Nitrogen metabolism and growth enhancement in tomato plants challenged with Trichoderma harzianum expressing the Aspergillus nidulans acetamidase amdS gene

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Sara Domínguez

2016-08-01

Full Text Available Trichoderma is a fungal genus that includes species that are currently being used as biological control agents and/or as biofertilizers. In addition to the direct application of Trichoderma spp. as biocontrol agents in plant protection, recent studies have focused on the beneficial responses exerted on plants, stimulating the growth, activating the defenses, and/or improving nutrient uptake. The amdS gene, encoding an acetamidase of Aspergillus, has been used as a selectable marker for the transformation of filamentous fungi, including Trichoderma spp., but the physiological effects of the introduction of this gene into the genome of these microorganisms still remains unexplored. No evidence of amdS orthologous genes has been detected within the Trichoderma spp. genomes and the amdS heterologous expression in T. harzianum T34 did not affect the growth of this fungus in media lacking acetamide. However, it did confer the ability for the fungus to use this amide as a nitrogen source. Although a similar antagonistic behavior was observed for T34 and amdS transformants in dual cultures against Rhizoctonia solani, Botrytis cinerea and Fusarium oxysporum, a significantly higher antifungal activity was detected in amdS transformants against F. oxysporum, compared to that of T34, in membrane assays on media lacking acetamide. In Trichoderma-tomato interaction assays, amdS transformants were able to promote plant growth to a greater extent than the wild-type T34, although compared with this strain the transformants showed similar capability to colonize tomato roots. Gene expression patterns from aerial parts of 3-week-old tomato plants treated with T34 and the amdS transformants have also been investigated using GeneChip Tomato Genome Arrays. The downregulation of defense genes and the upregulation of carbon and nitrogen metabolism genes observed in the microarrays were accompanied by i enhanced growth, ii increased carbon and nitrogen levels and iii a

Nitrogen Metabolism and Growth Enhancement in Tomato Plants Challenged with Trichoderma harzianum Expressing the Aspergillus nidulans Acetamidase amdS Gene.

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Domínguez, Sara; Rubio, M Belén; Cardoza, Rosa E; Gutiérrez, Santiago; Nicolás, Carlos; Bettiol, Wagner; Hermosa, Rosa; Monte, Enrique

2016-01-01

Trichoderma is a fungal genus that includes species that are currently being used as biological control agents and/or as biofertilizers. In addition to the direct application of Trichoderma spp. as biocontrol agents in plant protection, recent studies have focused on the beneficial responses exerted on plants, stimulating the growth, activating the defenses, and/or improving nutrient uptake. The amdS gene, encoding an acetamidase of Aspergillus, has been used as a selectable marker for the transformation of filamentous fungi, including Trichoderma spp., but the physiological effects of the introduction of this gene into the genome of these microorganisms still remains unexplored. No evidence of amdS orthologous genes has been detected within the Trichoderma spp. genomes and the amdS heterologous expression in Trichoderma harzianum T34 did not affect the growth of this fungus in media lacking acetamide. However, it did confer the ability for the fungus to use this amide as a nitrogen source. Although a similar antagonistic behavior was observed for T34 and amdS transformants in dual cultures against Rhizoctonia solani, Botrytis cinerea, and Fusarium oxysporum, a significantly higher antifungal activity was detected in amdS transformants against F. oxysporum, compared to that of T34, in membrane assays on media lacking acetamide. In Trichoderma-tomato interaction assays, amdS transformants were able to promote plant growth to a greater extent than the wild-type T34, although compared with this strain the transformants showed similar capability to colonize tomato roots. Gene expression patterns from aerial parts of 3-week-old tomato plants treated with T34 and the amdS transformants have also been investigated using GeneChip Tomato Genome Arrays. The downregulation of defense genes and the upregulation of carbon and nitrogen metabolism genes observed in the microarrays were accompanied by (i) enhanced growth, (ii) increased carbon and nitrogen levels, and (iii) a

The potential of selected macroalgal species for treatment of AMD at different pH ranges in temperate regions

CSIR Research Space (South Africa)

Oberholster, Paul J

2014-09-01

Full Text Available The metal bioaccumulation potential of selected macroalgae species at different pH ranges was study for usage as part of a possible secondary passive acid mine drainage (AMD) treatment technology in algae ponds. Two separate studies were conducted...

[Intravitreal Ranibizumab Injection for the Treatment of Occult and Classic CNV in Exsudative AMD].

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Maier, M M; Feucht, N; Fegert, C; Fiore, B; Winkler von Mohrenfels, C; Lohmann, C

2011-02-01

Double-blind, randomised, placebo-controlled and multicentre studies have proven an increase in visual acuity in one-third of the patients receiving Ranibizumab (0.5 mg) injections, who suffer from exsudative AMD. The purpose of this study was to evaluate the early effects of intravitreal Ranibizumab therapy in patients with mainly occult neovascular AMD in clinical applications. In a retrospective cohort study, 91 eyes with occult and classic neovascular AMD were treated with intravitreal injections of Ranibizumab (0.5 mg) at 30-day intervals. The treatment effects were evaluated according to best corrected visual acuity, optical coherence tomography (OCT) and intraocular pressure at baseline as well as 1, 3 and 6 months after the beginning of therapy. Furthermore, fluorescein angiography (FLA) was performed at baseline as well as 3 and 6 months after therapy. 74 % of the patients lost fewer than 15 letters on the EDTRS-scale 6 months after the beginning of therapy. Visual acuity improved by more than 15 letters in 11 % of the patients. Central retinal thickness, measured by OCT, decreased statistically significantly in each control compared to baseline (1 month: p = 0.045; 3 months: p = 0.001; 6 months: p = 0.006). Leakage and membranes, evaluated in FA, worsened in 31 % of the patients; in 67 % the findings were stable. No increase in intraocular pressure was detected. Intravitreal application of Ranibizumab was safe and well tolerated. In the clinical situation, visual acuity was stabilised in the short term. As opposed to phase-III studies, no improvement in visual acuity could be accomplished. Cental retinal thickness decreased and findings in fluorescein angiography were stable within a 6-month follow-up period. It is necessary to perform monthly controls and proceed with VA- and OCT-based injections in order to maintain the therapeutic effect. Futher clinical evaluations of Ranibizumab will be necessary to evaluate its long-term treatment effects. �

CFH Y402H confers similar risk of soft drusen and both forms of advanced AMD.

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Kristinn P Magnusson

2006-01-01

Full Text Available Age-related macular degeneration (AMD is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy and neovascular AMD, represent different pathological processes in the macula that lead to loss of central vision. Soft drusen, characterized by deposits in the macula without visual loss, are considered to be a precursor of advanced AMD. Recently, it has been proposed that a common missense variant, Y402H, in the Complement Factor H (CFH gene increases the risk for advanced AMD. However, its impact on soft drusen, GA, or neovascular AMD--or the relationship between them--is unclear.We genotyped 581 Icelandic patients with advanced AMD (278 neovascular AMD, 203 GA, and 100 with mixed neovascular AMD/GA, and 435 with early AMD (of whom 220 had soft drusen. A second cohort of 431 US patients from Utah, 322 with advanced AMD (244 neovascular AMD and 78 GA and 109 early-AMD cases with soft drusen, were analyzed. We confirmed that the CFH Y402H variant shows significant association to advanced AMD, with odds ratio of 2.39 in Icelandic patients (p = 5.9 x 10(-12 and odds ratio of 2.14 in US patients from Utah (p = 2.0 x 10(-9 with advanced AMD. Furthermore, we show that the Y402H variant confers similar risk of soft drusen and both forms of advanced AMD (GA or neovascular AMD.Soft drusen occur prior to progression to advanced AMD and represent a histological feature shared by neovascular AMD and GA. Our results suggest that CFH is a major risk factor of soft drusen, and additional genetic factors and/or environmental factors may be required for progression to advanced AMD.

Comparing humans and deep learning performance for grading AMD: A study in using universal deep features and transfer learning for automated AMD analysis.

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Burlina, Philippe; Pacheco, Katia D; Joshi, Neil; Freund, David E; Bressler, Neil M

2017-03-01

When left untreated, age-related macular degeneration (AMD) is the leading cause of vision loss in people over fifty in the US. Currently it is estimated that about eight million US individuals have the intermediate stage of AMD that is often asymptomatic with regard to visual deficit. These individuals are at high risk for progressing to the advanced stage where the often treatable choroidal neovascular form of AMD can occur. Careful monitoring to detect the onset and prompt treatment of the neovascular form as well as dietary supplementation can reduce the risk of vision loss from AMD, therefore, preferred practice patterns recommend identifying individuals with the intermediate stage in a timely manner. Past automated retinal image analysis (ARIA) methods applied on fundus imagery have relied on engineered and hand-designed visual features. We instead detail the novel application of a machine learning approach using deep learning for the problem of ARIA and AMD analysis. We use transfer learning and universal features derived from deep convolutional neural networks (DCNN). We address clinically relevant 4-class, 3-class, and 2-class AMD severity classification problems. Using 5664 color fundus images from the NIH AREDS dataset and DCNN universal features, we obtain values for accuracy for the (4-, 3-, 2-) class classification problem of (79.4%, 81.5%, 93.4%) for machine vs. (75.8%, 85.0%, 95.2%) for physician grading. This study demonstrates the efficacy of machine grading based on deep universal features/transfer learning when applied to ARIA and is a promising step in providing a pre-screener to identify individuals with intermediate AMD and also as a tool that can facilitate identifying such individuals for clinical studies aimed at developing improved therapies. It also demonstrates comparable performance between computer and physician grading. Copyright © 2017 Elsevier Ltd. All rights reserved.

AMD ja ATI kolivad kokku / Kalle Kose

Index Scriptorium Estoniae

Kose, Kalle

2006-01-01

Maailma suuruselt teise personaalarvutite protsessorite valmistaja Advanced Micro Devices (AMD) liitumisest graafikakaartide tootja ATI Technologies'iga (ATI). Vt. ka: 5 küsimust AMD-le. Küsimustele vastab AMD regiooni esindaja Stockholmis Martin Sjögren

Blood Pressure Drugs and AMD

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... Patient Stories Español Eye Health / News Research News: Blood Pressure Drugs and AMD Leer en Español: Noticias de ... also found an association between AMD and high blood pressure, but this has been inconsistent. To help clarify ...

Elusive drusen and changing terminology of AMD

NARCIS (Netherlands)

de Jong, P. T. V. M.

2018-01-01

The first descriptions of ageing macula disorder (AMD), be it under other names, appeared in 1855 and 1868. The earliest accounts of AMD linked the presence of drusen with visual loss. It took a century before these connections between drusen and AMD were generally accepted by medical science and in

Five-year follow-up of low-level laser therapy (LLLT) in patients with age-related macular degeneration (AMD)

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Koev, K.; Avramov, L.; Borissova, E.

2018-03-01

The objective of this study was to examine long-term effects of low-level laser therapy (LLLT) in patients with age-related macular degeneration (AMD). The research was implemented for a period of five years. For LLLT, a He-Ne Laser with continuous emission at 633 nm (0.1 mW/cm2) was used in patients with AMD of all stages (dry to wet exudative forms were included). In total, 33 patients (16 men and 17 women – 66 eyes) with AMD of various stages and a mean age of 68.7 ± 4.2 years were included in the study. Progressive, exudative AMD was diagnosed in 8 eyes. 58 eyes had drusen or were depigmented. Laser radiation was applied transpupillary to the macula for six times for three minutes once in two days; 22 patients with AMD (44 eyes) were randomly selected to receive mock treatment (control group 10 men and 12 women with a mean age of 69.3 ± 4.8 years). The visual acuity was followed for a five-year period. The perimetry and Amsler test were used to screen central scotomas. The fluorescein angiography of AMD and the control groups was examined. The visual acuity remained unchanged in all patients in the control group. There was a statistically significant increase in the visual acuity (p<0.001, end of study versus baseline) for AMD patients for the period of five years after the treatment. The edema and hemorrhage in the patients with progressive, exudative AMD significantly decreased. No side effects were observed during the therapy. The prevalence of metamorphopsia, scotoma in AMD group was reduced. In conclusion, this study shows that LLLT may be a novel long-lasting therapeutic option for both forms of AMD. It is a highly-effective treatment that results in a long-term improvement of the visual acuity.

Development of a Candida glabrata dominant nutritional transformation marker utilizing the Aspergillus nidulans acetamidase gene (amdS).

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Fu, Jianmin; Blaylock, Morganne; Wickes, Cameron F; Welte, William; Mehrtash, Adrian; Wiederhold, Nathan; Wickes, Brian L

2016-05-01

The gene encoding Aspergillus nidulans acetamidase (amdS) was placed under control of Candida albicans ACT1 promoter and terminator sequences and then cloned into a plasmid containing C. glabrata ARS10,CEN8 or ARS10+CEN8 sequences. All plasmids transformed C. glabrata wild-type cells to acetamide+, with the ARS-only containing plasmid transforming cells at the highest frequencies (>1.0 × 10(4) transformants μg(-1)). Plasmids were rapidly lost under non-selective conditions with the frequency dependent on chromosomal element, thus recycling the acetamide- phenotype. The amdS plasmid was used to transform a set of clinical isolates resistant to a variety of antifungal drugs. All strains were successfully transformed to the acetamide+ phenotype at high frequency, confirming that this plasmid construct could be used as a simple dominant marker on virtually any strain. Gap repair experiments demonstrated that just as in Saccharomyces cerevisiae, gap repair functions efficiently inC. glabrata, suggesting that C. glabrata has numerous similarities toS. cerevisiae with regard to ease of molecular manipulation. The amdS system is inexpensive and efficient, and combined with existing C. glabrata plasmid elements, confers a high transformation frequency for C. glabrata with a phenotype that can be easily recycled. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

AMDE-1 is a dual function chemical for autophagy activation and inhibition.

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Min Li

Full Text Available Autophagy is the process by which cytosolic components and organelles are delivered to the lysosome for degradation. Autophagy plays important roles in cellular homeostasis and disease pathogenesis. Small chemical molecules that can modulate autophagy activity may have pharmacological value for treating diseases. Using a GFP-LC3-based high content screening assay we identified a novel chemical that is able to modulate autophagy at both initiation and degradation levels. This molecule, termed as Autophagy Modulator with Dual Effect-1 (AMDE-1, triggered autophagy in an Atg5-dependent manner, recruiting Atg16 to the pre-autophagosomal site and causing LC3 lipidation. AMDE-1 induced autophagy through the activation of AMPK, which inactivated mTORC1 and activated ULK1. AMDE-1did not affect MAP kinase, JNK or oxidative stress signaling for autophagy induction. Surprisingly, treatment with AMDE-1 resulted in impairment in autophagic flux and inhibition of long-lived protein degradation. This inhibition was correlated with a reduction in lysosomal degradation capacity but not with autophagosome-lysosome fusion. Further analysis indicated that AMDE-1 caused a reduction in lysosome acidity and lysosomal proteolytic activity, suggesting that it suppressed general lysosome function. AMDE-1 thus also impaired endocytosis-mediated EGF receptor degradation. The dual effects of AMDE-1 on autophagy induction and lysosomal degradation suggested that its net effect would likely lead to autophagic stress and lysosome dysfunction, and therefore cell death. Indeed, AMDE-1 triggered necroptosis and was preferentially cytotoxic to cancer cells. In conclusion, this study identified a new class of autophagy modulators with dual effects, which can be explored for potential uses in cancer therapy.

Role of dissimilatory sulfate reduction in wetlands constructed for acid coal mine drainage (AMD) treatment. Master's thesis

International Nuclear Information System (INIS)

Taddeo, F.J.

1991-01-01

Five constructed wetlands with different organic substrates were exposed to the same quantity/quality of acid mine drainage (AMD). During the 16-month exposure to AMD, all wetlands accumulated S in the forms of organic and reduced inorganic S and Fe in the form of iron sulfides. Iron sulfide and probably most of the organic S(C-bonded S) accumulation were end products of bacterial dissimilatory sulfate reduction. Results of study support the notion that sulfate reduction and accumulation of Fe sulfides contribute to Fe retention in wetlands exposed to AMD. Detailed information is provided

The study of leachability and toxicity of sludge after neutralization of Saraka and Robule AMD wastewaters

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Gardić Vojka

2017-01-01

Full Text Available Acid mine drainage (AMD waters are one of the most important ecological risks at the global level because of its high heavy metals content and strong acidity. Treatment of AMD water is a complex and expensive. One of the most widely used treatment process is the neutralization process of AMD. The result of neutralization is the production of sludge which may contain various other (heavy metals, depending on the chemical characteristics of the mine water treated. In this paper, leachability and toxicity of the sludges obtained during the neutralization process of wastewater from Saraka and Robule acid mine drainage and the sludges after the stabilization process at different temperatures is tested. Sludge produced in the neutralization process of Robule AMD R4 (40 and stabilized on 105°C and 200°C shows a H8-corrosiveness characteristic. Stabilized sludge show tendency to lower leachability of zinc and copper, but without influence on sulphate leachability. Sludges that show a H8-corrosiveness needs additional stabilization/neutralization pretreatment prior temperature treatment.

Cigarette smoke induced autophagy-impairment regulates AMD pathogenesis mechanisms in ARPE-19 cells.

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Viren Kumar Govindaraju

Full Text Available Age related macular degeneration (AMD is one of the leading causes of blindness. Genetics, environmental insult, and age-related factors all play a key role in altering proteostasis, the homeostatic process regulating protein synthesis, degradation and processing. These factors also play a role in the pathogenesis of AMD and it has been well established that cigarette smoking (CS initiates AMD pathogenic mechanisms. The primary goal of this study is to elucidate whether CS can induce proteostasis/autophagy-impairment in retinal pigment epithelial (RPE cells. In our preliminary analysis, it was found that cigarette smoke extract (CSE induces accumulation of ubiquitinated proteins in the insoluble protein fraction (p < 0.01, which was subsequently mitigated through cysteamine (p < 0.01 or fisetin (p < 0.05 treatment. Further, it was verified that these CSE induced ubiquitinated proteins accumulated in the peri-nuclear spaces (p<0.05 that were cleared- off with cysteamine (p < 0.05 or fisetin (p < 0.05. Moreover, CSE-induced aggresome-formation (LC3B-GFP and Ub-RFP co-localization and autophagy-flux impairment was significantly (p<0.01 mitigated by cysteamine (p<0.05 or fisetin (p<0.05 treatment, indicating the restoration of CSE-mediated autophagy-impairment. CSE treatment was also found to induce intracellular reactive oxygen species (ROS, p < 0.001 while impacting cell viability (p < 0.001, which was quantified using CMH2DCFDA-dye (ROS and MTS (proliferation or propodium iodide staining (cell viability assays, respectively. Moreover, cysteamine and fisetin treatment ameliorated CS-mediated ROS production (p < 0.05 and diminished cell viability (p < 0.05. Lastly, CSE was found to induce cellular senescence (p < 0.001, which was significantly ameliorated by cysteamine (p < 0.001 or fisetin (p < 0.001. In conclusion, our study indicates that CS induced proteostasis/autophagy-impairment regulates mechanisms associated with AMD pathogenesis. Moreover

AMD genetics in India: The missing links

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Akshay eAnand

2016-05-01

Full Text Available Age related macular degeneration is a disease condition which occurs in aged peoples. There are various changes occurs at the cellular, molecular and physiological levels with age (Kaushal et al, 2013; Samiec et al 1988. Drusen deposition between RPE and Bruch’s membrane is one of the key features in AMD patients (Mullins RF et al, 2000; Hagemana et al, 2001 as Aβ/tau aggregates in AD patients. The primary goal of this review is to discuss whether the various candidate genes and associated biomarkers, that are supposed to play an independent role in progression of AMD, exert deleterious effect on phenotype, alone or in combination, in Indian AMD patients from the same ethnic group. A statistical model for probable interaction between genes could also be derived from such analysis. We can use multiple modalities to identify and enrol AMD patients based on established clinical criteria and examine the risk factors to determine if these genes are associated with risk factors, biomarkers or disease by Mendelian randomization. Similarly, there are large numbers of single nucleotide polymorphisms (SNPs identified in human population. Even non-synonymous SNPs (nsSNPs are believed to induce deleterious effects on the functionality of various proteins. The study of such snSNPs could provide a better genetic insight for diverse phenotypes of AMD patients, predicting significant risk factors for the disease. Therefore, the prediction of biological effect of nsSNPs in the candidate genes is highly solicited.Therefore, genotyping and levels of protein expression of various genes would provide bigger canvas in genetic complexity of AMD pathology which should be evaluated by valid statistical and bioinformatics’ tools. Longitudinal follow up of Indian AMD patients to evaluate the temporal effect of SNPs and biomarkers on progression of disease could also provide unique strategy in the field.

A novel fully automated molecular diagnostic system (AMDS for colorectal cancer mutation detection.

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Shiro Kitano

Full Text Available BACKGROUND: KRAS, BRAF and PIK3CA mutations are frequently observed in colorectal cancer (CRC. In particular, KRAS mutations are strong predictors for clinical outcomes of EGFR-targeted treatments such as cetuximab and panitumumab in metastatic colorectal cancer (mCRC. For mutation analysis, the current methods are time-consuming, and not readily available to all oncologists and pathologists. We have developed a novel, simple, sensitive and fully automated molecular diagnostic system (AMDS for point of care testing (POCT. Here we report the results of a comparison study between AMDS and direct sequencing (DS in the detection of KRAS, BRAF and PI3KCA somatic mutations. METHODOLOGY/PRINCIPAL FINDING: DNA was extracted from a slice of either frozen (n = 89 or formalin-fixed and paraffin-embedded (FFPE CRC tissue (n = 70, and then used for mutation analysis by AMDS and DS. All mutations (n = 41 among frozen and 27 among FFPE samples detected by DS were also successfully (100% detected by the AMDS. However, 8 frozen and 6 FFPE samples detected as wild-type in the DS analysis were shown as mutants in the AMDS analysis. By cloning-sequencing assays, these discordant samples were confirmed as true mutants. One sample had simultaneous "hot spot" mutations of KRAS and PIK3CA, and cloning assay comfirmed that E542K and E545K were not on the same allele. Genotyping call rates for DS were 100.0% (89/89 and 74.3% (52/70 in frozen and FFPE samples, respectively, for the first attempt; whereas that of AMDS was 100.0% for both sample sets. For automated DNA extraction and mutation detection by AMDS, frozen tissues (n = 41 were successfully detected all mutations within 70 minutes. CONCLUSIONS/SIGNIFICANCE: AMDS has superior sensitivity and accuracy over DS, and is much easier to execute than conventional labor intensive manual mutation analysis. AMDS has great potential for POCT equipment for mutation analysis.

Tapping Stem Cells to Target AMD: Challenges and Prospects

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Caroline Brandl

2015-01-01

Full Text Available Human pluripotent stem cells (hPSCs are increasingly gaining attention in biomedicine as valuable resources to establish patient-derived cell culture models of the cell type known to express the primary pathology. The idea of “a patient in a dish” aims at basic, but also clinical, applications with the promise to mimic individual genetic and metabolic complexities barely reflected in current invertebrate or vertebrate animal model systems. This may particularly be true for the inherited and complex diseases of the retina, as this tissue has anatomical and physiological aspects unique to the human eye. For example, the complex age-related macular degeneration (AMD, the leading cause of blindness in Western societies, can be attributed to a large number of genetic and individual factors with so far unclear modes of mutual interaction. Here, we review the current status and future prospects of utilizing hPSCs, specifically induced pluripotent stem cells (iPSCs, in basic and clinical AMD research, but also in assessing potential treatment options. We provide an outline of concepts for disease modelling and summarize ongoing and projected clinical trials for stem cell-based therapy in late-stage AMD.

A compensation controller based on a regional pole-assignment method for AMD control systems with a time-varying delay

Science.gov (United States)

Li, Zuohua; Chen, Chaojun; Teng, Jun; Wang, Ying

2018-04-01

Active mass damper/driver (AMD) control system has been proposed as an effective tool for high-rise buildings to resist strong dynamic loads. However, such disadvantage as time-varying delay in AMD control systems impedes their application in practices. Time-varying delay, which has an effect on the performance and stability of single-degree-of-freedom (SDOF) and multi-degree-of-freedom (MDOF) systems, is considered in the paper. In addition, a new time-delay compensation controller based on regional pole-assignment method is presented. To verify its effectiveness, the proposed method is applied to a numerical example of a ten-storey frame and an experiment of a single span four-storey steel frame. Both numerical and experimental results demonstrate that the proposed method can enhance the performances of an AMD control system with time-varying delays.

The complex model of risk and progression of AMD estimation

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V. S. Akopyan

2012-01-01

Full Text Available Purpose: to develop a method and a statistical model to estimate individual risk of AMD and the risk for progression to advanced AMD using clinical and genetic risk factors.Methods: A statistical risk assessment model was developed using stepwise binary logistic regression analysis. to estimate the population differences in the prevalence of allelic variants of genes and for the development of models adapted to the population of Moscow region genotyping and assessment of the influence of other risk factors was performed in two groups: patients with differ- ent stages of AMD (n = 74, and control group (n = 116. Genetic risk factors included in the study: polymorphisms in the complement system genes (C3 and CFH, genes at 10q26 locus (ARMS2 and HtRA1, polymorphism in the mitochondrial gene Mt-ND2. Clinical risk factors included in the study: age, gender, high body mass index, smoking history.Results: A comprehensive analysis of genetic and clinical risk factors for AMD in the study group was performed. Compiled statis- tical model assessment of individual risk of AMD, the sensitivity of the model — 66.7%, specificity — 78.5%, AUC = 0.76. Risk factors of late AMD, compiled a statistical model describing the probability of late AMD, the sensitivity of the model — 66.7%, specificity — 78.3%, AUC = 0.73. the developed system allows determining the most likely version of the current late AMD: dry or wet.Conclusion: the developed test system and the mathematical algorhythm for determining the risk of AMD, risk of progression to advanced AMD have fair diagnostic informative and promising for use in clinical practice.

AMD study of unstable nuclei

International Nuclear Information System (INIS)

Horiuchi, Hisashi; Dote, Akinobu; Kimura, Masaaki

2000-01-01

The formulation of AMD which can describe both mean-field states and clustering states is briefly explained. The results of the application of the AMD model to various isotopes are given. Many problems are discussed which include formation of molecular orbits, new-type of clustering near neutron drip-line, opposite deformation of neutron and proton density distributions, breaking of the neutron magic numbers N=8 and N=20, and so on. The discussions are not necessarily only for the ground states or ground rotational bands but also for the excited states or excited rotational bands in the case of Be isotopes. (author)

AMD study of unstable nuclei

Energy Technology Data Exchange (ETDEWEB)

Horiuchi, Hisashi; Dote, Akinobu; Kimura, Masaaki [Kyoto Univ. (Japan). Dept. of Physics; Kanada-En' yo, Yoshiko [Institute of Particle and Nuclear Studies, High Energy Accelerator Research Organization, Tsukuba, Ibaraki (Japan)

2000-01-01

The formulation of AMD which can describe both mean-field states and clustering states is briefly explained. The results of the application of the AMD model to various isotopes are given. Many problems are discussed which include formation of molecular orbits, new-type of clustering near neutron dripline, opposite deformation of neutron and proton density distributions, breaking of the neutron magic numbers N=8 and N=20, and so on. The discussions are not necessarily only for the ground states or ground rotational bands but also for the excited states or excited rotational bands in the case of Be isotopes. (author)

Oral docosahexaenoic acid in the prevention of exudative age-related macular degeneration: the Nutritional AMD Treatment 2 study.

Science.gov (United States)

Souied, Eric H; Delcourt, Cécile; Querques, Giuseppe; Bassols, Ana; Merle, Bénédicte; Zourdani, Alain; Smith, Theodore; Benlian, Pascale

2013-08-01

To evaluate the efficacy of docosahexaenoic acid (DHA)-enriched oral supplementation in preventing exudative age-related macular degeneration (AMD). The Nutritional AMD Treatment 2 study was a randomized, placebo-controlled, double-blind, parallel, comparative study. Two hundred sixty-three patients 55 years of age or older and younger than 85 years with early lesions of age-related maculopathy and visual acuity better than 0.4 logarithm of minimum angle of resolution units in the study eye and neovascular AMD in the fellow eye. Patients were assigned randomly to receive either 840 mg/day DHA and 270 mg/day eicosapentaenoic acid (EPA) from fish oil capsules or the placebo (olive oil capsules) for 3 years. The primary outcome measure was time to occurrence of choroidal neovascularization (CNV) in the study eye. Secondary outcome measures in the study eye were: incidence of CNV developing in patients, changes in visual acuity, occurrence and progression of drusen, and changes in EPA plus DHA level in red blood cell membrane (RBCM). Time to occurrence and incidence of CNV in the study eye were not significantly different between the DHA group (19.5±10.9 months and 28.4%, respectively) and the placebo group (18.7±10.6 months and 25.6%, respectively). In the DHA group, EPA plus DHA levels increased significantly in RBCM (+70%; P<0.001), suggesting that DHA easily penetrated cells, but this occurred unexpectedly also in the placebo group (+9%; P = 0.007). In the DHA-allocated group, patients steadily achieving the highest tertile of EPA plus DHA levels in RBCM had significantly lower risk (-68%; P = 0.047; hazard ratio, 0.32; 95% confidence interval, 0.10-0.99) of CNV developing over 3 years. No marked changes from baseline in best-corrected visual acuity, drusen progression, or geographic atrophy in the study eye were observed throughout the study in either group. In patients with unilateral exudative AMD, 3 years of oral DHA-enriched supplementation had the same

New constraint of clustering for AMD and its application to the study of the 2α-12C structure of 20Ne

International Nuclear Information System (INIS)

Taniguchi, Yasutaka; Horiuchi, Hisashi; Kimura, Masaaki

2004-01-01

A new constraint of clustering for the AMD calculation is proposed. This constraint yield a significant improvement in the investigation of the cluster structure using AMD, which sometimes meets with difficulty in producing certain specific cluster configuration. The usefulness of this constraint is verified by applying it to the study of the K π = 0 3 + band of 20 Ne, which has been conjectured to have 2α- 12 C structure. This band is not easy to construct with AMD. We show that the constraint in the AMD + GCM calculation is effective for the purpose of obtaining the K π 0 3 + band, which contains the 2α- 12 C structure as an important component. (author)

Proof of activity with AMD11070, an orally bioavailable inhibitor of CXCR4-tropic HIV type 1.

Science.gov (United States)

Moyle, Graeme; DeJesus, Edwin; Boffito, Marta; Wong, Rebecca S; Gibney, Colleen; Badel, Karin; MacFarland, Ron; Calandra, Gary; Bridger, Gary; Becker, Stephen

2009-03-15

The X4 Antagonist Concept Trial investigates the safety and antiviral activity of AMD11070, a potent inhibitor of X4-tropic human immunodeficiency virus (HIV) in vitro in HIV-infected patients harboring X4-tropic virus. Patients enrolled in the study had an X4 virus population 2000 relative luminescence units (rlu; by the Monogram Trofile Assay) and an HIV-1 RNA level 5000 copies/mL. Patients received AMD11070 monotherapy for 10 days. Coreceptor tropism, plasma HIV-1 RNA level, and CD4 cell count were measured at study entry, on day 5, and on day 10. Daily predose and serial samples on the last day of treatment were obtained for determination of plasma AMD11070 concentration. Ten patients were given AMD11070 monotherapy (200 mg to 8 patients and 100 mg to 2 patients) twice daily for 10 days. The median baseline CD4 cell count was 160 cells/mm(3), and the median HIV-1 RNA level was 91,447 copies/mL. Four of 9 evaluable patients achieved a reduction in X4 virus population of >or= rlu. The median change in X4 virus population at the end of treatment was -0.22 log(10) rlu (range, -1.90 to 0.23 log(10) rlu). Three of 4 patients who responded to therapy showed a tropism shift from dual- or mixed-tropic viruses to exclusively R5 virus by day 10. There were no drug-related serious adverse events, adverse events of greater than grade 2, or laboratory abnormalities. These results demonstrate the activity of AMD11070, the first oral CXCR4 antagonist, against X4-tropic HIV-1. The drug was well tolerated, with no serious safety concerns. AMD11070 is on clinical hold because of histologic changes to the liver observed in long-term animal studies; additional preclinical safety assessments are pending.

Photometric Evaluation of Soft Tissue Changes in CLP Patients: Le Fort I Advancement Osteotomy (ALO) Versus Anterior Maxillary Distraction (AMD).

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Paulose, Joby; Markose, Eldho

2014-12-01

This paper is a comparative photometric evaluation of soft tissue changes in patients with CLP associated with maxillary deficiency treated with conventional Le Fort I advancement osteotomy (ALO) and anterior maxillary distraction (AMD). Twenty patients with maxillary hypoplasia associated with cleft lip and palate who had undergone either LeFort I osteotomy or distraction osteogenesis with maxillary advancement were included in this study. Frontal and profile photographs were used to ascertain the changes post-surgically. Photographs were obtained before treatment and 1 year after surgical correction in both groups. Vertical as well as horizontal changes in pronasale was well observed in both groups. A substantial increase in nasal parameters was noted in case of AMD group in comparison to ALO group. Though maxillary advancement was quite evident in AMD and ALO groups, a significant and consistent change was observed in AMD group. Significant vertical and horizontal changes were seen with respect to subnasale and labrale superius in AMD group. The hard and soft tissue changes produced by AMD by intra oral distractors were being evaluated so far. The results of the above studies have proved the excellence of AMD over conventional osteotomies. The present study goes hand in hand with the research outcomes till date.

Utilization of AMD sludges from the anthracite region of Pennsylvania for removal of phosphorus from wastewater

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Sibrell, P.L.; Cravotta, C.A.; Lehman, W.G.; Reichert, W.

2010-01-01

Excess phosphorus (P) inputs from human sewage, animal feeding operations, and nonpoint source discharges to the environment have resulted in the eutrophication of sensitive receiving bodies of water such as the Great Lakes and Chesapeake Bay. Phosphorus loads in wastewater discharged from such sources can be decreased by conventional treatment with iron and aluminum salts but these chemical reagents are expensive or impractical for many applications. Acid mine drainage (AMD) sludges are an inexpensive source of iron and aluminum hydrous oxides that could offer an attractive alternative to chemical reagent dosing for the removal of P from local wastewater. Previous investigations have focused on AMD sludges generated in the bituminous coal region of western Pennsylvania, and confirmed that some of those sludges are good sorbents for P over a wide range of operating conditions. In this study, we sampled sludges produced by AMD treatment at six different sites in the anthracite region of Pennsylvania for potential use as P sequestration sorbents. Sludge samples were dried, characterized, and then tested for P removal from water. In addition, the concentrations of acid-extractable metals and other impurities were investigated. Test results revealed that sludges from four of the sites showed good P sorption and were unlikely to add contaminants to treated water. These results indicate that AMD sludges could be beneficially used to sequester P from the environment, while at the same time decreasing the expense of sludge disposal.

Molecular mechanism of AMD3100 antagonism in the CXCR4 receptor: transfer of binding site to the CXCR3 receptor

DEFF Research Database (Denmark)

Rosenkilde, Mette M; Gerlach, Lars-Ole; Jakobsen, Janus S

2004-01-01

, respectively. Metal ion binding in the cyclam rings of AMD3100 increased its dependence on Asp(262) and provided a tighter molecular map of the binding site, where borderline mutational hits became clear hits for the Zn(II)-loaded analog. The proposed binding site for AMD3100 was confirmed by a gradual build......-up in the rather distinct CXCR3 receptor, for which the compound normally had no effect. Introduction of only a Glu at position VII:06 and the removal of a neutralizing Lys residue at position VII:02 resulted in a 1000-fold increase in affinity of AMD3100 to within 10-fold of its affinity in CXCR4. We conclude...

Synthesis of AMD3100 for antagonist of CXCR4 and labeled with 99Tcm

International Nuclear Information System (INIS)

Gui Yuan; Xu Zhihong; Zhang Xiaojun; Zhang Shuwen; Liu Jian; Tian Jiahe; Zhang Jinming

2013-01-01

Most of human tumors over-express CXCR4. AMD3100, a nonpeptide antagonist for CXCR4 receptor, can be used for therapy of those tumors. It was found that metal ion complex, such as Cu 2+ , with AMD3100 enhanced its binding affinity to the receptor 10-fold higher as compared to AMD3100 alone. AMD3100 was synthesis from 3-aminopropyl ethylene diamine. 99 Tc m -AMD3100 was labeled directly. Biodistribution studies were carried out in NH mice. SPECT imaging was performed in Hep-G2 tumor bearing mouse. The synthetic yield was 5.8% from 3-aminopropyl ethylene diamine to AMD3100. The labeling yield of 99 Tc m -AMD3100 was over 98%. Biodistribution studies showed high accumulation of radio- tracer in liver which had high-expression of CXCR4. SPECT imaging results showed that uptake in Hep-G2 tumor was high. The results showed that 99 Tc m -AMD3100 was an attractive candidate for further development of SPECT radiotracer potentially suitable for CXCR4. (authors)

Potential of Induced Pluripotent Stem Cells (iPSCs for Treating Age-Related Macular Degeneration (AMD

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Mark Fields

2016-12-01

Full Text Available The field of stem cell biology has rapidly evolved in the last few decades. In the area of regenerative medicine, clinical applications using stem cells hold the potential to be a powerful tool in the treatment of a wide variety of diseases, in particular, disorders of the eye. Embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs are promising technologies that can potentially provide an unlimited source of cells for cell replacement therapy in the treatment of retinal degenerative disorders such as age-related macular degeneration (AMD, Stargardt disease, and other disorders. ESCs and iPSCs have been used to generate retinal pigment epithelium (RPE cells and their functional behavior has been tested in vitro and in vivo in animal models. Additionally, iPSC-derived RPE cells provide an autologous source of cells for therapeutic use, as well as allow for novel approaches in disease modeling and drug development platforms. Clinical trials are currently testing the safety and efficacy of these cells in patients with AMD. In this review, the current status of iPSC disease modeling of AMD is discussed, as well as the challenges and potential of this technology as a viable option for cell replacement therapy in retinal degeneration.

Potential of Induced Pluripotent Stem Cells (iPSCs) for Treating Age-Related Macular Degeneration (AMD).

Science.gov (United States)

Fields, Mark; Cai, Hui; Gong, Jie; Del Priore, Lucian

2016-12-08

The field of stem cell biology has rapidly evolved in the last few decades. In the area of regenerative medicine, clinical applications using stem cells hold the potential to be a powerful tool in the treatment of a wide variety of diseases, in particular, disorders of the eye. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are promising technologies that can potentially provide an unlimited source of cells for cell replacement therapy in the treatment of retinal degenerative disorders such as age-related macular degeneration (AMD), Stargardt disease, and other disorders. ESCs and iPSCs have been used to generate retinal pigment epithelium (RPE) cells and their functional behavior has been tested in vitro and in vivo in animal models. Additionally, iPSC-derived RPE cells provide an autologous source of cells for therapeutic use, as well as allow for novel approaches in disease modeling and drug development platforms. Clinical trials are currently testing the safety and efficacy of these cells in patients with AMD. In this review, the current status of iPSC disease modeling of AMD is discussed, as well as the challenges and potential of this technology as a viable option for cell replacement therapy in retinal degeneration.

[Fundus autofluorescence in dry AMD - impact on disease progression].

Science.gov (United States)

Vidinova, C N; Gouguchkova, P T; Vidinov, K N

2013-11-01

Fundus autofluorescence is a novel technique that gives us information about the RPE cells by evaluating the distribution of lipofuscin in the retina. The purpose of our study was to evaluate the diagnostic abilities of OCT, RTVue and fundus autofluorescence in predicting the progression of dry AMD. In our study 37 dry AMD patients were enrolled: 22 of them with druses and 15 with developed geographic atrophy. They all underwent complete ophthalmological examinations including OCT and autofluorescence. We used the RTVue OCT programmes HD line, Cross line, EMM5 and EMM5 progression in all cases. The autofluorescence was recorded with the help of the Canon CX1 fundus camera. OCT images in the AMD patients with dry AMD and large druses showed typical undulations in the RPE/choroid line and occasionally drusenoid detachment of the RPE. Autofluorescence showed different patterns. The confluent reticular autofluorescence was associated with the development of neovascular membranes. In geographic atrophy patient OCTs showed diminished retinal thickness measured with EMM5. On autofluorescence the findings at the border zone atrophic/normal retina were of particular importance. The diffuse increased autofluorescence in that area was considered to be a sign for further atrophy progression. Our results point out that OCT in combination with autofluorescence is important in following the progression of dry AMD. Pathological autofluorescence at the border of atrophic lesions is an important sign for disease activity. Although both OCT and autofluorescence visualise the changes in RPE, autofluorescence is of key importance in predicting the development of the disease. Georg Thieme Verlag KG Stuttgart · New York.

The use of alkali-activated fly ash grouts for the remediation of AMD from underground mines

International Nuclear Information System (INIS)

Eaker, C.A.; Longley, R.D.; Michaud, L.H.; Silsbee, M.R.

1996-01-01

In preparation for a field demonstration, laboratory studies were conducted using several fly ash grout formulations to determine the optimum grout for an underground mine environment. This paper discusses the portion of the overall project designed to examine grout-acid mine drainage (AMD) interactions including neutralization, leaching and armoring of the grouts. Leaching tests were performed to study the effects of fly ash grout on AMD, including the effects of armoring. The goal of this project is to study the feasibility of in-situ acid mine drainage treatment by injecting alkali-activated fly ash grout into an underground mine

A 5-year multicenter prospective cohort study on the long-term visual prognosis and predictive factors for visual outcome in Japanese patients with age-related macular degeneration: the AMD2000 study.

Science.gov (United States)

Akagi-Kurashige, Yumiko; Tsujikawa, Akitaka; Yuzawa, Mitsuko; Ishibashi, Tatsuro; Nakanishi, Hideo; Nakatani, Eiji; Teramukai, Satoshi; Fukushima, Masanori; Yoshimura, Nagahisa

2018-03-01

In this study (AMD2000), we aimed to determine the visual prognosis of Japanese patients with age-related macular degeneration (AMD). This was a multicenter prospective observational cohort study. In total, 460 patients with AMD were recruited from April 2006 to March 2009 from 18 clinical trial sites in Japan. They were followed up for 5 years, as they continued to receive medical treatment. Of the 409 study eyes followed up for at least 1 year, 243 eyes (59.4%) were treated with photodynamic therapy (PDT) using verteporfin, and 58 eyes (14.2%) were treated with intravitreal injections of antivascular endothelial growth factor agents as the initial treatment. The mean best-corrected visual acuities (BCVA) for typical AMD (tAMD; 0.688 ± 0.498) and polypoidal choroidal vasculopathy (PCV; 0.451 ± 0.395) were significantly less at 2 years (tAMD, 0.779 ± 0.632, P macular edema as well as the lesion size was associated with 5-year maintenance of the baseline BCVA. In some patients, the diagnosis changed: of the 192 eyes initially diagnosed with typical AMD, 19 were newly diagnosed with PCV during follow-up. Maintaining the baseline BCVA over the long term is difficult in Japanese eyes with wet AMD.

Multifragmentation in Au + Au collisions studied with AMD-V

Energy Technology Data Exchange (ETDEWEB)

Ono, Akira [Tohoku Univ., Sendai (Japan). Faculty of Science

1998-07-01

AMD-V is an optimum model for calculation of multifragmentation in Au + Au collisions. AMD-V consider anti-symmetry of incident nucleus, target nucleus and fragments, furthermore, it treat the quantum effect to exist many channels in the intermediate and final state. 150 and 250 MeV/nucleon incident energy were used in the experiments. The data of multifragment atom in {sup 197}Au + {sup 197}Au collisions was reproduced by AMD-V calculation using Gognny force, corresponding to the imcompressibility of nuclear substance K = 228 MeV and its mean field depend on momentum. When other interaction (SKG 2 force, corresponding to K = 373 KeV) was used an mean field does not depend on momentum, the calculation results could not reproduce the experimental values, because nucleus and deuteron were estimated too large and {alpha}-particle and intermediate fragments estimated too small. (S.Y.)

Aflibercept treatment for neovascular AMD beyond the first year: consensus recommendations by a UK expert roundtable panel, 2017 update

Directory of Open Access Journals (Sweden)

Patel PJ

2017-11-01

Full Text Available Praveen J Patel,1 Helen Devonport,2 Sobha Sivaprasad,1 Adam H Ross,3 Gavin Walters,4 Richard P Gale,5 Andrew J Lotery,6 Sajjad Mahmood,7 James S Talks,8 Jackie Napier9 1National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK; 2The Ophthalmology Department, Bradford Royal Infirmary, Bradford, UK; 3The Ophthalmology Department, Bristol Eye Hospital, Bristol, UK; 4Department of Ophthalmology, Harrogate District Hospital, Harrogate, UK; 5The Ophthalmology Department, The York Hospital and Department of Health Sciences, University of York, York, UK; 6Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; 7Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; 8Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UK; 9Medical Affairs, Bayer plc, Reading, Berkshire, UK Abstract: National recommendations on continued administration of aflibercept solution for injection after the first year of treatment for neovascular age-related macular degeneration (nAMD have been developed by an expert panel of UK retina specialists, based on clinician experience and treatment outcomes seen in year 2. The 2017 update reiterates that the treatment goal is to maintain or improve the macular structural and functional gains achieved in year 1 while attempting to reduce or minimize the treatment burden, recognizing the need for ongoing treatment. At the end of year 1 (ie, the decision visit at month 11, two treatment options should be considered: do not extend the treatment interval and maintain fixed 8-weekly dosing, or extend the treatment interval using a treat-and-extend regimen up to a maximum 12 weeks. Criteria for considering not extending the treatment interval are persistent macular fluid with stable

Analysis of the association between CFH Y402H polymorphism and response to intravitreal ranibizumab in patients with neovascular age-related macular degeneration (nAMD

Directory of Open Access Journals (Sweden)

Nur Afiqah Mohamad

2018-03-01

Full Text Available Pharmacogenetic studies indicate that a variable response to anti-vascular endothelial growth factor (VEGF therapy in patients with neovascular form of AMD (nAMD may be due to polymorphisms in the complement factor H gene (CFH. This study is the first to investigate the association between CFH Y402H polymorphism and the response to ranibizumab therapy in Malaysian patients with nAMD. We included 134 patients with nAMD, examined between September 2014 and February 2016. The diagnosis of nAMD was confirmed by ophthalmologic examination, before ranibizumab therapy was started. Each patient received an intravitreal injection of 0.5 mg/0.05 ml ranibizumab following a treat-and-extend (TE regimen. Best-corrected visual acuity (BCVA and central retinal thickness (CRT were recorded after 3 and 6 months following the first injection and compared with the baseline values. Genotyping of Y402H (rs1061170 polymorphism was performed using PCR-RFLP and the amplified product was digested with MluCI restriction enzyme. Association between the Y402H genotypes and response to treatment was determined by a logistic regression analysis of responder (n = 49 and non-responder (n = 84 group. Significantly worse mean BCVA was observed for the CC genotype compared to the TT + CT genotype in the total sample after 6-month follow-up (p = 0.018. Comparing the baseline and 6-month point measurements, improved mean BCVA was observed in responder group, while worse mean BCVA was recorded for non-responder group. However, our regression analysis, adjusted for confounding factors, showed no significant association between the Y402H genotypes and response to treatment in nAMD patients under the recessive model (p > 0.05. Overall, our results suggest that factors other than Y402H polymorphism may be involved in the progression of nAMD after treatment with anti-VEGF agents, in Malaysian population.

In vitro circumvention of cisplatin resistance by the novel sterically hindered platinum complex AMD473.

Science.gov (United States)

Holford, J.; Sharp, S. Y.; Murrer, B. A.; Abrams, M.; Kelland, L. R.

1998-01-01

A novel sterically hindered platinum complex, AMD473 [cis-aminedichloro(2-methylpyridine) platinum (II)], has been selected for phase I clinical trials due to commence in 1997. AMD473 was rationally designed to react preferentially with nucleic acids over sulphur ligands such as glutathione. This report documents the in vitro circumvention of acquired cisplatin resistance mechanisms in human ovarian carcinoma (HOC) cell lines by AMD473. In a panel of 11 HOC cell lines, AMD473 showed intermediate growth inhibition potency (mean IC50 of 8.1 microM) in comparison to cisplatin (mean IC50 of 2.6 microM) and carboplatin (mean IC50 of 20.3 microM). AMD473 showed only a 30.7-fold increase in IC50 value from the most sensitive to the most resistant HOC cell line, whereas for cisplatin it was 117.9-fold and for carboplatin 119.7-fold. AMD473 also showed significantly (P or = 14 h for AMD473) after equitoxic doses were exposed to HOC cells for 2 h. AMD473 ICLs in the CH1 HOC cell line were slowly formed and showed no visible signs of being repaired 24 h after removal of drug. This was paralleled by a slower, longer lasting induction of p53 protein by equitoxic doses of AMD473 in HOC cell lines with wild-type p53. This new class of sterically hindered platinum compound, selected for clinical trial in 1997, may therefore elicit improved clinical response in intrinsically and acquired cisplatin-resistant tumours in the clinic. Images Figure 9 PMID:9472630

MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias

Energy Technology Data Exchange (ETDEWEB)

Spinello, I; Quaranta, M T; Riccioni, R; Riti, V; Pasquini, L; Boe, A; Pelosi, E [Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome (Italy); Vitale, A; Foà, R [Department of Cellular Biotechnologies and Hematology, Division of Hematology, ‘Sapienza' University, Rome (Italy); Testa, U; Labbaye, C [Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome (Italy)

2011-06-01

CXCR4 is a negative prognostic marker in acute myeloid leukemias (AMLs). Therefore, it is necessary to develop novel ways to inhibit CXCR4 expression in leukemia. AMD3100 is an inhibitor of CXCR4 currently used to mobilize cancer cells. CXCR4 is a target of microRNA (miR)-146a that may represent a new tool to inhibit CXCR4 expression. We then investigated CXCR4 regulation by miR-146a in primary AMLs and found an inverse correlation between miR-146a and CXCR4 protein expression levels in all AML subtypes. As the lowest miR-146a expression levels were observed in M5 AML, we analyzed the control of CXCR4 expression by miR-146a in normal and leukemic monocytic cells and showed that the regulatory miR-146a/CXCR4 pathway operates during monocytopoiesis, but is deregulated in AMLs. AMD3100 treatment and miR-146a overexpression were used to inhibit CXCR4 in leukemic cells. AMD3100 treatment induces the decrease of CXCR4 protein expression, associated with miR-146a increase, and increases sensitivity of leukemic blast cells to cytotoxic drugs, this effect being further enhanced by miR-146a overexpression. Altogether our data indicate that miR-146a and AMD3100, acting through different mechanism, downmodulate CXCR4 protein levels, impair leukemic cell proliferation and then may be used in combination with anti-leukemia drugs, for development of new therapeutic strategies.

MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias

International Nuclear Information System (INIS)

Spinello, I; Quaranta, M T; Riccioni, R; Riti, V; Pasquini, L; Boe, A; Pelosi, E; Vitale, A; Foà, R; Testa, U; Labbaye, C

2011-01-01

CXCR4 is a negative prognostic marker in acute myeloid leukemias (AMLs). Therefore, it is necessary to develop novel ways to inhibit CXCR4 expression in leukemia. AMD3100 is an inhibitor of CXCR4 currently used to mobilize cancer cells. CXCR4 is a target of microRNA (miR)-146a that may represent a new tool to inhibit CXCR4 expression. We then investigated CXCR4 regulation by miR-146a in primary AMLs and found an inverse correlation between miR-146a and CXCR4 protein expression levels in all AML subtypes. As the lowest miR-146a expression levels were observed in M5 AML, we analyzed the control of CXCR4 expression by miR-146a in normal and leukemic monocytic cells and showed that the regulatory miR-146a/CXCR4 pathway operates during monocytopoiesis, but is deregulated in AMLs. AMD3100 treatment and miR-146a overexpression were used to inhibit CXCR4 in leukemic cells. AMD3100 treatment induces the decrease of CXCR4 protein expression, associated with miR-146a increase, and increases sensitivity of leukemic blast cells to cytotoxic drugs, this effect being further enhanced by miR-146a overexpression. Altogether our data indicate that miR-146a and AMD3100, acting through different mechanism, downmodulate CXCR4 protein levels, impair leukemic cell proliferation and then may be used in combination with anti-leukemia drugs, for development of new therapeutic strategies

Association between Antiplatelet or Anticoagulant Drugs and Retinal/subretinal Hemorrhage in the Comparison of AMD Treatments Trials (CATT)

Science.gov (United States)

Ying, Gui-shuang; Maguire, Maureen G.; Daniel, Ebenezer; Grunwald, Juan E; Ahmed, Osama; Martin, Daniel F.

2015-01-01

Objective To evaluate the association between use of antiplatelet (AP) or anticoagulant (AC) drugs and retinal/subretinal hemorrhage in participants with neovascular age-related macular degeneration (AMD) in the Comparison of AMD Treatments Trials (CATT). Design Cohort study within CATT. Methods 1185 CATT participants with untreated active neovascular AMD were interviewed for use of AP/AC drugs. Trained readers evaluated photographs for the presence and size of retinal/subretinal hemorrhage associated with the neovascular lesion at baseline and years 1 and 2. Associations between use of AP/AC drugs and hemorrhage were evaluated among all participants and by baseline hypertension status using Fisher exact test and multivariate logistic regression models. Main Outcome Measures Odds ratio for association with AP/AC use. Results Among 1165 participants with gradable photographs, 724 (62.1%) had retinal/subretinal hemorrhage at baseline, 84.4% of hemorrhages were ≤ 1 DA, 8.1% were 1 to 2 DA, and 7.5% were >2 DA. 608 (52.2%) participants used AP/AC drugs at baseline, including 514 (44.1%) AP only, 77 (6.6%) AC only, and 17 (1.5%) both AP and AC. Participants with retinal/subretinal hemorrhage at baseline were comparable to those without retinal/subretinal hemorrhage except that they were older (80 vs. 78 years, phemorrhage was present in 64.5% of AP/AC users and in 59.6% of non-users (p=0.09), the adjusted odds ratio (OR) was 1.18 (95% CI: 0.91–1.51, p=0.21). Neither presence nor size of baseline retinal/subretinal hemorrhage was associated with the type, dose or duration of AP/AC use. Forty-four (4.08%) of 1078 participants had retinal/subretinal hemorrhage detected on 1-year or 2-year photographs; these hemorrhages were not associated with AP/AC use at baseline (p=0.28) or during follow-up (p=0.64). Among participants with hypertension (N=807), AP/AC use was associated with higher rate of retinal/subretinal hemorrhage at baseline (66.8% vs. 56.4%, adjusted OR=1

Regression of Some High-risk Features of Age-related Macular Degeneration (AMD in Patients Receiving Intensive Statin Treatment

Directory of Open Access Journals (Sweden)

Demetrios G. Vavvas

2016-03-01

Conclusions: High-dose statins may result in resolution of drusenoid pigment epithelial detachments (PEDs and improvement in VA, without atrophy or neovascularization in a high-risk subgroup of AMD patients. Confirmation from larger studies is warranted.

AMD and the alternative complement pathway: genetics and functional implications.

Science.gov (United States)

Tan, Perciliz L; Bowes Rickman, Catherine; Katsanis, Nicholas

2016-06-21

Age-related macular degeneration (AMD) is an ocular neurodegenerative disorder and is the leading cause of legal blindness in Western societies, with a prevalence of up to 8 % over the age of 60, which continues to increase with age. AMD is characterized by the progressive breakdown of the macula (the central region of the retina), resulting in the loss of central vision including visual acuity. While its molecular etiology remains unclear, advances in genetics and genomics have illuminated the genetic architecture of the disease and have generated attractive pathomechanistic hypotheses. Here, we review the genetic architecture of AMD, considering the contribution of both common and rare alleles to susceptibility, and we explore the possible mechanistic links between photoreceptor degeneration and the alternative complement pathway, a cascade that has emerged as the most potent genetic driver of this disorder.

AMD's 64-bit Opteron processor

CERN Multimedia

CERN. Geneva

2003-01-01

This talk concentrates on issues that relate to obtaining peak performance from the Opteron processor. Compiler options, memory layout, MPI issues in multi-processor configurations and the use of a NUMA kernel will be covered. A discussion of recent benchmarking projects and results will also be included.BiographiesDavid RichDavid directs AMD's efforts in high performance computing and also in the use of Opteron processors...

Assessing individual risk for AMD with genetic counseling, family history, and genetic testing.

Science.gov (United States)

Cascella, R; Strafella, C; Longo, G; Manzo, L; Ragazzo, M; De Felici, C; Gambardella, S; Marsella, L T; Novelli, G; Borgiani, P; Sangiuolo, F; Cusumano, A; Ricci, F; Giardina, E

2018-02-01

PurposeThe goal was to develop a simple model for predicting the individual risk profile for age-related macular degeneration (AMD) on the basis of genetic information, disease family history, and smoking habits.Patients and methodsThe study enrolled 151 AMD patients following specific clinical and environmental inclusion criteria: age >55 years, positive family history for AMD, presence of at least one first-degree relative affected by AMD, and smoking habits. All of the samples were genotyped for rs1061170 (CFH) and rs10490924 (ARMS2) with a TaqMan assay, using a 7500 Fast Real Time PCR device. Statistical analysis was subsequently employed to calculate the real individual risk (OR) based on the genetic data (ORgn), family history (ORf), and smoking habits (ORsm).Results and conclusionThe combination of ORgn, ORf, and ORsm allowed the calculation of the Ort that represented the realistic individual risk for developing AMD. In this report, we present a computational model for the estimation of the individual risk for AMD. Moreover, we show that the average distribution of risk alleles in the general population and the knowledge of parents' genotype can be decisive to assess the real disease risk. In this contest, genetic counseling is crucial to provide the patients with an understanding of their individual risk and the availability for preventive actions.

Analysis OpenMP performance of AMD and Intel architecture for breaking waves simulation using MPS

Science.gov (United States)

Alamsyah, M. N. A.; Utomo, A.; Gunawan, P. H.

2018-03-01

Simulation of breaking waves by using Navier-Stokes equation via moving particle semi-implicit method (MPS) over close domain is given. The results show the parallel computing on multicore architecture using OpenMP platform can reduce the computational time almost half of the serial time. Here, the comparison using two computer architectures (AMD and Intel) are performed. The results using Intel architecture is shown better than AMD architecture in CPU time. However, in efficiency, the computer with AMD architecture gives slightly higher than the Intel. For the simulation by 1512 number of particles, the CPU time using Intel and AMD are 12662.47 and 28282.30 respectively. Moreover, the efficiency using similar number of particles, AMD obtains 50.09 % and Intel up to 49.42 %.

Use of a twin dataset to identify AMD-related visual patterns controlled by genetic factors

Science.gov (United States)

Quellec, Gwénolé; Abràmoff, Michael D.; Russell, Stephen R.

2010-03-01

The mapping of genotype to the phenotype of age-related macular degeneration (AMD) is expected to improve the diagnosis and treatment of the disease in a near future. In this study, we focused on the first step to discover this mapping: we identified visual patterns related to AMD which seem to be controlled by genetic factors, without explicitly relating them to the genes. For this purpose, we used a dataset of eye fundus photographs from 74 twin pairs, either monozygotic twins, who have the same genotype, or dizygotic twins, whose genes responsible for AMD are less likely to be identical. If we are able to differentiate monozygotic twins from dizygotic twins, based on a given visual pattern, then this pattern is likely to be controlled by genetic factors. The main visible consequence of AMD is the apparition of drusen between the retinal pigment epithelium and Bruch's membrane. We developed two automated drusen detectors based on the wavelet transform: a shape-based detector for hard drusen, and a texture- and color- based detector for soft drusen. Forty visual features were evaluated at the location of the automatically detected drusen. These features characterize the texture, the shape, the color, the spatial distribution, or the amount of drusen. A distance measure between twin pairs was defined for each visual feature; a smaller distance should be measured between monozygotic twins for visual features controlled by genetic factors. The predictions of several visual features (75.7% accuracy) are comparable or better than the predictions of human experts.

Subfoveal choroidal thickness predicts macular atrophy in age-related macular degeneration: results from the TREX-AMD trial.

Science.gov (United States)

Fan, Wenying; Abdelfattah, Nizar Saleh; Uji, Akihito; Lei, Jianqin; Ip, Michael; Sadda, SriniVas R; Wykoff, Charles C

2018-03-01

Our purpose was to evaluate the relationship between subfoveal choroidal thickness (SCT) and development of macular atrophy (MA) in eyes with age-related macular degeneration (AMD). This was a prospective, multicenter study. Sixty participants (120 eyes) in the TREX-AMD trial (NCT01648292) with treatment-naïve neovascular AMD (NVAMD) in at least one eye were included. SCT was measured by certified reading center graders at baseline using spectral domain optical coherence tomography (SDOCT). The baseline SCT was correlated with the presence of MA at baseline and development of incident MA by month 18. Generalized estimating equations were used to account for information from both eyes. Baseline SCT in eyes with MA was statistically significantly less than in those without MA in both the dry AMD (DAMD) (P = 0.04) and NVAMD (P = 0.01) groups. Comparison of baseline SCT between MA developers and non-MA developers revealed a statistically significant difference (P = 0.03). Receiver operating characteristic curve (ROC) analysis showed the cut-off threshold of SCT for predicting the development of MA in cases without MA at baseline was 124 μm (AUC = 0.772; Sensitivity = 0.923; Specificity = 0.5). Among eyes without MA at baseline, those with baseline SCT ≤124 μm were 4.3 times more likely to develop MA (Odds ratio: 4.3, 95% confidence interval: 1.6-12, P = 0.005) than those with baseline SCT >124 μm. Eyes with AMD and MA had less SCT than those without MA. Eyes with less baseline SCT also appear to be at higher risk to develop MA within 18 months.

Study of even-Z nuclei up to Mg with the Gogny force using AMD

Energy Technology Data Exchange (ETDEWEB)

Sugawa, Yoshio; Kimura, Masaaki; Horiuchi, Hisashi [Kyoto Univ. (Japan). Dept. of Physics

2001-12-01

Employing the Gogny force as an effective force, we study the ground state properties of light nuclei using antisymmetrized molecular dynamics (AMD). In this study, we are mainly concerned with the binding energies and radii of light even-Z isotopes, namely He, Be, C, O, Ne and Mg. Using a new technique to calculate the density dependent term of the effective force, we have realized fast and accurate calculations. From a comparison with Skyrme SIII results within the same AMD framework, we find that the Gogny and SIII forces well reproduce the experimental binding energies of stable nuclei. The two forces give almost equal radii, except in the case of {sup 7}Be and {sup 9}Be. For both forces, approximate treatment of the center-of-mass kinetic energy causes overestimation of the binding energy compared with the exact treatment. It also causes a decrease of the nuclear deformation compared with the exact treatment. We also carry out an energy variation after the parity projection. With regard to the binding energies and radii, parity-projected calculations do not exhibit a large difference compared to non-projected results, although the density distribution and clustering features are often significantly changed by the parity projection. (author)

Study of even-Z nuclei up to Mg with the Gogny force using AMD

International Nuclear Information System (INIS)

Sugawa, Yoshio; Kimura, Masaaki; Horiuchi, Hisashi

2001-01-01

Employing the Gogny force as an effective force, we study the ground state properties of light nuclei using antisymmetrized molecular dynamics (AMD). In this study, we are mainly concerned with the binding energies and radii of light even-Z isotopes, namely He, Be, C, O, Ne and Mg. Using a new technique to calculate the density dependent term of the effective force, we have realized fast and accurate calculations. From a comparison with Skyrme SIII results within the same AMD framework, we find that the Gogny and SIII forces well reproduce the experimental binding energies of stable nuclei. The two forces give almost equal radii, except in the case of 7 Be and 9 Be. For both forces, approximate treatment of the center-of-mass kinetic energy causes overestimation of the binding energy compared with the exact treatment. It also causes a decrease of the nuclear deformation compared with the exact treatment. We also carry out an energy variation after the parity projection. With regard to the binding energies and radii, parity-projected calculations do not exhibit a large difference compared to non-projected results, although the density distribution and clustering features are often significantly changed by the parity projection. (author)

[Treatment of macular hematoma complicating AMD by vitrectomy, subretinal r-TPA injection, intravitreal injection of bevacizumab combined with gas tamponade: Report of 4 cases].

Science.gov (United States)

Abboud, M; Benzerroug, M; Milazzo, S

2017-02-01

The occurrence of a subretinal hematoma in age-related macular degeneration (AMD) is a serious complication that can impact the visual prognosis with a poor functional recovery. The management of this complication remains controversial. Several therapeutic methods have been described. We report the results of four patients treated with a protocol combining: vitrectomy, subretinal injection of r-TPA 0.025mg/0.3ml, intravitreal injection of 0.05ml of bevacizumab and retinal tamponade with 20% SF6 gas. Our series consists of four patients with a submacular hematoma complicating AMD, included in succession between October 2013 and October 2014 and treated with the same treatment protocol and by the same surgeon. All patients underwent surgery within eight days after the onset of the macular hematoma. Patients with a consultation period longer than eight days did not undergo this treatment. Face down postoperative positioning was then carried out for seven days by the patients. We observed a shift in the macular hematoma in the four patients, which allowed the identification of secondary neovascularization responsible for the bleeding. The visual acuity improved in three patients from hand motion (HM) preoperatively to 2/10 at one month postoperatively. One patient maintained visual acuity 1/20 during the entire follow-up despite almost complete resorption of the subretinal hematoma. These visual acuities were stable at 6 months postoperatively. Macular subretinal hematoma can cause severe visual loss by several mechanisms. The blood accumulates between the neurosensory retina and the retinal pigment epithelium, which causes a toxic effect on the surrounding tissues, thus resulting in a loss of photoreceptors and cellular destruction in the pigment epithelium and choriocapillaris, evolving into a fibroglial scar. The therapeutic evaluation of this protocol in our series of four patients gives a favorable result. We observed an improvement in visual acuity in 3/4 of

Multi-surface segmentation of OCT images with AMD using sparse high order potentials.

Science.gov (United States)

Oliveira, Jorge; Pereira, Sérgio; Gonçalves, Luís; Ferreira, Manuel; Silva, Carlos A

2017-01-01

In age-related macular degeneration (AMD), the quantification of drusen is important because it is correlated with the evolution of the disease to an advanced stage. Therefore, we propose an algorithm based on a multi-surface framework for the segmentation of the limiting boundaries of drusen: the inner boundary of the retinal pigment epithelium + drusen complex (IRPEDC) and the Bruch's membrane (BM). Several segmentation methods have been considerably successful in segmenting retinal layers of healthy retinas in optical coherence tomography (OCT) images. These methods are successful because they incorporate prior information and regularization. Nonetheless, these factors tend to hinder the segmentation for diseased retinas. The proposed algorithm takes into account the presence of drusen and geographic atrophy (GA) related to AMD by excluding prior information and regularization just valid for healthy regions. However, even with this algorithm, prior information and regularization still cause the oversmoothing of drusen in some locations. Thus, we propose the integration of local shape prior in the form of a sparse high order potentials (SHOPs) into the algorithm to reduce the oversmoothing of drusen. The proposed algorithm was evaluated in a public database. The mean unsigned errors, relative to the average of two experts, for the inner limiting membrane (ILM), IRPEDC and BM were 2.94±2.69, 5.53±5.66 and 4.00±4.00 µ m, respectively. Drusen areas measurements were evaluated, relative to the average of two expert graders, by the mean absolute area difference and overlap ratio, which were 1579.7 ± 2106.8 µ m 2 and 0.78 ± 0.11, respectively.

Recent advances in treatment of wet age-related macular degeneration

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Ming Li

2015-02-01

Full Text Available Age-related macular degeneration(AMDis one of the important eye diseases of the WHO present three big blindness, is one of the main blinding eye disease in people over the age of 50, people over the age of 65, about 2% of the disease caused by monocular blindness, as the population ages, AMD prevalence is increasing in our country. AMD with respect to its clinical manifestations can be divided into dry AMD and wet AMD, wet AMD is the most harmful for the vision of patients, at present there are many treatments for AMD(mainly for wet age-related macular degeneration, mainly including laser treatment, drug therapy, surgical treatment, gene therapy,etc. The treatments of AMD would be illuminated in this article.

Association of Htra1 gene polymorphisms with the risk of developing AMD in Iranian population.

Science.gov (United States)

Askari, Mohammad; Nikpoor, Amin Reza; Gorjipour, Fazel; Mazidi, Mohsen; Sanati, Mohammad Hosein; Aryan, Hajar; Irani, Alireza; Ghasemi Falavarjani, Khalil; Nazari, Hossein; Mousavizadeh, Kazem

2015-10-01

Half of the cases of vision loss in people under 60 years of age have been attributed to age-related macular degeneration (AMD). This is a multifactorial disease with late onset. It has been demonstrated that many different genetic loci are implicated in the risk of developing AMD in different populations. In the current study, we investigated the association of high-temperature ‎requirement A-1 (HTRA1) gene polymorphisms with the risk of developing AMD in the Iranian population. Genomic DNA samples were extracted from 120 patients with AMD and 120 healthy age- and sex-matched controls. A 385 base-pair fragment of the HTRA1 gene promoter region was amplified using the polymerase chain reaction (PCR) technique and sequenced. The frequencies of the alleles were calculated and statistical analysis was performed using SPSS software. Our study demonstrated that the rate of polymorphisms rs11200638 -625 G>A and rs2672598 -487T>C were significantly greater in AMD patients than in healthy controls from the Iranian population. The results of our study indicate that HTRA1 gene promoter region polymorphisms are associated with the risk of developing AMD in the Iranian population.

[99mTc]O2-AMD3100 as a SPECT tracer for CXCR4 receptor imaging

International Nuclear Information System (INIS)

Hartimath, Siddesh V.; Domanska, Urszula M.; Walenkamp, Annemiek M.E.; Dierckx, Rudi A.J.O.; Vries, Erik F.J. de

2013-01-01

Purpose: CXCR4 plays an important role in HIV infection, tumor progression, neurogenesis, and inflammation. In-vivo imaging of CXCR4 could provide more insight in the role of this receptor in health and disease. The aim of this study was to investigate [ 99m Tc]O 2 -AMD3100 as a potential SPECT tracer for imaging of CXCR4. Method: AMD3100 was labelled with [ 99m Tc]pertechnetate. A cysteine challenge assay was performed to test the tracer stability. Heterologous and homologous receptor binding assay and internalization assay were performed in CXCR4 expressing Jurkat-T cells. Ex vivo biodistribution was studied in healthy mice at 30, 60, and 120 min after tracer injection. Tumor uptake of the tracer was determined by microSPECT imaging in nude mice xenografted with human PC-3 prostate tumor. Specificity of tracer uptake was determined by blocking studies using an excess of unlabelled AMD3100. Results: AMD3100 was labelled with technetium-99 m with a radiochemical yield of > 98%. The tracer was stable in PBS and mouse plasma for at least 6 h at 37 °C. Heterologous and homologous binding assays with AMD3100 showed IC 50 values of 240 ± 10 μM, and 92 ± 5 μM for [ 125 I]SDF-1α and [ 99m Tc]O 2 -AMD3100 respectively, with negligible receptor internalisation. The tracer showed high uptake in liver, lungs, spleen, thymus, intestine and bone. Blocking dose of AMD3100.8HCl (20 mg/kg) decreased the uptake in these organs (p 99m Tc]O 2 -AMD3100 showed specific tumor accumulation in mice bearing PC-3 xenografts model. Time activity curves (TAC) in AMD3100 pre-treated animals tracer showed 1.7 times less tumor uptake as compared to control animals (p 99m Tc]O 2 -AMD3100 is readily labelled, is stable in plasma and displays a favourable binding affinity for the CXCR4 receptors. [ 99m Tc O 2 -AMD3100 shows specific binding in organs with high CXCR4 expression and in CXCR4 positive tumors. These results justify further evaluation of this radiopharmaceutical as a potential

Anker Energy battles AMD in West Virginia

International Nuclear Information System (INIS)

Frey, T.J.

1998-01-01

To comply with the Surface Mining Control and Reclamation Act of 1977, Anker Energy has a number of reclamation projects in progress in northern West Virginia to fight acid mine drainage (AMD), the number one reclamation problem in the region. Anker's reclamation activities range from water treatment systems to the backhaul and use of coal ash from its customers. The article describes the passive treatment system - successive alkalinity producing system (SAPS) used at the Ankar subsidiary Upshur Property Inc., in Upshur Country, W.Va., and a similar passive system used at the Green Run site in Albright, W.Va. A backhaul and ash utilization water treatment system is used by Anker subsidiary Patriot Mining Co. Inc., for water discharged from a surface mine into the Cheat River in Albright. In another ash project, the Stacks Run Refuse Reprocessing Project in Preston County, W.Va., refuse placed 10 years ago in abandoned pits is excavated, mixed with coal, burned with limestone and the CFB ash used in reclamation. At Patriot's Osaga surface mine ditches are filled with slag from old steel mills to generate alkalinity. At Pete Dye a golf course has been built on land mined by Consolidation Coal. 7 photos

Aflibercept in wet AMD: specific role and optimal use

Directory of Open Access Journals (Sweden)

Semeraro F

2013-08-01

Full Text Available F Semeraro,1 F Morescalchi,1 S Duse,1 F Parmeggiani,2 E Gambicorti,1 C Costagliola31Department of Medical and Surgical Specialties, Radiological Specialties and Public Health, Ophthalmology Clinic, University of Brescia, Brescia, Italy; 2Department of Ophthalmology, University of Ferrara, Ferrara, Italy; 3Department of Health Science, Ophthalmology Clinic, University of Molise, Campobasso, ItalyBackground: Vascular endothelial growth factor (VEGF is a naturally occurring glycoprotein in the body that acts as a growth factor for endothelial cells. It regulates angiogenesis, enhances vascular permeability, and plays a major role in wet age-related macular degeneration. The consistent association between choroidal neovascularization and increased VEGF expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of this disorder. Blockade of VEGF activity is currently the most effective strategy for arresting choroidal angiogenesis and reducing vascular permeability, which is frequently the main cause of visual acuity deterioration. In recent years, a number of other molecules have been developed to increase the efficacy and to prolong the durability of the anti-VEGF effect. Aflibercept (EYLEA®; Regeneron Pharmaceutical Inc and Bayer, also named VEGF Trap-eye, is the most recent member of the anti-VEGF armamentarium that was approved by the US Food and Drug Administration in November 2011. Because of its high binding affinity and long duration of action, this drug is considered to be a promising clinically proven anti-VEGF agent for the treatment of wet maculopathy.Objective: This article reviews the current literature and clinical trial data regarding the efficacy and the pharmacological properties of VEGF-Trap eye and describes the possible advantages of its use over the currently used "older" anti-VEGF drugs.Methods: For this review, a search of PubMed from January 1989 to May 2013 was

Association of Htra1 Gene Polymorphisms with the Risk of Developing AMD in Iranian Population

Directory of Open Access Journals (Sweden)

Mohammad Askari

2015-10-01

Full Text Available Background: Half of the cases of vision loss in people under 60 years of age have been attributed to age-related macular degeneration (AMD. This is a multifactorial disease with late onset. It has been demonstrated that many different genetic loci are implicated in the risk of developing AMD in different populations. In the current study, we investigated the association of high-temperature requirement A-1 (HTRA1 gene polymorphisms with the risk of developing AMD in the Iranian population. Methods: Genomic DNA samples were extracted from 120 patients with AMD and 120 healthy age- and sex-matched controls. A 385 base-pair fragment of the HTRA1 gene promoter region was amplified using the polymerase chain reaction (PCR technique and sequenced. The frequencies of the alleles were calculated and statistical analysis was performed using SPSS software. Results: Our study demonstrated that the rate of polymorphisms rs11200638 -625 G>A and rs2672598 -487T>C were significantly greater in AMD patients than in healthy controls from the Iranian population. Conclusions: The results of our study indicate that HTRA1 gene promoter region polymorphisms are associated with the risk of developing AMD in the Iranian population

Vision Rehabilitation is Part of AMD Care

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August Colenbrander

2018-01-01

Full Text Available AMD does not just affect the retina. It severely affects people’s lives. Paying attention to this aspect will only become more important as the population ages and more otherwise healthy individuals become affected. This paper will discuss the need for teamwork to overcome the difference between medical care, which addresses the causes of AMD, and rehabilitative care, which addresses the consequences. Different aspects and different degrees of vision loss ask for different interventions. Loss of detailed vision can be addressed by a wide variety of magnification devices. The means to address this aspect are well recognized. Surround vision is largely processed pre-attentively. Its loss cannot be remediated by devices, but must be addressed through patient education to bring previously subconscious reactions to conscious awareness. Loss of contrast vision is an aspect that is not sufficiently studied. It is important for early detection, and for the safety of the patient. When the eye condition cannot be modified, environmental modifications provide the most effective remediation.

The Revival of a Failed Constructed Wetland Treating of a High Fe Load AMD

Science.gov (United States)

A.D. Karathanasis; C.D. Barton

1999-01-01

Acid mine drainage (AMD) from abandoned mines has significantly impaired water quality in eastern Kentucky. A small surface flow wetland constructed in 1989 to reduce AMD effects and subsequently failed after six months of operation was renovated by incorporating anoxic limestone drains (ALDs) and anaerobic subsurface drains promoting vertical flow through successive...

Modification of AMD wave functions and application to the breaking of the N=20 magic number

International Nuclear Information System (INIS)

Kimura, Masaaki; Horiuchi, Hisashi

2001-01-01

By using the deformed Gaussian instead of the spherical one, we have modified the AMD (Antisymmetrized Molecular Dynamics) wave functions. The calculation results with this modified AMD shows the drastic improvement of the deformation properties of Mg isotopes. This improvement means that this new version of AMD can treat the deformation of mean field properly than before and the deformation of mean field is important in Mg isotopes. With this new version of AMD, we have also calculated 32Mg in which the breaking of magic number N=20 is experimentally known. In this nucleus, β-energy surface is also drastically changed by the modification AMD wave function. Our results show that this nucleus is indeed deformed and neutron's 2p2h state is dominant in its ground state. This ground state reproduces the experimental data and shows the breaking of the magic number N=20 clearly. Additionally, near the ground state, there is also very interesting state which has neutron's 4p4h structure and shows parity violating density distribution and cluster-like nature. (author)

Modification of AMD wave functions and application to the breaking of the N=20 magic number

Energy Technology Data Exchange (ETDEWEB)

Kimura, Masaaki; Horiuchi, Hisashi [Kyoto Univ. (Japan). Dept. of Physics

2001-09-01

By using the deformed Gaussian instead of the spherical one, we have modified the AMD (Antisymmetrized Molecular Dynamics) wave functions. The calculation results with this modified AMD shows the drastic improvement of the deformation properties of Mg isotopes. This improvement means that this new version of AMD can treat the deformation of mean field properly than before and the deformation of mean field is important in Mg isotopes. With this new version of AMD, we have also calculated 32Mg in which the breaking of magic number N=20 is experimentally known. In this nucleus, {beta}-energy surface is also drastically changed by the modification AMD wave function. Our results show that this nucleus is indeed deformed and neutron's 2p2h state is dominant in its ground state. This ground state reproduces the experimental data and shows the breaking of the magic number N=20 clearly. Additionally, near the ground state, there is also very interesting state which has neutron's 4p4h structure and shows parity violating density distribution and cluster-like nature. (author)

Pathogenesis and prophylaxis of AMD: focus on oxidative stress and antioxidants

Directory of Open Access Journals (Sweden)

Anna Wiktorowska-Owczarek

2010-07-01

Full Text Available Age-related macular degeneration (AMD is the leading cause of severe visual loss and blindness in people over 55. Its pathogenesis – likely multifactorial, involving a complex interaction of metabolic, functional, genetic and environmental factors – remains poorly understood. Among molecular links in pathogenesis of AMD is the oxidative stress in the retina, a structure that is particularly susceptible to damage by reactive oxygen species (ROS since photoreceptor outer segment (POS membranes are rich in polyunsaturated fatty acids which can be readily oxidized and can initiate a cytotoxic chain reaction. Occurring in the neighborhood of photoreceptors, the retinal pigment epithelial cells (RPE actively contribute to both the retinoid cycle and catabolism of constantly shed and phagocytized parts of photoreceptor outer segments. Enzymatic degradation of photoreceptor fragments occurring in RPE phagolysosomes is not complete and undigested material in the form of insoluble aggregates, called lipofuscin, is deposited in lysosomes of RPE cells. Lipofuscin contains a mixture of diverse molecular components including retinoid-derived compounds, some of which displaying potent photoinducible properties, contributing to an enhancement and propagation of the oxidative stress. The retina possesses defense mechanisms against the oxidative stress that effectively neutralize the consequences of reactive oxygen species actions under normal conditions. A key role in the antioxidant defense plays an array of substances, including: xanthophylls (lutein and zeaxanthin, vitamin C and E, and glutathione. This paper surveys the current concepts on the role of the oxidative stress in pathophysiology of AMD, and describes major components of the antioxidant defense system, including their use in AMD prophylaxis and therapy.

The influence of biofilms on the migration of uranium in acid mine drainage (AMD) waters

Energy Technology Data Exchange (ETDEWEB)

Krawczyk-Baersch, E., E-mail: E.Krawczyk-Baersch@hzdr.de [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiochemistry, P.O. Box 51 01 19, D-01314 Dresden (Germany); Luensdorf, H. [Helmholtz Centre for Infection Research, Department of Vaccinology and Applied Microbiology, Inhoffenstr. 7, D-38124 Braunschweig (Germany); Arnold, T.; Brendler, V. [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiochemistry, P.O. Box 51 01 19, D-01314 Dresden (Germany); Eisbein, E. [TU Bergakademie Freiberg, Institute of Physical Chemistry, Akademiestrasse 6, D-09596 Freiberg (Germany); Jenk, U.; Zimmermann, U. [Wismut GmbH, Jagdschaenkenstr. 29, D-09117 Chemnitz (Germany)

2011-07-15

The uranium mine in Koenigstein (Germany) is currently in the process of being flooded. Huge mass of Ferrovum myxofaciens dominated biofilms are growing in the acid mine drainage (AMD) water as macroscopic streamers and as stalactite-like snottites hanging from the ceiling of the galleries. Microsensor measurements were performed in the AMD water as well as in the biofilms from the drainage channel on-site and in the laboratory. The analytical data of the AMD water was used for the thermodynamic calculation of the predominance fields of the aquatic uranium sulfate (UO{sub 2}SO{sub 4}) and UO{sub 2}{sup ++} speciation as well as of the solid uranium species Uranophane [Ca(UO{sub 2}){sub 2}(SiO{sub 3}OH){sub 2}{center_dot}5H{sub 2}O] and Coffinite [U(SiO{sub 4}){sub 1-x}(OH){sub 4x}], which are defined in the stability field of pH > 4.8 and Eh < 960 mV and pH > 0 and Eh < 300 mV, respectively. The plotting of the measured redox potential and pH of the AMD water and the biofilm into the calculated pH-Eh diagram showed that an aqueous uranium(VI) sulfate complex exists under the ambient conditions. According to thermodynamic calculations a retention of uranium from the AMD water by forming solid uranium(VI) or uranium(IV) species will be inhibited until the pH will increase to > 4.8. Even analysis by Energy-filtered Transmission Electron Microscopy (EF-TEM) and electron energy loss spectroscopy (EELS) within the biofilms did not provide any microscopic or spectroscopic evidence for the presence of uranium immobilization. In laboratory experiments the first phase of the flooding process was simulated by increasing the pH of the AMD water. The results of the experiments indicated that the F. myxofaciens dominated biofilms may have a substantial impact on the migration of uranium. The AMD water remained acid although it was permanently neutralized with the consequence that the retention of uranium from the aqueous solution by the formation of solid uranium species will be

The influence of biofilms on the migration of uranium in acid mine drainage (AMD) waters

International Nuclear Information System (INIS)

Krawczyk-Baersch, E.; Luensdorf, H.; Arnold, T.; Brendler, V.; Eisbein, E.; Jenk, U.; Zimmermann, U.

2011-01-01

The uranium mine in Koenigstein (Germany) is currently in the process of being flooded. Huge mass of Ferrovum myxofaciens dominated biofilms are growing in the acid mine drainage (AMD) water as macroscopic streamers and as stalactite-like snottites hanging from the ceiling of the galleries. Microsensor measurements were performed in the AMD water as well as in the biofilms from the drainage channel on-site and in the laboratory. The analytical data of the AMD water was used for the thermodynamic calculation of the predominance fields of the aquatic uranium sulfate (UO 2 SO 4 ) and UO 2 ++ speciation as well as of the solid uranium species Uranophane [Ca(UO 2 ) 2 (SiO 3 OH) 2 ·5H 2 O] and Coffinite [U(SiO 4 ) 1-x (OH) 4x ], which are defined in the stability field of pH > 4.8 and Eh 0 and Eh 4.8. Even analysis by Energy-filtered Transmission Electron Microscopy (EF-TEM) and electron energy loss spectroscopy (EELS) within the biofilms did not provide any microscopic or spectroscopic evidence for the presence of uranium immobilization. In laboratory experiments the first phase of the flooding process was simulated by increasing the pH of the AMD water. The results of the experiments indicated that the F. myxofaciens dominated biofilms may have a substantial impact on the migration of uranium. The AMD water remained acid although it was permanently neutralized with the consequence that the retention of uranium from the aqueous solution by the formation of solid uranium species will be inhibited. - Highlights: → Redox potential and pH of the biofilm differ significantly compared to the AMD water. → Formation of an aqueous uranium(VI) sulfate complex in the biofilm and in the AMD water. → Experiments revealed that the F. myxofaciens dominated biofilms have a substantial impact on the migration of uranium. → Due to homeostatic mechanisms the microbes maintain their intracellular pH even when the pH of the water increases.

DNA sequence variants in PPARGC1A, a gene encoding a coactivator of the ω-3 LCPUFA sensing PPAR-RXR transcription complex, are associated with NV AMD and AMD-associated loci in genes of complement and VEGF signaling pathways.

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John Paul SanGiovanni

Full Text Available Increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs and use of peroxisome proliferator activator receptor (PPAR-activating drugs are associated with attenuation of pathologic retinal angiogenesis. ω-3 LCPUFAs are endogenous agonists of PPARs. We postulated that DNA sequence variation in PPAR gamma (PPARG co-activator 1 alpha (PPARGC1A, a gene encoding a co-activator of the LCPUFA-sensing PPARG-retinoid X receptor (RXR transcription complex, may influence neovascularization (NV in age-related macular degeneration (AMD.We applied exact testing methods to examine distributions of DNA sequence variants in PPARGC1A for association with NV AMD and interaction of AMD-associated loci in genes of complement, lipid metabolism, and VEGF signaling systems. Our sample contained 1858 people from 3 elderly cohorts of western European ancestry. We concurrently investigated retinal gene expression profiles in 17-day-old neonatal mice on a 2% LCPUFA feeding paradigm to identify LCPUFA-regulated genes both associated with pathologic retinal angiogenesis and known to interact with PPARs or PPARGC1A.A DNA coding variant (rs3736265 and a 3'UTR-resident regulatory variant (rs3774923 in PPARGC1A were independently associated with NV AMD (exact P = 0.003, both SNPs. SNP-SNP interactions existed for NV AMD (P<0.005 with rs3736265 and a AMD-associated variant in complement factor B (CFB, rs512559. PPARGC1A influences activation of the AMD-associated complement component 3 (C3 promoter fragment and CFB influences activation and proteolysis of C3. We observed interaction (P ≤ 0.003 of rs3736265 with a variant in vascular endothelial growth factor A (VEGFA, rs3025033, a key molecule in retinal angiogenesis. Another PPARGC1A coding variant (rs8192678 showed statistical interaction with a SNP in the VEGFA receptor fms-related tyrosine kinase 1 (FLT1, rs10507386; P ≤ 0.003. C3 expression was down-regulated 2-fold in retinas of ω-3 LCPUFA-fed mice

Geophysical delineation of AMD in the Cradle of Humankind

CSIR Research Space (South Africa)

Van Schoor, Michael

2016-08-01

Full Text Available Acid mine drainage (AMD) and its effect on surface and groundwater resources in the Cradle of Humankind (COH) area near Krugersdorp is a pertinent and well-documented concern. In 2008, a water resources monitoring programme for the area...

Development of a new methodology for mitigating acid mine drainage (AMD) at reclaimed surface mines

International Nuclear Information System (INIS)

Ackman, T.E.; Kim, A.G.

1993-01-01

A 1.2 hectare (ha) experimental site located on a 14.5 ha reclaimed surface mine in Greene County, PA was injected with a 141 cubic meters (m 3 ) of fly ash and fluidized bed combustion (FBC) ash grout that included acid mine drainage (AMD) sludge. An evaluation of this AMD abatement approach by the Bureau of Mines found that the average net acidity and concentrations of several metal ions at the discharge seep and monitoring wells decreased after grouting. Changes in metal concentrations were assumed to be related to alkaline addition and/or encapsulation. Initial results indicate that this technique is potentially an effective AMD abatement method

Avati teaduskeskus maakula ealise degeneratsiooniga (AMD-ga) võitlemiseks

Index Scriptorium Estoniae

2007-01-01

Euroopa esimene silma kollatähni ehk makulaarse pigmendi uurimisgrupi keskus (MPRG) Iirimaal Waterfordi tehnoloogiainstituudis uurib toitumise mõju võitluses maailma enim levinud pimedaks jäämise põhjusega - kollatähni kärbumise ehk maakula ealise degeneratsiooniga (AMD-ga)

Removal of phosphorus using AMD-treated lignocellulosic material

Science.gov (United States)

James S. Han; Soo-Hong Min; Yeong-Kwan Kim

2005-01-01

Excess nutrients, including phosphorus, can cause eutrophication in surface water and reservoirs. We tested the phosphate removal capacity of juniper fiber through isotherm, kinetic, column, and field tests. Heavy metals from an acid mine drainage (AMD) site were precipitated on the surface ofjuniper fiber. The modified fiber was tested in laboratory- caled batch and...

Current drug and molecular therapies for the treatment of atrophic age-related macular degeneration: phase I to phase III clinical development.

Science.gov (United States)

Li, Huiling; Chintalapudi, Sumana R; Jablonski, Monica M

2017-10-01

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. Atrophic AMD, including early, intermediate and geographic atrophy (GA), accounts for ~90% of all cases. It is a multifactorial degeneration characterized by chronic inflammation, oxidative stress and aging components. Although no FDA-approved treatment yet exists for the late stage of atrophic AMD, multiple pathological mechanisms are partially known and several promising therapies are in various stages of development. Areas covered: Underlying mechanisms that define atrophic AMD will help provide novel therapeutic targets that will address this largely unmet clinical need. The purpose of this paper is to review current promising drugs that are being evaluated in clinical trials. Because no pharmacological treatments are currently available for late stage of atrophic AMD, any new therapy would have extensive market potential. Expert opinion: The number of AMD patients is predicted to increase to ~30 million worldwide by 2020. In response to this enormous unmet clinical need, new promising therapies are being developed and evaluated in clinical trials. We propose that the assessment of novel interventions will also need to consider the genotypes of participants, as the benefit may be determined by polymorphisms in an individual's genetic background.

The ARMOUR Study: Anti-VEGF in Neovascular AMD--Our Understanding in a Real-World Indian Setting.

Science.gov (United States)

Jain, Nimesh; Yadav, Naresh Kumar; Jayadev, Chaitra; Srinivasan, Priya; Mohan, Ashwin; Shetty, Bhujang K

2017-01-01

The aim of our study was to share our experience with anti-vascular endothelial growth factor (anti-VEGF) injections in the treatment of neovascular age-related macular degeneration (nAMD) in a real-world setting. A retrospective, observational study. Patients of Indian origin with nAMD receiving anti-VEGF with a minimum follow-up of 12 months were enrolled in this study. In group 1, patients were treated on a pro re nata (PRN) basis; in group 2, patients received a loading dose (3 injecti Results: Overall, we observed that 77.31% (92/119 eyes) of patients either maintained or had improved visual acuity at 12 months' follow-up. Similar visual outcome was observed in both groups. The average number of injections given in group 1 was 4.98 and in group 2 was 3.7. CDVA at 12 months was significantly correlated with type of drug molecule, CSFT at 3 and 12 months, baseline visual acuity, and CDVA at 3 months. PRN treatment with significantly fewer injections achieved similar anatomical and functional outcomes when compared with the loading dose group. The results of this study need to be validated with a larger study group and a longer follow-up. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

Baseline data from a multicenter, 5-year, prospective cohort study of Japanese age-related macular degeneration: an AMD2000 report.

Science.gov (United States)

Tsujikawa, Akitaka; Akagi-Kurashige, Yumiko; Yuzawa, Mitsuko; Ishibashi, Tatsuro; Nakanishi, Hideo; Nakatani, Eiji; Teramukai, Satoshi; Fukushima, Masanori; Yoshimura, Nagahisa

2018-03-01

To report research participants' baseline characteristics in the AMD2000 study, a prospective, multicenter, 5-year, observational cohort study of Japanese age-related macular degeneration (AMD). The characteristics were determined using multimodal imaging. Patients with AMD were recruited at 18 clinical sites in Japan between April 2006 and March 2009. Each patient underwent a complete ophthalmic examination, including measurement of best-corrected visual acuity (Landolt chart), indirect ophthalmoscopy, slit-lamp biomicroscopy with a contact lens, optical coherence tomography imaging, fundus photography, and fluorescein and indocyanine green angiography. Four hundred sixty participants (326 men [70.9%]) were included in the study. At enrollment, 131 eyes (28.5%) had hard drusen and 125 eyes (27.2%) had soft drusen in the macular area. A total of 455 eyes (98.9%) were diagnosed as having wet AMD, and 5 eyes (1.1%), as having dry AMD. Of the 455 eyes with wet AMD, 209 eyes (45.4%) had typical AMD, 228 eyes (49.6%) had polypoidal choroidal vasculopathy (PCV), and 18 eyes (3.9%) had retinal angiomatous proliferation. The size of choroidal neovascularization (CNV) was significantly smaller with indocyanine green angiography than with fluorescein angiography (P macular edema, older age, scar, extrafoveal macular edema, subfoveal CNV, large branching vascular network, and hard exudates. Japanese patients with AMD are predominantly male, lack drusen, and have a high rate of PCV.

Mitigating health problems associated with AMD in South Africa

CSIR Research Space (South Africa)

Schachtschneider, K

2012-03-01

Full Text Available on communities’ water supply and the water table. The CSIR has developed a novel process to reclaim high-quality precipitated calcium carbonate (PCC) from calcium-rich industrial solid waste. Calcium carbonate can be used to prevent AMD from becoming too acidic...

Association of OCT derived drusen measurements with AMD associated-genotypic SNPs in Amish population.

Science.gov (United States)

Chavali, Venkata Ramana Murthy; Diniz, Bruno; Huang, Jiayan; Ying, Gui-Shuang; Sadda, SriniVas R; Stambolian, Dwight

To investigate the association of OCT derived drusen measures in Amish age-related macular degeneration (AMD) patients with known loci for macular degeneration. Members of the Old Order Amish community in Pennsylvania ages 50 and older were assessed for drusen area, volume and regions of retinal pigment epithelium (RPE) atrophy using a Cirrus High- Definition-OCT. Measurements were obtained in the macula region within a central circle (CC) of 3 mm diameter and a surrounding perifoveal ring (PR) of 3 to 5 mm diameter using the Cirrus OCT RPE analysis software. Other demographic information including age, gender and smoking status were collected. Study subjects were further genotyped to determine their risk for the AMD associated SNPs in SYN3, LIPC, ARMS2, C3, CFB, CETP, CFI and CFH genes using TaqMan genotyping assays. The association of genotypes with OCT measures were assessed using linear trend p-values calculated from univariate and multivariate generalized linear models. 432 eyes were included in the analysis. Multivariate analysis (adjusted by age, gender and smoking status) confirmed the known significant association between AMD and macular drusen with the number of CFH risk alleles for drusen area (area increased 0.12 mm 2 for a risk allele increase, pAmish AMD population.

DNA sequence variants in PPARGC1A, a gene encoding a coactivator of the ω-3 LCPUFA sensing PPAR-RXR transcription complex, are associated with NV AMD and AMD-associated loci in genes of complement and VEGF signaling pathways.

Science.gov (United States)

SanGiovanni, John Paul; Chen, Jing; Sapieha, Przemyslaw; Aderman, Christopher M; Stahl, Andreas; Clemons, Traci E; Chew, Emily Y; Smith, Lois E H

2013-01-01

Increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) and use of peroxisome proliferator activator receptor (PPAR)-activating drugs are associated with attenuation of pathologic retinal angiogenesis. ω-3 LCPUFAs are endogenous agonists of PPARs. We postulated that DNA sequence variation in PPAR gamma (PPARG) co-activator 1 alpha (PPARGC1A), a gene encoding a co-activator of the LCPUFA-sensing PPARG-retinoid X receptor (RXR) transcription complex, may influence neovascularization (NV) in age-related macular degeneration (AMD). We applied exact testing methods to examine distributions of DNA sequence variants in PPARGC1A for association with NV AMD and interaction of AMD-associated loci in genes of complement, lipid metabolism, and VEGF signaling systems. Our sample contained 1858 people from 3 elderly cohorts of western European ancestry. We concurrently investigated retinal gene expression profiles in 17-day-old neonatal mice on a 2% LCPUFA feeding paradigm to identify LCPUFA-regulated genes both associated with pathologic retinal angiogenesis and known to interact with PPARs or PPARGC1A. A DNA coding variant (rs3736265) and a 3'UTR-resident regulatory variant (rs3774923) in PPARGC1A were independently associated with NV AMD (exact P = 0.003, both SNPs). SNP-SNP interactions existed for NV AMD (Pcomplement factor B (CFB, rs512559). PPARGC1A influences activation of the AMD-associated complement component 3 (C3) promoter fragment and CFB influences activation and proteolysis of C3. We observed interaction (P ≤ 0.003) of rs3736265 with a variant in vascular endothelial growth factor A (VEGFA, rs3025033), a key molecule in retinal angiogenesis. Another PPARGC1A coding variant (rs8192678) showed statistical interaction with a SNP in the VEGFA receptor fms-related tyrosine kinase 1 (FLT1, rs10507386; P ≤ 0.003). C3 expression was down-regulated 2-fold in retinas of ω-3 LCPUFA-fed mice - these animals also showed 70% reduction in retinal NV (P �

Physiological and behavioral responses of stonefly nymphs to enhanced limestone treatment of acid mine drainage.

Science.gov (United States)

Cole, M B; Arnold, D E; Watten, B J

2001-03-01

A new acid mine drainage (AMD) treatment system uses pulsed, fluidized beds of limestone, and carbon dioxide pretreatment of influent AMD, to enhance limestone neutralization of AMD. We conducted laboratory studies to evaluate the behavior and physiology of larval stoneflies (Pteronarcys proteus, Plecoptera) exposed to effluents produced by the treatment system. Survival, sodium balance, drift, and feeding responses by P. proteus to treated and untreated AMD were examined. P. proteus nymphs exhibited significant losses of whole body sodium in exposures to untreated AMD. Nymphs exposed to treated effluents experienced no loss of whole-body sodium. Nymphs exposed to untreated AMD showed elevated drift rates and depressed feeding rates relative to those of nymphs exposed to treated AMD, and to AMD-free controls. No significant differences in feeding or drift behavior occurred between nymphs exposed to treated effluents and those exposed to AMD-free controls. The treatment system, with and without CO2 pretreatment, provided water that was not toxic to the test animals, and that allowed normal behavioral and physiological function.

Age-related macular degeneration in a randomized controlled trial of low-dose aspirin: Rationale and study design of the ASPREE-AMD study

Directory of Open Access Journals (Sweden)

Liubov Robman

2017-06-01

Conclusion: The study findings will be of significant clinical and public interest due to a potential to identify a possible low cost therapy for preventing AMD worldwide and to determine risk/benefit balance of the aspirin usage by the AMD-affected elderly. The ASPREE-AMD study provides a unique opportunity to determine the effect of aspirin on AMD incidence and progression, by adding retinal imaging to an ongoing, large-scale primary prevention randomized clinical trial.

What effects has the cataract surgery on the development and progression of Age-Related Macular Degeneration (AMD?

Directory of Open Access Journals (Sweden)

Willich, Stefan N.

2006-12-01

Full Text Available Background: The cataract (Cataracta senilis is the most frequent eye disease of elderly people worldwide. In Germany, the cataract operation - with currently 450,000 interventions each year the most frequent operation in ophthalmology – can be seen as routine surgery. The age related macular degeneration (AMD is a further one of the most common, age-related eye diseases and the most frequent cause of blindness of elderly people in industrial nations. Due to demographic changes an increasing number of patients will suffer from cataract and AMD at the same time. This coincidence leads to a greater interest in the question of a mutual influence of both diseases, respectively their therapies, on each other. Objectives: The aim of this report was the evaluation of the medical and health economic effects of cataract operations on the development and progression of an age related macular degeneration (AMD. It was differentiated between first manifestations of AMD, progression of early stages of AMD and influence on further impairment in late stages of AMD. Methods: The relevant publications for this report were identified by DIMDI via structured database enquiry as well as common, self-made enquiry and were evaluated, based on the criteria of evidence based medicine. The present report included German and English literature published since 1983. Results: The database enquiry generated a record of 2769 issue-related publications. Eight medical publications were eligible for analysis in the course of the present HTA report. No relevant studies on health economical, ethical, social or legal issues could be included. Three epidemiological cohort studies provided some evidence for a promoting influence of cataract extractions on the progression of early types of AMD. Two of the epidemiological studies assessed the risk of first manifestation of AMD after cataract extraction. Both came up with up with increased incidences that did not reach statistical

Pharmacologic Treatment of Wet Type Age-related Macular Degeneration; Current and Evolving Therapies.

Science.gov (United States)

Shams Najafabadi, Hoda; Daftarian, Narsis; Ahmadieh, Hamid; Soheili, Zahra-Soheila

2017-08-01

Age-related macular degeneration as the major cause of blindness in the elderly population has remained at the epicenter of clinical research in ophthalmology. This retinal disorder is characterized by the photoreceptor and retinal pigment epithelial cells loss, occurring within the macula. The disease represents a spectrum of clinical manifestations. It is a multifactorial disease resulting from a combination of genetic predispositions and environmental risk factors. AMD is classified into two different types, dry and wet. Wet AMD is in close relation with angiogenesis and inflammatory processes.A variety of anti-angiogenesis and anti-inflammatory drugs have been proposed for the treatment of the disease. The purpose of this paper is to briefly review the pharmacological therapies of the wet form of AMD and focus on new drugs that are currently in different stages of research and development.

Bioremediation of Acidic and Metalliferous Drainage (AMD) through organic carbon amendment by municipal sewage and green waste.

