clearly suggests that there is an efficient process that can generate loop-like features at high galactic latitudes. Distances are provided for 30 loops. We also give an observational estimate on the volume filling factor of the hot gas in the Local Arm, 4.6% <= f_2nd <= 6.4%Comment: accepted for publication in Astronomy & Astrophysics Fig. 2, Appendix A, B and C are available at http://astro.elte.hu/CFIRL