Science.gov (United States)

McCullough, Clint D; Lund, Mark A

2011-10-01

Pit lakes (abandoned flooded mine pits) represent a potentially valuable water resource in hot arid regions. However, pit lake water is often characterised by low pH with high dissolved metal concentrations resulting from Acidic and Metalliferous Drainage (AMD). Addition of organic matter to pit lakes to enhance microbial sulphate reduction is a potential cost effective remediation strategy. However, cost and availability of suitable organic substrates are often limiting. Nevertheless, large quantities of sewage and green waste (organic garden waste) are often available at mine sites from nearby service towns. We treated AMD pit lake water (pH 2.4) from tropical, North Queensland, Australia, with primary-treated sewage sludge, green waste, and a mixture of sewage and green waste (1:1) in a controlled microcosm experiment (4.5 L). Treatments were assessed at two different rates of organic loading of 16:1 and 32:1 pit water:organic matter by mass. Combined green waste and sewage treatment was the optimal treatment with water pH increased to 5.5 in only 145 days with decreases of dissolved metal concentrations. Results indicated that green waste was a key component in the pH increase and concomitant heavy metal removal. Water quality remediation was primarily due to microbially-mediated sulphate reduction. The net result of this process was removal of sulphate and metal solutes to sediment mainly as monosulfides. During the treatment process NH(3) and H(2)S gases were produced, albeit at below concentrations of concern. Total coliforms were abundant in all green waste-treatments, however, faecal coliforms were absent from all treatments. This study demonstrates addition of low-grade organic materials has promise for bioremediation of acidic waters and warrants further experimental investigation into feasibility at higher scales of application such as pit lakes. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Bevasiranib for the Treatment of Wet, Age-Related Macular Degeneration

Directory of Open Access Journals (Sweden)

Adinoyi O. Garba

2010-01-01

Full Text Available Age- related Macular Degeneration (AMD is the leading cause of severe visual impairment in people 65 years and older in industrialized nations. Exudative, or “wet”, AMD is a late form of AMD (as distinguished from atrophic, so-called dry, AMD and is responsible for over 60% of all cases of blindness due to AMD. It is widely accepted that vascular endothelial growth factor (VEGF is a key component in the pathogenesis of choroidal neo-vascularization (CNV, which is a precursor to wet AMD. The current gold-standard for treating wet AMD is the monoclonal antibody fragment ranibizumab (trade name Lucentis, which targets VEGF. Other agents used to treat wet AMD include pegaptanib (Macugen, bevacizumab (Avastin; off-label use, and several other experimental agents. The advent of small interfering RNA (siRNA has presented a whole new approach to inhibiting VEGF. This article reviews the status of a novel siRNA-based therapeutic, bevasiranib, for the treatment of wet AMD. Bevasiranib is believed to work by down regulating VEGF production in the retina. Studies in human cell-lines and animal models have shown that VEGF siRNAs are effective in inhibiting VEGF production. Although there is a lack of sufficient published data on human studies supporting the use of bevasiranib for wet AMD, available data indicates that due to its unique mechanism of action, bevasiranib might hold some promise as a primary or adjunct treatment for wet AMD.

Forecasting age-related macular degeneration through the year 2050: the potential impact of new treatments.

Science.gov (United States)

Rein, David B; Wittenborn, John S; Zhang, Xinzhi; Honeycutt, Amanda A; Lesesne, Sarah B; Saaddine, Jinan

2009-04-01

To forecast age-related macular degeneration (AMD) and its consequences in the United States through the year 2050 with different treatment scenarios. We simulated cases of early AMD, choroidal neovascularization (CNV), geographic atrophy (GA), and AMD-attributable visual impairment and blindness with 5 universal treatment scenarios: (1) no treatment; (2) focal laser and photodynamic therapy (PDT) for CNV; (3) vitamin prophylaxis at early-AMD incidence with focal laser/PDT for CNV; (4) no vitamin prophylaxis followed by focal laser treatment for extra and juxtafoveal CNV and anti-vascular endothelial growth factor treatment; and (5) vitamin prophylaxis at early-AMD incidence followed by CNV treatment, as in scenario 4. Cases of early AMD increased from 9.1 million in 2010 to 17.8 million in 2050 across all scenarios. In non-vitamin-receiving scenarios, cases of CNV and GA increased from 1.7 million in 2010 to 3.8 million in 2050 (25% lower in vitamin-receiving scenarios). Cases of visual impairment and blindness increased from 620 000 in 2010 to 1.6 million in 2050 when given no treatment and were 2.4%, 22.0%, 16.9%, and 34.5% lower in scenarios 2, 3, 4, and 5, respectively. Prevalence of AMD will increase substantially by 2050, but the use of new therapies can mitigate its effects.

The potential of selected macroalgal species for treatment of AMD at different pH ranges in temperate regions.

Science.gov (United States)

Oberholster, Paul J; Cheng, Po-Hsun; Botha, Anna-Maria; Genthe, Bettina

2014-09-01

The metal bioaccumulation potential of selected macroalgae species at different pH ranges was study for usage as part of a possible secondary passive acid mine drainage (AMD) treatment technology in algae ponds. Two separate studies were conducted to determine the suitability of macroalgae for passive treatment when metabolic processes in macrophytes and microorganisms in constructed wetlands decrease during winter months. In the field study, the bioconcentration of metals (mg/kg dry weight) measured in the benthic macroalgae mats was in the following order: site 1. Oedogonium crassum Al > Fe > Mn > Zn; site 2. Klebsormidium klebsii, Al > Fe > Mn > Zn; site 3. Microspora tumidula, Fe > Al > Mn > Zn and site 4. M. tumidula, Fe > Mn > Al > Zn. In the laboratory study, cultured macroalgae K. klebsii, O. crassum and M. tumidula isolated from the field sampling sites were exposed to three different pH values (3, 5 and 7), while bioaccumulation of the metals, Al, Fe, Mn and Zn and glutathione S-transferase (GST) activity were measured in the different selected algae species at a constant water temperature of 14 °C. Bioaccumulation of Al was the highest for O. crassum followed by K. klebsii and M. tumidula (p macroalgae O. crassum at all three tested pH values under constant low water temperature. Copyright © 2014 Elsevier Ltd. All rights reserved.

PHMB: Utilización del apósito de espuma antimicrobiana (AMD KendallTM (PHMB 0,5% en el tratamiento de las heridas crónicas PHMB: The role ok KendallTM AMD Antimicrobial Foam Dressing (0.5% PHMB in the treatment of wounds

Directory of Open Access Journals (Sweden)

John Timmons

2010-03-01

Full Text Available Abordamos la parte más problemática del tratamiento de las heridas crónicas o agudas, de acuerdo con los profesionales especializados es la infección de la herida. La sobrecarga bacteriana puede retardar la curación de la herida y disminuir la calidad del paciente como consecuencia del aumento del dolor, del exudado y del posible mal olor. Se han recopilado casos clínicos durante los últimos 6 meses en una unidad especializada en el cuidado de heridas de los hospitales Doncaster y Bassetlaw, RU. Estos casos ilustran la variedad de tipos de herida que pueden tratarse con éxito con el nuevo apósito de Espuma antimicrobiano KendallTM AMD (PHMB 0,5%. Se pudo concluir que el apósito de Espuma KendallTM AMD actúa bien como antimicrobiano y como producto de vendaje moderno. Su utilización disminuye la carga bacteriana al tiempo que consigue la absorción del exudado y el mantenimiento de un ambiente óptimo para la curación de la herida.The most troublesome part of wound healing according to the care practitioners is the Wound infection. The presence of excess bacteria in the wound can lead to delayed healing that lead to a reduced quality of life for the patient due to increased pain, higher exudates levels and potential malodor. The following patient case report have been collated over the past six months in a specialist wound care clinic in Doncaster and Bassetlaw, UK. These cases illustrate the range of wound types that have been successfully treated with the new KendallTM AMD Antimicrobial Foam dressing (PHMB 0,5%. The conclusion was that KendallTM AMD Foam dressing functions well as an antimicrobial and a modern wound dressing product. This resulted in consistent lowering of the wound bioburden, absorption of exudates and maintenance of an optimal wound healing environment.

Ecological benefits of passive wetland treatment systems designed for acid mine drainage: With emphasis on watershed restoration

International Nuclear Information System (INIS)

McCleary, E.C.; Kepler, D.A.

1994-01-01

Western Pennsylvania has been a large source of coal for much of the US since the late 1800's. During the extraction of the coal resources, acid mine drainage (AMD) often resulted. AMD from abandoned discharges has effectively rendered thousands of kilometers of streams lifeless in the Appalachian coal region. Restoration of these streams has been limited in previous years primarily because of the lack of cost-effective treatment for AMD. Conventional treatment can treat AMD effectively but is costly to operate and maintain and is effective only when receiving human attention. Passive wetland treatment systems have proven to be the only realistic AMD treatment strategy, in terms of watershed restoration activities. If ecosystem health is the reason for implementing effluent standards then it can be reasonably argued that passive wetland treatment systems supply the most effective overall treatment, even if they do not meet one or more of the current effluent standards. Recent advancements in passive wetland treatment system technology have provided a management tool that could be used to treat the majority of AMD discharges cost-effectively, and when used strategically could reasonably be employed to restore the thousands of kilometers of AMD-affected streams in the coal regions of Appalachia. Secondary benefits that have been observed with passive wetland treatment systems suggest that these systems may be providing for accelerated ecological recovery independent of regulated effluent standards

Physiological and behavioral response of stonefly nymphs to enhanced limestone treatment of acid mine drainage

Energy Technology Data Exchange (ETDEWEB)

Cole, M.B.; Arnold, D.E.; Watten, B.J. [ABR Inc., PO Box 249, OR (USA). Environmental Research and Services

2001-07-01

A new acid mine drainage (AMD) treatment system uses pulsed, fluidized beds of limestone, and carbon dioxide pretreatment of influent AMD to enhance limestone neutralization of AMD. Laboratory studies were carried out to evaluate the behavior and physiology of larval stoneflies (Pteronarcys proteus, Plecoptera) exposed to effluents produced by the treatment system. Survival, sodium balance, drift, and feeding responses by P. proteus to treated and untreated AMD were examined. P. proteus nymphs exhibited significant losses of whole body sodium in exposures to untreated AMD. Nymphs exposed to treated effluents experienced no loss of whole-body sodium. No significant differences in feeding or drift behavior occurred between nymphs exposed to treated effluents and those exposed to AMD-free controls. The treatment system, with and without CO{sub 2} pretreatment, provided water that was not toxic to the test animals, and that allowed normal behavioral and physiological function.

Prevention and treatment of age-related macular degeneration: an update for pharmacists.

Science.gov (United States)

Marshall, Leisa L; Roach, J Michael

2013-11-01

Review the current recommendations for the prevention and treatment of age-related macular degeneration (AMD). Articles indexed in PubMed (National Library of Medicine), the Cochrane Reviews and Trials, Dynamed, and Iowa Drug Information Service (IDIS) in the last 10 years using the key words macular degeneration, agerelated macular degeneration (AMD), AMD and treatment, AMD and prevention. Sixty-nine published papers were reviewed, and criteria supporting the primary objective were used to identify useful resources. The literature included practice guidelines, original research articles, review articles, product prescribing information, and supplement product information for the prevention and treatment of AMD. AMD is a leading cause of visual impairment in older adults. At present there is no cure for advanced AMD, but intravitreal vascular endothelial growth factor inhibitors minimize and even reverse vision loss in patients with AMD of the neovascular type. In the Age-Related Eye Disease Study (AREDS), participants with intermediate AMD who received a supplement combination of vitamins C and E, beta-carotene, and zinc had a greater delay in progression to advanced AMD than those participants who received a portion of these supplements. In the second AREDS, AREDS2, the addition of lutein + zeaxanthin, docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), or lutein + zeaxanthin and DHA + EPA to the complete AREDS formulation did not further reduce the risk of progression to advanced AMD. Subgroup analyses indicated that additional research with lutein + zeaxanthin supplementation is warranted as it was beneficial in participants with low dietary intake of lutein + zeaxanthin. A formulation without beta-carotene may be best for most patients, especially smokers or former smokers. Health care professionals will want to consider patient-specific information before recommending ocular health supplements.

Why AMD is a disease of ageing and not of development: mechanisms and insights

Directory of Open Access Journals (Sweden)

Kaushal eSharma

2014-07-01

Full Text Available Age related macular degeneration (AMD is retinal degenerative disorder which starts with the progression of age. Metabolism plays important role in initiation of ageing related diseases. The cholesterol metabolism components and their oxidized products like 7-ketocholesterol have been shown impact on RPE cells degeneration. These molecules can initiate the mitochondrial apoptotic process and also influenced the complements factors and expression of angiogenic proteins like VEGF etc. In this review we have suggested that AMD is ageing disorder not developmental which has been substantiated with disrupted cholesterol metabolism as described in several age related degenerative diseases.

Overview of AMD (Automotive Metal Division)/USAMP projects

Energy Technology Data Exchange (ETDEWEB)

Demeri, M. [Ford Motor Co., Dearborn, MI (United States)

2001-07-01

This power point presentation described the mission of Ford's Automotive Metal Division (AMD) and presented a list of AMD projects. Their goal is to facilitate the development of improved materials and related manufacturing technologies for the automotive use of metals through cooperative, precompetitive programs, including those supporting PNGV. Some of the projects included: (1) magnesium casting for structural applications, (2) low cost powder metallurgy technology for particle reinforced aluminium, (3) sorting mixed alloys from shredded automobiles, (4) hydroforming aluminium tubes, (5) flexible binder controls for robust sampling, (6) long life electrodes for resistance spot welding of aluminium, sheet alloys, and coated high strength sheet steels, (7) NDE tools for evaluation of laser welded metals, (8) magnesium power train die cast components, (9) improved A206 alloy for cast automotive suspension components, (10) plasma arc welding of lightweight metals such as aluminium/magnesium, and (11) warm forming of aluminium alloys. The objectives, process controls and benefits of each of these projects were illustrated. Some of the issues that still need to be resolved include: an improved alloy with greater grain size and strength, an easily washable lubricant, a process to rapidly heat the blank and feed it into the heated dies, a method to achieve better thermal distribution in dies, and post forming mechanical properties. 5 figs.

A systematic review on zinc for the prevention and treatment of age-related macular degeneration.

Science.gov (United States)

Vishwanathan, Rohini; Chung, Mei; Johnson, Elizabeth J

2013-06-12

The objective of this systematic review was to examine the evidence on zinc intake from foods and supplements in the primary prevention and treatment of AMD. Randomized controlled trials (RCTs), prospective cohort, retrospective cohort, and case-control studies that investigated zinc intake from foods and/or supplements, and AMD in men and women with a mean age of 50 years or older were included. Medline and Cochrane Central were searched from inception to February 2012 and November 2012, respectively. Data extraction and quality appraisal were done on all eligible studies. TEN STUDIES WERE INCLUDED: four RCTs, four prospective cohort, and two retrospective cohort studies. Age-related Eye Disease Study (AREDS) showed zinc treatment to significantly reduce the risk of progression to advanced AMD. The risk of visual acuity loss was of similar magnitude, but not statistically significant. Two RCTs reported statistically significant increases in visual acuity in early AMD patients and one RCT showed no effect of zinc treatment on visual acuity in advanced AMD patients. Results from six cohort studies on associations between zinc intake and incidence of AMD were inconsistent. Current evidence on zinc intake for the prevention of AMD is inconclusive. Based on the strength of AREDS, we can conclude that zinc treatment may be effective in preventing progression to advanced AMD. Zinc supplementation alone may not be sufficient to produce clinically meaningful changes in visual acuity.

Optimizing Anti-VEGF Treatment Outcomes for Patients with Neovascular Age-Related Macular Degeneration.

Science.gov (United States)

Wykoff, Charles C; Clark, W Lloyd; Nielsen, Jared S; Brill, Joel V; Greene, Laurence S; Heggen, Cherilyn L

2018-02-01

The introduction of anti-vascular endothelial growth factor (anti-VEGF) drugs to ophthalmology has revolutionized the treatment of neovascular age-related macular degeneration (nAMD). Despite this significant progress, gaps and challenges persist in the diagnosis of nAMD, initiation of treatment, and management of frequent intravitreal injections. Thus, nAMD remains a leading cause of blindness in the United States. To present current knowledge, evidence, and expert perspectives on anti-VEGF therapies in nAMD to support managed care professionals and providers in decision making and collaborative strategies to overcome barriers to optimize anti-VEGF treatment outcomes among nAMD patients. Three anti-VEGF therapies currently form the mainstay of treatment for nAMD, including 2 therapies approved by the FDA for treatment of nAMD (aflibercept and ranibizumab) and 1 therapy approved by the FDA for oncology indications and used off-label for treatment of nAMD (bevacizumab). In clinical trials, each of the 3 agents maintained visual acuity (VA) in approximately 90% or more of nAMD patients over 2 years. However, in long-term and real-world settings, significant gaps and challenges in diagnosis, treatment, and management pose barriers to achieving optimal outcomes for patients with nAMD. Many considerations, including individual patient characteristics, on-label versus off-label treatment, repackaging, and financial considerations, add to the complexity of nAMD decision making and management. Many factors may contribute to additional challenges leading to suboptimal long-term outcomes among nAMD patients, such as delays in diagnosis and/or treatment approval and initiation, individual patient response to different anti-VEGF therapies, lapses in physician regimentation of anti-VEGF injection and monitoring, and inadequate patient adherence to treatment and monitoring. These latter factors highlight the considerable logistical, emotional, and financial burdens of long

A New System for Measuring Auto-Fluorescence Changes in Neovascular-AMD after Intravitreal Injection of Bavecizumab

OpenAIRE

Mohammad Norouzifard; Ali Soleymani; Jamshid Shanbehzadeh

2011-01-01

Age-Related Macular Degeneration (AMD) is the second disease diabetes which causes blindness in aged people. The only remedy for AMD is intravenous injection of bavecizumab. To prove the efficiency of remedy, the degenerated cells in Macula should be measured. In this article, a modern system is introduced to measure Auto-Fluorescence in Macula part of retina in order to obtain number of degenerated cells. The system consists of three main parts: Pre-processing stage is omission of margins an...

Microbiological monitoring of acid mine drainage treatment systems and aquatic surroundings using real-time PCR.

Science.gov (United States)

Han, J S; Kim, C G

2009-01-01

In general, acid mine drainage (AMD) causes low pH and high metal concentrations in mining areas and surroundings. The aim of this research was to achieve microbiological monitoring for AMD and to assess whether mine water outflows have any ecological effects on the aqueous ecosystem receiving effluents from different types of treatment system. The water quality of aquatic sample was analyzed and the molecular biological diversity of the samples was assessed using 16S rRNA methods, which were implemented to determine which bacteria existed throughout various unit processes for different AMD treatment systems and their receiving water environments. Acidiphilium cryptum, a heterotrophic acidophile, was found at the AMD sites, and Rhodoferax ferrireducens, which can reduce iron using insoluble Fe(III) as an electron acceptor, was detected at many AMD treatment facilities and downstream of the treatment processes. Subsequently, quantitative real-time PCR was conducted on specific genes of selected bacteria. Surprisingly, obvious trends were observed in the relative abundance of the various bacteria that corresponded to the water quality analytical results. The copy number of Desulfosporosinus orientus, a sulfate reducing bacteria, was also observed to decrease in response to decreases in metals according to the downstream flow of the AMD treatment system.

Role of antioxidant enzymes and small molecular weight antioxidants in the pathogenesis of age-related macular degeneration (AMD).

Science.gov (United States)

Tokarz, Paulina; Kaarniranta, Kai; Blasiak, Janusz

2013-10-01

Cells in aerobic condition are constantly exposed to reactive oxygen species (ROS), which may induce damage to biomolecules, including proteins, nucleic acids and lipids. In normal circumstances, the amount of ROS is counterbalanced by cellular antioxidant defence, with its main components-antioxidant enzymes, DNA repair and small molecular weight antioxidants. An imbalance between the production and neutralization of ROS by antioxidant defence is associated with oxidative stress, which plays an important role in the pathogenesis of many age-related and degenerative diseases, including age-related macular degeneration (AMD), affecting the macula-the central part of the retina. The retina is especially prone to oxidative stress due to high oxygen pressure and exposure to UV and blue light promoting ROS generation. Because oxidative stress has an established role in AMD pathogenesis, proper functioning of antioxidant defence may be crucial for the occurrence and progression of this disease. Antioxidant enzymes play a major role in ROS scavenging and changes of their expression or/and activity are reported to be associated with AMD. Therefore, the enzymes in the retina along with their genes may constitute a perspective target in AMD prevention and therapy.

Cost-effectiveness of anti-oxidant vitamins plus zinc treatment to prevent the progression of intermediate age-related macular degeneration. A Singapore perspective.

Science.gov (United States)

Saxena, Nakul; George, Pradeep Paul; Heng, Bee Hoon; Lim, Tock Han; Yong, Shao Onn

2015-06-01

To determine if providing high dose anti-oxidant vitamins and zinc treatment age-related eye disease study (AREDS formulation) to patients with intermediate age-related macular degeneration (AMD) aged 40-79 years from Singapore is cost-effective in preventing progression to wet AMD. A hypothetical cohort of category 3 and 4 AMD patients from Singapore was followed for 5 calendar years to determine the number of patients who would progress to wet AMD given the following treatment scenarios: (a) AREDS formulation or placebo followed by ranibizumab (as needed) for wet AMD. (b) AREDS formulation or placebo followed by bevacizumab (monthly) for wet AMD. (c) AREDS formulation or placebo followed by aflibercept (VIEW I and II trial treatment regimen). Costs were estimated for the above scenarios from the providers' perspective, and cost-effectiveness was measured by cost per disability-adjusted life year (DALY) averted with a disability weight of 0.22 for wet AMD. The costs were discounted at an annual rate of 3%. Over 5400 patients could be prevented from progressing to wet AMD cumulatively if AREDS formulation were prescribed. AREDS formulation followed by ranibizumab was cost-effective compared to placebo-ranibizumab or placebo-aflibercept combinations (cost per DALY averted: SGD$23,662.3 and SGD$21,138.8, respectively). However, bevacizumab (monthly injections) alone was more cost-effective compared to AREDS formulation followed by bevacizumab. Prophylactic treatment with AREDS formulation for intermediate AMD patients followed by ranibizumab or for patients who progressed to wet AMD was found to be cost-effective. These findings have implications for intermediate AMD screening, treatment and healthcare planning in Singapore.

Combination of Successive Alkalinity Producing System (SAPS) and Aeration for Passive Treatment of Highly Acidic Mine Drainage

Science.gov (United States)

Oh, C.; Ji, S.

2015-12-01

Passive treatment system has been widely used for remediation of mine drainage since its advantage of low installation and maintenance cost. The system, however, has also a disadvantage in assuring remediation and management efficiency if the drainage is highly acidic mine drainage. To remediate acid mine drainage (AMD) especially showing high acidity, passive treatment system which consists of successive alkalinity producing system (SAPS) and subsequent aeration pond was proposed and its mechanisms and efficiency was evaluated in this research. Target AMD was obtained from Waryong coal mine and showed typical characteristics of AMD having high metal concentration and low pH (acidity > 300 mg/L as CaCO3). Four experimental cases were conducted; untreated, treated with SAPS, treated with aeration, treated with SAPS and aeration to compare role and mechanism of each unit. Between organic matter and limestone layer which constitute SAPS, the former eliminated most of Fe(III) and Al in the AMD so that the latter was kept from being clogged by precipitates. Net acidity of the AMD rapidly decreased by supplement of alkalinity at the limestone layer. A primary function of SAPS, producing alkalinity constantly without clogging, was attained due to addition a portion of limestone particle into the organic matter layer. The discharge from SAPS had low ORP and DO values because of an anaerobic environment formed at the organic matter layer although its alkalinity was increased. This water quality was unfavorable for Fe(II) to be oxidized. Installation of aeration pond after SAPS, therefore, could be effective way of enhancing oxidation rate of Fe(II). Among the experimental cases, the combination of SAPS and aeration pond was only able to remediate the AMD. This concluded that to remediate highly acidic mine drainage with passive treatment system, three critical conditions were required; pre-precipitation of Fe(III) and Al at organic matter layer in SAPS, constant alkalinity

Bioelectrochemical treatment of acid mine drainage dominated with iron

International Nuclear Information System (INIS)

Lefebvre, Olivier; Neculita, Carmen M.; Yue, Xiaodi; Ng, How Yong

2012-01-01

Highlights: ► Treatment of AMD dominated with Fe is problematic due to its low pH. ► The goal of AMD treatment is pH increasing and Fe controlled removal. ► An MFC could fulfill both these requirements by treating AMD at the aerated cathode. ► The performance was proportional to the charge transfer up to 880 C. ► The treated AMD met the discharge limits both for Fe (>99% recovery) and pH (7.9). - Abstract: Treatment of acid mine drainage (AMD) dominated with iron (Fe), the most common metal, is a long-term expensive commitment, the goal of which is to increase the pH and remove Fe. In the present study, a proton exchange membrane microbial fuel cell (MFC) showed promise for the efficient treatment of an AMD dominated with ferric iron (pH 2.4 ± 0.1; 500 mg L −1 Fe 3+ ). Briefly, Fe 3+ was reduced to Fe 2+ at the cathode of the MFC, followed by Fe 2+ re-oxidation and precipitation as oxy(hydroxi)des. Oxygen reduction and cation transfer to the cathode of the MFC further caused a rise in pH. A linear relationship was observed between the charge transferred in the MFC and the performance of the system up to 880 C. Optimal conditions were found at a charge of 662 C, achieved within 7 d at an acetate concentration of 1.6 g L −1 in a membrane MFC. This caused the pH to rise to 7.9 and resulted in a Fe removal of 99%. Treated effluent met the pH discharge limits of 6.5–9. The maximum power generation achieved under these conditions averaged 8.6 ± 2.3 W m −3 , which could help reduce the costs of full-scale bioelectrochemical treatment of AMD dominated with Fe.

Microglia in the mouse retina alter the structure and function of retinal pigmented epithelial cells: a potential cellular interaction relevant to AMD.

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Wenxin Ma

2009-11-01

Full Text Available Age-related macular degeneration (AMD is a leading cause of legal blindness in the elderly in the industrialized word. While the immune system in the retina is likely to be important in AMD pathogenesis, the cell biology underlying the disease is incompletely understood. Clinical and basic science studies have implicated alterations in the retinal pigment epithelium (RPE layer as a locus of early change. Also, retinal microglia, the resident immune cells of the retina, have been observed to translocate from their normal position in the inner retina to accumulate in the subretinal space close to the RPE layer in AMD eyes and in animal models of AMD.In this study, we examined the effects of retinal microglia on RPE cells using 1 an in vitro model where activated retinal microglia are co-cultured with primary RPE cells, and 2 an in vivo mouse model where retinal microglia are transplanted into the subretinal space. We found that retinal microglia induced in RPE cells 1 changes in RPE structure and distribution, 2 increased expression and secretion of pro-inflammatory, chemotactic, and pro-angiogenic molecules, and 3 increased extent of in vivo choroidal neovascularization in the subretinal space.These findings share similarities with important pathological features found in AMD and suggest the relevance of microglia-RPE interactions in AMD pathogenesis. We speculate that the migration of retinal microglia into the subretinal space in early stages of the disease induces significant changes in RPE cells that perpetuate further microglial accumulation, increase inflammation in the outer retina, and fosters an environment conducive for the formation of neovascular changes responsible for much of vision loss in advanced AMD.

Validated automatic segmentation of AMD pathology including drusen and geographic atrophy in SD-OCT images.

Science.gov (United States)

Chiu, Stephanie J; Izatt, Joseph A; O'Connell, Rachelle V; Winter, Katrina P; Toth, Cynthia A; Farsiu, Sina

2012-01-05

To automatically segment retinal spectral domain optical coherence tomography (SD-OCT) images of eyes with age-related macular degeneration (AMD) and various levels of image quality to advance the study of retinal pigment epithelium (RPE)+drusen complex (RPEDC) volume changes indicative of AMD progression. A general segmentation framework based on graph theory and dynamic programming was used to segment three retinal boundaries in SD-OCT images of eyes with drusen and geographic atrophy (GA). A validation study for eyes with nonneovascular AMD was conducted, forming subgroups based on scan quality and presence of GA. To test for accuracy, the layer thickness results from two certified graders were compared against automatic segmentation results for 220 B-scans across 20 patients. For reproducibility, automatic layer volumes were compared that were generated from 0° versus 90° scans in five volumes with drusen. The mean differences in the measured thicknesses of the total retina and RPEDC layers were 4.2 ± 2.8 and 3.2 ± 2.6 μm for automatic versus manual segmentation. When the 0° and 90° datasets were compared, the mean differences in the calculated total retina and RPEDC volumes were 0.28% ± 0.28% and 1.60% ± 1.57%, respectively. The average segmentation time per image was 1.7 seconds automatically versus 3.5 minutes manually. The automatic algorithm accurately and reproducibly segmented three retinal boundaries in images containing drusen and GA. This automatic approach can reduce time and labor costs and yield objective measurements that potentially reveal quantitative RPE changes in longitudinal clinical AMD studies. (ClinicalTrials.gov number, NCT00734487.).

Kiibitootja AMD on võitmas turuosa suure rivaali Inteli käest / Lauri Matsulevitsh

Index Scriptorium Estoniae

Matsulevitsh, Lauri

2006-01-01

Arvutiprotsessorite tootja Advanced Micro Devices (AMD) näitas oma lõppenud kvartalis teenitud kasumiga, et hakkab konkurent Intelile järgi jõudma. Diagramm: Aktsia hind. Kommenteerib Peeter Teder

AMD3465, a monomacrocyclic CXCR4 antagonist and potent HIV entry inhibitor

DEFF Research Database (Denmark)

Hatse, Sigrid; Princen, Katrien; De Clercq, Erik

2005-01-01

The chemokine receptors CCR5 and CXCR4 function as coreceptors for human immunodeficiency virus (HIV) and are attractive targets for the development of anti-HIV drugs. The most potent CXCR4 antagonists described until today are the bicyclams. The prototype compound, AMD3100, exhibits potent and s...

Effect of the Gas6 c.834+7G>A polymorphism and the interaction of known risk factors on AMD pathogenesis in Hungarian patients.

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Gergely Losonczy

Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness in the elderly in the developed world. Numerous genetic factors contribute to the development of the multifactorial disease. We performed a case-control study to assess the risk conferred by known and candidate genetic polymorphisms on the development of AMD. We searched for genetic interactions and for differences in dry and wet AMD etiology. We enrolled 213 patients with exudative, 67 patients with dry AMD and 106 age and ethnically matched controls. Altogether 12 polymorphisms in Apolipoprotein E, complement factor H, complement factor I, complement component 3, blood coagulation factor XIII, HTRA1, LOC387715, Gas6 and MerTK genes were tested. No association was found between either the exudative or the dry form and the polymorphisms in the Apolipoprotein E, complement factor I, FXIII and MerTK genes. Gas6 c.834+7G>A polymorphism was found to be significantly protective irrespective of other genotypes, reducing the odds of wet type AMD by a half (OR = 0.50, 95%CI: 0.26-0.97, p = 0.04. Multiple regression models revealed an interesting genetic interaction in the dry AMD subgroup. In the absence of C3 risk allele, mutant genotypes of both CFH and HTRA1 behaved as strongly significant risk factors (OR = 7.96, 95%CI: 2.39 = 26.50, p = 0.0007, and OR = 36.02, 95%CI: 3.30-393.02, p = 0.0033, respectively, but reduced to neutrality otherwise. The risk allele of C3 was observed to carry a significant risk in the simultaneous absence of homozygous CFH and HTRA1 polymorphisms only, in which case it was associated with a near-five-fold relative increase in the odds of dry type AMD (OR = 4.93, 95%CI: 1.98-12.25, p = 0.0006. Our results suggest a protective role of Gas6 c.834+7G>A polymorphism in exudative AMD development. In addition, novel genetic interactions were revealed between CFH, HTRA1 and C3 polymorphisms that might contribute to the

Clinical Characteristics and Current Treatment of Age-Related Macular Degeneration

Science.gov (United States)

Yonekawa, Yoshihiro; Kim, Ivana K.

2015-01-01

Age-related macular degeneration (AMD) is a multifactorial degeneration of photoreceptors and retinal pigment epithelium. The societal impact is significant, with more than 2 million individuals in the United States alone affected by advanced stages of AMD. Recent progress in our understanding of this complex disease and parallel developments in therapeutics and imaging have translated into new management paradigms in recent years. However, there are many unanswered questions, and diagnostic and prognostic precision and treatment outcomes can still be improved. In this article, we discuss the clinical features of AMD, provide correlations with modern imaging and histopathology, and present an overview of treatment strategies. PMID:25280900

[AMD Annals: a model of continuous monitoring and improvement of the quality of diabetes care].

Science.gov (United States)

2011-01-01

in recent years, several initiatives have been launched by the Associazione medici diabetologi (AMD) in the context of a national quality improvement program.These activities include: identification of specific indicators of quality of diabetes care, development of a software to calculate such indicators by using routine clinical data, creation of a network of diabetes clinics and analysis and publication of the results in ad hoc reports (AMD Annals). Through the best performer approach, each centre could compare its own performance not only with the theoretical targets suggested by existing guidelines, but also with the results achieved by the best centres operating within the same healthcare system.We evaluated whether the involvement of diabetes clinics into the AMD Annals initiative improved the quality of care over 4 years. a controlled before and after study was performed to compare data collected from 2004 to 2007 by two groups of centres: group A included centres that had been involved in the project since the first edition of AMD Annals; group B included centres only involved in the last edition. overall, 124 diabetes clinics provided data on over 100,000 type 2 diabetes patients/year seen from 2004 to 2007. process indicators included the proportion of patients with at least one measurement of HbA1c, blood pressure and lipid profile during the previous 12 months. Intermediate outcomes included percentages of patients with levels of HbA1c ≤ 7%, blood pressure ≤ 130/85 mmHg and LDL-cholesterol improvements in the proportion of patients with LDL-cholesterol at target were documented in both groups (group A: +10.5%; group B: +12.2%.) The proportion of patients treated with insulin increased in group A only (+5.8%), while the use of statins grew by 20%in both groups.The proportion of individuals treated with two or more antihypertensive drugs increased by 3.6% in group A and by 1.6% in group B. the AMD Annals approach can be considered as a case model for

Secondary iron minerals present in AMD sediments from Smolník abandoned mine

Czech Academy of Sciences Publication Activity Database

Dakos, Z.; Kupka, D.; Kovařík, M.; Jablonovská, K.; Krištůfek, Václav; Achimovičová, M.

2012-01-01

Roč. 11, č. 2 (2012), s. 87-92 ISSN 1338-6905 Grant - others:Vedecká grantová agentúra(SK) VEGA 2/0166/11 Institutional support: RVO:60077344 Keywords : Acid ithiobacillus * acid mine drainage (AMD) * ochreous precipitates * schwertmannite Subject RIV: DB - Geology ; Mineralogy

CX3CL1/CX3CR1 and CCL2/CCR2 Chemokine/Chemokine Receptor Complex in Patients with AMD

DEFF Research Database (Denmark)

Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten

2014-01-01

PURPOSE: The chemokine receptors CX3CR1 and CCR2 have been implicated in the development of age-related macular degeneration (AMD). The evidence is mainly derived from experimental cell studies and murine models of AMD. The purpose of this study was to investigate the association between expression...... of CX3CR1 and CCR2 on different leukocyte subsets and AMD. Furthermore we measured the plasma levels of ligands CX3CL1 and CCL2. METHODS: Patients attending our department were asked to participate in the study. The diagnosis of AMD was based on clinical examination and multimodal imaging techniques...... positive correlation between CCR2 and CX3CR1 expression on CD8+ cells (r = 0.727, p = 0.0001). We found no difference in plasma levels of CX3CL1 and CCL2 among the groups. CONCLUSIONS: Our results show a down regulation of CX3CR1 on CD8+ cells; this correlated to a low expression of CCR2 on CD8+ cells...

Broad spectrum antiangiogenic treatment for ocular neovascular diseases.

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Ofra Benny

2010-09-01

Full Text Available Pathological neovascularization is a hallmark of late stage neovascular (wet age-related macular degeneration (AMD and the leading cause of blindness in people over the age of 50 in the western world. The treatments focus on suppression of choroidal neovascularization (CNV, while current approved therapies are limited to inhibiting vascular endothelial growth factor (VEGF exclusively. However, this treatment does not address the underlying cause of AMD, and the loss of VEGF's neuroprotective can be a potential side effect. Therapy which targets the key processes in AMD, the pathological neovascularization, vessel leakage and inflammation could bring a major shift in the approach to disease treatment and prevention. In this study we have demonstrated the efficacy of such broad spectrum antiangiogenic therapy on mouse model of AMD.Lodamin, a polymeric formulation of TNP-470, is a potent broad-spectrum antiangiogenic drug. Lodamin significantly reduced key processes involved in AMD progression as demonstrated in mice and rats. Its suppressive effects on angiogenesis, vascular leakage and inflammation were studied in a wide array of assays including; a Matrigel, delayed-type hypersensitivity (DTH, Miles assay, laser-induced CNV and corneal micropocket assay. Lodamin significantly suppressed the secretion of various pro-inflammatory cytokines in the CNV lesion including monocyte chemotactic protein-1 (MCP-1/Ccl2. Importantly, Lodamin was found to regress established CNV lesions, unlike soluble fms-like tyrosine kinase-1 (sFlk-1. The drug was found to be safe in mice and have little toxicity as demonstrated by electroretinography (ERG assessing retinal and by histology.Lodamin, a polymer formulation of TNP-470, was identified as a first in its class, broad-spectrum antiangiogenic drug that can be administered orally or locally to treat corneal and retinal neovascularization. Several unique properties make Lodamin especially beneficial for ophthalmic

Biological attenuation of arsenic and iron in a continuous flow bioreactor treating acid mine drainage (AMD).

Science.gov (United States)

Fernandez-Rojo, L; Héry, M; Le Pape, P; Braungardt, C; Desoeuvre, A; Torres, E; Tardy, V; Resongles, E; Laroche, E; Delpoux, S; Joulian, C; Battaglia-Brunet, F; Boisson, J; Grapin, G; Morin, G; Casiot, C

2017-10-15

Passive water treatments based on biological attenuation can be effective for arsenic-rich acid mine drainage (AMD). However, the key factors driving the biological processes involved in this attenuation are not well-known. Here, the efficiency of arsenic (As) removal was investigated in a bench-scale continuous flow channel bioreactor treating As-rich AMD (∼30-40 mg L -1 ). In this bioreactor, As removal proceeds via the formation of biogenic precipitates consisting of iron- and arsenic-rich mineral phases encrusting a microbial biofilm. Ferrous iron (Fe(II)) oxidation and iron (Fe) and arsenic removal rates were monitored at two different water heights (4 and 25 mm) and with/without forced aeration. A maximum of 80% As removal was achieved within 500 min at the lowest water height. This operating condition promoted intense Fe(II) microbial oxidation and subsequent precipitation of As-bearing schwertmannite and amorphous ferric arsenate. Higher water height slowed down Fe(II) oxidation, Fe precipitation and As removal, in relation with limited oxygen transfer through the water column. The lower oxygen transfer at higher water height could be partly counteracted by aeration. The presence of an iridescent floating film that developed at the water surface was found to limit oxygen transfer to the water column and delayed Fe(II) oxidation, but did not affect As removal. The bacterial community structure in the biogenic precipitates in the bottom of the bioreactor differed from that of the inlet water and was influenced to some extent by water height and aeration. Although potential for microbial mediated As oxidation was revealed by the detection of aioA genes, removal of Fe and As was mainly attributable to microbial Fe oxidation activity. Increasing the proportion of dissolved As(V) in the inlet water improved As removal and favoured the formation of amorphous ferric arsenate over As-sorbed schwertmannite. This study proved the ability of this bioreactor

Genetic variant of AMD1 is associated with obesity in urban Indian children.

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Rubina Tabassum

Full Text Available Hyperhomocysteinemia is regarded as a risk factor for cardiovascular diseases, diabetes and obesity. Manifestation of these chronic metabolic disorders starts in early life marked by increase in body mass index (BMI. We hypothesized that perturbations in homocysteine metabolism in early life could be a link between childhood obesity and adult metabolic disorders. Thus here we investigated association of common variants from homocysteine metabolism pathway genes with obesity in 3,168 urban Indian children.We genotyped 90 common variants from 18 genes in 1,325 children comprising of 862 normal-weight (NW and 463 over-weight/obese (OW/OB children in stage 1. The top signal obtained was replicated in an independent sample set of 1843 children (1,399 NW and 444 OW/OB in stage 2. Stage 1 association analysis revealed association between seven variants and childhood obesity at P<0.05, but association of only rs2796749 in AMD1 [OR = 1.41, P = 1.5×10(-4] remained significant after multiple testing correction. Association of rs2796749 with childhood obesity was validated in stage 2 [OR = 1.28, P = 4.2×10(-3] and meta-analysis [OR = 1.35, P = 1.9×10(-6]. AMD1 variant rs2796749 was also associated with quantitative measures of adiposity and plasma leptin levels that was also replicated and corroborated in combined analysis.Our study provides first evidence for the association of AMD1 variant with obesity and plasma leptin levels in children. Further studies to confirm this association, its functional significance and mechanism of action need to be undertaken.

Analysis on concentration of VEGF in aqueous humor in patients with wAMD after Ranibizumab treating at high altitude

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Rui-Juan Guan

2017-05-01

Full Text Available AIM: To study the concentration of vascular endothelial growth factor(VEGFin aqueous humor in patients with wet age-related macular degeneration(wAMDbefore and after Ranibizumab treating at high altitude and the correlation of VEGF concentration with central fovea macula thickness. METHODS: The patients with wAMD in our hospital from Jun. 2014. to Oct. 2015 were retrospectively analyzed, diagnosed after best corrected visual acuity, intraocular pressure, fundus examination, fundus color photography, fluorescence fundus angiography(FFAand optical coherence tomography(OCTinspection. Seventy- six patients with cataract without choroidal neovascularization(CNVwere selected as control group. In the 76 patients(76 eyes, 46 were male, 30 were female, aged 40-80(55±11.18. The course was 0.3-6mo. The corrected visual acuity was 0.01-0.6. The intraocular press was 15.24±3.12mmHg. The CNV in all cases was within the range of the 500μm in diameter. Under surface anesthesia, Ranibizumab(0.5mgwas injected into vitreous cavity. Before and after injection, aqueous humor was obtained and used to detect the concentration of VEGF through ELISA. Best corrected visual acuity, slit lamp microscope, intraocular pressure, OCT and FFA were observed after treatment. RESULTS:The clinical curative effect is the best at 1mo after treatment with statistical significance(PPPCONCLUSION: For wAMD patients, Ranibizumab injection is effective for it reduces the concentration of VEGF in aqueous humor and the central fovea macula thickness. The VEGF concentration in aqueous humor and foveal retinal thickness has a positive correlation.

Association of OCT-Derived Drusen Measurements with AMD-Associated Genotypic SNPs in the Amish Population

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Venkata Ramana Murthy Chavali

2015-02-01

Full Text Available Purpose: To investigate the association of optical coherence tomography (OCT-derived drusen measures in Amish age-related macular degeneration (AMD patients with known loci for macular degeneration. Methods: Members of the Old Order Amish community in Pennsylvania ages 50 and older were assessed for drusen area, volume and regions of retinal pigment epithelium (RPE atrophy using a Cirrus High-Definition OCT. Measurements were obtained in the macula region within a central circle (CC of 3 mm in diameter and a surrounding perifoveal ring (PR of 3 to 5 mm in diameter using the Cirrus OCT RPE analysis software. Other demographic information, including age, gender and smoking status, were collected. Study subjects were further genotyped to determine their risk for the AMD-associated SNPs in the SYN3, LIPC, ARMS2, C3, CFB, CETP, CFI and CFH genes using TaqMan genotyping assays. The association of genotypes with OCT measures were assessed using linear trend p-values calculated from univariate and multivariate generalized linear models. Results: 432 eyes were included in the analysis. Multivariate analysis (adjusted by age, gender and smoking status confirmed the known significant association between AMD and macular drusen with the number of CFH risk alleles for the drusen area (the area increased 0.12 mm2 for a risk allele increase, p < 0.01, drusen volume (the volume increased 0.01 mm3 for a risk allele increase, p ≤ 0.05 and the area of RPE atrophy (the area increased 0.43 mm2 for a risk allele increase, p = 0.003. SYN3 risk allele G is significantly associated with larger area PR (the area increased 0.09 mm2 for a risk allele increase, p = 0.03 and larger drusen volume in the central circle (the volume increased 0.01 mm3 for a risk allele increase, p = 0.04. Conclusion: Among the genotyped SNPs tested, the CFH risk genotype appears to play a major role in determining the drusen phenotype in the Amish AMD population.

[Economic Short-Term Cost Model for Stereotactic Radiotherapy of Neovascular AMD].

Science.gov (United States)

Neubauer, A S; Reznicek, L; Minartz, C; Ziemssen, F

2016-08-01

Stereotactic radiation therapy (Oraya, OT) is available as a second line therapy for patients who, despite intensive anti-VEGF therapy for neovascular AMD, do not show an improvement in CNV. As OT is expensive (5,308 €), the short term economics for starting this therapy were investigated. A short-term cost model was set up in MS Excel with a two year time horizon. On the basis of the data of the randomised, controlled INTREPID pivotal trial and current treatment practice in Germany, the costs were compared of conventional anti-VEGF therapy, with or without a single OT treatment. Patients with an active lesion after initial anti-VEGF therapy and a maximum lesion diameter ≤ 4 mm were included. Modeled cost components/aspects were direct savings from injection number, control follow-up examinations and aids, as well as anti-VEGF switches. Costs for Germany were employed and a univariate sensitivity analysis was performed to address the existing uncertainty. For the patients with a maximum AMD lesion diameter ≤ 4 mm and a macula volume > 7.4 mm(3), the INTREPID trial showed a mean reduction of 3.68 intravitreal injections for 16 Gy radiation versus sham over a time period of 2 years. These 3.68 IVM result in ~ 4,500 € direct cost savings. Moreover, due to the higher response rate with 16 Gy radiation, the number of follow-up visits and aids can be reduced, which results in savings between 207 € and 1,224 € over 2 years. After radiation, fewer anti-VEGF switches for low or non-responders are expected, which is modeled to result in ~ 1.7 fewer injections over 2 years. Due to overall fewer injections, fewer endophthalmitis cases would be expected. However, endophthalmitis and microvascular abnormalities, which can be observed in a few cases, are associated with low or non-quantifiable costs in this cost-cost comparison model. In summary, cost reductions of between 6,400 and 8,500 € are predicted in the model over two years

Deformation and clustering in even-Z nuclei up to Mg studied using AMD with the Gogny force

Energy Technology Data Exchange (ETDEWEB)

Kimura, Masaaki; Sugawa, Yoshio; Horiuchi, Hisashi [Kyoto Univ. (Japan). Dept. of Physics

2001-12-01

Employing the Gogny force as an effective force, we study the ground state properties of light nuclei using antisymmetrized molecular dynamics (AMD). In a previous paper, we discussed the nuclear binding energies and nuclear radii of He, Be, C, O, Ne and Mg isotopes. In this paper, we mainly consider the deformation properties and the clustering nature of these isotopes. By comparing the calculated results with the AMD results by use of the Skyrme-III (SIII) force, we investigated the differences and similarities between the SIII force and the Gogny force. We find that the Gogny force yields rather better binding energy and larger deformation than the SIII force. We carry out the parity-projected calculations. Parity projection enhances the parity-violating deformation and the cluster structure of certain nuclei. Shape of the deformation energy surface is also changed by parity projection. This causes a competition between the mean-field-like structure and the cluster-like structure. A modified version of AMD, which employs deformed Gaussian wave packets instead of spherical ones, is shown to give large quadrupole moments in the case of Mg isotopes. (author)

Deformation and clustering in even-Z nuclei up to Mg studied using AMD with the Gogny force

International Nuclear Information System (INIS)

Kimura, Masaaki; Sugawa, Yoshio; Horiuchi, Hisashi

2001-01-01

Employing the Gogny force as an effective force, we study the ground state properties of light nuclei using antisymmetrized molecular dynamics (AMD). In a previous paper, we discussed the nuclear binding energies and nuclear radii of He, Be, C, O, Ne and Mg isotopes. In this paper, we mainly consider the deformation properties and the clustering nature of these isotopes. By comparing the calculated results with the AMD results by use of the Skyrme-III (SIII) force, we investigated the differences and similarities between the SIII force and the Gogny force. We find that the Gogny force yields rather better binding energy and larger deformation than the SIII force. We carry out the parity-projected calculations. Parity projection enhances the parity-violating deformation and the cluster structure of certain nuclei. Shape of the deformation energy surface is also changed by parity projection. This causes a competition between the mean-field-like structure and the cluster-like structure. A modified version of AMD, which employs deformed Gaussian wave packets instead of spherical ones, is shown to give large quadrupole moments in the case of Mg isotopes. (author)

Age-related macular degeneration: epidemiology and optimal treatment

DEFF Research Database (Denmark)

la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

2002-01-01

Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

RECURRENCE OF CHOROIDAL NEOVASCULARIZATION LESION ACTIVITY AFTER AFLIBERCEPT TREATMENT FOR AGE-RELATED MACULAR DEGENERATION.

Science.gov (United States)

Wakazono, Tomotaka; Yamashiro, Kenji; Oishi, Akio; Ooto, Sotaro; Tamura, Hiroshi; Akagi-Kurashige, Yumiko; Hata, Masayuki; Takahashi, Ayako; Tsujikawa, Akitaka; Yoshimura, Nagahisa

2017-11-01

To examine the recurrence rate of choroidal neovascularization (CNV) lesion activity in age-related macular degeneration (AMD) and associated factors after 1-year aflibercept treatment. Age-related macular degeneration eyes with 1-year aflibercept fixed-regimen treatment and a follow-up period of at least 18 months from the initial aflibercept injection for treatment-naive exudative AMD were retrospectively evaluated. The recurrence rate was examined. Age, gender, visual acuity, AMD subtype, greatest linear dimension, and retinal and choroidal thicknesses at the 12th month examination were compared between eyes with and without recurrence. Presence of remnant polyps and pigment epithelial detachment (PED) morphology were also compared in polypoidal choroidal vasculopathy (PCV) eyes. Of the 98 eyes studied, 69 displayed a dry macula at the 12th month examination; 43.7% exhibited recurrence during the subsequent 12-month period in Kaplan-Meier analysis. Although no factors associated with recurrence were detected in AMD, remnant polyps and pigment epithelial detachment morphology at the 12th month examination were significantly associated with recurrence in polypoidal choroidal vasculopathy (P = 0.018 and 0.048, respectively). Continuous, proactive treatment would be considered overtreatment for more than half of the AMD eyes that achieved a dry macula. Angiography and optical coherence tomography analyses may be useful for predicting recurrence in polypoidal choroidal vasculopathy eyes.

A combined CaO/electrochemical treatment of the acid mine drainage from the "Robule" Lake.

Science.gov (United States)

Orescanin, Visnja; Kollar, Robert

2012-01-01

The purpose of this work was development and application of the purification system suitable for the treatment of the acid mine drainage (AMD) accumulated in the "Robule" Lake, which represents the part of the Bor copper mining and smelting complex, Serbia. The study was undertaken in order to minimize adverse effect on the environment caused by the discharge of untreated AMD, which was characterized with low pH value (2.63) and high concentration of heavy metals (up to 610 mg/L) and sulfates (up to 12,000 mg/L). The treatment of the effluent included pretreatment/pH adjustment with CaO followed by electrocoagulation using iron and aluminum electrode sets. Following the final treatment, the decrease in the concentration of heavy metals ranged from 40 up to 61000 times depending on the metal and its initial concentration. The parameters, color and turbidity were removed completely in the pretreatment step, while the removal efficiencies for other considered parameters were as follows: EC = 55.48%, SO(4) (2-) = 70.83%, Hg = 98.36%, Pb = 97.50%, V = 98.43%, Cr = 99.86%, Mn = 97.96%, Fe = 100.00%, Co = 99.96%, Ni = 99.78%, Cu = 99.99% and Zn = 99.94%. Because the concentrations of heavy metals in the electrochemically treated AMD (ranging from 0.001 to 0.336 mg/L) are very low, the negative impact of this effluent on the aquatic life and humans is not expected. The sludge generated during the treatment of AMD is suitable for reuse for at least two purposes (pretreatment of AMD and covering of the flotation waste heap). From the presented results, it could be concluded that electrochemical treatment is a suitable approach for the treatment of AMD.

Immunological Factors in the Pathogenesis and Treatment of Age-Related Macular Degeneration

NARCIS (Netherlands)

Kijlstra, A.; Heij, La E.C.; Hendrikse, F.

2005-01-01

Recent findings indicate that immunological factors are involved not only in the pathogenesis of age-related macular degeneration (AMD), but also in its treatment. Earlier data showing the presence of inflammatory cells in affected areas of AMD retinas support this statement. Although a possible

BIOREMEDIATION FOR ACID MINE DRAINAGE: ORGANIC SOLID WASTE AS CARBON SOURCES FOR SULFATE-REDUCING BACTERIA: A REVIEW

Directory of Open Access Journals (Sweden)

I. N. Jamil

2013-12-01

Full Text Available Biological sulfate reduction has been slowly replacing chemical unit processes to treat acid mine drainage (AMD. Bioremediations for AMD treatment are favored due to their low capital and maintenance cost. This paper describes the available AMD treatment, current SRB commercialization such as THIOPAQ® and BioSulphide® technologies, and also the factors and limitations faced. THIOPAQ® and BioSulphide® technologies use expensive carbon sources such as hydrogen as the electron donor. This paper discusses the possibility of organic solid waste as an alternative substrate as it is cheaper and abundant. A possible AMD treatment system setup was also proposed to test the efficiency of sulfate-reducing bacteria utilizing organic solid substrate.

Efficacy assessment of acid mine drainage treatment with coal mining waste using Allium cepa L. as a bioindicator.

Science.gov (United States)

Geremias, Reginaldo; Bortolotto, Tiago; Wilhelm-Filho, Danilo; Pedrosa, Rozangela Curi; de Fávere, Valfredo Tadeu

2012-05-01

The aim of this study was to evaluate the efficacy of the treatment of acid mine drainage (AMD) with calcinated coal mining waste using Allium cepa L. as a bioindicator. The pH values and the concentrations of aluminum, iron, manganese, zinc, copper, lead and sulfate were determined before and after the treatment of the AMD with calcinated coal mining waste. Allium cepa L. was exposed to untreated and treated AMD, as well as to mineral water as a negative control (NC). At the end of the exposure period, the inhibition of root growth was measured and the mean effective concentration (EC(50)) was determined. Oxidative stress biomarkers such as lipid peroxidation (TBARS), protein carbonyls (PC), catalase activity (CAT) and reduced glutathione levels (GSH) in the fleshy leaves of the bulb, as well as the DNA damage index (ID) in meristematic cells, were evaluated. The results indicated that the AMD treatment with calcinated coal mining waste resulted in an increase in the pH and an expressive removal of aluminum, iron, manganese and zinc. A high sub-chronic toxicity was observed when Allium cepa L. was exposed to the untreated AMD. However, after the treatment no toxicity was detected. Levels of TBARS and PC, CAT activity and the DNA damage index were significantly increased (P<0.05) in Allium cepa L. exposed to untreated AMD when compared to treated AMD and also to negative controls. No significant alteration in the GSH content was observed. In conclusion, the use of calcinated coal mining waste associated with toxicological tests on Allium cepa L. represents an alternative system for the treatment and biomonitoring of these types of environmental contaminants. Copyright © 2011 Elsevier Inc. All rights reserved.

A Reduced-Order Controller Considering High-Order Modal Information of High-Rise Buildings for AMD Control System with Time-Delay

Directory of Open Access Journals (Sweden)

Zuo-Hua Li

2017-01-01

Full Text Available Time-delays of control force calculation, data acquisition, and actuator response will degrade the performance of Active Mass Damper (AMD control systems. To reduce the influence, model reduction method is used to deal with the original controlled structure. However, during the procedure, the related hierarchy information of small eigenvalues will be directly discorded. As a result, the reduced-order model ignores the information of high-order mode, which will reduce the design accuracy of an AMD control system. In this paper, a new reduced-order controller based on the improved Balanced Truncation (BT method is designed to reduce the calculation time and to retain the abandoned high-order modal information. It includes high-order natural frequency, damping ratio, and vibration modal information of the original structure. Then, a control gain design method based on Guaranteed Cost Control (GCC algorithm is presented to eliminate the adverse effects of data acquisition and actuator response time-delays in the design process of the reduced-order controller. To verify its effectiveness, the proposed methodology is applied to a numerical example of a ten-storey frame and an experiment of a single-span four-storey steel frame. Both numerical and experimental results demonstrate that the reduced-order controller with GCC algorithm has an excellent control effect; meanwhile it can compensate time-delays effectively.

N-[C-11]Methyl-AMD3465 PET as a Tool for In Vivo Measurement of Chemokine Receptor 4 (CXCR4) Occupancy by Therapeutic Drugs

NARCIS (Netherlands)

Hartimath, Siddanna; Doorduin, Janine; Dierckx, Rudi; van Waarde, Aren; de Vries, Erik

Chemokine receptor 4 (CXCR4) is overexpressed in many cancers and a potential drug target. We have recently developed the tracer N-[C-11]methyl-AMD3465 for imaging of CXCR4 expression by positron emission tomography (PET). We investigated the pharmacokinetics of N-[C-11]methyl-AMD3465 in rats

Drilling techniques for mineral exploration (AMD Training Course Handbook. Vol. 1. 1992)

International Nuclear Information System (INIS)

Singh, Rajendra

1992-01-01

A training course on drilling techniques for mineral exploration was organised between 20 January to 7 February 1992 exclusively for drilling engineers of Atomic Minerals Division (AMD) of the Department of Atomic Energy. The objective was to give the engineers training in theoretical as well as practical aspects of drilling and resource management. The lectures delivered by the faculty members are included in this book. (M.G.B.)

Development and Validation of an Acid Mine Drainage Treatment Process for Source Water

Energy Technology Data Exchange (ETDEWEB)

Lane, Ann [Battelle Memorial Institute, Columbus, OH (United States)

2016-03-01

Throughout Northern Appalachia and surrounding regions, hundreds of abandoned mine sites exist which frequently are the source of Acid Mine Drainage (AMD). AMD typically contains metal ions in solution with sulfate ions which have been leached from the mine. These large volumes of water, if treated to a minimum standard, may be of use in Hydraulic Fracturing (HF) or other industrial processes. This project’s focus is to evaluate an AMD water treatment technology for the purpose of providing treated AMD as an alternative source of water for HF operations. The HydroFlex™ technology allows the conversion of a previous environmental liability into an asset while reducing stress on potable water sources. The technology achieves greater than 95% water recovery, while removing sulfate to concentrations below 100 mg/L and common metals (e.g., iron and aluminum) below 1 mg/L. The project is intended to demonstrate the capability of the process to provide AMD as alternative source water for HF operations. The second budget period of the project has been completed during which Battelle conducted two individual test campaigns in the field. The first test campaign demonstrated the ability of the HydroFlex system to remove sulfate to levels below 100 mg/L, meeting the requirements indicated by industry stakeholders for use of the treated AMD as source water. The second test campaign consisted of a series of focused confirmatory tests aimed at gathering additional data to refine the economic projections for the process. Throughout the project, regular communications were held with a group of project stakeholders to ensure alignment of the project objectives with industry requirements. Finally, the process byproduct generated by the HydroFlex process was evaluated for the treatment of produced water against commercial treatment chemicals. It was found that the process byproduct achieved similar results for produced water treatment as the chemicals currently in use. Further

Multimodal scanning laser ophthalmoscopy for image guided treatment of age-related macular degeneration

Science.gov (United States)

Hammer, Daniel X.; Ferguson, R. D.; Patel, Ankit H.; Iftimia, Nicusor V.; Mujat, Mircea; Husain, Deeba

2009-02-01

Subretinal neovascular membranes (SRNM) are a deleterious complication of laser eye injury and retinal diseases such as age-related macular degeneration (AMD), choroiditis, and myopic retinopathy. Photodynamic therapy (PDT) and anti-vascular endothelial growth factor (VEGF) drugs are approved treatment methods. PDT acts by selective dye accumulation, activation by laser light, and disruption and clotting of the new leaky vessels. However, PDT surgery is currently not image-guided, nor does it proceed in an efficient or automated manner. This may contribute to the high rate of re-treatment. We have developed a multimodal scanning laser ophthalmoscope (SLO) for automated diagnosis and image-guided treatment of SRNMs associated with AMD. The system combines line scanning laser ophthalmoscopy (LSLO), fluorescein angiography (FA), indocyanine green angiography (ICGA), PDT laser delivery, and retinal tracking in a compact, efficient platform. This paper describes the system hardware and software design, performance characterization, and automated patient imaging and treatment session procedures and algorithms. Also, we present initial imaging and tracking measurements on normal subjects and automated lesion demarcation and sizing analysis of previously acquired angiograms. Future pre-clinical testing includes line scanning angiography and PDT treatment of AMD subjects. The automated acquisition procedure, enhanced and expedited data post-processing, and innovative image visualization and interpretation tools provided by the multimodal retinal imager may eventually aid in the diagnosis, treatment, and prognosis of AMD and other retinal diseases.

Current Treatment Limitations in Age-Related Macular Degeneration and Future Approaches Based on Cell Therapy and Tissue Engineering

Science.gov (United States)

Fernández-Robredo, P.; Sancho, A.; Johnen, S.; Recalde, S.; Gama, N.; Thumann, G.; Groll, J.; García-Layana, A.

2014-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein. PMID:24672707

Acid Mine Drainage Treatment

National Research Council Canada - National Science Library

Fripp, Jon

2000-01-01

.... Acid mine drainage (AMD) can have severe impacts to aquatic resources, can stunt terrestrial plant growth and harm wetlands, contaminate groundwater, raise water treatment costs, and damage concrete and metal structures...

The emotional and physical impact of wet age-related macular degeneration: findings from the wAMD Patient and Caregiver Survey

Directory of Open Access Journals (Sweden)

Varano M

2016-02-01

Full Text Available Monica Varano,1 Nicole Eter,2 Steve Winyard,3 Kim U Wittrup-Jensen,4 Rafael Navarro,5 Julie Heraghty6 On behalf of the wAMD Patient and Caregiver Survey Committee members 1Department of Ophthalmology, Fondazione GB Bietti-IRCCS, Rome, Italy; 2Department of Ophthalmology, University of Münster, Münster, Germany; 3Department of Policy and Campaigns, Royal National Institute of Blind People, London, UK; 4Bayer Pharma AG, Berlin, Germany; 5Instituto de Microcirugia Ocular, Barcelona, Spain; 6Macular Disease Foundation Australia, Sydney, NSW, Australia Objectives: This was a cross-sectional survey to evaluate the physical and emotional impact of wet age-related macular degeneration (wAMD on a global cohort of patients who were receiving (or had previously received antivascular endothelial growth factor injections, and caregivers (paid and unpaid.Methods: The survey was performed in nine countries using an ophthalmologist-devised questionnaire.Results: A total of 910 patients and 890 caregivers completed the questionnaire. Most patients had been diagnosed and receiving antivascular endothelial growth factor injections for more than 1 year (74.7% and 63.8%, respectively, and many patients (82.1% received support from a caregiver (usually a child/grandchild [47.3%] or partner [23.3%]. wAMD had a negative impact on most patients (71.6%; many rated fear (44.9%, sadness (39.9%, frustration (37.3%, and depression (34.0% as common. It was linked to physical consequences, such as difficulty in reading (61.1%. Many effects were significantly greater in patients with a longer duration of disease or with wAMD in both eyes. Some caregivers (unpaid also reported that caregiving had a negative impact on them (31.1%; many reported emotions such as sadness (34.9% and depression (24.4%, but many also felt useful (48.4%. Overall, 27.2% of caregivers (unpaid rated caregiving as inconvenient; this was linked to days of employment/personal obligations missed

A preliminary study to design a floating treatment wetland for remediating acid mine drainage-impacted water using vetiver grass (Chrysopogon zizanioides).

Science.gov (United States)

Kiiskila, Jeffrey D; Sarkar, Dibyendu; Feuerstein, Kailey A; Datta, Rupali

2017-12-01

Acid mine drainage (AMD) is extremely acidic, sulfate-rich effluent from abandoned or active mine sites that also contain elevated levels of heavy metals. Untreated AMD can contaminate surface and groundwater and pose severe ecological risk. Both active and passive methods have been developed for AMD treatment consisting of abiotic and biological techniques. Abiotic techniques are expensive and can create large amounts of secondary wastes. Passive biological treatment mainly consists of aerobic or anaerobic constructed wetlands. While aerobic wetlands are economical, they are not effective if the pH of the AMD is systems declines overtime and requires continuous maintenance. Our objective is to develop an alternative, low-cost, and sustainable floating wetland treatment (FWT) system for AMD for the abandoned Tab-Simco coal mining site in Illinois using vetiver grass (Chrysopogon zizanioides). Tab-Simco AMD is highly acidic, with mean pH value of 2.64, and contains high levels of sulfate and metals. A greenhouse study was performed for a 30-day period in order to screen and optimize the necessary parameters to design a FWT system. Water quality and plant growth parameters were continuously monitored. Results show significant SO 4 2- removal, resulting in increased pH, particularly at higher planting densities. Vetiver also helped in metal removal; high amounts of Fe, Zn, and Cu were removed, with relatively lower amounts of Pb, Al, and Ni. Iron plaque formation on the root was observed, which increased metal stabilization in root and lowered root to shoot metal translocation. Vetiver was tolerant of AMD, showing minimal change in biomass and plant growth. Results obtained are encouraging, and a large scale mesocosm study is now in progress, as the next step to develop the vetiver-based system for AMD treatment.

A New System for Measuring Auto-Fluorescence Changes in Neovascular-AMD after Intravitreal Injection of Bavecizumab

Directory of Open Access Journals (Sweden)

Mohammad Norouzifard

2011-07-01

Full Text Available Age-Related Macular Degeneration (AMD is the second disease diabetes which causes blindness in aged people. The only remedy for AMD is intravenous injection of bavecizumab. To prove the efficiency of remedy, the degenerated cells in Macula should be measured. In this article, a modern system is introduced to measure Auto-Fluorescence in Macula part of retina in order to obtain number of degenerated cells. The system consists of three main parts: Pre-processing stage is omission of margins and reversion of images in retina. Analysis stage is in charge of classification of images and elicitation of their features. In classification the target areas are identified by methods like morphology, dynamic threshold and connected comportments and the features of target area including Euclidean distance to the center of image and density. In the stage of understanding by gathering the features of each class, we will get the measurable parameter of evaluating Auto Fluorescence by the help of which we can count the number of degenerated cells of Macula area. The results are coming from statistical analysis, including linear regression and correlation of data. Experiments have been done on a database of 34 retina images of AMD patients. The average statistical error rate is equal to76 percent. In clinical reviews, the founded relation to disinflation of Macula has been proved, while there were no proved relations to the vision decreasing or increasing of patients.

Interaction of acid mine drainage with Ordinary Portland Cement blended solid residues generated from active treatment of acid mine drainage with coal fly ash.

Science.gov (United States)

Gitari, Wilson M; Petrik, Leslie F; Key, David L; Okujeni, Charles

2011-01-01

Fly ash (FA) has been investigated as a possible treatment agent for Acid mine drainage (AMD) and established to be an alternative, cheap and economically viable agent compared to the conventional alkaline agents. However, this treatment option also leads to generation of solid residues (SR) that require disposal and one of the proposed disposal method is a backfill in coal mine voids. In this study, the interaction of the SR with AMD that is likely to be present in such backfill scenario was simulated by draining columns packed with SR and SR + 6% Ordinary Portland Cement (OPC) unsaturated with simulated AMD over a 6 month period. The evolving geochemistry of the liquid/solid (L/S) system was evaluated in-terms of the mineral phases likely or controlling contaminants attenuation at the different pH regimes generated. Stepwise acidification of the percolates was observed as the drainage progressed. Two pH buffer zones were observed (7.5-9 and 3-4) for SR and (11.2-11.3 and 3.5-4) for SR + 6% OPC. The solid residue cores (SR) appeared to have a significant buffering capacity, maintaining a neutral to slightly alkaline pH in the leachates for an extended period of time (97 days: L/S 4.3) while SR + 6% OPC reduced this neutralization capacity to 22 days (L/S 1.9). Interaction of AMD with SR or SR + 6% OPC generated alkaline conditions that favored precipitation of Fe, Al, Mn-(oxy) hydroxides, Fe and Ca-Al hydroxysulphates that greatly contributed to the contaminants removal. However, precipitation of these phases was restricted to the pH of the leachates remaining at neutral to circum-neutral levels. Backfill of mine voids with SR promises to be a feasible technology for the disposal of the SR but its success will greatly depend on the disposal scenario, AMD generated and the alkalinity generating potential of the SR. A disadvantage would be the possible re-dissolution of the precipitated phases at pH water column. However extrapolation of this concept to a field

A prospective study of treatment patterns and 1-year outcome of Asian age-related macular degeneration and polypoidal choroidal vasculopathy.

Directory of Open Access Journals (Sweden)

Chui Ming Gemmy Cheung

Full Text Available OBJECTIVE: To study the treatment patterns and visual outcome over one year in Asian patients with choroidal neovascular membrane secondary to age-related macular degeneration (AMD-CNV and polypoidal choroidal vasculopathy (PCV. DESIGN: Prospective cohort, non-interventional study. METHODS: 132 treatment-naïve patients who received treatment for AMD-CNV and PCV were included. All patients underwent standardized examination procedures including retinal imaging at baseline and follow-up. AMD-CNV and PCV were defined on fundus fluorescein angiography and indocyanine green angiography at baseline. Patients were treated according to standard of care.We report the visual acuity (VA and optical coherence tomography (OCT measurements at baseline, month 3 and month 12 The factors influencing month 12 outcomes were analyzed. MAIN OUTCOME MEASURE: Type of treatment, number of Anti-vascular endothelial growth factor (VEGF treatments, visual outcome over one year. RESULTS: Anti-VEGF monotherapy was the initial treatment in 89.1% of AMD-CNV, but only 15.1% of PCV. The mean number of anti-VEGF injections up to month 12 was 3.97 (4.51 AMD-CNV, 3.43 PCV, p = 0.021. Baseline OCT, month 3 OCT and month 3 VA were significant in determining continuation of treatment after month 3. At month 12, mean VA improved from 0.82 (∼20/132 at baseline to 0.68 (∼20/96 at month 12 (mean gain 6.5 ETDRS letters, p = 0.002. 34.2% of eyes (38/113 eyes gained ≥15 ETDRS letters and 14.4% (16/113 eyes lost ≥15 ETDRS letters. There were no significant differences in visual outcome between AMD-CNV and PCV (p = 0.51. Factors predictive of month 12 visual outcome were baseline VA, baseline OCT central macular thickness, month 3 VA and age. CONCLUSIONS: There is significant variation in treatment patterns in Asian eyes with exudative maculopathy. There is significant visual improvement in all treatment groups at one year. These data highlight the need for high quality

Hematopoietic stem cell mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSC niches and bone formation.

Science.gov (United States)

Winkler, I G; Pettit, A R; Raggatt, L J; Jacobsen, R N; Forristal, C E; Barbier, V; Nowlan, B; Cisterne, A; Bendall, L J; Sims, N A; Lévesque, J-P

2012-07-01

The CXCR4 antagonist AMD3100 is progressively replacing cyclophosphamide (CYP) as adjuvant to granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) for autologous transplants in patients who failed prior mobilization with G-CSF alone. It has recently emerged that G-CSF mediates HSC mobilization and inhibits bone formation via specific bone marrow (BM) macrophages. We compared the effect of these three mobilizing agents on BM macrophages, bone formation, osteoblasts, HSC niches and HSC reconstitution potential. Both G-CSF and CYP suppressed niche-supportive macrophages and osteoblasts, and inhibited expression of endosteal cytokines resulting in major impairment of HSC reconstitution potential remaining in the mobilized BM. In sharp contrast, although AMD3100 was effective at mobilizing HSC, it did not suppress osteoblasts, endosteal cytokine expression or reconstitution potential of HSC remaining in the mobilized BM. In conclusion, although G-CSF, CYP and AMD3100 efficiently mobilize HSC into the blood, their effects on HSC niches and bone formation are distinct with both G-CSF and CYP targeting HSC niche function and bone formation, whereas AMD3100 directly targets HSC without altering niche function or bone formation.

Co-treatment of abandoned mine drainage and Marcellus Shale flowback water for use in hydraulic fracturing.

Science.gov (United States)

He, Can; Zhang, Tieyuan; Vidic, Radisav D

2016-11-01

Flowback water generated during shale gas extraction in Pennsylvania is mostly reused for hydraulic fracturing operation. Abandoned mine drainage (AMD), one of the most widespread threats to water quality in Pennsylvania, can potentially serve as a make-up water source to enable flowback water reuse. This study demonstrated co-treatment of flowback water and AMD produced in northeastern Pennsylvania in a pilot-scale system consisting of rapid mix reactor, flocculation tank and sedimentation tank. Sulfate concentration in the finished water can be controlled at a desired level (i.e., below 100 mg/L) by adjusting the ratio of flowback water and AMD in the influent. Fe 3+ contained in the AMD can serve as a coagulant to enhance the removal of suspended solids, during which Fe 2+ is co-precipitated and the total iron is reduced to a desirable level. Solid waste generated in this process (i.e., barite) will incorporate over 99% of radium present in the flowback water, which offers the possibility to control the fate of naturally occurring radioactive materials (NORM) brought to the surface by unconventional gas extraction. Sludge recirculation in the treatment process can be used to increase the size of barite particles formed by mixing flowback water and AMD to meet specifications for use as a weighting agent in drilling fluid. This alternative management approach for NORM can be used to offset the treatment cost and promote flowback water reuse, reduce environmental impacts of AMD and reduce pressure on fresh water sources. Copyright © 2016 Elsevier Ltd. All rights reserved.

Knowledge discovery in ophthalmology: analysis of wet form of age-related macular degeneration treatment outcomes

Science.gov (United States)

Ulińska, Magdalena; Tataj, Emanuel; Mulawka, Jan J.; Szaflik, Jerzy

2009-06-01

Age-related Macular Degeneration (AMD), according to epidemiological data, is a main reason of social blindness among elderly people in developed countries. There are two forms of AMD: dry and wet. The first one is of good prognosis with low possibility of serious visual deterioration, while the second one usually leads to quick and severe visual impairment. The aim of our investigations is to analyse results of so called real-life treatment of wet AMD. We analysed outcomes of our patients treated with intravitreal injections of anti-VEGF drugs: Lucentis (61 patients) and Avastin (78 patients). We analysed changes in visual acuity (functional effect) and central retinal thickness (anatomic effect). Both drugs occurred to be efficient in treatment of wet form of AMD, however results were more satisfying in patients with better baseline visual acuity. In our approach we used R environment - an integrated suite of software facilities for data analysis and graphics.

ANALYSIS OF MUNICIPAL WASTEWATER AND ACID MINE DRAINAGE PASSIVE CO-TREATMENT AT CERRO RICO DE POTOSÍ, BOLIVIA

Directory of Open Access Journals (Sweden)

William H.J. Strosnider

2015-06-01

Full Text Available Acid mine drainage (AMD is a worldwide environmental problem. The passive co-treatment of AMD with municipal waste water (MWW is a cost effective approach that uses nutrients in MWW in order to treat high concentrations of metals and sulfate found in AMD. Cerro Rico de Potosí in Bolivia is one of the biggest mining cities in the world, and it is constantly facing problems with AMD. The goal of this study was to determine the reaction rates of Al, Fe, Mn, Zn, and other metals found in an AMD discharge from Cerro Rico by a three-stage reactor system. The AMD had a pH of 3.58 and acidity of 1080 mg/L as CaCO3 equivalent containing 12, 68, 17 and 550 mg/L of dissolved Al, Fe, Mn, and Zn respectively. The reaction rates of Al, Fe, Mn, and Zn were 1.43, 2.09, 0.01, and 0.10 d-1, respectively.

Treatments for dry age-related macular degeneration and Stargardt disease: a systematic review.

Science.gov (United States)

Waugh, Norman; Loveman, Emma; Colquitt, Jill; Royle, Pamela; Yeong, Jian Lee; Hoad, Geraldine; Lois, Noemi

2018-05-01

Age-related macular degeneration (AMD) is the leading cause of visual loss in older people. Advanced AMD takes two forms, neovascular (wet) and atrophic (dry). Stargardt disease (STGD) is the commonest form of inherited macular dystrophy. To carry out a systematic review of treatments for dry AMD and STGD, and to identify emerging treatments where future NIHR research might be commissioned. Systematic review. We searched MEDLINE, EMBASE, Web of Science and The Cochrane Library from 2005 to 13 July 2017 for reviews, journal articles and meeting abstracts. We looked for studies of interventions that aim to preserve or restore vision in people with dry AMD or STGD. The most important outcomes are those that matter to patients: visual acuity (VA), contrast sensitivity, reading speed, ability to drive, adverse effects of treatment, quality of life, progression of disease and patient preference. However, visual loss is a late event and intermediate predictors of future decline were accepted if there was good evidence that they are strong predictors of subsequent visual outcomes. These include changes detectable by investigation, but not necessarily noticed by people with AMD or STGD. ClinicalTrials.gov, the World Health Organization search portal and the UK Clinical Trials gateway were searched for ongoing and recently completed clinical trials. The titles and abstracts of 7948 articles were screened for inclusion. The full text of 398 articles were obtained for further screening and checking of references and 112 articles were included in the final report. Overall, there were disappointingly few good-quality studies (including of sufficient size and duration) reporting useful outcomes, particularly in STGD. However we did identify a number of promising research topics, including drug treatments, stem cells, new forms of laser treatment, and implantable intraocular lens telescopes. In many cases, research is already under way, funded by industry or governments. In AMD

Implementing an interval computation library for OCaml on x86/amd64 architectures

OpenAIRE

Alliot , Jean-Marc; Gotteland , Jean-Baptiste; Vanaret , Charlie; Durand , Nicolas; Gianazza , David

2012-01-01

International audience; In this paper, we present two implementations of interval arithmetic for OCaml on x86/amd64 architectures. The first implementation is a binding to the classical MPFI/MPFR library. It provides access to multi-precision floating-point arithmetic and multi-precision floating-point intervalarithmetic. The second implementation has been natively written in assembly language for low-level functions and in OCaml for higher-levelfunctions. It has proven as fast as classical C...

Magnetite and cobalt ferrite nanoparticles used as seeds for acid mine drainage treatment

Energy Technology Data Exchange (ETDEWEB)

Kefeni, Kebede K., E-mail: kkefeni@gmail.com; Mamba, Bhekie B.; Msagati, Titus A.M.

2017-07-05

Highlights: • Presence of α-Fe{sub 2}O{sub 3} and Fe{sub 3}O{sub 4} in AMD resulted in formation of crystalline ferrite. • Increasing settling time improved removal of Mg, Ca, Mn and Na from AMD. • Mixtures of ferrite nanoparticles were produced from AMD. • Formations of crystalline ferrite were more favored in the presence of heat. - Abstract: In this study, magnetite and cobalt ferrite nanoparticles were used as seeds for acid mine drainage (AMD) treatment at pH of 7.05 ± 0.35. Duplicate samples of AMD, one without heating and another with heating at 60 °C was treated under continuous stirring for 1 h. The filtrate analysis results from ICP-OES have shown complete removal of Al, Mg, and Mn, while for Fe, Ni and Zn over 90% removals were recorded. Particularly, settling time has significant effect on the removal of Mg, Ca and Na. The results from SQUID have shown superparamagnetic properties of the synthesised magnetic nanoparticles and ferrite sludge. The recovered nanoparticles from AMD are economically important and reduce the cost of waste disposal.

Current and emerging therapies for the treatment of age-related macular degeneration

Directory of Open Access Journals (Sweden)

M Vaughn Emerson

2008-06-01

Full Text Available M Vaughn Emerson, Andreas K LauerCasey Eye Institute, Oregon Health and Science University, Portland, OR, USAAbstract: Age-related macular degeneration (AMD is the leading cause of vision loss in the industrialized world. In the last few decades, the mainstay of treatment for choroidal neovascularization (CNV due to AMD has been thermal laser photocoagulation. In the last decade, photodynamic therapy with verteporfin extended treatment for more patients. While both of these treatments have prevented further vision loss in a subset of patients, improvement in visual acuity is rare. Anti-vascular endothelial growth factor A (VEGF therapy has revolutionized the treatment of AMD-related CNV. Pegaptanib, an anti-VEGF aptamer prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment and bevacizumab, a full-length humanized monoclonal antibody against VEGF have both shown promising results with improvements in visual acuity with either agent. VEGF trap, a modified soluble VEGF receptor analogue, binds VEGF more tightly than all other anti-VEGF agents and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering ribonucleic acid (RNA to inhibit VEGF production and VEGF receptor production. Steroids, including anecortave acetate in the treatment and prevention of CNV, have shown promise in controlled trials. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Other growth factors, including pigment epithelium-derived growth factor that has been administered via an adenoviral vector has shown promising initial results. In some patients ciliary

Small, hard macular drusen and peripheral drusen: associations with AMD genotypes in the Inter99 Eye Study

DEFF Research Database (Denmark)

Munch, Inger Christine; Ek, Jakob; Kessel, Line

2010-01-01

PURPOSE: To study associations of small, hard macular drusen and peripheral drusen with genotypes associated with age-related macular degeneration (AMD). METHODS: Digital grayscale fundus photographs recorded in red-free illumination were graded for the presence of drusen in 1107 subjects aged 30...... to 66 years. Participants were genotyped for AMD-related polymorphisms in complement factor H (CFH), in LOC387715, and in complement factor B (CFB). RESULTS: The prevalence of 20 or more small, hard macular drusen per eye was 14%, with no association to the investigated polymorphisms. Peripheral drusen...... were associated with CFHY402H (odds ratio [OR], 4.3; 95% confidence interval [95% CI], 1.4-13, for CC versus TT genotypes) as was macular drusen >63 microm (OR, 1.9; 95% CI, 1.1-3.1, for CC versus TT genotypes). Macular drusen >63 microm were associated with the presence of 20 or more small, hard...

TU-F-CAMPUS-T-02: Monte Carlo Evaluation of Kilovoltage Radiosurgery with AuNPs for Age Related Macular Degeneration (AMD)

International Nuclear Information System (INIS)

Brivio, D; Zygmanski, P; Sajo, E; Makrigiorgos, G; Ngwa, W

2015-01-01

Purpose: To evaluate the benefit of gold nanoparticles (AuNP) in radiosurgery of Age related Macular Degeneration (AMD) using Monte Carlo (MC) simulation. AMD disease causes vision loss due to a leaky vasculature of the endothelial cells. Radiosurgical therapy aims to destroy this vasculature while minimizing the delivered dose to healthy tissues of the eye. AuNP known to enhance local dose have been targeted to the macular choroidal endothelial cells to increase the therapeutic efficacy. Methods: Dose enhancement ratio (DER) in macula endothelial cells due to a thin layer of AuNP has been calculated by a MC radiation transport simulation. AuNP layer (10–100nm) has been placed on the bottom of the macula at 2.4cm depth in a water parallelepiped 3×3×6cm3. This layer has been modeled considering various concentrations of AuNP ranging from 5.5–200mg per gram of endothelial cell (volume 10×10×2um3). The x-ray source is 100kVp 4mm diameter beam tilted 0°-30° with respect to the lens. Results: DER in endothelial cell for AuNP concentration of 31mg/g (shown experimentally feasible) and 10–100nm sizes is about 1.8. Tilting 4mm-beam does not reduce the enhancement but allows to avoid the surrounding tissues. Dose distribution in the AuNP vicinity has a significant increase within 30um, peaked at AuNP interface. DER inside and outside of the irradiation 4mm-field are the same while the actual delivered dose is more than one order of magnitude lower outside the field. Compared to 100kVp, usage of filtered spectra with enhanced flux in the region 20keV-40keV shows further increase of DER by about 20%. Dose to the neighboring organs such as retina/optic nerve are reduced accordingly. Conclusion: The results of this MC simulation provide further confirmation of the potential to enhance DER with AuNP from previous analytical calculations. This study provides impetus to improve treatment effectiveness of AMD disease with radiotherapy

TU-F-CAMPUS-T-02: Monte Carlo Evaluation of Kilovoltage Radiosurgery with AuNPs for Age Related Macular Degeneration (AMD)

Energy Technology Data Exchange (ETDEWEB)

Brivio, D; Zygmanski, P [Brigham & Women’s Hospital, Boston, MA (United States); Sajo, E [Univ Massachusetts Lowell, Lowell, MA (United States); Makrigiorgos, G [Dana Farber Cancer Institute, Boston, MA (United States); Ngwa, W [Harvard Medical School, Boston, MA (United States)

2015-06-15

Purpose: To evaluate the benefit of gold nanoparticles (AuNP) in radiosurgery of Age related Macular Degeneration (AMD) using Monte Carlo (MC) simulation. AMD disease causes vision loss due to a leaky vasculature of the endothelial cells. Radiosurgical therapy aims to destroy this vasculature while minimizing the delivered dose to healthy tissues of the eye. AuNP known to enhance local dose have been targeted to the macular choroidal endothelial cells to increase the therapeutic efficacy. Methods: Dose enhancement ratio (DER) in macula endothelial cells due to a thin layer of AuNP has been calculated by a MC radiation transport simulation. AuNP layer (10–100nm) has been placed on the bottom of the macula at 2.4cm depth in a water parallelepiped 3×3×6cm3. This layer has been modeled considering various concentrations of AuNP ranging from 5.5–200mg per gram of endothelial cell (volume 10×10×2um3). The x-ray source is 100kVp 4mm diameter beam tilted 0°-30° with respect to the lens. Results: DER in endothelial cell for AuNP concentration of 31mg/g (shown experimentally feasible) and 10–100nm sizes is about 1.8. Tilting 4mm-beam does not reduce the enhancement but allows to avoid the surrounding tissues. Dose distribution in the AuNP vicinity has a significant increase within 30um, peaked at AuNP interface. DER inside and outside of the irradiation 4mm-field are the same while the actual delivered dose is more than one order of magnitude lower outside the field. Compared to 100kVp, usage of filtered spectra with enhanced flux in the region 20keV-40keV shows further increase of DER by about 20%. Dose to the neighboring organs such as retina/optic nerve are reduced accordingly. Conclusion: The results of this MC simulation provide further confirmation of the potential to enhance DER with AuNP from previous analytical calculations. This study provides impetus to improve treatment effectiveness of AMD disease with radiotherapy.

Investigation into the use of cement kiln dust in high density sludge (HDS) treatment of acid mine water.

Science.gov (United States)

Mackie, Allison L; Walsh, Margaret E

2015-11-15

The purpose of this study was to investigate the potential to replace lime with cement kiln dust (CKD) in high density sludge (HDS) treatment of acid mine drainage (AMD). The bench-scale study used two water samples: AMD sampled from a lead-zinc mine with high concentrations of iron (Fe), zinc (Zn), and arsenic (As) (Fe/Zn-AMD) and a synthetic AMD solution (Syn-AMD) spiked with ferric sulfate (Fe2(SO4)3). Arsenic was found to be significantly reduced with CKD-HDS treatment of Fe/Zn-AMD compared to lime-HDS treatment, to concentrations below the stringent mine effluent discharge regulation of 0.10 mg As/L (i.e., 0.04 ± 0.02 mg/L). Both CKD- and lime-HDS treatment of the two AMD samples resulted in settled water Fe concentrations above the stringent discharge guideline of 0.3 mg Fe/L. CKD addition in the HDS process also resulted in high settled water turbidity, above typical discharge guidelines of 15 mg TSS/L. CKD-HDS treatment was found to result in significantly improved settled solids (i.e., sludge) quality compared to that generated in the lime-HDS process. HDS treatment with CKD resulted in 25-88% lower sludge volume indices, 2 to 9 times higher % wet solids, and 10 to 20 times higher % dry solids compared to lime addition. XRD and XPS testing indicated that CKD-HDS sludge consisted of mainly CaCO3 and SiO2 with Fe(3+) precipitates attached at particle surfaces. XRD and XPS testing of the lime-HDS generated sludge showed that it consisted of non-crystalline Fe oxides typical of sludge formed from precipitates with a high water concentration. Increased sedimentation rates were also found for CKD (1.3 cm/s) compared to lime (0.3 cm/s). The increased solids loading with CKD addition compared to lime addition in the HDS process was suggested to both promote surface complexation of metal precipitates with insoluble CKD particles and increase compression effects during Type IV sedimentation. These mechanisms collectively contributed to the reduced water content of

Automatic age-related macular degeneration detection and staging

Science.gov (United States)

van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

2013-03-01

Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

Acid drainage (AD) in nature and environmental impact of acid mine drainage (AMD) in Southern Tuscany

International Nuclear Information System (INIS)

Di Lella, Luigi Antonello; Protano, Giuseppe; Riccobono, Francesco

2005-01-01

Acid drainage (AD) is a natural process occurring locally at the Earth's surface. It consists in a substantial increase of acidity of surface waters as a result of chemical reactions occurring in the atmosphere (i.e. acid rain) or involving reactive phases (i.e. pyrite) present in the percolated medium. Acidic surface waters (usually pH < 4) can be produced by oxidation of sulphides (mainly pyrite and other iron sulphides) exposed to atmospheric oxygen, while human activities, such as mining, can greatly enhance this process. Acid drainage promoted by mining activities is called acid mine drainage (AMD) and is a primary source of environmental pollution and a world-wide problem in both active and abandoned mining areas. In fact, exposure of iron sulphides to oxidising conditions produces strongly acidic drainage waters rich in sulphate and a variety of heavy elements (i.e. As, Cd, Pb, Sb). Several occurrences of active acid mine drainage have been found in the Metalliferous Hills (southern Tuscany). The most important AMD phenomena were observed in the Fenice Capanne and Niccioleta mining areas

Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report

NARCIS (Netherlands)

Joachim, N.; Colijn, J.M.; Kifley, A.; Lee, K.E.; Buitendijk, G.H.; Klein, B.E.; Myers, C.E.; Meuer, S.M.; Tan, A.G.; Holliday, E.G.; Attia, J.; Liew, G.; Iyengar, S.K.; Jong, p de; Hofman, A.; Vingerling, J.R.; Mitchell, P.; Klaver, C.C.W.; Klein, R.; Wang, J.J.

2017-01-01

PURPOSE: To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors. DESIGN: Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study. METHODS:

Five-year progression of unilateral age-related macular degeneration to bilateral involvement : the Three Continent AMD Consortium report

NARCIS (Netherlands)

Joachim, Nichole; Colijn, Johanna Maria; Kifley, Annette; Lee, Kristine E; Buitendijk, Gabriëlle H S; Klein, Barbara E K; Myers, Chelsea E; Meuer, Stacy M; Tan, Ava G; Holliday, Elizabeth G; Attia, John; Liew, Gerald; Iyengar, Sudha K; de Jong, Paulus T V M; Hofman, Albert; Vingerling, Johannes R; Mitchell, Paul; Klaver, Caroline C W; Klein, Ronald; Wang, Jie Jin

2017-01-01

PURPOSE: To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors. DESIGN: Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study. METHODS:

Fluidized bed ash and passive treatment reduce the adverse effects of acid mine drainage on aquatic organisms.

Science.gov (United States)

Porter, Clint M; Nairn, Robert W

2010-10-15

Elevated concentrations of acidity and metals in acid mine drainage (AMD) may be effectively addressed by active and passive treatment technologies. However, typical evaluations consider only chemical water quality with little if any regard for biological metrics. Robust evaluations including both chemical and biological indicators of water quality improvement are needed. In this study, injection of alkaline fluidized bed ash (FBA) into a flooded underground coal mine was coupled with a five-cell passive treatment system to ameliorate an abandoned AMD discharge in eastern Oklahoma. The passive system included process units promoting both aerobic and anaerobic treatment mechanisms. Resulting water quality changes and biological responses were evaluated. Organisms of two distinct functional groups (the filter-feeding mollusk Corbicula fluminea and the wide-spectrum feeding fish Lepomis macrochirus) were exposed to mine waters in several treatment cells. The combination of treatment technologies was hypothesized to limit potential negative effects on these aquatic organisms. Tissues were harvested and analyzed for concentrations of several metals (Al, Fe, Mn, Mg, Ca, Ni, Cu and Zn) of interest. Organismal responses, such as hepatosomatic index, condition factor, and condition index, did not vary significantly among organisms exposed within different treatment cells when compared to non-AMD impaired waters. Metal tissue accumulation trends, compared to aqueous concentrations, were observed for Fe, Ni and Zn. Exposure experiments with these two organisms indicated that FBA introductions coupled with passive treatment decreased the potential adverse effects of AMD to biological systems. Copyright © 2010 Elsevier B.V. All rights reserved.

Assessing quality of life in the treatment of patients with age-related macular degeneration: clinical research findings and recommendations for clinical practice.

Science.gov (United States)

Yuzawa, Mitsuko; Fujita, Kyoko; Tanaka, Erika; Wang, Edward C Y

2013-01-01

The importance of incorporating quality-of-life (QoL) assessments into medical practice is growing as health care practice shifts from a "disease-based" to a "patient-centered" model. The prevalence of age-related macular degeneration (AMD) is increasing in today's aging population. The purpose of this paper is: (1) to discuss, by reviewing the current literature, the impact of AMD on patients' QoL and the utility of QoL assessments in evaluating the impact of AMD and its treatment; and (2) to make a recommendation for incorporating QoL into clinical practice. We conducted a PubMed and an open Internet search to identify publications on the measurement of QoL in AMD, as well as the impact of AMD and the effect of treatment on QoL. A total of 28 articles were selected. AMD has been found to cause a severity-dependent decrement in QoL that is comparable to systemic diseases such as cancer, ischemic heart disease, and stroke. QoL impairment manifests as greater social dependence, difficulty with daily living, higher rates of clinical depression, increased risk of falls, premature admission to nursing homes, and suicide. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) is the most widely used eye disease-specific QoL instrument in AMD. It has been shown to correlate significantly with visual acuity (VA). QoL reflects aspects of AMD including psychological well-being, functional capacity, and the ability to perform patients' valued activities, which are not captured by a single, numerical VA score. The literature shows that the adverse impact of AMD on QoL is comparable to serious systemic disease. Eye disease-specific instruments for measuring QoL, such as the NEI VFQ-25, have shown a significant correlation of QoL decrement with measures of disease severity, as well as significant QoL improvement with treatment. The NEI VFQ-25 and other validated instruments provide a wide-ranging assessment of vision-related functioning that is important to

Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report

NARCIS (Netherlands)

Joachim, Nichole; Colijn, Johanna Maria; Kifley, Annette; Lee, Kristine E.; Buitendijk, Gabriëlle H. S.; Klein, Barbara E. K.; Myers, Chelsea E.; Meuer, Stacy M.; Tan, Ava G.; Holliday, Elizabeth G.; Attia, John; Liew, Gerald; Iyengar, Sudha K.; de Jong, Paulus T. V. M.; Hofman, Albert; Vingerling, Johannes R.; Mitchell, Paul; Klaver, Caroline C. W.; Klein, Ronald; Wang, Jie Jin

2017-01-01

Purpose To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors. Design Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study. Methods Retinal

Human progenitor cells rapidly mobilized by AMD3100 repopulate NOD/SCID mice with increased frequency in comparison to cells from the same donor mobilized by granulocyte colony stimulating factor

DEFF Research Database (Denmark)

Hess, David A; Bonde, Jesper; Craft, Timothy P

2007-01-01

) or purified CD34(+) cells was compared at limiting dilution into NOD/SCID mice. Human AMD3100-mobilized MNC possessed enhanced repopulating frequency in comparison to G-CSF-mobilized MNC from paired donors, and purified CD34(+) progenitors were at least as efficient as the G-CSF mobilized cells....... The frequencies of NOD/SCID repopulating cells (SRC) were 1 SRC in 8.7 x 10(6) AMD3100-mobilized MNC compared to 1 SRC in 29.0 x 10(6) G-CSF-mobilized MNC, and 1 SRC in 1.2 x 10(5) AMD3100-mobilized CD34(+) cells compared to 1 SRC in 1.8 x 10(5) G-CSF-mobilized CD34(+) cells. Hematopoietic differentiation...

Hyperhomocysteinemia and Age-related Macular Degeneration: Role of Inflammatory Mediators and Pyroptosis; A Proposal.

Science.gov (United States)

Singh, Mahavir; Tyagi, Suresh C

2017-08-01

Age-related macular degeneration (AMD) and pyroptosis cause irreversible vascular changes in the eyes leading to central vision loss in patients. It is the most common eye disease affecting millions of people aged 50years or older, and is slowly becoming a major health problem worldwide. The disease mainly affects macula lutea, an oval-shaped pigmented area surrounding fovea near the center of retina, a region responsible for visual acuity. It is fairly a complex disease as genetics of patients, environmental triggers as well as risk factors such as age, family history of CVDs, diabetes, gender, obesity, race, hyperopia, iris color, smoking, diabetes, exposure to sun light and pyroptosis have all been clubbed together as probable causes of macular degeneration. Among genes that are known to play a role include variant polymorphisms in the complement cascade components such as CFH, C2, C3, and CFB as potential genetic risk factors. So far, AMD disease hypothesized theories have not resulted into the anticipated impact towards the development of effective or preventive therapies in order to help alleviate patients' suffering because, as of today, it is still unclear what actually initiates or leads to this dreaded eye condition. Based upon our extensive work on the metabolism of homocysteine (Hcy) in various disease conditions we, therefore, are proposing a novel hypothesis for AMD pathogenesis as we strongly believe that Hcy and events such as pyroptosis make a greater contribution to the overall etiology of AMD disease in a target population of susceptible hosts by inciting and accelerating the inherent inflammatory changes in the retina of these patients (Fig. 2). In this context, we further state that Hcy and pyroptosis should be considered as legitimate and valuable markers of retinal dysfunction as they not only aid and abet in the development but also in the progression of AMD in older people as discussed in this paper. This discussion should open up new

The mantle cells lymphoma: a proposed treatment

International Nuclear Information System (INIS)

Chavez Martinez, Marlene Elizabeth

2012-01-01

A literature review was performed on mantle cells lymphoma in the therapeutic schemes. The literature that has been used is published in journals of medicine specializing in hematology, oncology, radiation therapy, molecular biology and internal medicine. The literature review was performed to propose a scheme of treatment according to Costa Rica. Epigenetic alterations have been revealed in patients with mantle lymphoma on current researches. The mantle lymphoma pathology has been described in various forms of clinical and histological presentation, stressing the importance of detailing the different methods and diagnostic reports. Working groups have proposed and developed various chemotherapy regimens and concluded that CHOP alone is without effect in mantle cell lymphoma unlike R-hyper-CVAD, CHOP / DHAP, high-dose Ara-C. Researchers have tried to develop new treatments based vaccines, use of modified viruses, specific monoclonal antibodies. The classic treatment has been triple intrathecal therapy. The central nervous system has been one of the most momentous sites of mantle cell lymphoma infiltration because poorer patient prognosis [es

Treatment satisfaction of patients undergoing ranibizumab therapy for neovascular age-related macular degeneration in a real-life setting

Directory of Open Access Journals (Sweden)

Gohil R

2016-05-01

Full Text Available Rishma Gohil,1,2 Roxanne Crosby-Nwaobi,1,2 Angus Forbes,2 Ben J Burton,3 Philip Hykin,1 Sobha Sivaprasad1,4 1National Institute for Health Research Moorfields Biomedical Research Centre, London, 2Diabetes Nursing, King’s College London, London, 3Ophthalmology Department, James Paget University Hospital, Great Yarmouth, 4Laser and Retinal Research Unit, King’s College Hospital, London, UK Context: Treatment satisfaction with a loading phase of monthly injections for 3 months followed by a pro-re-nata regimen of ranibizumab in neovascular age-related macular degeneration (nAMD remains unclear.Aims: The aim was to evaluate the treatment satisfaction of persons with nAMD treated with ranibizumab in a real-life setting.Settings and design: A cross-sectional study was conducted across three eye clinics within the National Health Service in the UK, where treatment is provided free at point of contact.Materials and methods: A total of 250 patients were selected randomly for the study. Treatment satisfaction was assessed using the Macular Treatment Satisfaction Questionnaire. Data were collected on satisfaction of the service provided (Client Service Questionnaire-8 and the patients’ demographic and quality of life and treatment history. Factors governing treatment questionnaire were determined.Results: The most important factors that determined the satisfaction were the service provided at the clinic (Client Service Questionnaire-8, health-related quality of life (EQ-5D-3L, and duration of AMD. Visual acuity changes were rated as less important than one would have expected.Conclusion: The study result suggested that treatment satisfaction for nAMD was governed by the perception of being reviewed and injected regularly over a long period of time than the actual change in visual acuity from the treatment. Keyword: macular treatment satisfaction questionnaire, patient related outcome measure, treatment history, quality of life 

Association of OCT-Derived Drusen Measurements with AMD-Associated Genotypic SNPs in the Amish Population

OpenAIRE

Chavali, Venkata Ramana Murthy; Diniz, Bruno; Huang, Jiayan; Ying, Gui-Shuang; Sadda, SriniVas R.; Stambolian, Dwight

2015-01-01

Purpose: To investigate the association of optical coherence tomography (OCT)-derived drusen measures in Amish age-related macular degeneration (AMD) patients with known loci for macular degeneration. Methods: Members of the Old Order Amish community in Pennsylvania ages 50 and older were assessed for drusen area, volume and regions of retinal pigment epithelium (RPE) atrophy using a Cirrus High-Definition OCT. Measurements were obtained in the macula region within a central circle (CC) of 3...

Proposed Site Treatment Plan (PSTP). STP reference document

International Nuclear Information System (INIS)

1995-01-01

The Department of Energy (DOE) is required by Section 3021(b) of the Resource Conservation and Recovery Act (RCRA), as amended by the Federal Facility Compliance Act (FFCAct), to prepare a plan describing the development of treatment capacities and technologies for treating mixed waste (hazardous/radioactive waste). DOE decided to prepare its site treatment plan in a three phased approach. The first phase, called the Conceptual Site Treatment Plan (CSTP), was issued in October 1993. At the Savannah River Site (SRS) the CSTP described mixed waste streams generated at SRS and listed treatment scenarios for each waste stream utilizing an onsite, offsite DOE, and offsite or onsite commercial or vendor treatment option. The CSTP is followed by the Draft Site Treatment Plan (DSTP), due to be issued in August 1994. The DSTP, the current activity., will narrow the options discussed in the CSTP to a preferred treatment option, if possible, and will include waste streams proposed to be shipped to SRS from other DOE facilities as well as waste streams SRS may send offsite for treatment. The SRS DSTP process has been designed to address treatment options for each of the site's mixed waste streams. The SRS Proposed Site Treatment Plan (PSTP) is due to be issued in February 1995. The compliance order would be derived from the PSTP

Downflow limestone beds for treatment of net-acidic, oxic, iron-laden drainage from a flooded Anthracite Mine, Pennsylvania, USA: 1. Field evaluation

Science.gov (United States)

Cravotta, C.A.; Ward, S.J.

2008-01-01

Passive-treatment systems that route acidic mine drainage (AMD) through crushed limestone and/or organic-rich substrates have been used to remove the acidity and metals from various AMD sources, with a wide range of effects. This study evaluates treatment of net-acidic, oxic, iron-laden AMD with limestone alone, and with organic-rich compost layered with the limestone. In the fall of 2003, a treatment system consisting of two parallel, 500-m2 downflow cells followed by a 400-m2 aerobic settling pond and wetland was installed to neutralize the AMD from the Bell Mine, a large source of AMD and baseflow to the Schuylkill River in the Southern Anthracite Coalfield, in east-central Pennsylvania. Each downflow cell consisted of a lower substrate layer of 1,090 metric tons (t) of dolomitic limestone (60 wt% CaCO3) and an upper layer of 300 t of calcitic limestone (95 wt% CaCO3); one of the downflow cells also included a 0.3 m thick layer of mushroom compost over the limestone. AMD with pH of 3.5-4.3, dissolved oxygen of 6.6-9.9 mg/L, iron of 1.9-5.4 mg/L, and aluminum of 0.8-1.9 mg/L flooded each cell to a depth 0.65 m above the treatment substrates, percolated through the substrates to underlying, perforated outflow pipes, and then flowed through the aerobic pond and wetland before discharging to the Schuylkill River. Data on the flow rates and chemistry of the effluent for the treatment system indicated substantial neutralization by the calcitic limestone but only marginal effects from the dolomitic limestone or compost. Because of its higher transmissivity, the treatment cell containing only limestone neutralized greater quantities of acidity than the cell containing compost and limestone. On average, the treatment system removed 62% of the influent acidity, 47% of the dissolved iron, 34% of the dissolved aluminum, and 8% of the dissolved manganese. Prior to treatment of the Bell Discharge, the Schuylkill River immediately below its confluence with the discharge had p

Polarisation-sensitive OCT is useful for evaluating retinal pigment epithelial lesions in patients with neovascular AMD.

Science.gov (United States)

Schütze, Christopher; Teleky, Katharina; Baumann, Bernhard; Pircher, Michael; Götzinger, Erich; Hitzenberger, Christoph K; Schmidt-Erfurth, Ursula

2016-03-01

To examine the reproducibility of lesion dimensions of the retinal pigment epithelium (RPE) in neovascular age-related macular degeneration (AMD) with polarisation-sensitive optical coherence tomography (PS-OCT), specifically imaging the RPE. Twenty-six patients (28 eyes) with neovascular AMD were included in this study, and examined by a PS-OCT prototype. Each patient was scanned five times at a 1-day visit. The PS-OCT B-scan located closest to the macular centre presenting with RPE atrophy was identified, and the longitudinal diameter of the lesion was quantified manually using AutoCAD 2008. This procedure was followed for the identical B-scan position in all five scans per eye and patient. Reproducibility of qualitative changes in PS-OCT was evaluated. Interobserver variability was assessed. Results were compared with intensity-based spectral-domain OCT (SD-OCT) imaging. Mean variability of all atrophy lesion dimensions was 0.10 mm (SD±=0.06 mm). Coefficient of variation (SD±/mean) was 0.06 on average (SD±=0.03). Interobserver variability assessment showed a mean difference of 0.02 mm across all patients regarding RPE lesion size evaluation (paired t test: p=0.38). Spearman correlation coefficient was r=0.98, p<0.001. Results revealed a good overall reproducibility of ∼90%. PS-OCT specifically detected the RPE in all eyes compared with conventional intensity-based SD-OCT that was not capable to clearly identify RPE atrophy in 25 eyes (89.3%, p<0.01). PS-OCT offers good reproducibility of RPE atrophy assessment in neovascular AMD, and may be suitable for precise RPE evaluation in clinical practice. PS-OCT unambiguously identifies RPE changes in choroidal neovascularisation compared with intensity-based SD-OCT that does not identify the RPE status reliably. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Alpha-tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice

International Nuclear Information System (INIS)

Singh, Vijay K.; Wise, Stephen Y.; Fatanmi, Oluseyi O.; Beattie, Lindsay A.; Ducey, Elizabeth J.; Seed, Thomas M.

2014-01-01

The purpose of this study was to elucidate the role of alpha-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5–12.5 Gy) of 60 Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans. (author)

Downflow limestone beds for treatment of net-acidic, oxic, iron-laden drainage from a flooded anthracite mine, Pennsylvania, USA: 2. Laboratory evaluation

Science.gov (United States)

Cravotta, C.A.; Ward, S.J.; Hammarstrom, J.M.

2008-01-01

Acidic mine drainage (AMD) containing elevated concentrations of dissolved iron and other metals can be neutralized to varying degrees by reactions with limestone in passive treatment systems. We evaluated the chemical and mineralogical characteristics and the effectiveness of calcitic and dolomitic limestone for the neutralization of net-acidic, oxic, iron-laden AMD from a flooded anthracite mine. The calcitic limestone, with CaCO3 and MgCO3 contents of 99.8 and treatment system in 2003 at the Bell Mine, a large source of AMD and baseflow to the Schuylkill River in the Southern Anthracite Coalfield, in east-central Pennsylvania. In the winter of 2002-2003, laboratory neutralization-rate experiments evaluated the evolution of effluent quality during 2 weeks of continuous contact between AMD from the Bell Mine and the crushed calcitic or dolomitic limestone in closed, collapsible containers (cubitainers). The cubitainer tests showed that: (1) net-alkaline effluent could be achieved with detention times greater than 3 h, (2) effluent alkalinities and associated dissolution rates were equivalent for uncoated and Fe(OH)3-coated calcitic limestone, and (3) effluent alkalinities and associated dissolution rates for dolomitic limestone were about half those for calcitic limestone. The dissolution rate data for the cubitainer tests were used with data on the volume of effuent and surface area of limestone in the treatment system at the Bell Mine to evaluate the water-quality data for the first 1.5 years of operation of the treatment system. These rate models supported the interpretation of field results and indicated that treatment benefits were derived mainly from the dissolution of calcitic limestone, despite a greater quantity of dolomitic limestone within the treatment system. The dissolution-rate models were extrapolated on a decadal scale to indicate the expected decreases in the mass of limestone and associated alkalinities resulting from the long-term reaction of

Effect of Phospholipid on Pyrite Oxidation and Microbial Communities under Simulated Acid Mine Drainage (AMD) Conditions.

Science.gov (United States)

Pierre Louis, Andro-Marc; Yu, Hui; Shumlas, Samantha L; Van Aken, Benoit; Schoonen, Martin A A; Strongin, Daniel R

2015-07-07

The effect of phospholipid on the biogeochemistry of pyrite oxidation, which leads to acid mine drainage (AMD) chemistry in the environment, was investigated. Metagenomic analyses were carried out to understand how the microbial community structure, which developed during the oxidation of pyrite-containing coal mining overburden/waste rock (OWR), was affected by the presence of adsorbed phospholipid. Using columns packed with OWR (with and without lipid adsorption), the release of sulfate (SO4(2-)) and soluble iron (FeTot) was investigated. Exposure of lipid-free OWR to flowing pH-neutral water resulted in an acidic effluent with a pH range of 2-4.5 over a 3-year period. The average concentration of FeTot and SO4(2-) in the effluent was ≥20 and ≥30 mg/L, respectively. In contrast, in packed-column experiments where OWR was first treated with phospholipid, the effluent pH remained at ∼6.5 and the average concentrations of FeTot and SO4(2-) were ≤2 and l.6 mg/L, respectively. 16S rDNA metagenomic pyrosequencing analysis of the microbial communities associated with OWR samples revealed the development of AMD-like communities dominated by acidophilic sulfide-oxidizing bacteria on untreated OWR samples, but not on refuse pretreated with phospholipid.

Proposed rulemaking to risk-inform special treatment requirements

International Nuclear Information System (INIS)

Reed, Timothy A.; McKenna, Eileen M.

2003-01-01

This paper presents the status of Nuclear Regulatory Commission (NRC) rulemaking efforts to risk-inform special treatment requirements that reside in Title 10 of the Code of Federal Regulations, 10 CFR Part 21, Part 50, and Part 100. The staff has prepared a proposed rulemaking to add a new section to 10 CFR Part 50 to provide an alternative set of requirements for treatment of structures, systems and components (SSCs), using a risk-informed categorization process to determine safety significance of the SSCs. These requirements can be voluntarily adopted by light-water reactor licensees and applicants. The proposed rule is based upon extensive interactions with stakeholders (including consideration of public comments on draft rule language made available on the NRC rulemaking web site), experience with pilot plants, and guidance development activities. The NRC staff expects that stakeholder input provided in response to the proposed rule issuance will be valuable and support the efforts to issue the final rule. (author)

Mineralogical and geochemical characterization of the Old Tailings Dam, Australia: Evaluating the effectiveness of a water cover for long-term AMD control

International Nuclear Information System (INIS)

Jackson, Laura M.; Parbhakar-Fox, Anita

2016-01-01

Establishing a shallow water cover over tailings deposited in a designated storage facility is one option to limit oxygen diffusion and retard oxidation of sulfides which have the potential to form acid mine drainage (AMD). The Old Tailings Dam (OTD) located at the Savage River mine, western Tasmania contains 38 million tonnes of pyritic tailings deposited from 1967 to 1982, and is actively generating AMD. The OTD was constructed on a natural gradient, resulting in sub-aerial exposure of the southern area, with the northern area under a natural water cover. This physical contrast allowed for the examination of tailings mineralogy and geochemistry as a function of water cover depth across the OTD. Tailings samples (n = 144, depth: ≤ 1.5 m) were collected and subjected to a range of geochemical and mineralogical evaluations. Tailings from the southern and northern extents of the OTD showed similar AMD potential based on geochemical (NAG pH range: 2.1 to 4.2) and bulk mineralogical parameters, particularly at depth. However, sulfide alteration index (SAI) assessments highlighted the microscale contrast in oxidation. In the sub-aerial zone pyrite grains are moderately oxidized to a depth of 0.3 m (maximum SAI of 6/10), under both gravel fill and oxidized covers, with secondary minerals (e.g., ferrihydrite and goethite) developed along rims and fractures. Beneath this, mildly oxidized pyrite is seen in fresh tailings (SAI = 2.9/10 to 5.8/10). In the sub-aqueous zone, the degree of pyrite oxidation demonstrates a direct relationship with cover depth, with unoxidized, potentially reactive tailings identified from 2.5 m, directly beneath an organic-rich sediment layer (SAI = 0 to 1/10). These findings are broadly similar to other tailings storage facilities e.g., Fox Lake, Sherritt-Gordon Zn−Cu mine, Canada and Stekenjokk mine, Sweden where water covers up to 2 m have successfully reduced AMD. Whilst geotechnical properties of the OTD restrict the extension

Mutations at the CXCR4 interaction sites for AMD3100 influence anti-CXCR4 antibody binding and HIV-1 entry

DEFF Research Database (Denmark)

Hatse, Sigrid; Princen, Katrien; Vermeire, Kurt

2003-01-01

The interaction of the CXCR4 antagonist AMD3100 with its target is greatly influenced by specific aspartate residues in the receptor protein, including Asp(171) and Asp(262). We have now found that aspartate-to-asparagine substitutions at these positions differentially affect the binding of four...

Acid Water Neutralization Using Microbial Fuel Cells: An Alternative for Acid Mine Drainage Treatment

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Eduardo Leiva

2016-11-01

Full Text Available Acid mine drainage (AMD is a complex environmental problem, which has adverse effects on surface and ground waters due to low pH, high toxic metals, and dissolved salts. New bioremediation approach based on microbial fuel cells (MFC can be a novel and sustainable alternative for AMD treatment. We studied the potential of MFC for acidic synthetic water treatment through pH neutralization in batch-mode and continuous-flow operation. We observed a marked pH increase, from ~3.7 to ~7.9 under batch conditions and to ~5.8 under continuous-flow operation. Likewise, batch reactors (non-MFC inoculated with different MFC-enriched biofilms showed a very similar pH increase, suggesting that the neutralization observed for batch operation was due to a synergistic influence of these communities. These preliminary results support the idea of using MFC technologies for AMD remediation, which could help to reduce costs associated with conventional technologies. Advances in this configuration could even be extrapolated to the recovery of heavy metals by precipitation or adsorption processes due to the acid neutralization.

Assessing quality of life in the treatment of patients with age-related macular degeneration: clinical research findings and recommendations for clinical practice

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Yuzawa M

2013-07-01

Full Text Available Mitsuko Yuzawa,1 Kyoko Fujita,1 Erika Tanaka,2 Edward C Y Wang21Department of Ophthalmology, Nihon University School of Medicine, Surugadai, Kanda, Chiyoda-ku, Tokyo, Japan; 2Health Economics and Outcomes Research, Bayer Yakuhin Ltd, Marunouchi, Chiyoda-ku, Tokyo, JapanBackground: The importance of incorporating quality-of-life (QoL assessments into medical practice is growing as health care practice shifts from a “disease-based” to a “patient-centered” model. The prevalence of age-related macular degeneration (AMD is increasing in today’s aging population. The purpose of this paper is: (1 to discuss, by reviewing the current literature, the impact of AMD on patients’ QoL and the utility of QoL assessments in evaluating the impact of AMD and its treatment; and (2 to make a recommendation for incorporating QoL into clinical practice.Methods: We conducted a PubMed and an open Internet search to identify publications on the measurement of QoL in AMD, as well as the impact of AMD and the effect of treatment on QoL. A total of 28 articles were selected.Results: AMD has been found to cause a severity-dependent decrement in QoL that is comparable to systemic diseases such as cancer, ischemic heart disease, and stroke. QoL impairment manifests as greater social dependence, difficulty with daily living, higher rates of clinical depression, increased risk of falls, premature admission to nursing homes, and suicide. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25 is the most widely used eye disease-specific QoL instrument in AMD. It has been shown to correlate significantly with visual acuity (VA. QoL reflects aspects of AMD including psychological well-being, functional capacity, and the ability to perform patients’ valued activities, which are not captured by a single, numerical VA score.Conclusion: The literature shows that the adverse impact of AMD on QoL is comparable to serious systemic disease. Eye disease

Comparison between research data processing capabilities of AMD and NVIDIA architecture-based graphic processors

International Nuclear Information System (INIS)

Dudnik, V.A.; Kudryavtsev, V.I.; Us, S.A.; Shestakov, M.V.

2015-01-01

A comparative analysis has been made to describe the potentialities of hardware and software tools of two most widely used modern architectures of graphic processors (AMD and NVIDIA). Special features and differences of GPU architectures are exemplified by fragments of GPGPU programs. Time consumption for the program development has been estimated. Some pieces of advice are given as to the optimum choice of the GPU type for speeding up the processing of scientific research results. Recommendations are formulated for the use of software tools that reduce the time of GPGPU application programming for the given types of graphic processors

The chemistry of conventional and alternative treatment systems for the neutralization of acid mine drainage

International Nuclear Information System (INIS)

Kalin, Margarete; Fyson, Andrew; Wheeler, William N.

2006-01-01

The oxidation of pyritic mining waste is a self-perpetuating corrosive process which generates acid mine drainage (AMD) effluent for centuries or longer. The chemical neutralization of these complex, buffered effluents result in unstable, metal-laden sludges, which require disposal to minimize long-term environmental consequences. A variety of passive treatment systems for AMD, developed in the past two decades, combine limestone and organic substrates in constructed wetlands. These systems work well initially but over the longer term fail due to clogging with and the depletion of available organic carbon. However, some ecologically engineered systems, which exploit the activities of acid reducing microbes in the sediment, rely on photosynthesis in the water column as a source of organic matter. The primary productivity in the water column, which also generates some alkalinity, provides electron donors for the microbial reduction processes in the sediment. In its consideration of 'passive' systems, the literature has placed undue emphasis on sulphate reduction; thermodynamical iron reduction is equally important as is the need to prevent iron oxidation. Secondary precipitates of iron play a significant role in sediment-driven biomineralization processes, which affect the anaerobic degradation of organic matter and the stability of the resulting metal sulfides. One such passive system, which utilized a floating root mass as a source of organic carbon, is described. An extensive review of the literature and the chemical and biogeochemical reactions of AMD treatment systems, lead to the conclusion, that sediment based ecological systems offer the greatest potential for the sustainable treatment of AMD

The chemistry of conventional and alternative treatment systems for the neutralization of acid mine drainage.

Science.gov (United States)

Kalin, Margarete; Fyson, Andrew; Wheeler, William N

2006-08-01

The oxidation of pyritic mining waste is a self-perpetuating corrosive process which generates acid mine drainage (AMD) effluent for centuries or longer. The chemical neutralization of these complex, buffered effluents result in unstable, metal-laden sludges, which require disposal to minimize long-term environmental consequences. A variety of passive treatment systems for AMD, developed in the past two decades, combine limestone and organic substrates in constructed wetlands. These systems work well initially but over the longer term fail due to clogging with and the depletion of available organic carbon. However, some ecologically engineered systems, which exploit the activities of acid reducing microbes in the sediment, rely on photosynthesis in the water column as a source of organic matter. The primary productivity in the water column, which also generates some alkalinity, provides electron donors for the microbial reduction processes in the sediment. In its consideration of 'passive' systems, the literature has placed undue emphasis on sulphate reduction; thermodynamical iron reduction is equally important as is the need to prevent iron oxidation. Secondary precipitates of iron play a significant role in sediment-driven biomineralization processes, which affect the anaerobic degradation of organic matter and the stability of the resulting metal sulfides. One such passive system, which utilized a floating root mass as a source of organic carbon, is described. An extensive review of the literature and the chemical and biogeochemical reactions of AMD treatment systems, lead to the conclusion, that sediment based ecological systems offer the greatest potential for the sustainable treatment of AMD.

Pegaptanib sodium treatment in neovascular age-related macular degeneration: clinical experience in Germany

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Nikolaus Feucht

2008-06-01

Full Text Available Nikolaus Feucht, Huebner Matthias, Chris P Lohmann, Mathias MaierAugenklinik rechts der Isar, Technical University Munich, GermanyBackground: The VEGF Inhibition Study In Ocular Neovascularisation (VISION reported the efficacy of intravitreal (ITV vascular endothelial growth factor (VEGF inhibition with pegaptanib sodium (Macugen® for the treatment of neovascular age-related macular degeneration (AMD. This paper reports clinical experience with pegaptanib sodium for the treatment of occult or minimally classic choroidal neovascularization (CNV due to AMD.Material and methods: The study included 50 eyes (in 49 patients with either occult CNV or minimally classic CNV secondary to neovascular AMD who were not eligible for photodynamic therapy (PDT. Study data were analyzed retrospectively. During the 6-month study, patients were administered an average 2.74 injections of 0.3 mg ITV pegaptanib sodium. Angiography and optical coherence tomography (OCT examinations were carried out and intraocular pressure (IOP and visual acuity (VA were measured at baseline, at 3 months and at 6 months. An eye examination was performed and VA was measured the 2 days following treatment and then again at weeks 4–6, and at 3 and 6 months. OCT, VA, and IOP were also assessed at 1 month.Results: ITV pegaptanib sodium was well tolerated and no treatment complications arose. Mean VA was measured as: 0.37 ± 0.24 at baseline; 0.37 ± 0.25 at 1 month; 0.37 ± 0.25 at 3 months and 0.40 ± 0.26 at 6 months. VA was stabilized in approximately 90% of eyes treated with pegaptanib sodium. OCT examination showed a minimal change in central retinal thickness (CRT during the course of the study, from 251.19 µm at baseline to 251.63 µm at 6 months. No elevation in IOP was measured during treatment at 4–6 months in patients receiving pegaptanib sodium.Conclusions: ITV therapy with pegaptanib sodium for occult and minimally classic CNV secondary to neovascular AMD offered good

RETINAL PIGMENT EPITHELIAL TEAR AFTER INTRAVITREAL RANIBIZUMAB TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

Science.gov (United States)

Cho, Han Joo; Kim, Hyoung Seok; Yoo, Seul Gi; Han, Jung Il; Lew, Young Ju; Cho, Sung Won; Lee, Tae Gon; Kim, Jong Woo

2016-10-01

To evaluate the risk factors for retinal pigment epithelium (RPE) tears after intravitreal ranibizumab injections in neovascular age-related macular degeneration (nAMD) and to determine the efficacy of continued ranibizumab treatment after RPE tears. A total of 407 treatment-naïve eyes (377 patients) with nAMD were retrospectively included. All patients were treated with an initial series of 3 monthly loading injections, followed by further injections as required. Baseline characteristics and pigment epithelial detachment (PED) lesion features were evaluated as potential risk factors for RPE tear. The visual and anatomical outcomes after treatment during 12 months were also evaluated. By 12 months, RPE tears developed in 32 eyes (7.9%). Pigment epithelial detachment height was associated with a higher risk of RPE tear (odds ratio [OR], 1.318; 95% confidence interval [CI], 1.217-2.031, P = 0.018). Fibrovascular PED compared with serous PED had a higher risk of developing tears (OR, 9.129; 95% CI, 6.228-32.124, P = 0.039), and typical nAMD (OR, 4.166; 95% CI, 2.030-14.913, P = 0.031) and retinal angiomatous proliferation (OR, 3.778; 95% CI, 2.185-9.277, P = 0.040) had a higher risk of developing tears compared with polypoidal choroidal vasculopathy. Mean best-corrected visual acuity (BCVA) of RPE tear patients showed no significant improvement after treatment at 12 months; however, patients with RPE tears without foveal involvement (19 eyes) showed significant BCVA improvement at 12 months (P = 0.034). PED type and nAMD subtype are associated with the development of RPE tears after intravitreal ranibizumab injections. Continued ranibizumab therapy after RPE tear development can maintain visual acuity when the fovea is not involved.

[Prevention and preventive therapy of age-related macular degeneration through the beneficial effect of treatment of endothelial dysfunction].

Science.gov (United States)

Fischer, Tamás

2006-12-24

The beneficial effect achieved by the treatment of endothelial dysfunction in chronic cardiovascular diseases is already an evidence belonging to the basic treatment of the disease. Given the fact that the vascular system is uniform and consubstantial both physiologically, pathophysiologically and in terms of therapy, and that it plays a key role in age-related macular degeneration (AMD) - a disease leading to tragic loss of vision with its etiology and therapy being unknown -, endothelial dysfunction should be treated. The pleiotropic effects of ACE-inhibitors, AR-blockers and statins help to restitute the balance between vasodilators and vasoconstrictors in endothelial dysfunction caused by oxidative stress, the balance of growth factors and their inhibitors, pro- and anti-inflammatory substances and prothrombotic and fibrinolytic factors, inhibit the formation of oxidative stress and its harmful effects; while aspirin with its pleiotropic effects acting as an antiaggregation substance on platelets helps to set the endothelial layer back to its normal balance regarding its vasodilating, antithrombotic, anti-adhesive and anti-inflammatory functions. For the above reasons it is suggested that, as a part of long term primary and/or secondary prevention, the following groups of patients with AMD receive - taking into consideration all possible side effects - ACE-inhibitor and/or AR-blocker and statin and aspirin treatment: 1) those without maculopathy but being over the age of 50 and having risk factors inducing endothelial dysfunction; 2) those, who already developed AMD in one eye as a prevention in the second, unaffected eye; and 3) those patients who developed AMD in both eyes in order to ameliorate or merely slow the progression of the disease. Besides, it is advisory to inhibit AMD risk factors inducing oxidative stress with consecutive endothelial dysfunction.

V3-independent competitive resistance of a dual-X4 HIV-1 to the CXCR4 inhibitor AMD3100.

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Yosuke Maeda

Full Text Available A CXCR4 inhibitor-resistant HIV-1 was isolated from a dual-X4 HIV-1 in vitro. The resistant variant displayed competitive resistance to the CXCR4 inhibitor AMD3100, indicating that the resistant variant had a higher affinity for CXCR4 than that of the wild-type HIV-1. Amino acid sequence analyses revealed that the resistant variant harbored amino acid substitutions in the V2, C2, and C4 regions, but no remarkable changes in the V3 loop. Site-directed mutagenesis confirmed that the changes in the C2 and C4 regions were principally involved in the reduced sensitivity to AMD3100. Furthermore, the change in the C4 region was associated with increased sensitivity to soluble CD4, and profoundly enhanced the entry efficiency of the virus. Therefore, it is likely that the resistant variant acquired the higher affinity for CD4/CXCR4 by the changes in non-V3 regions. Taken together, a CXCR4 inhibitor-resistant HIV-1 can evolve using a non-V3 pathway.

Prevalence and treatment patterns of ranibizumab and photodynamic therapy in a tertiary care setting in Malaysia.

Science.gov (United States)

Mohamad, Nur Afiqah; Ramachandran, Vasudevan; Ismail, Patimah; Mohd Isa, Hazlita; Chan, Yoke Mun; Ngah, Nor Fariza; Md Bakri, Norshakimah; Ching, Siew Mooi; Hoo, Fan Kee; Wan Sulaiman, Wan Aliaa

2017-01-01

To describe the prevalence and changes in treatment patterns of ranibizumab and photodynamic therapy (PDT) among retinal disease patients who attended the Ophthalmology Clinic in the tertiary care Hospital Selayang from 2010 to 2014. Study subjects were recruited retrospectively using the Electronic Medical Record (EMR) database software in Hospital Selayang. Demographic data, medical history, diagnostic procedure, treatments and diagnosis of patients were recorded. The five-year analysis included 821 patients with a mean age of 65.9±11.73y. Overall, there were a higher number of males (63.1%) and a higher number of Chinese (47.4%) patients. Among the 821 patients, 62.9% received ranibizumab injection followed by 19.2% PDT therapy and 17.9% had ranibizumab combined with PDT therapy. Age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) were the most common retinal eye diseases reported, recording prevalence of 25.0% and 45.6%, respectively. The trend in ranibizumab treatment was reported to increase while PDT showed a decrease in trend from year 2010 to 2014. In terms of treatment, following multiple logistic regression, AMD was associated with the subjects being more likely to have received ranibizumab monotherapy ( P Malaysia is consistent with management of patients from other countries whereby ranibizumab is the most common treatment given to patients with AMD, while PCV patients most commonly receive PDT and ranibizumab combined with PDT therapy.

A human apoB100 transgenic mouse expresses human apoB100 in the RPE and develops features of early AMD

DEFF Research Database (Denmark)

Fujihara, Masashi; Bartels, Emil; Nielsen, Lars B

2009-01-01

changes consistent with early human AMD including loss of basal infoldings and accumulation of cytoplasmic vacuoles in the RPE, and basal laminar deposits containing long-spacing collagen and heterogeneous debris in Bruch membrane of apoB100 mice. In apoB100 mice given a high-fat diet, basal linear...... transgenic for a human genomic fragment encoding the full length human apoB ("apoB100" mice) and litter-mate control mice were given a normal chow or high-fat diet for 12 months. Mice were evaluated for human apoB mRNA expression in the RPE/choroid and liver by RT-qPCR. Phenotypic changes associated......-like deposits were identified in 12-month-old mice. Linear regression analysis showed that the genotype (human apoB transgene) was a stronger influencing factor than high-fat diet in producing AMD-like lesions used in this study. Human apoB100 transgenic mice overexpress apoB in RPE and, with time, develop...

Comparison of intravitreal bevacizumab treatment between phakic and pseudophakic neovascular age-related macular degeneration.

Science.gov (United States)

Ozkaya, Abdullah; Alkin, Zeynep; Perente, Irfan; Yuksel, Kemal; Baz, Okkes; Alagoz, Cengiz; Yazici, Ahmet Taylan; Demirok, Ahmet

2014-01-01

Before the era of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment, only prevention for visual loss might have been achieved in a limited number of neovascular age-related macular generation (nAMD) patients with different treatment options. To compare the efficacy of intravitreal bevacizumab (IVB) for the treatment of nAMD between phakic and pseudophakic eyes. The newly diagnosed nAMD patients were included in this retrospective study. The patients were divided into the phakic and pseudophakic groups. Initially, the patients received three consecutive, monthly, IVB injections, and then the treatment was continued on an as-needed regimen. The patients were examined monthly, and the data at the baseline, at 3, 6, 9, and 12 months and at the last follow-up were evaluated. The changes in the visual acuity (VA), central retinal thickness (CRT) and the number of injections were compared between the two groups. The study included 62 eyes of 62 patients (39 phakic, and 23 pseudophakic patients). The mean follow-up time was 19.7 and 17.2 months in the phakic and pseudophakic groups, respectively (p=0.06). The mean Log MAR VA at the baseline, 12 months and the last follow-up was 0.82, 0.72 and 0.75 in the phakic group and 0.77, 0.67, and 0.68 in the pseudophakic group, respectively. The change in the mean BCVA from the baseline to 12 months and at the last follow-up was not statistically different between the two groups (p=0.9 and p=0.7, respectively). The mean injection number at 12 months was 4.5 and 4.9 in the phakic and pseudophakic group, respectively (p=0.2). The beneficial effect of IVB is equal in both the phakic and pseudophakic group of nAMD patients. The functional and anatomical outcomes of the treatment and the number of injections were similar in the two groups. © NEPjOPH.

Alternative substrates of bacterial sulphate reduction suitable for the biological-chemical treatment of acid mine drainage

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Alena Luptakova

2012-12-01

Full Text Available The impacts of AMD pollution on biological systems are mostly severe and the problem may persist from many decadesto thousands of years. Consequently AMD prior to being released into the environment must be treated to meet government standardsfor the amount of metal and non-metal ions contained in the water. One of the best available technologies for the removal of metals fromAMD is precipitation as metal sulphides. SRB applications for AMD treatment involve a few principal stages. The first stageis the cultivation of SRB i.e. the bacterial sulphate reduction. At the laboratory conditions the sodium lactate is the energetic substratefor the growth of bacteria. Its price is not economic for the application in the practice and is needed investigate the alternativesubstitutes. The aim of this work was the cultivation of SRB using the selected energetic substrates such as: calcium lactate, ethanol,saccharose, glucose and whey. Experimental studies confirm that in the regard to the amount of reduced sulphates the calcium lactateand ethanol are the best alternative substrates for the bacterial sulphate-reduction.

Age, sex, and type of medication predict the effect of anti-VEGF treatment on central retinal thickness in wet age-related macular degeneration

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Bek T

2018-03-01

Full Text Available Toke Bek, Sidsel Ehlers Klug Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark Purpose: Randomized clinical trials studying the effects of VEGF inhibition on wet age-related macular degeneration (wAMD are designed so that the effects of individually varying risk factors on the treatment response are eliminated. The influence of these risk factors can be studied in large data sets from real-life experience.Patients and methods: All 2,255 patients diagnosed with wAMD requiring anti-VEGF treatment in at least one eye over more than 9 years in a defined Danish population with 0.9 million inhabitants were studied. The predictive value of eye laterality, sex, current smoking status, type of anti-VEGF compound, membrane position, membrane type, leakage area, number of injections, number of visits, age, time to follow-up, visual acuity, and central retinal thickness (CRT at baseline on change in CRT after three monthly injections with anti-VEGF compound followed by treatment pro re nata for up to 12 months was assessed.Results: After 12 months, 67 patients had died, 903 had had stable CRT for at least 6 months, and 1,285 patients had not achieved stable CRT. The reduction in CRT was -84.8±118.3 µm, whereas the increase in visual acuity was 2.2±14.7 Early Treatment Diabetic Retinopathy Study letters. The risk factors included contributed to 64% of the variation in CRT reduction. High age and high CRT at baseline predicted high CRT reduction, whereas more injections, treatment with ranibizumab, and male sex predicted a low CRT reduction.Conclusion: Age, sex, and type of anti-VEGF medication can be used to plan treatment and inform patients about the expected response of anti-VEGF treatment in wAMD. Keywords: wet AMD, anti-VEGF treatment, risk factors, real-life experience 

Preliminary study of Conbercept injected intravitreally for the treatment of wet age-related macular degeneration

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Ying Qin

2017-08-01

Full Text Available AIM:To observe the preliminary efficacy of conbercept injected intravitreally for the treatment of wet age-related macular degeneration(wAMD.METHODS:Seventeen wAMD patients(18 eyeswere selected to receive conbercept injection. All patients were given a single conbercept injection every month, 3 times. Before and after 1, 2, 3mo of the injection, the best corrected visual acuity(BCVA, intraocular pressure(IOP, measured by Non-contact tonometer, fundus photography, fundus fluorescein angiography(FFA, indocyanine green angiography(ICG, optical coherence tomography(OCTexamination and the complications incidence were compared.RESULTS:Three months after conbercept injection, the BCVA improved in 15 eyes(83%, stable in 3 eyes(17%. Before treatment, the average central macular thickness was 421.72±54.43μm, at 1 and 2 and 3mo after treatment, the average central macular thickness was 337.89±25.88μm, 293.56±26.87μm, 266.89±19.10μm respectively. There were significant differences compared with before and after injection(PCONCLUSION:Intravitreal injection conbercept for wAMD can significantly improve the visual function, reduce the macular edema and the leakage with higher safety and less complications. However the prolonged efficacy needs further observation.

Interventions to treat mental disorders during pregnancy: A systematic review and multiple treatment meta-analysis.

Directory of Open Access Journals (Sweden)

Leontien M van Ravesteyn

Full Text Available For women suffering from an antepartum mental disorder (AMD, there is lack of evidence-based treatment algorithms due to the complicated risk-benefit analysis for both mother and unborn child. We aimed to provide a comprehensive overview of pharmacological and non-pharmacological interventions to treat AMD and performed a meta-analysis of the estimated treatment effect on the psychiatric symptoms during pregnancy.MedLine, PsycINFO and Embase databases were searched by two independent reviewers for clinical trials with a control condition on treatment of women with AMD, i.e. major depressive (MDD, anxiety, psychotic, eating, somatoform and personality disorders. We inventoried the effect of the treatment, i.e. decrease of psychiatric symptoms at the end of the treatment or postpartum. We adhered to the PRISMA-protocol.Twenty-nine trials were found involving 2779 patients. Trials studied patients with depressive disorders (k = 28, and anxiety disorders (k = 1. No pharmacological trials were detected. A form of psychotherapy, like Cognitive Behavioural Therapy (g = -0.61; 95%CI:-0.73 to -0.49, I2 = 0%; k = 7 or Interpersonal Psychotherapy (g = -0.67; 95%CI:-1.27 to -0.07; I2 = 79%; k = 4, holds robust benefit for pregnant women with MDD. Body-oriented interventions (g = -0.43; 95%CI:-0.61 to -0.25; I2 = 17%; k = 7 and acupuncture (g = -0.43; 95%CI:-0.80 to -0.06; I2 = 0%; k = 2 showed medium sized reduction of depressive symptoms. Bright light therapy (g = -0.59; 95%CI:-1.25 to 0.06; I2 = 0%; k = 2, and food supplements (g = -0.51; 95%CI:-1.02 to 0.01; I2 = 20%; k = 3 did not show significant treatment effects. One study was found on Integrative Collaborative Care.This meta-analysis found a robust moderate treatment effect of CBT for MDD during pregnancy, and to a lesser extent for IPT. As an alternative, positive results were found for body-oriented interventions and acupuncture. No evidence was found for bright light therapy and food supplements

Federal Facility Compliance Act, Proposed Site Treatment Plan: Background Volume. Executive Summary

International Nuclear Information System (INIS)

1995-01-01

This Federal Facility Compliance Act Site Treatment Plan discusses the options of radioactive waste management for Ames Laboratory. This is the background volume which discusses: site history and mission; framework for developing site treatment plans; proposed plan organization and related activities; characterization of mixed waste and waste minimization; low level mixed waste streams and the proposed treatment approach; future generation of TRU and mixed wastes; the adequacy of mixed waste storage facilities; and a summary of the overall DOE activity in the area of disposal of mixed waste treatment residuals

Automated detection of age-related macular degeneration in OCT images using multiple instance learning

Science.gov (United States)

Sun, Weiwei; Liu, Xiaoming; Yang, Zhou

2017-07-01

Age-related Macular Degeneration (AMD) is a kind of macular disease which mostly occurs in old people，and it may cause decreased vision or even lead to permanent blindness. Drusen is an important clinical indicator for AMD which can help doctor diagnose disease and decide the strategy of treatment. Optical Coherence Tomography (OCT) is widely used in the diagnosis of ophthalmic diseases, include AMD. In this paper, we propose a classification method based on Multiple Instance Learning (MIL) to detect AMD. Drusen can exist in a few slices of OCT images, and MIL is utilized in our method. We divided the method into two phases: training phase and testing phase. We train the initial features and clustered to create a codebook, and employ the trained classifier in the test set. Experiment results show that our method achieved high accuracy and effectiveness.

The Mitochondria-Targeted Antioxidant SkQ1 Downregulates Aryl Hydrocarbon Receptor-Dependent Genes in the Retina of OXYS Rats with AMD-Like Retinopathy

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M. L. Perepechaeva

2014-01-01

Full Text Available The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard development of age-related diseases. It has been shown that SkQ1 reduces clinical signs of retinopathy in senescence-accelerated OXYS rats, which are a known animal model of human age-related macular degeneration (AMD. The aim of this work was to test whether SkQ1 affects transcriptional activity of AhR (aryl hydrocarbon receptor and Nrf2 (nuclear factor erythroid 2-related factor 2, which are considered as AMD-associated genes in the retina of OXYS and Wistar rats. Our results showed that only AhR and AhR-dependent genes were sensitive to SkQ1. Dietary supplementation with SkQ1 decreased the AhR mRNA level in both OXYS and Wistar rats. At baseline, the retinal Cyp1a1 mRNA level was lower in OXYS rats. SkQ1 supplementation decreased the Cyp1a1 mRNA level in Wistar rats, but this level remained unchanged in OXYS rats. Baseline Cyp1a2 and Cyp1b1 mRNA expression was stronger in OXYS than in Wistar rats. In the OXYS strain, Cyp1a2 and Cyp1b1 mRNA levels decreased as a result of SkQ1 supplementation. These data suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1.

Novel passive co-treatment of acid mine drainage and municipal wastewater.

Science.gov (United States)

Strosnider, William H J; Winfrey, Brandon K; Nairn, Robert W

2011-01-01

A laboratory-scale, four-stage continuous-flow reactor system was constructed to test the viability of high-strength acid mine drainage (AMD) and municipal wastewater (MWW) passive co-treatment. Synthetic AMD of pH 2.6 and acidity of 1870 mg L(-1) as CaCO3 equivalent containing a mean 46, 0.25, 2.0, 290, 55, 1.2, and 390 mg L(-1) of Al, As, Cd, Fe, Mn, Pb, and Zn, respectively, was added at a 1:2 ratio with raw MWW from the City of Norman, OK, to the system which had a total residence time of 6.6 d. During the 135-d experiment, dissolved Al, As, Cd, Fe, Mn, Pb, and Zn concentrations were consistently decreased by 99.8, 87.8, 97.7, 99.8, 13.9, 87.9, and 73.4%, respectively, pH increased to 6.79, and net acidic influent was converted to net alkaline effluent. At a wasting rate of 0.69% of total influent flow, the system produced sludge with total Al, As, Cd, Cr, Cu, Fe, Pb, and Zn concentrations at least an order of magnitude greater than the influent mix, which presents a metal reclamation opportunity. Results indicate that AMD and MWW passive co-treatment is a viable approach to use wastes as resources to improve water quality with minimal use of fossil fuels and refined materials.

The availability of second generation feedstocks for the treatment of acid mine drainage and to improve South Africa's bio-based economy.

Science.gov (United States)

Westensee, Dirk Karl; Rumbold, Karl; Harding, Kevin G; Sheridan, Craig M; van Dyk, Lizelle D; Simate, Geoffrey S; Postma, Ferdinand

2018-10-01

South Africa has a wide range of mining activities making mineral resources important economic commodities. However, the industry is responsible for several environmental impacts; one of which is acid mine drainage (AMD). Despite several years of research, attempts to prevent AMD generation have proven to be difficult. Therefore, treatment of the resulting drainage has been common practice over the years. One of the recommended treatment methods is the use of second generation feedstocks (lignocellulosic biomass). This biomass is also acknowledged to be an important feedstock for bio-refineries as it is abundant, has a high carbon content and is available at minimal cost. It can also potentially be converted to fermentable sugars (e.g. glucose) through different treatment steps, which could further yield other valuable commodities (cellulase, poly-β-hydroxybutyric acid (PHB) and penicillin V). It is estimated by a generic flowsheet model that 7 tons of grass biomass can produce 1400 kg of glucose which can subsequently produce 205 kg, 438 kg and 270 kg of cellulase, PHB and Penicillin V, respectively. In this paper we investigate the feasibility of grass as feedstock for AMD treatment and the subsequent conversion of this acid pre-treated grass into valuable bio-products. Copyright © 2018 Elsevier B.V. All rights reserved.

Geochemistry of rare earth elements in a passive treatment system built for acid mine drainage remediation.

Science.gov (United States)

Prudêncio, Maria Isabel; Valente, Teresa; Marques, Rosa; Sequeira Braga, Maria Amália; Pamplona, Jorge

2015-11-01

Rare earth elements (REE) were used to assess attenuation processes in a passive system for acid mine drainage treatment (Jales, Portugal). Hydrochemical parameters and REE contents in water, soils and sediments were obtained along the treatment system, after summer and winter. A decrease of REE contents in the water resulting from the interaction with limestone after summer occurs; in the wetlands REE are significantly released by the soil particles to the water. After winter, a higher water dynamics favors the AMD treatment effectiveness and performance since REE contents decrease along the system; La and Ce are preferentially sequestered by ochre sludge but released to the water in the wetlands, influencing the REE pattern of the creek water. Thus, REE fractionation occurs in the passive treatment systems and can be used as tracer to follow up and understand the geochemical processes that promote the remediation of AMD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Improved AMD counters quicky type to achieve a level of 0.2 log derivative mSv output in counts refills; Mejora de la AMD en contadores tipo quicky para conseguir un nivel derivado de registro de 0,2 mSV en contajes de salida en recargas

Energy Technology Data Exchange (ETDEWEB)

Bravp Perez-Tinao, B.; Marchena Gonzalez, P.; Sollet Danudo, E.

2011-07-01

To ensure that no worker receives contract exposed by internal exposure dose computed not exceed 1 mSv / year, the Nuclear Security Council requested the Spanish nuclear power plants and Tecnatom that in 2010 would ensure a level derived from registration in internal dosimetry counts refills output equal to or less than 0.2 mSv, which represented a reduction of AMD computers.

Radiotherapy of macular lesions in age-related macular degeneration (A.M.D.): preliminary results of a clinical study conducted in Lyon, France

International Nuclear Information System (INIS)

Martin, P.; Mauget, M.; Gerard, J.P.

1997-01-01

To evaluate irradiation effects on functional signs and choroidal neo-vascular lesions in age-related macular degeneration (AMD) that does not respond to laser therapy. Since 1994, 250 consecutive AMD patients were treated by two radiotherapy teams for sub-foveal neo-vascular lesions. At the end of september 1996, 52 patients were evaluable with a 1-year follow-up. Group 1 (Department de Radiotherapie Oncologie, Centre Hospitalo-Universitaire Lyon Sud) included 26 patients who were treated with a lateral beam of 6 MV photons. The irradiation dose were 20 Gy in five fractions for small lesions and 28.8 Gy in eight fractions for larger lesions. Group 2 (Centre Oncologie Radiotherapie Saint-Jean) was composed of 26 patients treated with a mini-beam of 25 MV photons via lateral arc-therapy. Beam diameters (14 and 18 mm) were adapted to the lesion size. The total dose was 16 Gy in four fractions or 20 Gy in five fractions. Functional and anatomical results were assessed at 3, 6, 9 months and 1 year after radiation therapy. Stable visual acuity was observed in 44 % (23/52) of the patients and visual acuity was improved in 35 % (18/52) of the patients at 6 months. Good functional results reached 79 % (41/52) at 6 months and 74 % (17/23) at 12 months. There was no statistical difference between the two groups and dose levels. All severe complications (1 cataract, 3 dilated choroidal vessels, and 2 papillitis) occurred in group 1. Though it is too early to conclude on the best dose level, radiotherapy of sub-foveal neo-vascular lesions of AMD that cannot be treated via laser therapy provides encouraging results. The technique used must be very precise to adequately irradiate the fovea and spare surrounding sensitive areas. Further studies and trials involving patients' randomization are necessary to confirm these preliminary results. (author)

Performance assessment of laboratory and field-scale multi-step passive treatment of iron-rich acid mine drainage for design improvement.

Science.gov (United States)

Rakotonimaro, Tsiverihasina V; Neculita, Carmen Mihaela; Bussière, Bruno; Genty, Thomas; Zagury, Gérald J

2018-04-17

Multi-step passive systems for the treatment of iron-rich acid mine drainage (Fe-rich AMD) perform satisfactorily at the laboratory scale. However, their field-scale application has revealed dissimilarities in performance, particularly with respect to hydraulic parameters. In this study, the assessment of factors potentially responsible for the variations in performance of laboratory and field-scale multi-step systems was undertaken. Three laboratory multi-step treatment scenarios, involving a combination of dispersed alkaline substrate (DAS) units, anoxic dolomitic drains, and passive biochemical reactors (PBRs), were set up in 10.7-L columns. The field-scale treatment consisted of two PBRs separated by a wood ash (WA) reactor. The parameters identified as possibly influencing the performances of the laboratory and field-scale experiments were the following: AMD chemistry (electrical conductivity and Fe and SO 4 2- concentrations), flow rate (Q), and saturated hydraulic conductivity (k sat ). Based on these findings, the design of an efficient passive multi-step treatment system is suggested to consider the following: (1) Fe pretreatment, using materials with high k sat and low HRT. If a PBR is to be used, the Fe load should be PBR/DAS filled with a mixture with at least 20% of neutralizing agent; (3) include Q and k sat (> 10 -3  cm/s) in the long-term prediction. Finally, mesocosm testing is strongly recommended prior to construction of full-scale systems for the treatment of Fe-rich AMD.

Biochemical oxygen demand and nutrient processing in a novel multi-stage raw municipal wastewater and acid mine drainage passive co-treatment system.

Science.gov (United States)

Strosnider, W H; Winfrey, B K; Nairn, R W

2011-01-01

A laboratory-scale, four-stage continuous flow reactor system was constructed to test the viability of high-strength acid mine drainage (AMD) and municipal wastewater (MWW) passive co-treatment. The synthetic AMD had pH 2.60 and 1860 mg/L acidity as CaCO(3) equivalent with 46, 0.25, 2, 290, 55, 1.2 and 390 mg/L of Al, As, Cd, Fe, Mn, Pb and Zn, respectively. The AMD was introduced to the system at a 1:2 ratio with raw MWW from the City of Norman, Oklahoma USA containing 265 ± 94 mg/L BOD(5), 11.5 ± 5.3 mg/L PO(4)(-3), and 20.8 ± 1.8 mg/L NH(4)(+)-N. During the 135 d experiment, PO(4)(-3) and NH(4)(+)-N were decreased to treatment is a viable ecological engineering approach for the developed and developing world that can be optimized and applied to improve water quality with minimal use of fossil fuels and refined materials. Copyright © 2010 Elsevier Ltd. All rights reserved.

Radical proposal for the treatment of malignant astrocytoma

International Nuclear Information System (INIS)

Karlsson, U.; Black, P.; Nair, S.; Yablon, J.S.; Brady, L.W.

1991-01-01

The traditional treatment for anaplastic astrocytoma (AAF) and glioblastoma multiforme (GBM) leads to local relapse. The recurring element is assumed to be previously radioresistant, reorganizing hypoxic cells that require up to three times the traditional photon irradiation dose for inactivation. We are proposing to coagulate the original lesion with high-dose precision brachytherapy, immediately followed by resection to save the patient from secondary effects of the necrotic region. The treatment then continues with adjuvant external beam radiation therapy to the local surrounding brain and concomitant chemotherapy. The approach inverts the traditional regimen. It has the virtue of being precise, avoiding secondary effects of the necrotic tumor, and satisfying accepted radiobiological principles

Breaking of the magic number N = 20 studied with the new version of AMD

International Nuclear Information System (INIS)

Kimura, Masaaki; Horiuchi, Hisashi

2002-01-01

The neutron-rich nuclei 32 Mg and 30 Ne are studied using a new version of antisymmetrized molecular dynamics (AMD). After the angular-momentum projection, 32 Mg and 30 Ne have largely deformed ground states, and the experimental data for 32 Mg are reproduced with reasonable accuracy. The ground states of these nuclei have neutron 2p2h structure. We also have studied the negative-parity states of these nuclei. Their lowest negative-parity states which have spin-parity 1 - have quite small excitation energies compared to stable N = 20 isotones. By using the Gogny force, their excitation energies have calculated to be 2.4 MeV for 30 Ne and 2.3 MeV for 32 Mg and these 1 - states have neutron 3p3h structure. (author)

CXCR4 antagonist AMD3100 reverses the neurogenesis and behavioral recovery promoted by forced limb-use in stroke rats.

Science.gov (United States)

Zhao, Shanshan; Qu, Huiling; Zhao, Yi; Xiao, Ting; Zhao, Mei; Li, Yong; Jolkkonen, Jukka; Cao, Yunpeng; Zhao, Chuansheng

2015-01-01

Forced limb-use can enhance neurogenesis and behavioral recovery as well as increasing the level of stromal cell-derived factor-1 (SDF-1) in stroke rats. We examined whether the SDF-1/CXCR4 pathway is involved in the enhanced neurogenesis and promoted behavioral recovery induced by forced limb-use in the chronic phase of stroke. The CXCR4 antagonist, AMD3100, was used to block the SDF-1/CXCR4 pathway in the ischemic rats. Brain ischemia was induced by endothelin-1. One week after ischemia, the unimpaired forelimb of rats was immobilized for 3 weeks. The proliferation, migration, and survival of DCX-positive cells in the subventricular zone (SVZ), and the dendritic complexity of DCX-positive cells in the dentate gyrus (DG), as well as the inflammatory response in the infarcted striatum were analyzed by immunohistochemistry. Functional recovery was assessed in beam-walking and water maze tests. Forced limb-use enhanced the proliferation, migration, dendritic complexity and the survival of newborn neurons. Furthermore, forced limb-use suppressed the inflammatory response and improved both motor and cognitive functions after stroke. AMD3100 significantly abrogated the enhanced neurogenesis and behavioral recovery induced by forced limb-use without influencing the inflammatory response. SDF-1/CXCR4 pathway seems to be involved in the enhancement of neurogenesis and behavioral recovery induced by post-stroke forced limb-use.

Evaluating expected outcomes of acid remediation in an intensively mined Appalachian watershed.

Science.gov (United States)

Watson, Andrew S; Merovich, George T; Petty, J Todd; Gutta, J Brady

2017-07-01

Assessments of watershed-based restoration efforts are rare but are essential for the science of stream restoration to advance. We conducted a watershed scale assessment of Abram Creek before and after implementation of a watershed-based plan designed to maximize ecological recovery from acid mine drainage (AMD) impairment. We surveyed water chemistry, physical habitat, benthic macroinvertebrates, and fish community structure in three stream types: AMD-impacted (14 streams), AMD-treated (13 streams), and unimpaired reference (4 streams). We used in-stream measurements to quantify ecological loss from AMD, the amount of ecological recovery expected through remediation, and the observed degree of post-treatment recovery. Sites impaired by AMD improved in water quality with AMD treatment. Dissolved metals and acidity declined significantly in treated streams, but sulfate and specific conductance did not. Likewise, sites impaired by AMD improved in bio-condition scores with AMD treatment. EPT genera increased significantly but were lower compared to unimpaired streams. We found fish at nine treated sites that had none before treatment. Community-level analyses indicated improved but altered assemblages with AMD treatment. Analysis of pre-treatment conditions indicated that only 30% of the historic fishery remained. Remediation was expected to recover 66% of the historic fishery value, and assessment of post-treatment conditions indicates that 52% of the historic fishery has been recovered after 3 years. Developing expected endpoints for restoration outcomes provides a tool to objectively evaluate successes and can guide adaptive management strategies.

Characterization of limestone reacted with acid-mine drainage in a pulsed limestone bed treatment system at the Friendship Hill National Historical Site, Pennsylvania, USA

Science.gov (United States)

Hammarstrom, J.M.; Sibrell, P.L.; Belkin, H.E.

2003-01-01

Armoring of limestone is a common cause of failure in limestone-based acid-mine drainage (AMD) treatment systems. Limestone is the least expensive material available for acid neutralization, but is not typically recommended for highly acidic, Fe-rich waters due to armoring with Fe(III) oxyhydroxide coatings. A new AMD treatment technology that uses CO2 in a pulsed limestone bed reactor minimizes armor formation and enhances limestone reaction with AMD. Limestone was characterized before and after treatment with constant flow and with the new pulsed limestone bed process using AMD from an inactive coal mine in Pennsylvania (pH = 2.9, Fe = 150 mg/l, acidity = 1000 mg/l CaCO3). In constant flow experiments, limestone is completely armored with reddish-colored ochre within 48 h of contact in a fluidized bed reactor. Effluent pH initially increased from the inflow pH of 2.9 to over 7, but then decreased to 6 during operation. Limestone removed from a pulsed bed pilot plant is a mixture of unarmored, rounded and etched limestone grains and partially armored limestone and refractory mineral grains (dolomite, pyrite). The ???30% of the residual grains in the pulsed flow reactor that are armored have thicker (50- to 100-??m), more aluminous coatings and lack the gypsum rind that develops in the constant flow experiment. Aluminium-rich zones developed in the interior parts of armor rims in both the constant flow and pulsed limestone bed experiments in response to pH changes at the solid/solution interface. ?? 2003 Elsevier Ltd. All rights reserved.

Aflibercept: a review of its use in the treatment of choroidal neovascularization due to age-related macular degeneration

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Balaratnasingam C

2015-12-01

Full Text Available Chandrakumar Balaratnasingam,1–3 Elona Dhrami-Gavazi,1,2,4 Jesse T McCann,1,2,4,5 Quraish Ghadiali,1,2 K Bailey Freund1,2,4,5 1Vitreous-Retina-Macula Consultants of New York, NY, USA; 2LuEsther T Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, NY, USA; 3Centre for Ophthalmology and Visual Sciences, Lions Eye Institute, University of Western Australia, Perth, WA, Australia; 4Department of Ophthalmology, Edward S Harkness Eye Institute, Columbia University College of Physicians and Surgeons, New York, NY, USA; 5Department of Ophthalmology, New York University School of Medicine, New York, NY, USA Abstract: Choroidal neovascularization (CNV due to age-related macular degeneration (AMD is an important cause of visual morbidity globally. Modern treatment strategies for neovascular AMD achieve regression of CNV by suppressing the activity of key growth factors that mediate angiogenesis. Vascular endothelial growth factor (VEGF has been the major target of neovascular AMD therapy for almost two decades, and there have been several intravitreally-administered agents that have enabled anatomical restitution and improvement in visual function with continual dosing. Aflibercept (EYLEA®, initially named VEGF Trap-eye, is the most recent anti-VEGF agent to be granted US Food and Drug Administration approval for the treatment of neovascular AMD. Biologic advantages of aflibercept include its greater binding affinity for VEGF, a longer intravitreal half-life relative to other anti-VEGF agents, and the capacity to antagonize growth factors other than VEGF. This paper provides an up-to-date summary of the molecular mechanisms mediating CNV. The structural, pharmacodynamic, and pharmacokinetic advantages of aflibercept are also reviewed to rationalize the utility of this agent for treating CNV. Results of landmark clinical investigations, including VIEW 1 and 2 trials, and other important studies are then summarized and used to

Proceedings of the 14. annual British Columbia MEND ML/ARD workshop : challenges in collection and treatment of mine drainage

International Nuclear Information System (INIS)

2008-03-01

Metal leaching and acid rock drainage (ML/ARD) are among the largest environmental challenge facing the mining industry. Efforts are underway to open new mines without long-term consequences of acid drainage. This Mine Environment Neutral Drainage (MEND) workshop focused on the development and application of new technologies that prevent and control acid mine drainage (AMD). It presented a broad range of options that are now available to the mining industry which address this issue. The workshop focused on the collection and treatment of mine drainage. The treatment of effluent during and after closure of a mining property may be complicated by the presence of AMD which may require long term collection and treatment. Known chemical and passive treatment technologies were reviewed with reference to their costs of construction, operation and maintenance, as well as their ability to meet regulations and control toxicity. The conference featured 24 presentations, of which 3 has been catalogued separately for inclusion in this database. refs., tabs., figs

Interventions to treat mental disorders during pregnancy: A systematic review and multiple treatment meta-Analysis

NARCIS (Netherlands)

L.M. van Ravesteyn (Leontien); M.P. Lambregtse-van den Berg (Mijke); W.J.G. Hoogendijk (Witte); A.M. Kamperman (Astrid)

2017-01-01

textabstractBackground For women suffering from an antepartum mental disorder (AMD), there is lack of evidencebased treatment algorithms due to the complicated risk-benefit analysis for both mother and unborn child. We aimed to provide a comprehensive overview of pharmacological and

Predictive Factors in OCT Analysis for Visual Outcome in Exudative AMD

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Maria-Andreea Gamulescu

2012-01-01

Full Text Available Background. Reliable predictive factors for therapy outcome may enable treating physicians to counsel their patients more efficiently concerning probability of improvement or time point of discontinuation of a certain therapy. Methods. This is a retrospective analysis of 87 patients with exudative age-related macular degeneration who received three monthly intravitreal ranibizumab injections. Visual acuity before initiation of intravitreal therapy and 4–6 weeks after last intravitreal injection was compared and related to the preoperative visualisation of continuity of the outer retinal layers as assessed by OCT: external limiting membrane (ELM, inner photoreceptor segments (IPS, junction between inner and outer segments (IS/OS, and outer photoreceptor segments (OPS. Results. Visual acuity increased in 40 of 87 (46.0% patients, it remained stable in 25 (28.7%, and 22 (25.3% patients had decreased visual acuity four to six weeks after triple intravitreal ranibizumab injections. No statistically significant predictive value could be demonstrated for grade of continuity of outer retinal layers concerning visual acuity development. Conclusions. In our series of AMD patients, grade of continuity of outer retinal layers was not a significant predictive value for visual acuity development after triple ranibizumab injections.

Integrated acid mine drainage management using fly ash.

Science.gov (United States)

Vadapalli, Viswanath R K; Gitari, Mugera W; Petrik, Leslie F; Etchebers, Olivier; Ellendt, Annabelle

2012-01-01

Fly Ash (FA) from a power station in South Africa was investigated to neutralise and remove contaminants from Acid Mine Drainage (AMD). After this primary treatment the insoluble FA residue namely solid residue (SR) was investigated as a suitable mine backfill material by means of strength testing. Moreover, SR was used to synthesise zeolite-P using a two-step synthesis procedure. Furthermore, the zeolite-P was investigated to polish process water from the primary FA-AMD reaction. The main objective of this series of investigations is to achieve zero waste and to propose an integrated AMD management using FA. Fly Ash was mixed with AMD at various predetermined FA-AMD ratios until the mixtures achieved circumneutral pH or higher. The supernatants were then analyzed using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and Ion Chromatography (IC) for cations and anions respectively. The physical strength testing of SR was carried out by mixing it with 3% Ordinary Portland Cement (OPC) and curing for 410 days. Synthesis of zeolite-P using SR was carried out by two step synthesis procedure: ageing for 24 hours followed by a mild hydrothermal synthesis at 100°C for 4 days. The polishing of process water from primary AMD treatment using FA was ascertained by mixing the process water with zeolite at a liquid to solid ratio of 100:1 for 1 hour. The results indicated that FA can be successfully used to ameliorate AMD. High removal of major AMD contaminants Fe, Al, Mg, Mn and sulphate was achieved with the ash treatment and trace elements such as Zn, Ni, Cu and Pb were also removed by the FA. Strength testing over 410 days indicated that the material gained strength over the testing period. The maximum unconfined compressive strength and elastic modulus was observed to be approximately 0.3 MPa and 150 Mpa respectively. The X-ray diffraction (XRD) analysis of the synthesized product indicated that SR was successfully converted into zeolite-P with some mullite phase

Breaking of the magic number N = 20 studied with the new version of AMD

Energy Technology Data Exchange (ETDEWEB)

Kimura, Masaaki; Horiuchi, Hisashi [Kyoto Univ., Dept. of Physics, Kyoto (Japan)

2002-12-01

The neutron-rich nuclei {sup 32}Mg and {sup 30}Ne are studied using a new version of antisymmetrized molecular dynamics (AMD). After the angular-momentum projection, {sup 32}Mg and {sup 30}Ne have largely deformed ground states, and the experimental data for {sup 32}Mg are reproduced with reasonable accuracy. The ground states of these nuclei have neutron 2p2h structure. We also have studied the negative-parity states of these nuclei. Their lowest negative-parity states which have spin-parity 1{sup -} have quite small excitation energies compared to stable N = 20 isotones. By using the Gogny force, their excitation energies have calculated to be 2.4 MeV for {sup 30}Ne and 2.3 MeV for {sup 32}Mg and these 1{sup -} states have neutron 3p3h structure. (author)

Possible role of Rhodotorula sp. in the formation of jarosite in the AMD environment of Muskau Arch, Poland

Science.gov (United States)

Jakus, Natalia; Chlebicki, Andrzej; Bożęcki, Piotr; Manecki, Maciej

2016-04-01

enzymatic catalysis of the oxidation of pyrite. Jarosite precipitates from solution containing sulphate, possibly product of active enzymatic oxidation of sulphur compounds by Rhodotorula. As a result of this investigation a model of sulphur transformation mediated by Rhodotorula in AMD environment and its role in precipitation of jarosite was proposed. This work is partially funded by AGH research grant no 11.11.140.319. López-Archilla, A., González, A., Terrón, M., Amils, R. 2004. Ecological study of the fungal populations of the acidic Tinto River in southwestern Spain. Canadian Journal of Microbiology, 50 (11), 923-934. Oggerin, M., Rodriguez, N., del Moral, C., Amils, R. 2014. Fungal jarosite biomineralization in Rio Tinto. Research in Microbiology. 165, 719-725.

Predictors of Visual Response to Intravitreal Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration

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Kai Fang

2013-01-01

Full Text Available Purpose. To identify the predictors of visual response to the bevacizumab treatment of neovascular age-related macular degeneration (AMD. Design. A cohort study within the Neovascular AMD Treatment Trial Using Bevacizumab (NATTB. Methods. This was a multicenter trial including 144 participants from the NATTB study. Visual outcomes measured by change in visual acuity (VA score, proportion gaining ≥15 letters, and change in central retinal thickness (CRT were compared among groups according to the baseline, demographic, and ocular characteristics and genotypes. Results. Mean change in the VA score was 9.2 ± 2.3 SD letters with a total of 46 participants (31.9% gaining ≥15 letters. Change in median CRT was −81.5 μm. Younger age, lower baseline VA score, shorter duration of neovascular AMD, and TT genotype in rs10490924 were significantly associated with greater VA score improvement (P=0.028, P<0.001, P=0.02, and P=0.039, resp.. Lower baseline VA score and TT genotype in rs10490924 were significantly associated with a higher likelihood of gaining ≥15 letters (P=0.028, and P=0.021, resp.. Conclusions. Baseline VA and genotype of rs10490924 were both important predictors for visual response to bevacizumab at 6 months. This trial is registered with the Registration no. NCT01306591.

Two-stage combined treatment of acid mine drainage and municipal wastewater.

Science.gov (United States)

Deng, Dongyang; Lin, Lian-Shin

2013-01-01

This study examined the feasibility of the combined treatment of field-collected acid mine drainages (AMD, pH = 4.2 ± 0.9, iron = 112 ± 118 mg/L, sulfate = 1,846 ± 594 mg/L) and municipal wastewater (MWW, avg. chemical oxygen demand (COD) = 234-333 mg/L) using a two-stage process. The process consisted of batch mixing of the two wastes to condition the mixture solutions, followed by anaerobic biological treatment. The mixings performed under a range of AMD/MWW ratios resulted in phosphate removal of 9 to ∼100%, the mixture pH of 6.2-7.9, and COD/sulfate concentration ratio of 0.05-5.4. The biological treatment consistently removed COD and sulfate by >80% from the mixture solutions for COD/sulfate ratios of 0.6-5.4. Alkalinity was produced in the biological treatment causing increased pH and further removal of metals from the solutions. Scanning electron microscopy of produced sludge with energy dispersion analysis suggested chemical precipitation and associated adsorption and co-precipitation as the mechanisms for metal removal (Fe: >99%, Al: ∼100%, Mn: 75 to ∼100%, Ca: 52-81%, Mg: 13-76%, and Na: 56-76%). The study showed promising results for the treatment method and denoted the potential of developing innovative technologies for combined management of the two wastes in mining regions.

Treatment Frequency and Dosing Interval of Ranibizumab and Aflibercept for Neovascular Age-Related Macular Degeneration in Routine Clinical Practice in the USA.

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Alberto Ferreira

Full Text Available To compare treatment patterns of intravitreal ranibizumab and aflibercept for the management of neovascular age-related macular degeneration (nAMD in a real-world setting over the first 12 months of treatment.A proprietary clinical database was used to identify treatment-naïve patients with nAMD in the USA with claims for ranibizumab or aflibercept between November 1, 2011 and November 30, 2013 and with follow-up of at least 12 months. Patients were considered treatment-naïve if they had no anti-VEGF treatment code for 6 months before the index date. Mean numbers of injections and of non-injection visits to a treating physician were compared between the two treatment cohorts (ranibizumab or aflibercept. In addition, the mean interval between doses was also investigated.Patient characteristics were similar for those receiving either ranibizumab (n = 5421 or aflibercept (n = 3506 at the index date. The mean (± standard deviation numbers of injections received by patients treated with ranibizumab (4.9 ± 3.3 or aflibercept (5.2 ± 2.9 were not clinically different. The mean number of non-injection visits was 2.8 ± 2.8 and 2.1 ± 2.5 for ranibizumab and aflibercept, respectively. Mean dosing interval was 51.0 days (± 41.8 days in patients receiving ranibizumab and 54.1 days (± 36.0 days in those receiving aflibercept. Results were robust to sensitivity analyses for definition of treatment-naïve, length of follow-up and treatment in the index eye only.Limited data exist regarding real-world treatment patterns of aflibercept for the management of nAMD. Our results suggest that, in routine clinical practice, patients receive a comparable number of injections in the first year of treatment with ranibizumab or aflibercept.

Designing clinical trials for age-related geographic atrophy of the macula: enrollment data from the geographic atrophy natural history study.

Science.gov (United States)

Sunness, Janet S; Applegate, Carol A; Bressler, Neil M; Hawkins, Barbara S

2007-02-01

To derive information from the Geographic Atrophy (GA) Natural History Study that is relevant to recruiting patients and designing clinical trials for GA. A prospective natural history study with annual follow-up enrolled patients with GA and no choroidal neovascularization (CNV) in at least one eye. Characteristics of recruited and enrolled patients are analyzed, in the context of progression data from the study. The data show that GA from age-related macular degeneration (AMD) was seen in 82% of the referred patients, there was an attrition rate of 14%, and 60% of the patients with GA from AMD had bilateral GA without CNV. Within the 83 patients in the bilateral GA group with follow-up, 50 patients (60%) met both the proposed visual acuity and the proposed GA area criteria for a treatment trial in one or both eyes. These data should be helpful in planning future treatment trials for GA.

Efficacy and Safety of Monthly versus Quarterly Ranibizumab Treatment in Neovascular Age-related Macular Degeneration: The EXCITE Study

NARCIS (Netherlands)

Schmidt-Erfurth, Ursula; Eldem, Bora; Guymer, Robyn; Korobelnik, Jean-Franc̦ois; Schlingemann, Reinier O.; Axer-Siegel, Ruth; Wiedemann, Peter; Simader, Christian; Gekkieva, Margarita; Weichselberger, Andreas

2011-01-01

Objective: To demonstrate noninferiority of a quarterly treatment regimen to a monthly regimen of ranibizumab in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Design: A 12-month, multicenter, randomized, double-masked,

GPU accelerated real-time confocal fluorescence lifetime imaging microscopy (FLIM) based on the analog mean-delay (AMD) method

Science.gov (United States)

Kim, Byungyeon; Park, Byungjun; Lee, Seungrag; Won, Youngjae

2016-01-01

We demonstrated GPU accelerated real-time confocal fluorescence lifetime imaging microscopy (FLIM) based on the analog mean-delay (AMD) method. Our algorithm was verified for various fluorescence lifetimes and photon numbers. The GPU processing time was faster than the physical scanning time for images up to 800 × 800, and more than 149 times faster than a single core CPU. The frame rate of our system was demonstrated to be 13 fps for a 200 × 200 pixel image when observing maize vascular tissue. This system can be utilized for observing dynamic biological reactions, medical diagnosis, and real-time industrial inspection. PMID:28018724

Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging.

Science.gov (United States)

Bowes Rickman, Catherine; Farsiu, Sina; Toth, Cynthia A; Klingeborn, Mikael

2013-12-13

Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either "wet" neovascular AMD, "dry" atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti-vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays.

Dry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging

Science.gov (United States)

Bowes Rickman, Catherine; Farsiu, Sina; Toth, Cynthia A.; Klingeborn, Mikael

2013-01-01

Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either “wet” neovascular AMD, “dry” atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti–vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays. PMID:24335072

Age-Related Macular Degeneration: Clinical Findings following Treatment with Antiangiogenic Drugs

Directory of Open Access Journals (Sweden)

Ricardo Casaroli-Marano

2014-01-01

Full Text Available Purpose. To survey the management of patients with neovascular age-related macular degeneration (nvAMD in Spain. Methods. An observational retrospective multicenter study was conducted. The variables analyzed were sociodemographic characteristics, foveal and macular thickness, visual acuity (VA, type of treatment, number of injections, and the initial administration of a loading dose of an antiangiogenic drug. Results. 208 patients were followed up during 23.4 months in average. During the first and second years, patients received a mean of 4.5±1.8 and 1.6±2.1 injections of antiangiogenic drugs, and 5.4±2.8 and 3.6±2.2 follow-up visits were performed, respectively. The highest improvement in VA was observed at 3 months of follow-up, followed by a decrease in the response that stabilized above baseline values until the end of the study. Patients who received an initial loading dose presented greater VA gains than those without. Conclusions. Our results suggest the need for a more standardized approach in the management and diagnosis of nvAMD receiving VEGF inhibitors. To achieve the visual outcomes reported in pivotal trials, an early diagnosis, proactive approach (more treating than follow-up visits, and a close monitoring might be the key to successfully manage nvAMD.

A local freshwater impact – proposing a groundwater indicator AGWaRe

DEFF Research Database (Denmark)

Gejl, Ryle Nørskov; Bjerg, Poul Løgstrup; Rasmussen, Jens

on the water resource. Furthermore a local water stress indicator is necessary for benchmarking regional water supplies against each other. AWaRe is the freshwater impact recommended by the Lifecycle Initiative (developed by WULCA). It is defined as the inverse function of Availability Minus Demand (AMD) which......Currently there are several world maps showing the water stress in regions or nations. They give a good indication of water stress on a larger scale, but do not have information on a local scale that may assist a water utility in their prioritization of well fields to lower the overall pressure...... is compared to the world average AMD. The AMD represents the water remaining after human consumption and environmental requirements. This is done for a grid of 50x50km worldwide, but it does not give sufficient information on a local scale. Therefore we modified the AWaRe indicator so that it can account...

Decision Support System for Age-Related Macular Degeneration Using Convolutional Neural Networks

Directory of Open Access Journals (Sweden)

Mostafa Langarizadeh

2017-09-01

Full Text Available Introduction: Age-related macular degeneration (AMD is one of the major causes of visual loss among the elderly. It causes degeneration of cells in the macula. Early diagnosis can be helpful in preventing blindness. Drusen are the initial symptoms of AMD. Since drusen have a wide variety, locating them in screening images is difficult and time-consuming. An automated digital fundus photography-based screening system help overcome such drawbacks. The main objective of this study was to suggest a novel method to classify AMD and normal retinal fundus images. Materials and Methods: The suggested system was developed using convolutional neural networks. Several methods were adopted for increasing data such as horizontal reflection, random crop, as well as transfer and combination of such methods. The suggested system was evaluated using images obtained from STARE database and a local dataset. Results: The local dataset contained 3195 images (2070 images of AMD suspects and 1125 images of healthy retina and the STARE dataset comprised of 201 images (105 images of AMD suspects and 96 images of healthy retina. According to the results, the accuracies of the local and standard datasets were 0.95 and 0.81, respectively. Conclusion: Diagnosis and screening of AMD is a time-consuming task for specialists. To overcome this limitation, we attempted to design an intelligent decision support system for the diagnosis of AMD fundus using retina images. The proposed system is an important step toward providing a reliable tool for supervising patients. Early diagnosis of AMD can lead to timely access to treatment.

Is Spectral-Domain Optical Coherence Tomography Essential for Flexible Treatment Regimens with Ranibizumab for Neovascular Age-Related Macular Degeneration?

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Abdullah Ozkaya

2013-01-01

Full Text Available Purpose. To evaluate the ability of spectral-domain optical coherence tomography to detect subtle amounts of retinal fluid when the choroidal neovascularization is detected as inactive via time-domain optical coherence tomography and clinical examination in neovascular age-related macular degeneration (nAMD patients. Methods. Forty-nine eyes of 49 patients with nAMD after ranibizumab treatment were included in this cross-sectional, prospective study. All patients were imaged with TD-OCT and SD-OCT at the same visit one month after a ranibizumab injection. The presence of subretinal, intraretinal, and subretinal pigment epithelium fluid (subRPE in SD-OCT was evaluated; also mean central retinal thickness (CRT and the rate of vitreoretinal surface disorders detected via the two devices were evaluated. Results. The mean CRT via TD-OCT and SD-OCT was 218.1±51.3 and 325.7±78.8 microns. Sixteen patients (32.6% showed any kind of retinal fluid via SD-OCT. In detail, 8 patients (16.3% showed subretinal fluid, 10 patients (20.4% showed intraretinal fluid, and 3 patients (6.1% showed SubRPE fluid. The ability of detecting vitreoretinal surface disorders was comparable between the two devices, except vitreomacular traction. Conclusion. SD-OCT is essential for the nAMD patients who are on an as-needed treatment regimen with ranibizumab. Only TD-OCT and clinical examination may cause insufficient treatment in this group of patients.

DEMONSTRATION OF AQUAFIX AND SAPS PASSIVE MINE WATER TREATMENT TECHNOLOGIES AT SUMMITVILLE MINE SITE, INNOVATIVE TECHNOLOGY EVALUATION REPORT

Science.gov (United States)

As part of the Superfund Innovative Technology Evaluation (SITE) Program, the U.S. Environmental Protection Agency evaluated two passive water treatment (PWT) technologies for metals removal from acid mine drainage (AMD) at the Summitville Mine Superfund Site in southern Colorado...

Mine Water Treatment in Hongai Coal Mines

Science.gov (United States)

Dang, Phuong Thao; Dang, Vu Chi

2018-03-01

Acid mine drainage (AMD) is recognized as one of the most serious environmental problem associated with mining industry. Acid water, also known as acid mine drainage forms when iron sulfide minerals found in the rock of coal seams are exposed to oxidizing conditions in coal mining. Until 2009, mine drainage in Hongai coal mines was not treated, leading to harmful effects on humans, animals and aquatic ecosystem. This report has examined acid mine drainage problem and techniques for acid mine drainage treatment in Hongai coal mines. In addition, selection and criteria for the design of the treatment systems have been presented.

Implementation studies of ranibizumab for neovascular age-related macular degeneration.

Science.gov (United States)

Bloch, Sara Brandi

2013-11-01

The pathogenesis of AMD is associated with age changes plus pathological changes involving oxidative stress and an altered inflammatory response leading to injury of retinal pigment epithelial cells and the adjacent choroidea and photoreceptor cells. AMD is divided into early, intermediate and advanced AMD. The advanced form of AMD is further divided into non-neovascular AMD and neovascular AMD. The diagnosis of neovascular AMD is based on FA and clinical characteristics of the eyes. The CNV lesions are by their growth pattern divided into type 1 CNV lesions, which grow primarily beneath the RPE, and type 2 CNV lesions, which have penetrated the RPE and evolve within the subretinal space. The natural course of neovascular AMD leads to visual disability in a majority of cases within the first years after onset, primarily caused by the development of subfoveal fibrous tissue and atrophy of the RPE. The prognosis of visual acuity in neovascular AMD has been markedly improved by the introduction of an intravitreal administered VEGF inhibitor (ranibizumab) given on a monthly basis. Treatment with ranibizumab for neovascular AMD was introduced in Denmark in 2006 under a fully reimbursed national healthcare plan. Treatment with ranibizumab is given in a variable dosing regimen that varies from the monthly dosing regimen administered in the studies that led to the approval of ranibizumab for neovascular AMD in Europe. The main objectives of this PhD thesis were to evaluate and potentially improve treatment with ranibizumab in a variable OCT guided regimen for neovascular AMD. Another intension of this PhD thesis was to prepare the conditions for future research to further improve the visual prognosis in neovascular AMD treated with anti-VEGF agents. The first study revealed that vision was improved in eyes with active neovascular AMD treated for 1 year in a variable ranibizumab treatment regimen as compared to PDT and the natural course of the disease. We assumed by

A systematic review on zinc for the prevention and treatment of age-related macular degeneration

Science.gov (United States)

Zinc is a potential candidate for the prevention and treatment of age-related macular degeneration (AMD) due to its high concentration in the retina and role as a cofactor for antioxidant enzymes. The objective of this work was to conduct a systematic review of studies that investigated dietary inta...

Recent Developments for Remediating Acidic Mine Waters Using Sulfidogenic Bacteria

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Ivan Nancucheo

2017-01-01

Full Text Available Acidic mine drainage (AMD is regarded as a pollutant and considered as potential source of valuable metals. With diminishing metal resources and ever-increasing demand on industry, recovering AMD metals is a sustainable initiative, despite facing major challenges. AMD refers to effluents draining from abandoned mines and mine wastes usually highly acidic that contain a variety of dissolved metals (Fe, Mn, Cu, Ni, and Zn in much greater concentration than what is found in natural water bodies. There are numerous remediation treatments including chemical (lime treatment or biological methods (aerobic wetlands and compost bioreactors used for metal precipitation and removal from AMD. However, controlled biomineralization and selective recovering of metals using sulfidogenic bacteria are advantageous, reducing costs and environmental risks of sludge disposal. The increased understanding of the microbiology of acid-tolerant sulfidogenic bacteria will lead to the development of novel approaches to AMD treatment. We present and discuss several important recent approaches using low sulfidogenic bioreactors to both remediate and selectively recover metal sulfides from AMD. This work also highlights the efficiency and drawbacks of these types of treatments for metal recovery and points to future research for enhancing the use of novel acidophilic and acid-tolerant sulfidogenic microorganisms in AMD treatment.

Synthesising acid mine drainage to maintain and exploit indigenous mining micro-algae and microbial assemblies for biotreatment investigations.

Science.gov (United States)

Orandi, Sanaz; Lewis, David M

2013-02-01

The stringent regulations for discharging acid mine drainage (AMD) has led to increased attention on traditional or emerging treatment technologies to establish efficient and sustainable management for mine effluents. To assess new technologies, laboratory investigations on AMD treatment are necessary requiring a consistent supply of AMD with a stable composition, thus limiting environmental variability and uncertainty during controlled experiments. Additionally, biotreatment systems using live cells, particularly micro-algae, require appropriate nutrient availability. Synthetic AMD (Syn-AMD) meets these requirements. However, to date, most of the reported Syn-AMDs are composed of only a few selected heavy metals without considering the complexity of actual AMD. In this study, AMD was synthesised based on the typical AMD characteristics from a copper mine where biotreatment is being considered using indigenous AMD algal-microbes. Major cations (Ca, Na, Cu, Zn, Mg, Mn and Ni), trace metals (Al, Fe, Ag, Na, Co, Mo, Pb and Cr), essential nutrients (N, P and C) and high SO(4) were incorporated into the Syn-AMD. This paper presents the preparation of chemically complex Syn-AMD and the challenges associated with combining metal salts of varying solubility that is not restricted to one particular mine site. The general approach reported and the particular reagents used can produce alternative Syn-AMD with varying compositions. The successful growth of indigenous AMD algal-microbes in the Syn-AMD demonstrated its applicability as appropriate generic media for cultivation and maintenance of mining microorganisms for future biotreatment studies.

Recent advances in the management of dry age-related macular degeneration: A review [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Francesco Bandello

2017-03-01

Full Text Available Age-related macular degeneration (AMD, the most important cause of vision loss in elderly people, is a degenerative disorder of the central retina with a multifactorial etiopathology. AMD is classified in dry AMD (d-AMD or neovascular AMD depending on the presence of choroidal neovascularization. Currently, no therapy is approved for geographic atrophy, the late form of d-AMD, because no treatment can restore the damage of retinal pigment epithelium (RPE or photoreceptors. For this reason, all treatment approaches in d-AMD are only likely to prevent and slow down the progression of existing atrophy. This review focuses on the management of d-AMD and especially on current data about potential targets for therapies evaluated in clinical trials. Numerous examinations are available in clinics to monitor morphological changes in the retina, RPE and choroid of d-AMD patients. Fundus autofluorescence and optical coherence tomography (OCT are considered the most useful tools in the diagnosis and follow-up of d-AMD alterations, including the monitoring of atrophy area progression. Instead, OCT-angiography is a novel imaging tool that may add further information in patients affected by d-AMD. Several pathways, including oxidative stress, deposits of lipofuscin, chronic inflammation and choroidal blood flow insufficiency, seem to play an important role in the pathogenesis of d-AMD and represent possible targets for new therapies. A great number of treatments for d-AMD are under investigation with promising results in preliminary studies. However, only few of these drugs will enter the market, offering a therapeutic chance to patients affected by the dry form of AMD and help them to preserve a good visual acuity. Further studies with a long-term follow-up would be important to test the real safety and efficacy of drugs under investigation.

Recent advances in the management of dry age-related macular degeneration: A review.

Science.gov (United States)

Bandello, Francesco; Sacconi, Riccardo; Querques, Lea; Corbelli, Eleonora; Cicinelli, Maria Vittoria; Querques, Giuseppe

2017-01-01

Age-related macular degeneration (AMD), the most important cause of vision loss in elderly people, is a degenerative disorder of the central retina with a multifactorial etiopathology. AMD is classified in dry AMD (d-AMD) or neovascular AMD depending on the presence of choroidal neovascularization. Currently, no therapy is approved for geographic atrophy, the late form of d-AMD, because no treatment can restore the damage of retinal pigment epithelium (RPE) or photoreceptors. For this reason, all treatment approaches in d-AMD are only likely to prevent and slow down the progression of existing atrophy. This review focuses on the management of d-AMD and especially on current data about potential targets for therapies evaluated in clinical trials. Numerous examinations are available in clinics to monitor morphological changes in the retina, RPE and choroid of d-AMD patients. Fundus autofluorescence and optical coherence tomography (OCT) are considered the most useful tools in the diagnosis and follow-up of d-AMD alterations, including the monitoring of atrophy area progression. Instead, OCT-angiography is a novel imaging tool that may add further information in patients affected by d-AMD. Several pathways, including oxidative stress, deposits of lipofuscin, chronic inflammation and choroidal blood flow insufficiency, seem to play an important role in the pathogenesis of d-AMD and represent possible targets for new therapies. A great number of treatments for d-AMD are under investigation with promising results in preliminary studies. However, only few of these drugs will enter the market, offering a therapeutic chance to patients affected by the dry form of AMD and help them to preserve a good visual acuity. Further studies with a long-term follow-up would be important to test the real safety and efficacy of drugs under investigation.

Fixation stability and implication for multifocal electroretinography in patients with neovascular age-related macular degeneration after anti-VEGF treatment

DEFF Research Database (Denmark)

Pedersen, Karen Bjerg; Sjølie, Anne Katrin; Vestergaard, Anders Højslet

2016-01-01

Purpose: To quantify fixation stability in patients with neovascular age-related macular degeneration (nAMD) at baseline, 3 and 6 months after anti-vascular endothelial growth factor (anti-VEGF) treatment and furthermore asses the implications of an unsteady fixation for multifocal...

Relationship of retinal morphology and retinal sensitivity in the treatment of neovascular age-related macular degeneration using aflibercept.

Science.gov (United States)

Sulzbacher, Florian; Roberts, Philipp; Munk, Marion R; Kaider, Alexandra; Kroh, Maria Elisabeth; Sacu, Stefan; Schmidt-Erfurth, Ursula

2014-12-11

To relate the functional response to distinct morphological features of the retina during aflibercept treatment for neovascular AMD (nAMD). A total of 726 retinal locations in 22 consecutive eyes presenting with treatment-naive nAMD underwent a standardized examination with spectral-domain optical coherence tomography (SD-OCT) and topographic microperimetry (MP) at baseline, after 3 and 12 months of continuous intravitreal aflibercept therapy. The retinal sensitivity at each stimulus location was registered to the corresponding location on SD-OCT morphology. Subsequently, the microperimetric responses were evaluated with respect to the following underlying SD-OCT features: neovascular complex (NVC), subretinal fluid (SRF), intraretinal fluid (IRF), intraretinal cystoid space (IRC), serous pigment epithelium detachment (sPED), and fibrovascular pigment epithelium detachment (fPED). Baseline sensitivity was reduced to mean values of 1.8 dB in NVC, 2.2 dB in IRC, 2.8 dB in IRF, 2.6 dB in sPED, 3.6 dB in SRF, and 4.6 dB in fPED. Improvements in retinal sensitivity were most pronounced during the initial 3-month interval, when significant recovery was documented for SRF and sPED with +4.0/5.5 dB (P 0.05 for each category). Significant functional benefits following intravitreal aflibercept treatment could be detected over all defined morphological pathologies. The level of improvement varied dependent on the associated feature with the best prognosis for visual improvement in SRF and sPED and least with intraretinal fluid and particularly intraretinal cysts. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

PHMB: Utilización del apósito de espuma antimicrobiana (AMD KendallTM (PHMB 0,5% en el tratamiento de las heridas crónicas

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John Timmons

Full Text Available Abordamos la parte más problemática del tratamiento de las heridas crónicas o agudas, de acuerdo con los profesionales especializados es la infección de la herida. La sobrecarga bacteriana puede retardar la curación de la herida y disminuir la calidad del paciente como consecuencia del aumento del dolor, del exudado y del posible mal olor. Se han recopilado casos clínicos durante los últimos 6 meses en una unidad especializada en el cuidado de heridas de los hospitales Doncaster y Bassetlaw, RU. Estos casos ilustran la variedad de tipos de herida que pueden tratarse con éxito con el nuevo apósito de Espuma antimicrobiano KendallTM AMD (PHMB 0,5%. Se pudo concluir que el apósito de Espuma KendallTM AMD actúa bien como antimicrobiano y como producto de vendaje moderno. Su utilización disminuye la carga bacteriana al tiempo que consigue la absorción del exudado y el mantenimiento de un ambiente óptimo para la curación de la herida.

Suppression of radiation mutagenesis by dactinomycin in Chinese hamster cells

International Nuclear Information System (INIS)

Tokita, N.; Capenter, S.G.; Chen, D.J.; MacInnes, M.A.; Raju, M.R.

1985-01-01

Dactinomycin (AMD) suppression of radiation mutagenesis was investigated using an in vitro mutation assay (6-thioguanine resistance) in Chinese hamster ovary cells. Cells were exposed to acute single doses of x rays followed by 1 hr-treatment with 0.1 or 1 μg/ml AMD. The cell survival curves plotted as a function of x-ray doses were similar for radiation alone and radiation plus AMD. The results suggest that AMD treatment was only slightly mutagenic, however, when given immediately after irradiation, it suppressed radiatiion mutagenesis at higher x-ray dose regions (below 10% survival levels). Higher AMD concentrations appeared more suppressive than lower concentrations. Dose-response data analyzed based on Poisson distribution models suggest the stochastic dependence of x-ray mutagenesis and AMD cytotoxity

Risk assessment of CST-7 proposed waste treatment and storage facilities Volume I: Limited-scope probabilistic risk assessment (PRA) of proposed CST-7 waste treatment & storage facilities. Volume II: Preliminary hazards analysis of proposed CST-7 waste storage & treatment facilities

Energy Technology Data Exchange (ETDEWEB)

Sasser, K.

1994-06-01

In FY 1993, the Los Alamos National Laboratory Waste Management Group [CST-7 (formerly EM-7)] requested the Probabilistic Risk and Hazards Analysis Group [TSA-11 (formerly N-6)] to conduct a study of the hazards associated with several CST-7 facilities. Among these facilities are the Hazardous Waste Treatment Facility (HWTF), the HWTF Drum Storage Building (DSB), and the Mixed Waste Receiving and Storage Facility (MWRSF), which are proposed for construction beginning in 1996. These facilities are needed to upgrade the Laboratory`s storage capability for hazardous and mixed wastes and to provide treatment capabilities for wastes in cases where offsite treatment is not available or desirable. These facilities will assist Los Alamos in complying with federal and state requlations.

Cost effectiveness of pegaptanib for the treatment of age-related macular degeneration in the UK.

Science.gov (United States)

Wolowacz, Sorrel E; Roskell, Neil; Kelly, Steven; Maciver, Fiona M; Brand, Chris S

2007-01-01

Age-related macular degeneration (AMD) is the primary cause of vision loss in the elderly and results in significant economic and humanistic burden. The selective vascular endothelial growth factor inhibitor, pegaptanib (Macugen) is indicated for patients with neovascular AMD. Guidance is needed regarding the cost effectiveness of treatment, any variation between sub-populations of differing clinical characteristics and the optimum duration of treatment. To estimate the cost effectiveness of pegaptanib versus best supportive care (BSC) for AMD from the perspective of the UK government, and to evaluate the impact of patient characteristics and differing treatment discontinuation scenarios. A cohort of 1000 patients aged >45 years with a best-corrected visual acuity (VA) in their better-seeing eye of age, gender, lesion type or lesion size as covariates. Mortality rates were adjusted for the age, gender and VA of the population. Cost effectiveness was expressed as the incremental cost (IC) per vision-year saved and IC/QALY. Uncertainty was explored by probabilistic and univariate sensitivity analysis. Costs (year 2005 values) and outcomes were discounted at 3.5% per anum. In the base-case analysis, treatment was targeted to patients with a VA of 6/12 to 6/95 and discontinued after 2 years, or earlier if VA fell below 6/95 or by > or =6 lines. The IC/QALY was estimated as 8023 pounds(upper 95% CI 20,641 pounds). Cost effectiveness varied by age (age age > or =75 years = 11,657 pounds/QALY) and by pre-treatment VA (6/12-6/95 = 8023 pounds/QALY; 6/12-6/60 = 6664 pounds/QALY; 6/12-6/24 = 1920 pounds/QALY). Gender and lesion type or size had little effect. Cost effectiveness was not sensitive to precise rules for treatment discontinuation, but was maximised if treatment was discontinued in patients no longer likely to benefit. The results suggest that pegaptanib treatment is likely to be cost effective across all groups studied, and marginally more cost effective in

The relationship between vascular endothelial dysfunction and treatment frequency in neovascular age-related macular degeneration.

Science.gov (United States)

Ueda-Consolvo, Tomoko; Hayashi, Atsushi; Ozaki, Mayumi; Nakamura, Tomoko; Yagou, Takaaki; Abe, Shinya

2017-07-01

To assess the correlation between endothelial dysfunction and frequency of antivascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD). We examined 64 consecutive patients with nAMD who were evaluated for endothelial function by use of peripheral arterial tonometry (EndoPAT 2000; Itamar Medical, Caesarea, Israel) at Toyama University Hospital from January 2015. We tallied the number of anti-VEGF treatments between January 2014 and December 2015 and determined the correlation between the number of anti-VEGF injections and endothelial function expressed as the reactive hyperemia index (RHI). Multiple regression analysis was also performed to identify the independent predictors of a larger number of injections. The mean number of anti-VEGF injections was 8.2 ± 3.3. The mean lnRHI was 0.47 ± 0.17. The lnRHI correlated with the number of anti-VEGF injections (r = -0.56; P = 0.030). The multiple regression analysis revealed that endothelial function, neovascular subtypes, and treatment regimens were associated with the number of injections. Endothelial dysfunction may affect the efficacy of anti-VEGF therapy. Neovascular subtypes may also predict a larger number of injections.

[A new possible strategy for prevention and preventive treatment of age-related macular degeneration resting on recent clinical and pathophysiological observations].

Science.gov (United States)

Fischer, Tamás

2009-03-15

The beneficial effect achieved by the treatment of endothelial dysfunction in chronic cardiovascular diseases is already an evidence belonging to the basic treatment of the disease. Given the fact that the vascular system is uniform and consubstantial both physiologically, pathophysiologically and in terms of therapy, and that it plays a key role in age-related macular degeneration (AMD)--a disease leading to tragic loss of vision with its etiology and therapy being unknown--endothelial dysfunction should be treated. The pleiotropic effects of ACE-inhibitors, AR-blockers and statins and third generation beta blockers help to restitute the balance between vasodilators and vasoconstrictors in endothelial dysfunction caused by oxidative stress, the balance of growth factors and their inhibitors, pro- and anti-inflammatory substances and prothrombotic and fibrinolytic factors, inhibit the formation of oxidative stress and its harmful effects; while aspirin with its pleiotropic effects acting as an antiaggregation substance on platelets helps to set the endothelial layer back to its normal balance regarding its vasodilating, antithrombotic, antiadhesive and anti-inflammatory functions; trimetazidine as an adjuvant agent helps to normalize, to restore the disturbed metabolism of the retinal tissue functioning insufficiently, in the end. The angiotensin II receptor blocker telmisartan with its peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist effect inhibits the development of choroidal neovascularisation (CNV) and improves it clinically favourably. The third generation beta adrenergic receptor blocker carvedilol and nebivolol as well as the peroxisome proliferator-activated receptor-gamma agonist pioglitazone elicit their antioxidant vascular protective effects mitochondrially. For the above reasons it is suggested that, as a part of long term primary and/or secondary prevention, the following groups of patients with AMD receive--taking into

Mine Water Treatment in Hongai Coal Mines

Directory of Open Access Journals (Sweden)

Dang Phuong Thao

2018-01-01

Full Text Available Acid mine drainage (AMD is recognized as one of the most serious environmental problem associated with mining industry. Acid water, also known as acid mine drainage forms when iron sulfide minerals found in the rock of coal seams are exposed to oxidizing conditions in coal mining. Until 2009, mine drainage in Hongai coal mines was not treated, leading to harmful effects on humans, animals and aquatic ecosystem. This report has examined acid mine drainage problem and techniques for acid mine drainage treatment in Hongai coal mines. In addition, selection and criteria for the design of the treatment systems have been presented.

Acid Mine Drainage Research in Gauteng Highlighting Impacts on Infrastructure and Innovation of Concrete-Based Remedial Systems

Science.gov (United States)

Diop, S.; Ekolu, S.; Azene, F.

2013-12-01

Acid mine drainage (AMD) is presently one of the most important environmental problems in in the densely populated Gauteng Province, South Africa. The threat of acid mine drainage has demanded short-term interventions (some of which are being implemented by government) but more importantly sustainable long-term innovative solutions. There have been moments of public apprehension with some media reports dubbing the current scenario as a future 'nightmare of biblical proportions' and 'South Africa's own Chernobyl' that could cause dissolving of concrete foundations of buildings and reinforcement steel, leading to collapse of structures. In response to the needs of local and provincial authorities, this research was conducted to (1) generate scientific understanding of the effects of AMD on infrastructure materials and structures, and (2) propose innovative long-term remedial systems based on cementitious materials for potential AMD treatment applications of engineering scale. Two AMD solutions from the goldfields and two others from the coalfields were used to conduct corrosion immersion tests on mild steel, stainless steel, mortars, pastes and concretes. Results show that AMD water from the gold mines is more corrosive than that from the coal mines, the corrosion rate of the former being about twice that of the latter. The functionality of metal components of mild steel can be expected to fail within one month of exposure to the mine water. The investigation has also led to development of a pervious concrete filter system of water-cement ratio = 0.27 and cement content = 360 kg/m3, to be used as a permeable reactive barrier for AMD treatment. Early results show that the system was effective in removing heavy metal contaminants with removal levels of 30% SO4, 99% Fe, 50-83% Mn, 85% Ca, and 30% TDS. Further work is on-going to improve and optimise the system prior to field demonstration studies.

Towards Treatment of Stargardt Disease: Workshop Organized and Sponsored by the Foundation Fighting Blindness.

Science.gov (United States)

Sears, Avery E; Bernstein, Paul S; Cideciyan, Artur V; Hoyng, Carel; Charbel Issa, Peter; Palczewski, Krzysztof; Rosenfeld, Philip J; Sadda, SriniVas; Schraermeyer, Ulrich; Sparrow, Janet R; Washington, Ilyas; Scholl, Hendrik P N

2017-09-01

Accumulation of fluorescent metabolic byproducts of the visual (retinoid) cycle is associated with photoreceptor and retinal pigment epithelial cell death in both Stargardt disease and atrophic (nonneovascular) age-related macular degeneration (AMD). As a consequence of this observation, small molecular inhibitors of enzymes in the visual cycle were recently tested in clinical trials as a strategy to protect the retina and retinal pigment epithelium in patients with atrophic AMD. To address the clinical translational needs for therapies aimed at both diseases, a workshop organized by the Foundation Fighting Blindness was hosted by the Department of Pharmacology at Case Western Reserve University on February 17, 2017, at the Tinkham Veale University Center, Cleveland, OH, USA. Invited speakers highlighted recent advances in the understanding of the pathophysiology of Stargardt disease, in terms of its clinical characterization and the development of endpoints for clinical trials, and discussed the comparability of therapeutic strategies between atrophic age-related macular degeneration (AMD) and Stargardt disease. Investigators speculated that reducing the concentrations of visual cycle precursor substances and/or their byproducts may provide valid therapeutic options for the treatment of Stargardt disease. Here we review the workshop's presentations in the context of published literature to help shape the aims of ongoing research endeavors and aid the development of therapies for Stargardt disease.

The results of diagnostic and treatment of patients with diabetic retinopathy and age-related macular degeneration at a diabetes type 2.

Directory of Open Access Journals (Sweden)

I. V. Vorobyova

2014-10-01

Full Text Available Purpose: Explore the changing clinical and functional and morphological changes of the retina against application of angiogenesis inhibitor in patients with diabetes type 2 with comorbidity fundus: diabetic retinopathy (DR and agerelated macular degeneration (AMD.Patients and Methods. In the main study group included 22 patients (22 eyes with type 2 diabetes with combined fundus pathology DR and AMD. All patients before and after intravitreal injection of an angiogenesis inhibitor ranibizumab (Lucentis, Novartis was assessed visual acuity, macular thickness and macular morphology based on the results of OCT, the retinal sensitivity according to the data of microperimetry (MAIA. The control group study included 30 people (15 healthy and 15 with type 2 diabetes without DR.Results. When comparing the main group with the control group was revealed that visual acuity in the main group (0,27±0,05 was significantly lower than in the control group (0,8±0,01, p <0.05; retinal thickness was significantly higher in the control group, and the retinal sensitivity was significantly lower. On the background of intravitreal injection of ranibizumab all patients with DR and AMD had significantly increase in visual acuity on average by 37 % (from 0,27±0,05 before treatment to 0,37±0,05 after treatment, a significantly reduction of macular thickness in 9 out of 9 areas, including the fovea centralis, an average of 32.6 % and increase retinal sensitivity by 24 % (from 11,75±1,68 (dB to 14,58±1,68 (dB, (p <0.05. The correlations were found between visual acuity and retinal thickness, as well as between visual acuity and retinal sensitivity of the macula, before treatment r = –0,26, p <0.01 and r = 0,7 p <0.01, respectively, after treatment with r = –0,14, p <0.01 and r = 0,64, p <0.01, respectively. Conclusions. Intravitreal injection of angiogenesis inhibitor ranibizumab to patients with comorbidity fundus DR and AMD on a background of

The results of diagnostic and treatment of patients with diabetic retinopathy and age-related macular degeneration at a diabetes type 2.

Directory of Open Access Journals (Sweden)

I. V. Vorobyova

2014-01-01

Full Text Available Purpose: Explore the changing clinical and functional and morphological changes of the retina against application of angiogenesis inhibitor in patients with diabetes type 2 with comorbidity fundus: diabetic retinopathy (DR and agerelated macular degeneration (AMD.Patients and Methods. In the main study group included 22 patients (22 eyes with type 2 diabetes with combined fundus pathology DR and AMD. All patients before and after intravitreal injection of an angiogenesis inhibitor ranibizumab (Lucentis, Novartis was assessed visual acuity, macular thickness and macular morphology based on the results of OCT, the retinal sensitivity according to the data of microperimetry (MAIA. The control group study included 30 people (15 healthy and 15 with type 2 diabetes without DR.Results. When comparing the main group with the control group was revealed that visual acuity in the main group (0,27±0,05 was significantly lower than in the control group (0,8±0,01, p <0.05; retinal thickness was significantly higher in the control group, and the retinal sensitivity was significantly lower. On the background of intravitreal injection of ranibizumab all patients with DR and AMD had significantly increase in visual acuity on average by 37 % (from 0,27±0,05 before treatment to 0,37±0,05 after treatment, a significantly reduction of macular thickness in 9 out of 9 areas, including the fovea centralis, an average of 32.6 % and increase retinal sensitivity by 24 % (from 11,75±1,68 (dB to 14,58±1,68 (dB, (p <0.05. The correlations were found between visual acuity and retinal thickness, as well as between visual acuity and retinal sensitivity of the macula, before treatment r = –0,26, p <0.01 and r = 0,7 p <0.01, respectively, after treatment with r = –0,14, p <0.01 and r = 0,64, p <0.01, respectively. Conclusions. Intravitreal injection of angiogenesis inhibitor ranibizumab to patients with comorbidity fundus DR and AMD on a background of

Proposal of an environmental performance index to assess solid waste treatment technologies

International Nuclear Information System (INIS)

Goulart Coelho, Hosmanny Mauro; Lange, Liséte Celina; Coelho, Lineker Max Goulart

2012-01-01

Highlights: ► Proposal of a new concept in waste management: Cleaner Treatment. ► Development of an index to assess quantitatively waste treatment technologies. ► Delphi Method was carried out so as to define environmental indicators. ► Environmental performance evaluation of waste-to-energy plants. - Abstract: Although the concern with sustainable development and environment protection has considerably grown in the last years it is noted that the majority of decision making models and tools are still either excessively tied to economic aspects or geared to the production process. Moreover, existing models focus on the priority steps of solid waste management, beyond waste energy recovery and disposal. So, in order to help the lack of models and tools aiming at the waste treatment and final disposal, a new concept is proposed: the Cleaner Treatment, which is based on the Cleaner Production principles. This paper focuses on the development and validation of the Cleaner Treatment Index (CTI), to assess environmental performance of waste treatment technologies based on the Cleaner Treatment concept. The index is formed by aggregation (summation or product) of several indicators that consists in operational parameters. The weights of the indicator were established by Delphi Method and Brazilian Environmental Laws. In addition, sensitivity analyses were carried out comparing both aggregation methods. Finally, index validation was carried out by applying the CTI to 10 waste-to-energy plants data. From sensitivity analysis and validation results it is possible to infer that summation model is the most suitable aggregation method. For summation method, CTI results were superior to 0.5 (in a scale from 0 to 1) for most facilities evaluated. So, this study demonstrates that CTI is a simple and robust tool to assess and compare the environmental performance of different treatment plants being an excellent quantitative tool to support Cleaner Treatment implementation.

Cellular models and therapies for age-related macular degeneration

Directory of Open Access Journals (Sweden)

David L. Forest

2015-05-01

Full Text Available Age-related macular degeneration (AMD is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD. A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease.

Fundus autofluorescence imaging in dry AMD: 2014 Jules Gonin lecture of the Retina Research Foundation.

Science.gov (United States)

Holz, Frank G; Steinberg, Julia S; Göbel, Arno; Fleckenstein, Monika; Schmitz-Valckenberg, Steffen

2015-01-01

Fundus autofluorescence (FAF) imaging allows for topographic mapping of intrisnic fluorophores in the retinal pigment epithelial cell monolayer, as well as mapping of other fluorophores that may occur with disease in the outer retina and the sub-neurosensory space. FAF imaging provides information not obtainable with other imaging modalities. Near-infrared fundus autofluorescence images can also be obtained in vivo, and may be largely melanin-derived. FAF imaging has been shown to be useful in a wide spectrum of macular and retinal diseases. The scope of applications now includes identification of diseased RPE in macular/retinal diseases, elucidating pathophysiological mechanisms, identification of early disease stages, refined phenotyping, identification of prognostic markers for disease progression, monitoring disease progression in the context of both natural history and interventional therapeutic studies, and objective assessment of luteal pigment distribution and density as well as RPE melanin distribution. Here, we review the use of FAF imaging in various phenotypic manifestations of dry AMD.

Neutralisation treatment of AMD at affordable cost

African Journals Online (AJOL)

2012-06-11

Jun 11, 2012 ... capital cost of a pump station and pipeline that can transport. 25 Mℓ/d water over ... with a fine bubble diffuser for mixing and aeration. Each batch test was ... solids were allowed to settle, clear water was decanted and then replaced with a ..... steel tank, lined to protect the metal from corrosion. It is equipped ...

The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration.

Science.gov (United States)

Gorusupudi, Aruna; Nelson, Kelly; Bernstein, Paul S

2017-01-01

Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. With an increasingly aged population worldwide, the need for the prevention of AMD is rising. Multiple studies investigating AMD with the use of animal models and cell culture have identified oxidative stress-related retinal damage as an important contributing factor. In general, diet is an excellent source of the antioxidants, vitamins, and minerals necessary for healthy living; moreover, the general public is often receptive to recommendations made by physicians and health care workers regarding diet and supplements as a means of empowering themselves to avoid common and worrisome ailments such as AMD, which has made epidemiologists and clinicians enthusiastic about dietary intervention studies. A wide variety of nutrients, such as minerals, vitamins, ω-3 (n-3) fatty acids, and various carotenoids, have been associated with reducing the risk of AMD. Initial results from the Age-Related Eye Disease Study (AREDS) indicated that supplementation with antioxidants (β-carotene and vitamins C and E) and zinc was associated with a reduced risk of AMD progression. The AREDS2 follow-up study, designed to improve upon the earlier formulation, tested the addition of lutein, zeaxanthin, and ω-3 fatty acids. In this review, we examine the science behind the nutritional factors included in these interventional studies and the reasons for considering their inclusion to lower the rate of AMD progression. © 2017 American Society for Nutrition.

Two-Year Outcome of Aflibercept in Patients with Pigment Epithelial Detachment due to Neovascular Age-Related Macular Degeneration (nAMD) Refractory to Ranibizumab

Science.gov (United States)

Dumas, Stéphane; Coscas, Florence

2017-01-01

Purpose To evaluate the response of intravitreal aflibercept injection (IAI) in eyes with detachment of retinal pigment epithelium (DEP) secondary to nAMD refractory to monthly ranibizumab. Patients and Methods This is a retrospective, multicenter study. All patients received 3 IAI then treated as needed every 4 weeks for 12 months. During the second year, the eyes were treated with a treat- and-extend regimen. Results Forty-four eyes were included. Best-corrected visual acuity improved significantly after the loading phase (3.1 ± 6.4 letters) and at 6 months (2.8 ± 6.4 letters), but change was not significant at 1 year and 2 years. The height of the DEP was significantly decreased at 3 months and 6 months, but the difference did not reach statistical difference at 1 and 2 years. Rate of eyes with complete resolution of exudation was 59% after the loading phase and 34.3% at 2 years. Mean interval of anti-VEGF injection was extended from 31 ± 2.6 days to 61 ± 5 days after conversion. Conclusions Aflibercept intravitreal injection in patients with fibrovascular DEP due to nAMD who respond poorly to monthly ranibizumab led to short-term functional and anatomical improvement. Reduction of intravitreal injection frequency was obtained until 2 years of follow-up. PMID:29093970

Baseline Predictors of Visual Acuity Outcome in Patients with Wet Age-Related Macular Degeneration

Directory of Open Access Journals (Sweden)

Xinyuan Zhang

2018-01-01

Full Text Available Age-related macular degeneration (AMD is one of the leading causes of severe vision loss in people over 60 years. Wet AMD (wAMD causes more severe visual acuity (VA loss compared with the dry form due to formation of choroidal neovascularization (CNV. Antivascular endothelial growth factor (anti-VEGF agents such as ranibizumab and aflibercept are now the standard of care treatment for wAMD. Unfortunately, up to a quarter of anti-VEGF-treated wAMD patients might not fully benefit from intravitreal injections and CNV activity may not respond to the treatment and these patients are called anti-VEGF nonresponders. This article aims to discuss the baseline factors associated with VA outcome such as age, initial VA, lesion types, disease duration, optical coherence tomography (OCT features, fundus autofluorescence findings, and the presence of particular genotype risk alleles in patients with wAMD. Recommendations are provided regarding when to consider discontinuation of therapy because of either success or futility. Understanding the predictive factors associated with VA outcome and treatment frequency response to anti-VEGF therapy may help retina specialists to manage patients’ expectations and guide treatment decisions from the beginning of treatment on the basis of “personalized medicine.”

Assessment of the proposed decontamination and waste treatment facility at LLNL

International Nuclear Information System (INIS)

Cohen, J.J.

1987-01-01

To provide a centralized decontamination and waste treatment facility (DWTF) at LLNL, the construction of a new installation has been planned. Objectives for this new facility were to replace obsolete, structurally and environmentally sub-marginal liquid and solid waste process facilities and decontamination facility and to bring these facilities into compliance with existing federal, state and local regulations as well as DOE orders. In a previous study, SAIC conducted a preliminary review and evaluation of existing facilities at LLNL and cost effectiveness of the proposed DWTF. This document reports on a detailed review of specific aspects of the proposed DWTF

Risk assessment of CST-7 proposed waste treatment and storage facilities Volume I: Limited-scope probabilistic risk assessment (PRA) of proposed CST-7 waste treatment ampersand storage facilities. Volume II: Preliminary hazards analysis of proposed CST-7 waste storage ampersand treatment facilities

International Nuclear Information System (INIS)

Sasser, K.

1994-06-01

In FY 1993, the Los Alamos National Laboratory Waste Management Group [CST-7 (formerly EM-7)] requested the Probabilistic Risk and Hazards Analysis Group [TSA-11 (formerly N-6)] to conduct a study of the hazards associated with several CST-7 facilities. Among these facilities are the Hazardous Waste Treatment Facility (HWTF), the HWTF Drum Storage Building (DSB), and the Mixed Waste Receiving and Storage Facility (MWRSF), which are proposed for construction beginning in 1996. These facilities are needed to upgrade the Laboratory's storage capability for hazardous and mixed wastes and to provide treatment capabilities for wastes in cases where offsite treatment is not available or desirable. These facilities will assist Los Alamos in complying with federal and state requlations

Age-related macular degeneration: using morphological predictors to modify current treatment protocols.

Science.gov (United States)

Ashraf, Mohammed; Souka, Ahmed; Adelman, Ron A

2018-03-01

To assess predictors of treatment response in neovascular age-related macular degeneration (AMD) in an attempt to develop a patient-centric treatment algorithm. We conducted a systematic search using PubMed, EMBASE and Web of Science for prognostic indicators/predictive factors with the key words: 'age related macular degeneration', 'neovascular AMD', 'choroidal neovascular membrane (CNV)', 'anti-vascular endothelial growth factor (anti-VEGF)', 'aflibercept', 'ranibizumab', 'bevacizumab', 'randomized clinical trials', 'post-hoc', 'prognostic', 'predictive', 'response' 'injection frequency, 'treat and extend (TAE), 'pro re nata (PRN)', 'bi-monthly' and 'quarterly'. We only included studies that had an adequate period of follow-up (>1 year), a single predefined treatment regimen with a predetermined re-injection criteria, an adequate number of patients, specific morphological [optical coherence tomography (OCT)] criteria that predicted final visual outcomes and injection frequency and did not include switching from one drug to the other. We were able to identify seven prospective studies and 16 retrospective studies meeting our inclusion criteria. There are several morphological and demographic prognostic indicators that can predict response to therapy in wet AMD. Smaller CNV size, subretinal fluid (SRF), retinal angiomatous proliferation (RAP) and response to therapy at 12 weeks (visual, angiographic or OCT) can all predict good visual outcomes in patients receiving anti-VEGF therapy. Patients with larger CNV, older age, pigment epithelial detachment (PED), intraretinal cysts (IRC) and vitreomacular adhesion (VMA) achieved less visual gains. Patients having VMA/VMT required more intensive treatment with increased treatment frequency. Patients with both posterior vitreous detachment (PVD) and SRF require infrequent injections. Patients with PED are prone to recurrences of fluid activity with a reduction in visual acuity (VA). A regimen that involves less intensive

Synthesis of porous magnesite-bentonite clay composite and its application for neutralisation and attenuation of inorganic contaminants in acidic and metalliferous mine drainage

CSIR Research Space (South Africa)

Masindi, Vhahangwele

2015-08-01

Full Text Available This paper evaluated the application of cryptocrystalline magnesite-bentonite clay composite for treatment of acid mine drainage (AMD). Bench laboratory studies were used to evaluate the treatment of AMD....

Fate of the naturally occurring radioactive materials during treatment of acid mine drainage with coal fly ash and aluminium hydroxide.

Science.gov (United States)

Madzivire, Godfrey; Maleka, Peane P; Vadapalli, Viswanath R K; Gitari, Wilson M; Lindsay, Robert; Petrik, Leslie F

2014-01-15

Mining of coal is very extensive and coal is mainly used to produce electricity. Coal power stations generate huge amounts of coal fly ash of which a small amount is used in the construction industry. Mining exposes pyrite containing rocks to H2O and O2. This results in the oxidation of FeS2 to form H2SO4. The acidic water, often termed acid mine drainage (AMD), causes dissolution of potentially toxic elements such as, Fe, Al, Mn and naturally occurring radioactive materials such as U and Th from the associated bedrock. This results in an outflow of AMD with high concentrations of sulphate ions, Fe, Al, Mn and naturally occurring radioactive materials. Treatment of AMD with coal fly ash has shown that good quality water can be produced which is suitable for irrigation purposes. Most of the potentially toxic elements (Fe, Al, Mn, etc) and substantial amounts of sulphate ions are removed during treatment with coal fly ash. This research endeavours to establish the fate of the radioactive materials in mine water with coal fly ash containing radioactive materials. It was established that coal fly ash treatment method was capable of removing radioactive materials from mine water to within the target water quality range for drinking water standards. The alpha and beta radioactivity of the mine water was reduced by 88% and 75% respectively. The reduced radioactivity in the mine water was due to greater than 90% removal of U and Th radioactive materials from the mine water after treatment with coal fly ash as ThO2 and UO2. No radioisotopes were found to leach from the coal fly ash into the mine water. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration123

Science.gov (United States)

Gorusupudi, Aruna; Nelson, Kelly; Bernstein, Paul S

2017-01-01

Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. With an increasingly aged population worldwide, the need for the prevention of AMD is rising. Multiple studies investigating AMD with the use of animal models and cell culture have identified oxidative stress–related retinal damage as an important contributing factor. In general, diet is an excellent source of the antioxidants, vitamins, and minerals necessary for healthy living; moreover, the general public is often receptive to recommendations made by physicians and health care workers regarding diet and supplements as a means of empowering themselves to avoid common and worrisome ailments such as AMD, which has made epidemiologists and clinicians enthusiastic about dietary intervention studies. A wide variety of nutrients, such as minerals, vitamins, ω-3 (n–3) fatty acids, and various carotenoids, have been associated with reducing the risk of AMD. Initial results from the Age-Related Eye Disease Study (AREDS) indicated that supplementation with antioxidants (β-carotene and vitamins C and E) and zinc was associated with a reduced risk of AMD progression. The AREDS2 follow-up study, designed to improve upon the earlier formulation, tested the addition of lutein, zeaxanthin, and ω-3 fatty acids. In this review, we examine the science behind the nutritional factors included in these interventional studies and the reasons for considering their inclusion to lower the rate of AMD progression. PMID:28096126

Bench-scale study of active mine water treatment using cement kiln dust (CKD) as a neutralization agent.

Science.gov (United States)

Mackie, Allison L; Walsh, Margaret E

2012-02-01

The overall objective of this study was to investigate the potential impact on settled water quality of using cement kiln dust (CKD), a waste by-product, to replace quicklime in the active treatment of acidic mine water. Bench-scale experiments were conducted to evaluate the treatment performance of calcium hydroxide (Ca(OH)(2)) slurries generated using four different CKD samples compared to a control treatment with quicklime (CaO) in terms of reducing acidity and metals concentrations in acid mine drainage (AMD) samples taken from the effluent of a lead/zinc mine in Atlantic Canada. Results of the study showed that all of the CKD samples evaluated were capable of achieving greater than 97% removal of total zinc and iron. The amount of solid alkaline material required to achieve pH targets required for neutralization of the AMD was found to be higher for treatment with the CKD slurries compared to the quicklime slurry control experiments, and varied linearly with the free lime content of the CKD. The results of this study also showed that a potential benefit of treating mine water with CKD could be reduced settled sludge volumes generated in the active treatment process, and further research into the characteristics of the sludge generated from the use of CKD-generated calcium hydroxide slurries is recommended. Copyright © 2011 Elsevier Ltd. All rights reserved.

Biologically-induced precipitation of sphalerite-wurtzite nanoparticles by sulfate-reducing bacteria: implications for acid mine drainage treatment.

Science.gov (United States)

Castillo, Julio; Pérez-López, Rafael; Caraballo, Manuel A; Nieto, José M; Martins, Mónica; Costa, M Clara; Olías, Manuel; Cerón, Juan C; Tucoulou, Rémi

2012-04-15

Several experiments were conducted to evaluate zinc-tolerance of sulfate-reducing bacteria (SRB) obtained from three environmental samples, two inocula from sulfide-mining districts and another inoculum from a wastewater treatment plant. The populations of SRB resisted zinc concentrations of 260 mg/L for 42 days in a sulfate-rich medium. During the experiments, sulfate was reduced to sulfide and concentrations in solution decreased. Zinc concentrations also decreased from 260 mg/L to values below detection limit. Both decreases were consistent with the precipitation of newly-formed sphalerite and wurtzite, two polymorphs of ZnS, forming <2.5-μm-diameter spherical aggregates identified by microscopy and synchrotron-μ-XRD. Sulfate and zinc are present in high concentrations in acid mine drainage (AMD) even after passive treatments based on limestone dissolution. The implementation of a SRB-based zinc removal step in these systems could completely reduce the mobility of all metals, which would improve the quality of stream sediments, water and soils in AMD-affected landscapes. Copyright © 2012 Elsevier B.V. All rights reserved.

Towards Treatment of Stargardt Disease: Workshop Organized and Sponsored by the Foundation Fighting Blindness

Science.gov (United States)

Sears, Avery E.; Bernstein, Paul S.; Cideciyan, Artur V.; Hoyng, Carel; Charbel Issa, Peter; Palczewski, Krzysztof; Rosenfeld, Philip J.; Sadda, SriniVas; Schraermeyer, Ulrich; Sparrow, Janet R.; Washington, Ilyas; Scholl, Hendrik P.N.

2017-01-01

Accumulation of fluorescent metabolic byproducts of the visual (retinoid) cycle is associated with photoreceptor and retinal pigment epithelial cell death in both Stargardt disease and atrophic (nonneovascular) age-related macular degeneration (AMD). As a consequence of this observation, small molecular inhibitors of enzymes in the visual cycle were recently tested in clinical trials as a strategy to protect the retina and retinal pigment epithelium in patients with atrophic AMD. To address the clinical translational needs for therapies aimed at both diseases, a workshop organized by the Foundation Fighting Blindness was hosted by the Department of Pharmacology at Case Western Reserve University on February 17, 2017, at the Tinkham Veale University Center, Cleveland, OH, USA. Invited speakers highlighted recent advances in the understanding of the pathophysiology of Stargardt disease, in terms of its clinical characterization and the development of endpoints for clinical trials, and discussed the comparability of therapeutic strategies between atrophic age-related macular degeneration (AMD) and Stargardt disease. Investigators speculated that reducing the concentrations of visual cycle precursor substances and/or their byproducts may provide valid therapeutic options for the treatment of Stargardt disease. Here we review the workshop's presentations in the context of published literature to help shape the aims of ongoing research endeavors and aid the development of therapies for Stargardt disease. PMID:28920007

Nutritional Supplementation Inhibits the Increase in Serum Malondialdehyde in Patients with Wet Age-Related Macular Degeneration

Directory of Open Access Journals (Sweden)

Toshiyuki Matsuura

2017-01-01

Full Text Available Purpose. To compare serum levels of malondialdehyde (MDA in patients with wet age-related macular degeneration (wAMD, patients with dry AMD (dAMD, and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD. Methods. MDA levels were measured in sera from 20 patients with wAMD, 20 with dAMD, and 24 without AMD. Patients with wAMD were randomized to receive or not receive nutritional supplementation (10 patients in each group, and MDA levels were measured after 3 months of treatment. Results. MDA levels in patients with wAMD were significantly greater compared with patients without AMD. In eyes with wAMD, there was a significant correlation between MDA levels and choroidal neovascularization lesion area. Serum MDA levels decreased in most patients that received supplementation and significantly increased in those who did not. Conclusion. Baseline serum MDA levels were elevated in patients with wAMD, and MDA levels were directly correlated with choroidal neovascularization lesion area. In addition, nutritional supplementation appeared to exert a protective effect against oxidative stress in patients with wAMD.

Air Emissions Damages from Municipal Drinking Water Treatment Under Current and Proposed Regulatory Standards.

Science.gov (United States)

Gingerich, Daniel B; Mauter, Meagan S

2017-09-19

Water treatment processes present intersectoral and cross-media risk trade-offs that are not presently considered in Safe Drinking Water Act regulatory analyses. This paper develops a method for assessing the air emission implications of common municipal water treatment processes used to comply with recently promulgated and proposed regulatory standards, including concentration limits for, lead and copper, disinfection byproducts, chromium(VI), strontium, and PFOA/PFOS. Life-cycle models of electricity and chemical consumption for individual drinking water unit processes are used to estimate embedded NO x , SO 2 , PM 2.5 , and CO 2 emissions on a cubic meter basis. We estimate air emission damages from currently installed treatment processes at U.S. drinking water facilities to be on the order of $500 million USD annually. Fully complying with six promulgated and proposed rules would increase baseline air emission damages by approximately 50%, with three-quarters of these damages originating from chemical manufacturing. Despite the magnitude of these air emission damages, the net benefit of currently implemented rules remains positive. For some proposed rules, however, the promise of net benefits remains contingent on technology choice.

Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

NARCIS (Netherlands)

Bennis, A.; Gorgels, T.G.M.F.; ten Brink, J.B.; van der Spek, P.J.; Bossers, K.; Heine, V.M.; Bergen, A.A.

2015-01-01

Background The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles : Potential Implications for Age-Related Macular Degeneration

NARCIS (Netherlands)

Bennis, Anna; Gorgels, Theo G M F; Ten Brink, Jacoline B; van der Spek, Peter J; Bossers, Koen; Heine, Vivi M; Bergen, Arthur A

2015-01-01

BACKGROUND: The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

NARCIS (Netherlands)

Bennis, Anna; Gorgels, Theo G. M. F.; ten Brink, Jacoline B.; van der Spek, Peter J.; Bossers, Koen; Heine, Vivi M.; Bergen, Arthur A.

2015-01-01

The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new

Optimization of HNO3 leaching of copper from old AMD Athlon processors using response surface methodology.

Science.gov (United States)

Javed, Umair; Farooq, Robina; Shehzad, Farrukh; Khan, Zakir

2018-04-01

The present study investigates the optimization of HNO 3 leaching of Cu from old AMD Athlon processors under the effect of nitric acid concentration (%), temperature (°C) and ultrasonic power (W). The optimization study is carried out using response surface methodology with central composite rotatable design (CCRD). The ANOVA study concludes that the second degree polynomial model is fitted well to the fifteen experimental runs based on p-value (0.003), R 2 (0.97) and Adj-R 2 (0.914). The study shows that the temperature is the most significant process variable to the leaching concentration of Cu followed by nitric acid concentration. However, ultrasound power shows no significant impact on the leaching concentration. The optimum conditions were found to be 20% nitric acid concentration, 48.89 °C temperature and 5.52 W ultrasound power for attaining maximum concentration of 97.916 mg/l for Cu leaching in solution. Copyright © 2018 Elsevier Ltd. All rights reserved.

Passive aerobic treatment of net-alkaline, iron-laden drainage from a flooded underground anthracite mine, Pennsylvania, USA

Science.gov (United States)

Cravotta, C.A.

2007-01-01

This report evaluates the results of a continuous 4.5-day laboratory aeration experiment and the first year of passive, aerobic treatment of abandoned mine drainage (AMD) from a typical flooded underground anthracite mine in eastern Pennsylvania, USA. During 1991-2006, the AMD source, locally known as the Otto Discharge, had flows from 20 to 270 L/s (median 92 L/s) and water quality that was consistently suboxic (median 0.9 mg/L O2) and circumneutral (pH ??? 6.0; net alkalinity >10) with moderate concentrations of dissolved iron and manganese and low concentrations of dissolved aluminum (medians of 11, 2.2, and treatment system was conceptualized consisting of a 2 m deep pond with innovative aeration and recirculation to promote rapid oxidation of Fe2+, two 0.3 m deep wetlands to facilitate iron solids removal, and a supplemental oxic limestone drain for dissolved manganese and trace-metal removal. The system was constructed, but without the aeration mechanism, and began operation in June 2005. During the first 12 months of operation, estimated detention times in the treatment system ranged from 9 to 38 h. However, in contrast with 80-100% removal of Fe2+ over similar elapsed times during the laboratory aeration experiment, the treatment system typically removed less than 35% of the influent Fe2+. Although concentrations of dissolved CO2 decreased progressively within the treatment system, the PCO2 values for treated effluent remained elevated (10-2.4 to 10-1.7atm). The elevated PCO 2 maintained the pH within the system at values less than 7 and hence slowed the rate of Fe2+ oxidation compared to the aeration experiment. Kinetic models of Fe2+ oxidation that consider effects of pH and dissolved O2 were incorporated in the geochemical computer program PHREEQC to evaluate the effects of detention time, pH, and other variables on Fe2+ oxidation and removal rates. These models and the laboratory aeration experiment indicate that performance of this and other aerobic

PPAR-α Ligands as Potential Therapeutic Agents for Wet Age-Related Macular Degeneration

Directory of Open Access Journals (Sweden)

Marisol del V Cano

2008-01-01

Full Text Available The peroxisome proliferator-activated receptors (PPAR's are members of the steroid/thyroid nuclear receptor, superfamily of transcription factors. There are currently three known PPAR subtypes, α, β, and γ. The PPARs are now recognized participants in a number of biological pathways some of which are implicated in the pathogenesis of age-related macular degeneration (AMD. These include immune modulation, lipid regulation, and oxidant/antioxidant pathways important to the onset and progression of “dry” AMD, and vascular endothelial growth factor (VEGF mediated pathways that stimulate choroidal neovascularization (CNV, characteristic of “wet” AMD. PPAR-α is found in retina and also on vascular cells important to formation of CNV. At this time, however, relatively little is known about potential contributions of PPAR-α to the pathogenesis of dry and wet AMD. This review examines current literature for potential roles of PPAR-α in the pathogenesis and potential treatment of AMD with emphasis on prevention and treatment of wet AMD.

Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells.

Science.gov (United States)

Muniyan, Sakthivel; Chou, Yu-Wei; Ingersoll, Matthew A; Devine, Alexus; Morris, Marisha; Odero-Marah, Valerie A; Khan, Shafiq A; Chaney, William G; Bu, Xiu R; Lin, Ming-Fong

2014-10-10

Metastatic prostate cancer (mPCa) relapses after a short period of androgen deprivation therapy and becomes the castration-resistant prostate cancer (CR PCa); to which the treatment is limited. Hence, it is imperative to identify novel therapeutic agents towards this patient population. In the present study, antiproliferative activities of novel imidazopyridines were compared. Among three derivatives, PHE, AMD and AMN, examined, AMD showed the highest inhibitory activity on LNCaP C-81 cell proliferation, following dose- and time-dependent manner. Additionally, AMD exhibited significant antiproliferative effect against a panel of PCa cells, but not normal prostate epithelial cells. Further, when compared to AMD, its derivative DME showed higher inhibitory activities on PCa cell proliferation, clonogenic potential and in vitro tumorigenicity. The inhibitory activity was apparently in part due to the induction of apoptosis. Mechanistic studies indicate that AMD and DME treatments inhibited both AR and PI3K/Akt signaling. The results suggest that better understanding of inhibitory mechanisms of AMD and DME could help design novel therapeutic agents for improving the treatment of CR PCa. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Ecological surveys of the proposed high explosives wastewater treatment facility region

International Nuclear Information System (INIS)

Haarmann, T.

1995-07-01

Los Alamos National Laboratory (LANL) proposes to improve its treatment of wastewater from high explosives (HE) research and development activities. The proposed project would focus on a concerted waste minimization effort to greatly reduce the amount of wastewater needing treatment. The result would be a 99% decrease in the HE wastewater volume, from the current level of 6,760,000 L/mo (1,786,000 gal./mo) to 41,200 L/mo (11,000 gal./mo). This reduction would entail closure of HE wastewater outfalls, affecting some wetland areas that depend on HE wastewater effluents. The outfalls also provide drinking water for many wildlife species. Terminating the flow of effluents at outfalls would represent an improvement in water quality in the LANL region but locally could have a negative effect on some wetlands and wildlife species. None of the affected species are protected by any state or federal endangered species laws. The purpose of this report is to briefly discuss the different biological studies that have been done in the region of the project area. This report is written to give biological information and baseline data and the biota of the project area

Ecological surveys of the proposed high explosives wastewater treatment facility region

Energy Technology Data Exchange (ETDEWEB)

Haarmann, T.

1995-07-01

Los Alamos National Laboratory (LANL) proposes to improve its treatment of wastewater from high explosives (HE) research and development activities. The proposed project would focus on a concerted waste minimization effort to greatly reduce the amount of wastewater needing treatment. The result would be a 99% decrease in the HE wastewater volume, from the current level of 6,760,000 L/mo (1,786,000 gal./mo) to 41,200 L/mo (11,000 gal./mo). This reduction would entail closure of HE wastewater outfalls, affecting some wetland areas that depend on HE wastewater effluents. The outfalls also provide drinking water for many wildlife species. Terminating the flow of effluents at outfalls would represent an improvement in water quality in the LANL region but locally could have a negative effect on some wetlands and wildlife species. None of the affected species are protected by any state or federal endangered species laws. The purpose of this report is to briefly discuss the different biological studies that have been done in the region of the project area. This report is written to give biological information and baseline data and the biota of the project area.

Divergence in the lived experience of people with macular degeneration.

Science.gov (United States)

McCloud, Christine; Khadka, Jyoti; Gilhotra, Jagjit Singh; Pesudovs, Konrad

2014-08-01

The aim of this study was to understand people's experience with age-related macular degeneration (AMD) in light of new treatment successes. An interpretive qualitative methodology was used to facilitate understanding of the experience of people with AMD. Rich in-depth data were collected using focus groups and individual interviews. Thematic analysis of the data occurred through the processes of line-by-line coding, aggregation, and theme development using the NVivo 10 software. A total of 4 focus groups and 16 individual interviews were conducted with 34 people (median age = 81 years; range = 56 to 102 years; 19 females) with AMD. Four major themes arose from the narratives of the participants: cautious optimism, enduring, adaptation, and profound loss. Cautious optimism resonated for participants who had received successful treatment and stabilization of AMD. Enduring emerged as participants with exudative AMD described an ongoing need for invasive and frequent treatments (anti-vascular endothelial growth factor injections) that maintained their vision. Adaptation was evident in the narratives of all participants and was directly related to the physical and psychological limitations that were a consequence of visual disability. Profound loss encompassed both physical and emotional aspects of deteriorating vision and was most evident in patients for whom treatment had failed or had not been considered appropriate for their disease. The findings of this study shed new light on the influence of underlying pathology, disease trajectory, and success of new treatments on quality of life of people living with AMD. Optimism toward maintaining vision in the presence of exudative AMD was described by participants, moderated by ongoing caution and a need for endurance of frequent and often problematic intravitreal treatments. These findings add a deeper understanding of this complex and life-changing experience.

Prevention of age-related macular degeneration.

Science.gov (United States)

Wong, Ian Yat Hin; Koo, Simon Chi Yan; Chan, Clement Wai Nang

2011-02-01

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula.

Pilot-scale passive bioreactors for the treatment of acid mine drainage: efficiency of mushroom compost vs. mixed substrates for metal removal.

Science.gov (United States)

Song, Hocheol; Yim, Gil-Jae; Ji, Sang-Woo; Neculita, Carmen Mihaela; Hwang, Taewoon

2012-11-30

Pilot-scale field-testing of passive bioreactors was performed to evaluate the efficiency of a mixture of four substrates (cow manure compost, mushroom compost, sawdust, and rice straw) relative to mushroom compost alone, and of the effect of the Fe/Mn ratio, during the treatment of acid mine drainage (AMD) over a 174-day period. Three 141 L columns, filled with either mushroom compost or the four substrate mixture (in duplicate), were set-up and fed with AMD from a closed mine site, in South Korea, using a 4-day hydraulic retention time. In the former bioreactor, effluent deterioration was observed over 1-2 months, despite the good efficiency predicted by the physicochemical characterization of mushroom compost. Steady state effluent quality was then noted for around 100 days before worsening in AMD source water occurred in response to seasonal variations in precipitation. Such changes in AMD quality resulted in performance deterioration in all reactors followed by a slow recovery toward the end of testing. Both substrates (mushroom compost and mixtures) gave satisfactory performance in neutralizing pH (6.1-7.8). Moreover, the system was able to consistently reduce sulfate from day 49, after the initial leaching out from organic substrates. Metal removal efficiencies were on the order of Al (∼100%) > Fe (68-92%) > Mn (49-61%). Overall, the mixed substrates showed comparable performance to mushroom compost, while yielding better effluent quality upon start-up. The results also indicated mushroom compost could release significant amounts of Mn and sulfate during bioreactor operation. Copyright © 2012 Elsevier Ltd. All rights reserved.

The proposed combustion standards and DOE thermal treatment systems

International Nuclear Information System (INIS)

McFee, J.; Hinman, M.B.; Eaton, D.; NcNeel, K.

1997-01-01

Under the provisions of the Clean Air Act (CAA) concerning emission of hazardous air pollutants (HAPs), the Environmental Protection Agency (EPA) published the proposed Revised Standards for Hazardous Waste Combustors on April 19, 1996 (EPA, 1996). These standards would apply to the existing Department of Energy (DOE) radioactive and mixed waste incinerators, and may be applied to several developing alternatives to incineration. The DOE has reviewed the basis for these regulations and prepared extensive comments to present concerns about the bases and implications of the standards. DOE is now discussing compliance options with the EPA for regulation of radioactive and mixed waste thermal treatment systems

Gut microbiota modify risk for dietary glycemia-induced age-related macular degeneration.

Science.gov (United States)

Rowan, Sheldon; Taylor, Allen

2018-03-21

Age-related macular degeneration (AMD) is a leading cause of blindness world-wide. Although the etiology of AMD is multifactorial, diet and nutrition have strong epidemiologic associations with disease onset and progression. Recent studies indicate a role for gut microbiota in development of AMD in mouse models and in some forms of human AMD. We previously found that consuming lower glycemia diets is associated with protection against AMD in humans and switching from higher to lower glycemia diets arrests AMD phenotypes in mice. Gut microbiota populations and circulating microbial cometabolites were altered in response to dietary carbohydrates, indicating a gut-retina axis. Here we explore additional gut microbiota-AMD interactions that point toward pathogenic roles for some gut microbiota families, including Ruminococcaceae and Lachnospiraceae, and individual members of Turicibacteraceae, Clostridiaceae, and Mogibacteriaceae. We also speculate on potential mechanisms by which gut microbiota influence AMD, with the objective of devising new AMD diagnoses and treatments.

Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables.

Science.gov (United States)

Seddon, Johanna M; Reynolds, Robyn; Maller, Julian; Fagerness, Jesen A; Daly, Mark J; Rosner, Bernard

2009-05-01

The joint effects of genetic, ocular, and environmental variables were evaluated and predictive models for prevalence and incidence of AMD were assessed. Participants in the multicenter Age-Related Eye Disease Study (AREDS) were included in a prospective evaluation of 1446 individuals, of which 279 progressed to advanced AMD (geographic atrophy or neovascular disease) and 1167 did not progress during 6.3 years of follow-up. For prevalent AMD, 509 advanced cases were compared with 222 controls. Covariates for the incidence analysis included age, sex, education, smoking, body mass index (BMI), baseline AMD grade, and the AREDS vitamin-mineral treatment assignment. DNA specimens were evaluated for six variants in five genes related to AMD. Unconditional logistic regression analyses were performed for prevalent and incident advanced AMD. An algorithm was developed and receiver operating characteristic curves and C statistics were calculated to assess the predictive ability of risk scores to discriminate progressors from nonprogressors. All genetic polymorphisms were independently related to prevalence of advanced AMD, controlling for genetic factors, smoking, BMI, and AREDS treatment. Multivariate odds ratios (ORs) were 3.5 (95% confidence interval [CI], 1.7-7.1) for CFH Y402H; 3.7 (95% CI, 1.6-8.4) for CFH rs1410996; 25.4 (95% CI, 8.6-75.1) for LOC387715 A69S (ARMS2); 0.3 (95% CI, 0.1-0.7) for C2 E318D; 0.3 (95% CI, 0.1-0.5) for CFB; and 3.6 (95% CI, 1.4-9.4) for C3 R102G, comparing the homozygous risk/protective genotypes to the referent genotypes. For incident AMD, all these variants except CFB were significantly related to progression to advanced AMD, after controlling for baseline AMD grade and other factors, with ORs from 1.8 to 4.0 for presence of two risk alleles and 0.4 for the protective allele. An interaction was seen between CFH402H and treatment, after controlling for all genotypes. Smoking was independently related to AMD, with a multiplicative joint

Cigarette smoke-related hydroquinone dysregulates MCP-1, VEGF and PEDF expression in retinal pigment epithelium in vitro and in vivo.

Directory of Open Access Journals (Sweden)

Marianne Pons

2011-02-01

Full Text Available Age-related macular degeneration (AMD is the leading cause of legal blindness in the elderly population. Debris (termed drusen below the retinal pigment epithelium (RPE have been recognized as a risk factor for dry AMD and its progression to wet AMD, which is characterized by choroidal neovascularization (CNV. The underlying mechanism of how drusen might elicit CNV remains undefined. Cigarette smoking, oxidative damage to the RPE and inflammation are postulated to be involved in the pathophysiology of the disease. To better understand the cellular mechanism(s linking oxidative stress and inflammation to AMD, we examined the expression of pro-inflammatory monocyte chemoattractant protein-1 (MCP-1, pro-angiogenic vascular endothelial growth factor (VEGF and anti-angiogenic pigment epithelial derived factor (PEDF in RPE from smoker patients with AMD. We also evaluated the effects of hydroquinone (HQ, a major pro-oxidant in cigarette smoke on MCP-1, VEGF and PEDF expression in cultured ARPE-19 cells and RPE/choroids from C57BL/6 mice.MCP-1, VEGF and PEDF expression was examined by real-time PCR, Western blot, and ELISA. Low levels of MCP-1 protein were detected in RPE from AMD smoker patients relative to controls. Both MCP-1 mRNA and protein were downregulated in ARPE-19 cells and RPE/choroids from C57BL/6 mice after 5 days and 3 weeks of exposure to HQ-induced oxidative injury. VEGF protein expression was increased and PEDF protein expression was decreased in RPE from smoker patients with AMD versus controls resulting in increased VEGF/PEDF ratio. Treatment with HQ for 5 days and 3 weeks increased the VEGF/PEDF ratio in vitro and in vivo.We propose that impaired RPE-derived MCP-1-mediated scavenging macrophages recruitment and phagocytosis might lead to incomplete clearance of proinflammatory debris and infiltration of proangiogenic macrophages which along with increased VEGF/PEDF ratio favoring angiogenesis might promote drusen accumulation and

Long-term longitudinal study of patients treated with ranibizumab for neovascular age-related macular degeneration

DEFF Research Database (Denmark)

Rasmussen, Annette; Sander, Birgit

2014-01-01

PURPOSE OF REVIEW: To review the current literature regarding long-term treatment beyond 2 years with anti-vascular endothelial growth factor (VEGF) inhibition for neovascular age-related macular degeneration (nv-AMD). RECENT FINDINGS: Only few studies of anti-VEGF treatment for nv-AMD exist beyond...

Haematological and physiological responses of brook charr, to untreated and limestone-neutralized acid mine drainage

Energy Technology Data Exchange (ETDEWEB)

Cole, M.B.; Arnold, D.E.; Watten, B.J.; Krise, W.F. [ABR Inc, Forest Grove, OR (USA). Environmental Research and Services

2001-07-01

Brook charr, Salvelinus fontinalis, exhibited depressed plasma sodium and elevated plasma glucose concentrations in untreated acid mine drainage effluent (AMD), at two dilutions. Plasma sodium and glucose concentrations remained stable in treated AMD, pulsed, fluidized beds of limestone and carbon-dioxide pre-treatment of influent, and in AMD-free water. Results indicate that effluents produced by this treatment system were not toxic to these fish, despite still containing moderate concentrations of manganese (3-4 mg l{sup 1} following dilution in exposure systems), and provide justification for field deployment and further biological testing of this treatment in the field.

Functional impact of treatment with ranibizumab under a reactive strategy in patients with neovascular age-related macular degeneration.

Science.gov (United States)

Gallego-Pinazo, R; Dolz-Marco, R; Andreu-Fenoll, M; Farrés, J; Monclús, L

2017-03-01

To analyse the functional recovery using a pro re nata (PRN) dosing strategy with intravitreal injections of ranibizumab for patients with neovascular age-related macular degeneration (AMD). An observational, retrospective, single-centre study, was conducted on patients with neovascular AMD managed with a PRN strategy with ranibizumab, and were followed-up for a minimum of 18 months. Sociodemographic and clinical data were collected from medical records. The percentage of visual acuity (VA) recovered after losing 5 or more letters was calculated taking into account the previous visit, as well as considering the best VA recorded prior to the retreament. The analysis included 128 patients. The mean (SD) follow-up period was 18.9 (2.3) months. The mean (SD) elapsed days between onset of symptoms and diagnosis, and between prescription and administration of treatment was 50.2 (57.4) and 10.9 (16.0), respectively. Only 108 patients were prescribed ranibizumab after losing 5 or more letters of VA. The mean (SD) VA recovery compared to the previous VA was 70.3% (114.4). On the other hand, the mean (SD) VA recovery when considering the best VA registered before the retreatment was 43.5% (112.9), with 59.4% of re-treatments having a VA recovery below 75%, and with 11.7% not presenting any VA recovery. A PRN dosing strategy with intravitreal ranibizumab for neovascular AMD may not be efficient in preserving and/or recovering VA in the long-term, due to a cumulative irreversible VA loss. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Clinical course over two to six years of age-related macular degeneration with or without radiation

International Nuclear Information System (INIS)

Kameda, Takanori; Noami, Sachiyo; Akita, Joe

2002-01-01

We previously reported about the long-term outcome as long as three years after radiation therapy for choroidal neovascularization secondary to age-related macular degeneration (AMD). Though MPS (Macular Photocoagulation Study) Group reported the long-term natural course of AMD, such reports have not been provided concerned about Japanese AMD patients. Furthermore, there is not report that revealed the course of AMD with radiation therapy more than three years. We evaluated the long-term natural course and long-term effect of low-dose radiation on AMD. The fundus ophthalmoscopic evaluation and visual outcome were compared retrospectively among control group and two treated groups; seven eyes received 10 Gy, and eight eyes 20 Gy. The control group consisted of 10 eyes without treatment. All patients were followed at least four years, and the average follow-up duration was 6.56 years. The course of median visual acuity without treatment showed the similar result to that of MPS Group's report. In control group, visual acuity (VA) after four years was better in no eyes, unchanged in two eyes, and worse in eight eyes; in treated group, better in four eyes, unchanged in one eye, and worse in ten eyes. After four years VA was kept 20/200 or higher in 2 eyes without treatment, 4 eyes with 10 Gy, and 4 eyes with 20 Gy of radiation. Then maximum VA was 20/125 with no treatment, and 20/50 with radiation therapy. The natural course of the AMD of Japanese patients showed similar results to US patients. All eyes of AMD withort treatment got worse in VA, and some showed better outcome with radiation therapy; but it was not statistically significant. (author)

Clinical course over two to six years of age-related macular degeneration with or without radiation

Energy Technology Data Exchange (ETDEWEB)

Kameda, Takanori; Noami, Sachiyo; Akita, Joe [Kyoto Univ. (Japan). Graduate School of Medicine] (and others)

2002-10-01

We previously reported about the long-term outcome as long as three years after radiation therapy for choroidal neovascularization secondary to age-related macular degeneration (AMD). Though MPS (Macular Photocoagulation Study) Group reported the long-term natural course of AMD, such reports have not been provided concerned about Japanese AMD patients. Furthermore, there is not report that revealed the course of AMD with radiation therapy more than three years. We evaluated the long-term natural course and long-term effect of low-dose radiation on AMD. The fundus ophthalmoscopic evaluation and visual outcome were compared retrospectively among control group and two treated groups; seven eyes received 10 Gy, and eight eyes 20 Gy. The control group consisted of 10 eyes without treatment. All patients were followed at least four years, and the average follow-up duration was 6.56 years. The course of median visual acuity without treatment showed the similar result to that of MPS Group's report. In control group, visual acuity (VA) after four years was better in no eyes, unchanged in two eyes, and worse in eight eyes; in treated group, better in four eyes, unchanged in one eye, and worse in ten eyes. After four years VA was kept 20/200 or higher in 2 eyes without treatment, 4 eyes with 10 Gy, and 4 eyes with 20 Gy of radiation. Then maximum VA was 20/125 with no treatment, and 20/50 with radiation therapy. The natural course of the AMD of Japanese patients showed similar results to US patients. All eyes of AMD withort treatment got worse in VA, and some showed better outcome with radiation therapy; but it was not statistically significant. (author)

The reactivation time in the treatment of AMD: a forgotten key parameter?

Science.gov (United States)

Real, J P; Luna, J D; Palma, S D

2018-06-01

Summarize and compare the available evidence on the reactivation times in patients with age-related macular degeneration treated with Ranibizumab (RNB). Systematic review of studies that reported the reactivation time of patients (direct method) or the number of injections received in a certain period of follow-up (indirect method). Only 18 of 89 selected studies reported the average reactivation time of patients in a manifest form, without the need of any calculation. The average calculated, weighted reactivation time was 101.8 days with the direct method and 99.8 days in the indirect method (84 studies included). With both methods, it was found that the average reactivation time of the RCTs was between 2 and 3 weeks less than the average time identified in the observational studies. These differences are also reflected in the clinical results, there being a correlation between the number of doses received and the change in BCVA. The analysis of 11 comparative studies showed a difference in reactivation times between patients treated with RNB or Bevacizumab (BVZ). There are few direct studies of reactivation time, but calculation from the PRN dose number turns out to be a good approximation for retrospective study of the variable. The use of the PRN, with criteria not based on optical coherence tomography scans, delays the application of doses between 2 or 3 weeks, and patients suffer loss of clinical benefits. RNB enables patients to receive less injections than BVZ throughout treatment.

A Historical Analysis of the Quest for the Origins of Aging Macula Disorder, the Tissues Involved, and Its Terminology

Science.gov (United States)

de Jong, Paulus T.V.M.

2016-01-01

Although ocular tissues involved in aging macula disorder (AMD) were already known in 300 BC, the last type of photoreceptors was discovered only 10 years ago. The earliest descriptions of AMD appeared around 1850. It took over 150 years, till a clearer concept of AMD was formulated and even longer to grasp its pathophysiology. The uncertainty of researchers about the pathogenesis of AMD over the last century is reflected in its changing terminology. The evolution of this terminology is provided in a table to afford the reader a better insight into explanations proposed by researchers during this quest. PMID:27812291

Immunology of age-related macular degeneration

Science.gov (United States)

Ambati, Jayakrishna; Atkinson, John P.; Gelfand, Bradley D.

2014-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population. PMID:23702979

Tumor necrosis factor-alpha potentiates the cytotoxicity of amiodarone in Hepa1c1c7 cells: roles of caspase activation and oxidative stress.

Science.gov (United States)

Lu, Jingtao; Miyakawa, Kazuhisa; Roth, Robert A; Ganey, Patricia E

2013-01-01

Amiodarone (AMD), a class III antiarrhythmic drug, causes idiosyncratic hepatotoxicity in human patients. We demonstrated previously that tumor necrosis factor-alpha (TNF-α) plays an important role in a rat model of AMD-induced hepatotoxicity under inflammatory stress. In this study, we developed a model in vitro to study the roles of caspase activation and oxidative stress in TNF potentiation of AMD cytotoxicity. AMD caused cell death in Hepa1c1c7 cells, and TNF cotreatment potentiated its toxicity. Activation of caspases 9 and 3/7 was observed in AMD/TNF-cotreated cells, and caspase inhibitors provided minor protection from cytotoxicity. Intracellular reactive oxygen species (ROS) generation and lipid peroxidation were observed after treatment with AMD and were further elevated by TNF cotreatment. Adding water-soluble antioxidants (trolox, N-acetylcysteine, glutathione, or ascorbate) produced only minor attenuation of AMD/TNF-induced cytotoxicity and did not influence the effect of AMD alone. On the other hand, α-tocopherol (TOCO), which reduced lipid peroxidation and ROS generation, prevented AMD toxicity and caused pronounced reduction in cytotoxicity from AMD/TNF cotreatment. α-TOCO plus a pancaspase inhibitor completely abolished AMD/TNF-induced cytotoxicity. In summary, activation of caspases and oxidative stress were observed after AMD/TNF cotreatment, and caspase inhibitors and a lipid-soluble free-radical scavenger attenuated AMD/TNF-induced cytotoxicity.

LONG-TERM SD-OCT/SLO IMAGING OF NEURORETINA AND RETINAL PIGMENT EPITHELIUM AFTER SUB-THRESHOLD INFRARED LASER TREATMENT OF DRUSEN

Science.gov (United States)

MOJANA, FRANCESCA; BRAR, MANPREET; CHENG, LINGYUN; BARTSCH, DIRK-UWE G.; FREEMAN, WILLIAM R.

2012-01-01

PURPOSE To determine the long-term effect of sub-threshold diode laser treatment for drusen in patients with non-exudative age-related macular degeneration (AMD) with spectral domain optical coherence tomography combined with simultaneous scanning laser ophthalmoscope (SD-OCT/SLO). METHODS 8 eyes of 4 consecutive AMD patients with bilateral drusen previously treated with sub-threshold diode laser were imaged with SD-OCT/SLO. Abnormalities in the outer retina layers reflectivity as seen with SD-OCT/SLO were retrospectively analyzed and compared with color fundus pictures and autofluorescence images (AF) acquired immediately before and after the laser treatment. RESULTS A focal discrete disruptions in the reflectivity of the outer retinal layers was noted in 29% of the laser lesions. The junction in between the inner and outer segment of the photoreceptor was more frequently affected, with associated focal damage of the outer nuclear layer. Defects of the RPE were occasionally detected. These changes did not correspond to threshold burns on color fundus photography, but corresponded to focal areas of increased AF in the majority of the cases. CONCLUSIONS Sub-threshold diode laser treatment causes long-term disruption of the retinal photoreceptor layer as analyzed by SD-OCT/SLO. The concept that sub-threshold laser treatment can achieve a selected RPE effect without damage to rods and cones may be flawed. PMID:21157398

Adaptive Multidimensional Scaling : The Spatial Representation of Brand Consideration and Dissimilarity Judgments

NARCIS (Netherlands)

Bijmolt, T.H.A.; Wedel, M.; DeSarbo, W.S.

2002-01-01

We propose Adaptive Multidimensional Scaling (AMDS) for simultaneously deriving a brand map and market segments using consumer data on cognitive decision sets and brand dissimilarities.In AMDS, the judgment task is adapted to the individual respondent: dissimilarity judgments are collected only for

Age-related macular degeneration: prevention and treatment. A review

Directory of Open Access Journals (Sweden)

K. A. Mirzabekova

2014-07-01

Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

Age-related macular degeneration: prevention and treatment. A review

Directory of Open Access Journals (Sweden)

K. A. Mirzabekova

2014-01-01

Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

Cognitive-behavior therapy for problem gambling: a critique of current treatments and proposed new unified approach.

Science.gov (United States)

Tolchard, Barry

2017-06-01

There is evidence supporting the use of cognitive-behavioral therapy (CBT) in the treatment of problem gambling. Despite this, little is known about how CBT works and which particular approach is most effective. This paper aims to synthesize the evidence for current CBT and propose a more unified approach to treatment. A literature review and narrative synthesis of the current research evidence of CBT for the treatment of problem gambling was conducted, focusing on the underlying mechanisms within the treatment approach. Several CBT approaches were critiqued. These can be divided into forms of exposure therapy (including aversion techniques, systematic desensitization and other behavioral experiments) those focusing on cognitive restructuring techniques (such as reinforcement of nongambling activity, use of diaries, motivational enhancement and audio-playback techniques and third wave techniques including mindfulness. Findings, in relation to the treatment actions, from this synthesis are reported. The debate surrounding the treatment of problem gambling has been conducted as an either/or rather than a both/and discourse. This paper proposes a new, unified approach to the treatment of problem gambling that incorporates the best elements of both exposure and cognitive restructuring techniques, alongside the use of techniques borrowed from mindfulness and other CBT approaches.

Predictors of 1-year visual outcome in neovascular age-related macular degeneration following intravitreal ranibizumab treatment

DEFF Research Database (Denmark)

Bloch, Sara Brandi; la Cour, Morten; Sander, Birgit

2013-01-01

Purpose: To describe predictors of visual outcome in patients treated with intravitreal ranibizumab for choroidal neovascularisation (CNV) in age-related macular degeneration (AMD). Methods: Retrospective review of 279 patients with CNV in AMD who fulfilled MARINA/ANCHOR study eligibility criteria...

Pigment epithelial detachment followed by retinal cystoid degeneration leads to vision loss in treatment of neovascular age-related macular degeneration.

Science.gov (United States)

Schmidt-Erfurth, Ursula; Waldstein, Sebastian M; Deak, Gabor-Gyoergy; Kundi, Michael; Simader, Christian

2015-04-01

Intravitreal antiangiogenic therapy is the major therapeutic breakthrough in neovascular age-related macular degeneration (AMD). Optical coherence tomography (OCT) is the leading diagnostic tool, but solid criteria for optimal therapeutic outcomes are lacking. A comprehensive analysis of structure/function correlations using Food and Drug Administration- and European Medicines Agency-approved substances and fixed and flexible regimens was performed. Post hoc analysis of a prospective, randomized multicenter clinical trial including 189 study sites. A total of 1240 patients with active neovascular AMD. Participants received intravitreal ranibizumab or aflibercept. A fixed regimen was used for 48 weeks followed by a flexible regimen until week 96. At monthly intervals, best-corrected visual acuity (BCVA) was measured and retinal morphology was assessed by standardized OCT, including intraretinal cysts (IRCs), subretinal fluid (SRF), and pigment epithelial detachment (PED), presenting with a width ≥400 μm or a height of ≥200 μm. Results were correlated for each regimen, feature, and time. The BCVA outcomes in relation to retinal pathomorphology based on noninferiority for all treatment arms. In neovascular AMD, only IRC at baseline and persistent through week 12 had a negative impact on BCVA. With therapeutic intervention, exudative features such as IRC and SRF resolved rapidly in 74% of eyes, whereas PED responded only slowly with 38%. Independent of the type of regimen, fixed or flexible, retinal morphology correlated tightly with visual function. Intraretinal cysts consistently showed the lowest BCVA gains with either regimen or substance. With the switch from a fixed to a flexible pro re nata (PRN) regimen, progressive visual loss occurred exclusively in the group with primary PED presenting as the hallmark of neovascular activity and was induced by secondary formation of IRC in the neurosensory retina. The efficacy of antiangiogenic therapy in neovascular

A geochemical approach to the restoration plans for the Odiel River basin (SW Spain), a watershed deeply polluted by acid mine drainage.

Science.gov (United States)

Macías, Francisco; Pérez-López, Rafael; Caraballo, Manuel A; Sarmiento, Aguasanta M; Cánovas, Carlos R; Nieto, Jose M; Olías, Manuel; Ayora, Carlos

2017-02-01

The Odiel River Basin (SW Spain) drains the central part of the Iberian Pyrite Belt (IPB), a world-class example of sulfide mining district and concomitantly of acid mine drainage (AMD) pollution. The severe AMD pollution and the incipient state of remediation strategies implemented in this region, coupled with the proximity of the deadline for compliance with the European Water Framework Directive (WFD), urge to develop a restoration and water resources management strategy. Furthermore, despite the presence of some reservoirs with acid waters in the Odiel basin, the construction of the Alcolea water reservoir has already started. On the basis of the positive results obtained after more than 10 years of developing a specific passive remediation technology (dispersed alkaline substrate (DAS)) for the highly polluted AMD of this region, a restoration strategy is proposed. The implementation of 13 DAS treatment plants in selected acid discharges along the Odiel and Oraque sub-basins and other restoration measurements of two acidic creeks is proposed as essential to obtain a good water quality in the future Alcolea reservoir. This restoration strategy is also suggested as an economically and environmentally sustainable approach to the extreme metal pollution affecting the waters of the region and could be considered the starting point for the future compliance with the WFD in the Odiel River Basin.

Intraocular Vascular Endothelial Growth Factor Levels in Pachychoroid Neovasculopathy and Neovascular Age-Related Macular Degeneration.

Science.gov (United States)

Hata, Masayuki; Yamashiro, Kenji; Ooto, Sotaro; Oishi, Akio; Tamura, Hiroshi; Miyata, Manabu; Ueda-Arakawa, Naoko; Takahashi, Ayako; Tsujikawa, Akitaka; Yoshimura, Nagahisa

2017-01-01

To investigate the difference in intraocular vascular endothelial growth factor (VEGF) concentration between pachychoroid neovasculopathy and neovascular age-related macular degeneration (nAMD) and its associations with responses to three monthly anti-VEGF injections as an initial treatment for the two conditions. This study included nine eyes with treatment-naïve pachychoroid neovasculopathy and 21 eyes with treatment-naïve nAMD. Before the initial intravitreal anti-VEGF injection, aqueous humor samples were collected and the concentration of VEGF was measured using enzyme-linked immunosorbent assay. The concentration was compared between the two conditions, and its associations with responses to anti-VEGF therapy were investigated. The mean VEGF concentration in pachychoroid neovasculopathy was significantly lower than that in nAMD (63.4 ± 17.8 pg/ml and 89.8 ± 45.0 pg/ml, respectively; P = 0.035). The VEGF concentration was associated with the presence or absence of drusen (β = 0.503, P = 0.004). After anti-VEGF therapy, 6 (66.7%) of 9 eyes with pachychoroid neovasculopathy and 17 (81.0%) of 21 eyes with nAMD achieved dry macula (P = 0.640). Dry macula at 3 months and 12 months was significantly associated with a low VEGF concentration in pachychoroid neovasculopathy (P = 0.013 and P = 0.042, respectively), but not in nAMD (P = 0.108 and P = 0.219). The mean VEGF concentration in pachychoroid neovasculopathy was lower than that in nAMD, suggesting that the way in which VEGF is involved in angiogenesis may differ between pachychoroid neovasculopathy and nAMD.

Efficacy of treat-and-extend regimen with aflibercept for pachychoroid neovasculopathy and Type 1 neovascular age-related macular degeneration.

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Matsumoto, Hidetaka; Hiroe, Takashi; Morimoto, Masahiro; Mimura, Kensuke; Ito, Arisa; Akiyama, Hideo

2018-03-01

To evaluate the efficacy of intravitreal aflibercept therapy using a treat-and-extend regimen on treatment-naïve pachychoroid neovasculopathy (PNV) and Type 1 neovascular age-related macular degeneration (AMD). We retrospectively studied 42 eyes with PNV and 60 eyes with Type 1 neovascular AMD. We assessed best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and total number of injections over 2 years. The BCVA and CMT improvements during the 2-year treatment period did not differ significantly between PNV and AMD; however, CCT decreased significantly in PNV than in AMD (P<0.05). Management of PNV required significantly fewer injections than AMD during the 2-year period (P<0.05). There were no significant differences in BCVA, CMT and CCT changes between PNV with and without polypoidal lesions (28 vs. 14 eyes) during the 2 year period. Significantly fewer injections were needed for PNV with polypoidal lesions than for PNV without (P<0.01). There were no significant differences in BCVA, CMT and CCT changes, or in the number of injections during the 2-year treatment period, between AMD with and without polypoidal lesions (30 vs. 30 eyes). Treat-and-extend regimen of intravitreal aflibercept injection may be equally effective in terms of improvement of BCVA and exudative changes both in eyes with PNV and those with Type 1 neovascular AMD requiring fewer injections for the former. Among eyes with PNV, those with polypoidal lesions needed fewer injections than those without polypoidal lesions.

Treatment of peri-implant diseases: a review of the literature and protocol proposal.

Science.gov (United States)

Armas, Joshé; Culshaw, Shauna; Savarrio, Lee

2013-01-01

Over 100,000 implants were placed in the UK in 2010. As the numbers of patients with implant-retained prostheses increases, operators are encountering an increasing number of biological implant complications, most commonly peri-implant mucositis and peri-implantitis. The effective management of these complications is crucial to maintain patients' oral health. In particular, in contrast to common periodontal infections, some peri-implant infections may benefit from surgical intervention as a first line approach. This article reviews the literature on the treatment options for peri-implant mucositis and peri-implantitis and proposes a protocol for their treatment.

Statistical characterization and segmentation of drusen in fundus images.

Science.gov (United States)

Santos-Villalobos, H; Karnowski, T P; Aykac, D; Giancardo, L; Li, Y; Nichols, T; Tobin, K W; Chaum, E

2011-01-01

Age related Macular Degeneration (AMD) is a disease of the retina associated with aging. AMD progression in patients is characterized by drusen, pigmentation changes, and geographic atrophy, which can be seen using fundus imagery. The level of AMD is characterized by standard scaling methods, which can be somewhat subjective in practice. In this work we propose a statistical image processing approach to segment drusen with the ultimate goal of characterizing the AMD progression in a data set of longitudinal images. The method characterizes retinal structures with a statistical model of the colors in the retina image. When comparing the segmentation results of the method between longitudinal images with known AMD progression and those without, the method detects progression in our longitudinal data set with an area under the receiver operating characteristics curve of 0.99.

Statistical Characterization and Segmentation of Drusen in Fundus Images

Energy Technology Data Exchange (ETDEWEB)

Santos-Villalobos, Hector J [ORNL; Karnowski, Thomas Paul [ORNL; Aykac, Deniz [ORNL; Giancardo, Luca [ORNL; Li, Yaquin [University of Tennessee, Knoxville (UTK); Nichols, Trent L [ORNL; Tobin Jr, Kenneth William [ORNL; Chaum, Edward [University of Tennessee, Knoxville (UTK)

2011-01-01

Age related Macular Degeneration (AMD) is a disease of the retina associated with aging. AMD progression in patients is characterized by drusen, pigmentation changes, and geographic atrophy, which can be seen using fundus imagery. The level of AMD is characterized by standard scaling methods, which can be somewhat subjective in practice. In this work we propose a statistical image processing approach to segment drusen with the ultimate goal of characterizing the AMD progression in a data set of longitudinal images. The method characterizes retinal structures with a statistical model of the colors in the retina image. When comparing the segmentation results of the method between longitudinal images with known AMD progression and those without, the method detects progression in our longitudinal data set with an area under the receiver operating characteristics curve of 0.99.

Age-Related Macular Degeneration: Advances in Management and Diagnosis

Directory of Open Access Journals (Sweden)

Yoshihiro Yonekawa

2015-02-01

Full Text Available Age-related macular degeneration (AMD is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies.

Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal

Directory of Open Access Journals (Sweden)

Kent David M

2010-08-01

Full Text Available Abstract Mounting evidence suggests that there is frequently considerable variation in the risk of the outcome of interest in clinical trial populations. These differences in risk will often cause clinically important heterogeneity in treatment effects (HTE across the trial population, such that the balance between treatment risks and benefits may differ substantially between large identifiable patient subgroups; the "average" benefit observed in the summary result may even be non-representative of the treatment effect for a typical patient in the trial. Conventional subgroup analyses, which examine whether specific patient characteristics modify the effects of treatment, are usually unable to detect even large variations in treatment benefit (and harm across risk groups because they do not account for the fact that patients have multiple characteristics simultaneously that affect the likelihood of treatment benefit. Based upon recent evidence on optimal statistical approaches to assessing HTE, we propose a framework that prioritizes the analysis and reporting of multivariate risk-based HTE and suggests that other subgroup analyses should be explicitly labeled either as primary subgroup analyses (well-motivated by prior evidence and intended to produce clinically actionable results or secondary (exploratory subgroup analyses (performed to inform future research. A standardized and transparent approach to HTE assessment and reporting could substantially improve clinical trial utility and interpretability.

Automated age-related macular degeneration classification in OCT using unsupervised feature learning

Science.gov (United States)

Venhuizen, Freerk G.; van Ginneken, Bram; Bloemen, Bart; van Grinsven, Mark J. J. P.; Philipsen, Rick; Hoyng, Carel; Theelen, Thomas; Sánchez, Clara I.

2015-03-01

Age-related Macular Degeneration (AMD) is a common eye disorder with high prevalence in elderly people. The disease mainly affects the central part of the retina, and could ultimately lead to permanent vision loss. Optical Coherence Tomography (OCT) is becoming the standard imaging modality in diagnosis of AMD and the assessment of its progression. However, the evaluation of the obtained volumetric scan is time consuming, expensive and the signs of early AMD are easy to miss. In this paper we propose a classification method to automatically distinguish AMD patients from healthy subjects with high accuracy. The method is based on an unsupervised feature learning approach, and processes the complete image without the need for an accurate pre-segmentation of the retina. The method can be divided in two steps: an unsupervised clustering stage that extracts a set of small descriptive image patches from the training data, and a supervised training stage that uses these patches to create a patch occurrence histogram for every image on which a random forest classifier is trained. Experiments using 384 volume scans show that the proposed method is capable of identifying AMD patients with high accuracy, obtaining an area under the Receiver Operating Curve of 0:984. Our method allows for a quick and reliable assessment of the presence of AMD pathology in OCT volume scans without the need for accurate layer segmentation algorithms.

External beam radiotherapy for subretinal neovascularization in age-related macular degeneration: is this treatment efficient?

International Nuclear Information System (INIS)

Staar, Susanne; Krott, Ralf; Mueller, Rolf-Peter; Bartz-Schmidt, Karl U.; Heimann, Klaus

1999-01-01

Purpose: Control of the natural course of sub retinal neovascularization (SRNV) in age-related macular degeneration (AMD) is difficult. Only a subset of patients is suitable for laser coagulation. This prospective study aimed to determine the efficacy and individual benefit of external beam radiotherapy (EBRT). Methods and Materials: The prospective trial included 287 patients with subfoveal neovascularization due to AMD which was verified by fluorescein angiography. Patients have been treated between January 1996 and October 1997. All patients received a total dose of 16 Gy in 2-Gy daily fractions with 5-6 MeV photons based on computerized treatment planning in individual head mask fixation. This first analysis is based on 73 patients (50 women, 23 men, median age 74.3 years), with a median follow-up of 13.3 months and a minimum follow-up of 11 months. Results: All patients completed therapy and tolerability was good. First clinical control with second angiography was performed 6 weeks after irradiation, then in 3-month intervals. Eighteen patients with SRNV refusing radiotherapy served as a control group and were matched with 18 irradiated patients. After 7 months median visual acuity (VA) was 20/160 for the irradiated and 20/400 for the untreated patients. One year after radiotherapy final median VA was 20/400 in both groups. Conclusion: These results suggest that 16 Gy of conventionally fractionated external beam irradiation slows down the visual loss in exudative AMD for only a few months. Patients' reading vision could not be saved for a long-term run

The Application of Sulphate-Reducing Bacteria for the Heavy Metals Elimination from Acid Mine Drainage

Directory of Open Access Journals (Sweden)

Alena Luptáková

2004-12-01

Full Text Available One of the most important problems affecting mining companies around the world is the treatment of acid mine drainage (AMD. AMD is characterised by its high acidity, high concentration of metals (Cu, Zn, Cd,… and high concentration of dissolved sulphates. The techniques traditionally used for the treatment of AMD have been based on chemical methods of neutralization and precipitation. A possible alternative to the chemical treatment of AMD is bioremediation using anaerobic sulphate-reducing bacteria (SRB. The treatment of AMD by SRB is based on the ability of SRB to reduce sulphates to hydrogen sulphide, which binds readily with metals to form sparingly soluble precipitates. In this study we have attempted to investigate the feasibility of anaerobic biotreatment of the copper contaminated model solution and a real effluent AMD from the shaft Pech (the locality Smolnik using SRB. This method involves three stages: The H2S production by sulphate-reducing bacteria, the metals precipitation by the biologically produced H2S and the metal sulphides filtration. The studies confirm that copper was effectively recovered from the solution using bacterial produced H2S. An initial copper concentration 10 mg.l-1 was decreased to less than 0.05 mg.l-1 after 3 hours. The most adequate pH value for cooper precipitation was 2.5. Results of the copper precipitation from the areal effluent indicates that the optimal pH value for the copper precipitation is 3.5, but the created precipitates contain a mixture of copper and iron sulphides.

Hydraulic retention time and pH affect the performance and microbial communities of passive bioreactors for treatment of acid mine drainage.

Science.gov (United States)

Aoyagi, Tomo; Hamai, Takaya; Hori, Tomoyuki; Sato, Yuki; Kobayashi, Mikio; Sato, Yuya; Inaba, Tomohiro; Ogata, Atsushi; Habe, Hiroshi; Sakata, Takeshi

2017-12-01

For acceleration of removing toxic metals from acid mine drainage (AMD), the effects of hydraulic retention time (HRT) and pH on the reactor performance and microbial community structure in the depth direction of a laboratory-scale packed-bed bioreactor containing rice bran as waste organic material were investigated. The HRT was shortened stepwise from 25 to 12 h, 8 h, and 6 to 5 h under the neutral condition using AMD neutralized with limestone (pH 6.3), and from 25 to 20 h, 12 h, and 8 to 7 h under the acid condition using AMD (pH 3.0). Under the neutral condition, the bioreactor stably operated up to 6 h HRT, which was shorter than under the acid condition (up to 20 h HRT). During stable sulfate reduction, both the organic matter-remaining condition and the low oxidation-reduction potential condition in lower parts of the reactor were observed. Principal coordinate analysis of Illumina sequencing data of 16S rRNA genes revealed a dynamic transition of the microbial communities at the boundary between stable and unstable operation in response to reductions in HRT. During stable operation under both the neutral and acid conditions, several fermentative operational taxonomic units (OTUs) from the phyla Firmicutes and Bacteroidetes dominated in lower parts of the bioreactor, suggesting that co-existence of these OTUs might lead to metabolic activation of sulfate-reducing bacteria. In contrast, during unstable operation at shorter HRTs, an OTU from the candidate phylum OP11 were found under both conditions. This study demonstrated that these microorganisms can be used to monitor the treatment of AMD, which suggests stable or deteriorated performance of the system.

Soft Tissue Changes in Cleft Lip and Palate Patients: Anterior Maxillary Distraction versus Conventional Le-Fort I Osteotomy.

Science.gov (United States)

Markose, Eldho; Paulose, Joby; Paul, Eldho T

2013-12-01

The purpose of the study was to compare the soft tissue changes after maxillary advancement in patients with maxillary deficiency associated with cleft lip and palate (CLP) by two approaches-anterior maxillary distraction (AMD) and advancement LeFort I osteotomy (ALO). Twenty patients with maxillary hypoplasia associated with cleft lip and palate who had undergone either LeFort I osteotomy or distraction osteogenesis with maxillary advancement were included in this study. Lateral cephalogram taken at various intervals of time were used to evaluate soft tissue and hard tissue changes over time. In both groups, vertical as well as horizontal changes in pronasale was well observed. A substantial increase in nasal parameters was noted in case of AMD group in comparison to ALO. Though maxillary advancement was evident in both the groups, a significant and consistent change was observed in AMD. Significant vertical and horizontal changes were seen with respect to subnasale and labrale superius in AMD group. Soft tissue as well as hard tissue relapse was greater in ALO group than AMD group. Significant soft tissue and hard tissue changes were clearly observed in both the groups, but the treatment results were more consistent in cases treated with AMD. Hence AMD could be considered as a better treatment of choice in cases of maxillary hypoplasia associated with cleft lip and palate.

Nutrition and age-related macular degeneration: research evidence in practice.

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Downie, Laura Elizabeth; Keller, Peter Richard

2014-08-01

Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment in developed countries. In the absence of effective treatments to slow AMD progression, it is predicted that the prevalence of AMD will double over the next 20 years. One area of significant interest is the potential role that nutrition may play in preventing and/or delaying the progression of AMD. Specifically, is there any benefit in oral antioxidant and/or mineral supplementation? This review critically evaluates the currently available evidence relating to nutrition and AMD, with particular reference to the key findings of two large National Eye Institute-sponsored clinical studies, namely, the Age-Related Eye Disease Study (AREDS) and AREDS2. Topical controversies relating to nutrition and AMD are considered and analyzed in the context of the published literature to guide practitioners through assessing the merit, or otherwise, of common claims. This article provides a foundation for clinicians to provide informed advice to AMD patients based on available research evidence.

Association of Genetic Variants With Response to Anti-Vascular Endothelial Growth Factor Therapy in Age-Related Macular Degeneration.

Science.gov (United States)

Lorés-Motta, Laura; Riaz, Moeen; Grunin, Michelle; Corominas, Jordi; van Asten, Freekje; Pauper, Marc; Leenders, Mathieu; Richardson, Andrea J; Muether, Philipp; Cree, Angela J; Griffiths, Helen L; Pham, Connie; Belanger, Marie-Claude; Meester-Smoor, Magda A; Ali, Manir; Heid, Iris M; Fritsche, Lars G; Chakravarthy, Usha; Gale, Richard; McKibbin, Martin; Inglehearn, Chris F; Schlingemann, Reinier O; Omar, Amer; Chen, John; Koenekoop, Robert K; Fauser, Sascha; Guymer, Robyn H; Hoyng, Carel B; de Jong, Eiko K; Lotery, Andrew J; Mitchell, Paul; den Hollander, Anneke I; Baird, Paul N; Chowers, Itay

2018-05-31

gain, 1.7; β, 0.034; SE, 0.008; P = 1.38 × 10-5). Genome-wide gene-based optimal unified sequence kernel association test of rare variants showed genome-wide significant associations for the C10orf88 (P = 4.22 × 10-7) and UNC93B1 (P = 6.09 × 10-7) genes, in both cases leading to a worse treatment outcome. Patients carrying rare variants in the C10orf88 and UNC93B1 genes lost a mean (SD) VA of 30.6 (17.4) ETDRS score letters (ie, loss of 6.09 lines) and 26.5 (13.8) ETDRS score letters (ie, loss of 5.29 lines), respectively, after 3 months of anti-VEGF treatment. We propose that there is a limited contribution of common genetic variants to variability in nAMD treatment response. Our results suggest that rare protein-altering variants in the C10orf88 and UNC93B1 genes are associated with a worse response to anti-VEGF therapy in patients with nAMD, but these results require further validation in other cohorts.

Intake of key micronutrients and food groups in patients with late-stage age-related macular degeneration compared with age-sex-matched controls.

Science.gov (United States)

Gopinath, Bamini; Liew, Gerald; Russell, Joanna; Cosatto, Victoria; Burlutsky, George; Mitchell, Paul

2017-08-01

Knowledge of the risk factor profile of patients presenting with late-stage age-related macular degeneration (AMD) could help identify the most frequent modifiable AMD precursors among people who are referred for treatment. We aimed to assess dietary behaviours by comparing adjusted mean intakes of micronutrients and major food groups (fruits, vegetables, fish) among patients with AMD and a sample of age-sex-matched controls. Cross-sectional analysis of 480 late AMD cases and 518 population-based age-sex-matched controls with no AMD signs. AMD cases (aged 60+ years) were those presenting for treatment to a hospital eye clinic in Sydney, Australia, during 2012-2015. The comparator group were obtained from a cohort study (Blue Mountains Eye Study; Sydney, Australia) during 2002-2009. Dietary intake was assessed using a semiquantitative food-frequency questionnaire. AMD lesions were assessed from retinal photographs. After multivariable adjustment, patients with late-stage AMD compared with controls had significantly lower intakes of vitamin E (7.4 vs 9.8 mg/day; p<0.0001), beta-carotene (6232 vs 7738 μg/day; p<0.0001), vitamin C (161 vs 184 mg/day; p=0.0002) and folate (498.3 vs 602 μg/day; p<0.0001); but had higher intakes of zinc (13.0 vs 11.9 mg/day; p<0.0001). A significantly lower proportion of patients with late AMD met the recommended intake of vegetables than controls: 52.9% versus 64.5%; p=0.0002. This study showed significant differences in intakes of vitamins C and E, beta-carotene, folate and vegetables between patients with late-stage AMD and healthy controls, and thus has provided a better understanding of the nutritional intake of patients presenting with advanced AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Autologous Translocation of the Retinal Pigment Epithelium and Choroid in the Treatment of Exudative Age-related Macular Degeneration

NARCIS (Netherlands)

K.J.M. Maaijwee (Kristel Johanna Maria)

2008-01-01

textabstractAge-related macular degeneration (AMD) is the most important cause of irreversible legal blindness in elderly persons in industrialized countries. AMD has two forms: atrophic (dry) and exudative (wet). In the wet form, abnormal blood vessels, arising from the choriocapillaris (choroidal

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future.

Science.gov (United States)

Colijn, Johanna M; Buitendijk, Gabriëlle H S; Prokofyeva, Elena; Alves, Dalila; Cachulo, Maria L; Khawaja, Anthony P; Cougnard-Gregoire, Audrey; Merle, Bénédicte M J; Korb, Christina; Erke, Maja G; Bron, Alain; Anastasopoulos, Eleftherios; Meester-Smoor, Magda A; Segato, Tatiana; Piermarocchi, Stefano; de Jong, Paulus T V M; Vingerling, Johannes R; Topouzis, Fotis; Creuzot-Garcher, Catherine; Bertelsen, Geir; Pfeiffer, Norbert; Fletcher, Astrid E; Foster, Paul J; Silva, Rufino; Korobelnik, Jean-François; Delcourt, Cécile; Klaver, Caroline C W

2017-12-01

Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Meta-analysis of prevalence data. A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Prevalence of early and late AMD, BCVA, and number of AMD cases. Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%-5.0%) in those aged 55-59 years to 17.6% (95% CI 13.6%-21.5%) in those aged ≥85 years; for late AMD these figures were 0.1% (95% CI 0.04%-0.3%) and 9.8% (95% CI 6.3%-13.3%), respectively. We observed a decreasing prevalence of late AMD after 2006, which became most prominent after age 70. Prevalences were similar for gender across all age groups except for late AMD in the oldest age category, and a trend was found showing a higher prevalence of CNV in Northern Europe. After 2006, fewer eyes and fewer ≥80-year-old subjects with CNV were visually impaired (P = 0.016). Projections of AMD showed an almost doubling of affected persons despite a decreasing prevalence. By 2040, the number of individuals in Europe with early AMD will range between 14.9 and 21.5 million, and for late AMD between 3.9 and 4.8 million. We observed a decreasing prevalence of AMD and an improvement

Association between CFH, CFB, ARMS2, SERPINF1, VEGFR1 and VEGF polymorphisms and anatomical and functional response to ranibizumab treatment in neovascular age-related macular degeneration.

Science.gov (United States)

Cobos, Estefania; Recalde, Sergio; Anter, Jaouad; Hernandez-Sanchez, Maria; Barreales, Carla; Olavarrieta, Leticia; Valverde, Alicia; Suarez-Figueroa, Marta; Cruz, Fernando; Abraldes, Maximino; Pérez-Pérez, Julian; Fernández-Robredo, Patricia; Arias, Luis; García-Layana, Alfredo

2018-03-01

We sought to determine if specific genetic single nucleotide polymorphisms (SNPs) influence vascular endothelial growth factor inhibition response to ranibizumab in neovascular age-related macular degeneration (AMD). A total of 403 Caucasian patients diagnosed with exudative AMD were included. After a three-injection loading phase, a pro re nata regimen was followed. Nine SNPs from six different genes (CFH, CFB, ARMS2, SERPINF1, VEGFR1, VEGF) were genotyped. Non-genetic risk factors (gender, smoking habit and hypertension) were also assessed. Patients were classified as good or poor responders (GR or PR) according to functional (visual acuity), anatomical (foveal thickness measured by OCT) and fluid criteria (fluid/no fluid measured by OCT). Hypertension was the environmental factor with the strongest poor response association with ranibizumab in the anatomical measure after the loading phase (p = 0.0004; OR 3.7; 95% CI, 2.4-5.8) and after 12 months of treatment (p = 10 -5 ; OR 2.3; 95% CI, 1.5-3.4). The genetic variants rs12614 (CFB), rs699947 (VEGFA) and rs7993418 (VEGFR1) predisposed patients to a good response, while rs12603486 and rs1136287 (SERPINF1) were associated with a poor response. The protective genotype of rs800292 variant (CFH) was also associated with a poor anatomical response (p 0.0048). All these data suggest that genetics play an important role in treatment response in AMD patients. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Do Nutritional Supplements Have a Role in Age Macular Degeneration Prevention?

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Maria D. Pinazo-Durán

2014-01-01

Full Text Available Purpose. To review the proposed pathogenic mechanisms of age macular degeneration (AMD, as well as the role of antioxidants (AOX and omega-3 fatty acids (ω-3 supplements in AMD prevention. Materials and Methods. Current knowledge on the cellular/molecular mechanisms of AMD and the epidemiologic/experimental studies on the effects of AOX and ω-3 were addressed all together with the scientific evidence and the personal opinion of professionals involved in the Retina Group of the OFTARED (Spain. Results. High dietary intakes of ω-3 and macular pigments lutein/zeaxanthin are associated with lower risk of prevalence and incidence in AMD. The Age-Related Eye Disease study (AREDS showed a beneficial effect of high doses of vitamins C, E, beta-carotene, and zinc/copper in reducing the rate of progression to advanced AMD in patients with intermediate AMD or with one-sided late AMD. The AREDS-2 study has shown that lutein and zeaxanthin may substitute beta-carotene because of its potential relationship with increased lung cancer incidence. Conclusion. Research has proved that elder people with poor diets, especially with low AOX and ω-3 micronutrients intake and subsequently having low plasmatic levels, are more prone to developing AMD. Micronutrient supplementation enhances antioxidant defense and healthy eyes and might prevent/retard/modify AMD.

Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development

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Agarwal A

2015-06-01

Full Text Available Aniruddha Agarwal, William R Rhoades, Mostafa Hanout, Mohamed Kamel Soliman, Salman Sarwar, Mohammad Ali Sadiq, Yasir Jamal Sepah, Diana V Do, Quan Dong Nguyen Stanley M Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, USA Abstract: Contemporary management of neovascular age-related macular degeneration (AMD has evolved significantly over the last few years. The goal of treatment is shifting from merely salvaging vision to maintaining a high quality of life. There have been significant breakthroughs in the identification of viable drug targets and gene therapies. Imaging tools with near-histological precision have enhanced our knowledge about pathophysiological mechanisms that play a role in vision loss due to AMD. Visual, social, and vocational rehabilitation are all important treatment goals. In this review, evidence from landmark clinical trials is summarized to elucidate the optimum modern-day management of neovascular AMD. Therapeutic strategies currently under development, such as gene therapy and personalized medicine, are also described. Keywords: AMD, neovascular AMD, choroidal neovascular membrane, pharmacogenomics, VEGF, low-vision rehabilitation, gene therapy

KUS121, an ATP regulator, mitigates chorioretinal pathologies in animal models of age-related macular degeneration

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Yuki Muraoka

2018-05-01

Full Text Available Age-related macular degeneration (AMD is a leading cause of blindness among elderly people. The appearance of drusen is a clinical manifestation and a harbinger of both exudative and atrophic AMD. Recently, antibody-based medicines have been used to treat the exudative type. However, they do not restore good vision in patients. Moreover, no effective treatment is available for atrophic AMD. We have created small chemicals (Kyoto University Substances; KUSs that act as ATP regulators inside cells. In the present study, we examined the in vivo efficacy of KUS121 in C-C chemokine receptor type 2-deficient mice, a mouse model of AMD. Systemic administration of KUS121 prevented or reduced drusen-like lesions and endoplasmic reticulum stress, and then substantially mitigated chorioretinal pathologies with significant preservation of visual function. Additionally, we confirmed that long-term oral administration of KUS121 caused no systemic complications in drusen-affected monkeys. ATP regulation by KUSs may represent a novel strategy in the treatment of drusen and prevention of disease progression in AMD.

Nutritional supplements in age-related macular degeneration.

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Schmidl, Doreen; Garhöfer, Gerhard; Schmetterer, Leopold

2015-03-01

Age-related macular degeneration (AMD) is the most frequent cause of blindness in the Western World. While with new therapies that are directed towards vascular endothelial growth factor (VEGF), a potentially efficient treatment option for the wet form of the disease has been introduced, a therapeutic regimen for dry AMD is still lacking. There is evidence from several studies that oral intake of supplements is beneficial in preventing progression of the disease. Several formulations of micronutrients are currently available. The present review focuses on the role of supplements in the treatment and prevention of AMD and sums up the current knowledge about the most frequently used micronutrients. In addition, regulatory issues are discussed, and future directions for the role of supplementation in AMD are highlighted. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Repressed SIRT1/PGC-1α pathway and mitochondrial disintegration in iPSC-derived RPE disease model of age-related macular degeneration.

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Golestaneh, Nady; Chu, Yi; Cheng, Shuk Kei; Cao, Hong; Poliakov, Eugenia; Berinstein, Daniel M

2016-12-20

-iPSC-RPE as compared to normal RPE-iPSC-RPE. Our studies suggest SIRT1/PGC-1α as underlying pathways contributing to AMD pathophysiology, and open new avenues for development of targeted drugs for treatment of this devastating neurodegenerative disease of the visual system.

Avaliação de desempenho e consumo energético para configurações de Wavefront pools de uma GPU AMD

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Ariel Gustavo Zuquello

2016-07-01

Full Text Available O uso de sistemas heterogêneos CPU-GPU para atender à crescente demanda por aplicações com grande paralelismo de dados resulta na necessidade de estudar e avaliar tais arquiteturas para melhorá-las continuamente. Neste artigo foram feitas simulações da execução de uma suíte de benchmark em uma GPU AMD ATI RadeonTM HD 7970, de modo a avaliar o impacto sobre o desempenho e o consumo energético quando alterado o número de Wavefront Pools presentes em cada compute unit da GPU, que é 4 por padrão. O resultado mais significante evidencia um aumento de velocidade de cerca de 5,7% para a configuração com duas Wavefront Pools em conjunto com um aumento no consumo de energia de cerca de 5,1%. Todavia, as outras configurações avaliadas também representam opções para diferentes tipos de necessidades, conforme a categoria de demanda computacional.Palavras-chave: Sistemas heterogêneos. Simulações. Desempenho.Performance evaluation and energy consumption for settings of Wavefront pools of a GPU AMDAbstractThe use of CPU-GPU heterogeneous systems to meet the growing demand for applications with large data parallelism results in the need to study and evaluate these architectures in order to improve them continuously. In this paper we made simulations of running a benchmark suite on an AMD GPU ATI RadeonTM HD 7970 in order to assess the impact on performance and power consumption when tuning the number of Wavefront Pools present in each GPU compute unit, which is 4 by default. The most significant result shows a speedup of about 5.7% for configuration with two Wavefront Pools in conjunction with an increase of about 5.1% in the energy consumption. However, the other evaluated configuration also represent options for different kinds of needs, according to   the  computational demand.Keyworks: Heterogeneous systems. Simulation. Performance.

Proposal of an environmental performance index to assess solid waste treatment technologies.

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Coelho, Hosmanny Mauro Goulart; Lange, Liséte Celina; Coelho, Lineker Max Goulart

2012-07-01

Although the concern with sustainable development and environment protection has considerably grown in the last years it is noted that the majority of decision making models and tools are still either excessively tied to economic aspects or geared to the production process. Moreover, existing models focus on the priority steps of solid waste management, beyond waste energy recovery and disposal. So, in order to help the lack of models and tools aiming at the waste treatment and final disposal, a new concept is proposed: the Cleaner Treatment, which is based on the Cleaner Production principles. This paper focuses on the development and validation of the Cleaner Treatment Index (CTI), to assess environmental performance of waste treatment technologies based on the Cleaner Treatment concept. The index is formed by aggregation (summation or product) of several indicators that consists in operational parameters. The weights of the indicator were established by Delphi Method and Brazilian Environmental Laws. In addition, sensitivity analyses were carried out comparing both aggregation methods. Finally, index validation was carried out by applying the CTI to 10 waste-to-energy plants data. From sensitivity analysis and validation results it is possible to infer that summation model is the most suitable aggregation method. For summation method, CTI results were superior to 0.5 (in a scale from 0 to 1) for most facilities evaluated. So, this study demonstrates that CTI is a simple and robust tool to assess and compare the environmental performance of different treatment plants being an excellent quantitative tool to support Cleaner Treatment implementation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Amiodarone increases the accumulation of DEA in a human alveolar epithelium-derived cell line.

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Seki, Satoru; Itagaki, Shirou; Kobayashi, Masaki; Hirano, Takeshi; Iseki, Ken

2008-07-01

Amiodarone (AMD)-induced pulmonary toxicity (AIPT) is the most life-threatening side-effect of AMD treatment. N-Monodesethylamiodarone (DEA), an active metabolite of AMD, also exhibits cytotoxicity and tends to accumulate in the lung more intensively than AMD. In this study, we characterized the mechanism of DEA accumulation using A549 cells as a model of the alveolar epithelium. Typical ATP-depletion compounds caused an approximately 30% increase in the accumulation of DEA in A549 cells, although these effects were less than those in Caco-2 cells. Triiodothyronine (T(3)), which exhibited an inhibitory effect on DEA efflux in Caco-2 cells, did not affect the accumulation of DEA in A549 cells. On the other hand, 100 microM AMD caused an approximately 200% increase in DEA content in A549 cells, although AMD accumulation was not affected by 100 microM DEA. Since the reducing effect of AMD on cellular ATP levels and that of FCCP were similar, the mechanism by which DEA accumulation is increased by AMD might be different from the ATP-dependent DEA efflux mechanism. The decrease in cell viability by DEA in the presence of AMD (IC(50) value of DEA for A549 cell viability: 25.4+/-2.4 microM) was more pronounced than that by DEA alone (IC(50) value: 11.5+/-3.0 microM). This further DEA accumulation by AMD might be a factor responsible for the greater accumulation of DEA than that of AMD in the lung in long-term AMD-treated patients.

Hot Flashes amd Night Sweats (PDQ)

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... Professionals Questions to Ask about Your Treatment Research Hot Flashes and Night Sweats (PDQ®)–Patient Version Overview ... quality of life in many patients with cancer. Hot flashes and night sweats may be side effects ...

Plan for injection of coal combustion byproducts into the Omega Mine for the reduction of acid mine drainage

International Nuclear Information System (INIS)

Gray, T.A.; Moran, T.C.; Broschart, D.W.; Smith, G.A.

1998-01-01

The Omega Mine Complex is located outside of Morgantown, West Virginia. The mine is in the Upper Freeport Coal, an acid-producing coal seam. The coal was mined in a manner that has resulted in acid mine drainage (AMD) discharges at multiple points. During the 1990's, the West Virginia Division of Environmental Protection (WVDEP) assumed responsibility for operating a collection and treatment system for the AMD. Collection and treatment costs are approximately $300,000 per year. Injecting grout into the mine workings to reduce AMD (and thus reducing treatment costs) is proposed. The procedure involves injecting grout mixes composed primarily of coal combustion byproducts (CCB's) and water, with a small quantity of cement. The intention of the injection program is to fill the mine voids in the north lobe of the Omega Mine (an area where most of the acidity is believed to be generated) with the grout, thus reducing the contact of air and water with potentially acidic material. The grout mix design consists of an approximate 1:1 ratio of fly ash to byproducts from fluidized bed combustion. Approximately 100 gallons of water per cubic yard of grout is used to achieve flowability. Observation of the mine workings via subsurface borings and downhole video camera confirmed that first-mined areas were generally open while second-mined areas were generally partially collapsed. The injection program was developed to account for this by utilizing closer injection hole spacing in second-mined areas. Construction began in January 1998, with grout injection expected to commence in mid-April 1998

Savannah River Site mixed waste Proposed Site Treatment Plan (PSTP). Volumes 1 and 2 and reference document: Revision 2

International Nuclear Information System (INIS)

Helmich, E.; Noller, D.K.; Wierzbicki, K.S.; Bailey, L.L.

1995-01-01

The DOE is required by the Resource Conservation and Recovery Act to prepare site treatment plans describing the development of treatment capacities and technologies for treating mixed waste. This proposed plan contains Savannah River Site's preferred options and schedules for constructing new facilities, and otherwise obtaining treatment for mixed wastes. The proposed plan consists of 2 volumes. Volume 1, Compliance Plan, identifies the capacity to be developed and the schedules as required. Volume 2, Background, provides a detailed discussion of the preferred options with technical basis, plus a description of the specific waste streams. Chapters are: Introduction; Methodology; Mixed low level waste streams; Mixed transuranic waste; High level waste; Future generation of mixed waste streams; Storage; Process for evaluation of disposal issues in support of the site treatment plans discussions; Treatment facilities and treatment technologies; Offsite waste streams for which SRS treatment is the Preferred Option (Naval reactor wastes); Summary information; and Acronyms and glossary. This revision does not contain the complete revised report, but only those pages that have been revised

Newly diagnosed exudative age-related macular degeneration treated with pegaptanib sodium monotherapy in US community-based practices: medical chart review study

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Xu Xiao

2010-02-01

Full Text Available Abstract Background Studies have shown that early detection and treatment of neovascular age-related macular degeneration (NV-AMD can delay vision loss and blindness. The objective of this study was to evaluate the efficacy/safety of intravitreal pegaptanib sodium monotherapy in treatment-naïve subjects with newly diagnosed NV-AMD and to gain insight into characteristics of lesions treated in community-based practices. Methods From seven private US practices, charts were retrospectively reviewed on 73 subjects with previously untreated subfoveal choroidal NV-AMD treated with their first dose of pegaptanib monotherapy on/after 4/1/2005 through 6/5/2006, receiving ≥4 treatments at 6-week intervals over 21 weeks. Primary endpoint: mean visual acuity (VA change from baseline to month 6. Results 75% of lesions were occult, and 82% were subfoveal. From baseline to month 6, mean VA change was -0.68 lines; 58% and 16% gained ≥0 and ≥3 lines of VA, and 70% were responders ( Conclusion Pegaptanib is effective in real-world patients with treatment-naïve NV-AMD in uncontrolled community-based retina practices.

Animal models of age related macular degeneration

Science.gov (United States)

Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

2013-01-01

Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

NLRP3 Inflammasome: Activation and Regulation in Age-Related Macular Degeneration

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Jiangyuan Gao

2015-01-01

Full Text Available Age-related macular degeneration (AMD is the leading cause of legal blindness in the elderly in industrialized countries. AMD is a multifactorial disease influenced by both genetic and environmental risk factors. Progression of AMD is characterized by an increase in the number and size of drusen, extracellular deposits, which accumulate between the retinal pigment epithelium (RPE and Bruch’s membrane (BM in outer retina. The major pathways associated with its pathogenesis include oxidative stress and inflammation in the early stages of AMD. Little is known about the interactions among these mechanisms that drive the transition from early to late stages of AMD, such as geographic atrophy (GA or choroidal neovascularization (CNV. As part of the innate immune system, inflammasome activation has been identified in RPE cells and proposed to be a causal factor for RPE dysfunction and degeneration. Here, we will first review the classic model of inflammasome activation, then discuss the potentials of AMD-related factors to activate the inflammasome in both nonocular immune cells and RPE cells, and finally introduce several novel mechanisms for regulating the inflammasome activity.

Nanosecond laser therapy reverses pathologic and molecular changes in age-related macular degeneration without retinal damage.

Science.gov (United States)

Jobling, A I; Guymer, R H; Vessey, K A; Greferath, U; Mills, S A; Brassington, K H; Luu, C D; Aung, K Z; Trogrlic, L; Plunkett, M; Fletcher, E L

2015-02-01

Age-related macular degeneration (AMD) is a leading cause of vision loss, characterized by drusen deposits and thickened Bruch's membrane (BM). This study details the capacity of nanosecond laser treatment to reduce drusen and thin BM while maintaining retinal structure. Fifty patients with AMD had a single nanosecond laser treatment session and after 2 yr, change in drusen area was compared with an untreated cohort of patients. The retinal effect of the laser was determined in human and mouse eyes using immunohistochemistry and compared with untreated eyes. In a mouse with thickened BM (ApoEnull), the effect of laser treatment was quantified using electron microscopy and quantitative PCR. In patients with AMD, nanosecond laser treatment reduced drusen load at 2 yr. Retinal structure was not compromised in human and mouse retina after laser treatment, with only a discrete retinal pigment epithelium (RPE) injury, and limited mononuclear cell response observed. BM was thinned in the ApoEnull mouse 3 mo after treatment (ApoEnull treated 683 ± 38 nm, ApoEnull untreated 890 ± 60 nm, C57Bl6J 606 ± 43 nm), with the expression of matrix metalloproteinase-2 and -3 increased (>260%). Nanosecond laser resolved drusen independent of retinal damage and improved BM structure, suggesting this treatment has the potential to reduce AMD progression. © FASEB.

Abandoned mine drainage in the Swatara Creek Basin, southern anthracite coalfield, Pennsylvania, USA: 2. performance of treatment systems

Science.gov (United States)

Cravotta, Charles A.

2010-01-01

A variety of passive and semi-passive treatment systems were constructed by state and local agencies to neutralize acidic mine drainage (AMD) and reduce the transport of dissolved metals in the upper Swatara Creek Basin in the Southern Anthracite Coalfield in eastern Pennsylvania. To evaluate the effectiveness of selected treatment systems installed during 1995–2001, the US Geological Survey collected water-quality data at upstream and downstream locations relative to each system eight or more times annually for a minimum of 3 years at each site during 1996–2007. Performance was normalized among treatment types by dividing the acid load removed by the size of the treatment system. For the limestone sand, open limestone channel, oxic limestone drain, anoxic limestone drain (ALD), and limestone diversion well treatment systems, the size was indicated by the total mass of limestone; for the aerobic wetland systems, the size was indicated by the total surface area of ponds and wetlands. Additionally, the approximate cost per tonne of acid treated over an assumed service life of 20 years was computed. On the basis of these performance metrics, the limestone sand, ALD, oxic limestone drain, and limestone diversion wells had similar ranges of acid-removal efficiency and cost efficiency. However, the open limestone channel had lower removal efficiency and higher cost per ton of acid treated. The wetlands effectively attenuated metals transport but were relatively expensive considering metrics that evaluated acid removal and cost efficiency. Although the water-quality data indicated that all treatments reduced the acidity load from AMD, the ALD was most effective at producing near-neutral pH and attenuating acidity and dissolved metals. The diversion wells were effective at removing acidity and increasing pH of downstream water and exhibited unique potential to treat moderate to high flows associated with storm flow conditions.

Anxiety and depression in patients with advanced macular degeneration: current perspectives

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Cimarolli VR

2015-12-01

Full Text Available Verena R Cimarolli,1 Robin J Casten,2 Barry W Rovner,3–5 Vera Heyl,6 Silvia Sörensen,7,8 Amy Horowitz9 1Research Institute on Aging, Jewish Home Lifecare, New York, NY, USA; 2Department of Psychiatry and Human Behavior, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA; 3Department of Neurology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA; 4Department of Psychiatry, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA; 5Department of Ophthalmology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA; 6Institute of Special Education, University of Education, Heidelberg, Germany; 7Warner School of Education and Human Development, University of Rochester, Rochester, NY, USA; 8Department of Ophthalmology, Flaum Eye Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA; 9Graduate School of Social Service, Fordham University, New York, NY, USA Abstract: Age-related macular degeneration (AMD – despite advances in prevention and medical treatment options – remains prevalent among older adults, often resulting in functional losses that negatively affect the mental health of older adults. In particular, the prevalence of both anxiety and depression in patients with AMD is high. Along with medical treatment options, low vision rehabilitation and AMD-specific behavioral and self-management programs have been developed and have demonstrated effectiveness in improving the mental health of AMD patients. This article reviews the prevalence of anxiety and depression in patients with advanced AMD, discusses potential mechanisms accounting for the development of depression and anxiety in AMD patients, presents the state-of the-art of available interventions for addressing anxiety and depression in AMD patients, and delineates recommendations for eye care professionals regarding how to

Proposed site treatment plan (PSTP) Volumes I ampersand II ampersand reference document, Revision 3

International Nuclear Information System (INIS)

Helmich, E.; Noller, D.K.; Wierzbicki, K.S.

1995-01-01

The Federal Facility Compliance Act requires the Department of Energy to undertake a national effort to develop Site Treatment Plans for each of its sites generating or storing mixed waste. Mixed waste contains both a hazardous waste subject to the Resource Conservation and Recovery Act and radioactive material subject to the Atomic Energy Act of 1954. The Site Treatment Plan for the Savannah River Site proposes how SRS will treat mixed waste that is now stored on the site and mixed waste that Will be generated in the future. Also, the Site Treatment Plan identifies Savannah River Site mixed wastes that other Department of Energy facilities could treat and mixed waste from other facilities that the Savannah River Site could treat. The Site Treatment Plan has been approved by the State of South Carolina. The Department of Energy Will enter into a consent order with the State of South Carolina by October 6, 1995. The consent order will contain enforceable commitments to treat mixed waste

Prevalence of Age-Related Macular Degeneration in Europe

NARCIS (Netherlands)

Colijn, Johanna M.; Buitendijk, Gabriëlle H. S.; Prokofyeva, Elena; Alves, Dalila; Cachulo, Maria L.; Khawaja, Anthony P.; Cougnard-Gregoire, Audrey; Merle, Bénédicte M. J.; Korb, Christina; Erke, Maja G.; Bron, Alain; Anastasopoulos, Eleftherios; Meester-Smoor, Magda A.; Segato, Tatiana; Piermarocchi, Stefano; de Jong, Paulus T. V. M.; Vingerling, Johannes R.; Topouzis, Fotis; Creuzot-Garcher, Catherine; Bertelsen, Geir; Pfeiffer, Norbert; Fletcher, Astrid E.; Foster, Paul J.; Silva, Rufino; Korobelnik, Jean-François; Delcourt, Cécile; Klaver, Caroline C. W.; Ajana, Soufiane; Arango-Gonzalez, Blanca; Arndt, Verena; Bhatia, Vaibhav; Bhattacharya, Shomi S.; Biarnés, Marc; Borrell, Anna; Bühren, Sebastian; Calado, Sofia M.; Cougnard-Grégoire, Audrey; Dammeier, Sascha; de Jong, Eiko K.; de la Cerda, Berta; den Hollander, Anneke I.; Diaz-Corrales, Francisco J.; Diether, Sigrid; Emri, Eszter; Endermann, Tanja; Ferraro, Lucia L.; Garcia, Míriam; Heesterbeek, Thomas J.; Honisch, Sabina; Bergen, Arthur

2017-01-01

Purpose: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in

Prevalence of Age-Related Macular Degeneration in Europe

DEFF Research Database (Denmark)

Colijn, Johanna M; Buitendijk, Gabriëlle H S; Prokofyeva, Elena

2017-01-01

PURPOSE: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD...

Laser treatment of drusen to prevent progression to advanced age-related macular degeneration.

Science.gov (United States)

Virgili, Gianni; Michelessi, Manuele; Parodi, Maurizio B; Bacherini, Daniela; Evans, Jennifer R

2015-10-23

Drusen are amorphous yellowish deposits beneath the sensory retina. People with drusen, particularly large drusen, are at higher risk of developing age-related macular degeneration (AMD). The most common complication in AMD is choroidal neovascularisation (CNV), the growth of new blood vessels in the centre of the macula. The risk of CNV is higher among people who are already affected by CNV in one eye.It has been observed clinically that laser photocoagulation of drusen leads to their disappearance and may prevent the occurrence of advanced disease (CNV or geographic atrophy) associated with visual loss. To examine the effectiveness and adverse effects of laser photocoagulation of drusen in AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2015), EMBASE (January 1980 to August 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 3 August 2015. Randomised controlled trials (RCTs) of laser treatment of drusen in AMD in which laser treatment had been compared with no intervention or sham treatment. Two types of trials were included. Some trials studied one eye of each participant (unilateral studies); other studies recruited participants with bilateral drusen and randomised one eye to photocoagulation or control and the fellow eye to the other group. Two review authors independently selected studies and extracted data. We pooled data from unilateral and bilateral

Treatment of the acid mine drainage residue for uranium recovery

International Nuclear Information System (INIS)

Dias, M.M.; Horta, D.G.; Fukuma, H.T.; Villegas, R.A.S.; Carvalho, C.H.T. de; Silva, A.C. da

2017-01-01

Acid mine drainage (AMD) is a process that occurs in many mining that have sulfide ores. With water and oxygen, several metals are oxidized, one example being uranium. At the mine pit of the Osamu Utsumi Mine located at INB - Caldas and in two other boot-wastes (mining waste pile), AMD is present and currently, without a technological solution. The acidic water present in the pit is treated with hydrated lime, generating water for disposal and an alkaline residue called calcium diuranate - DUCA. The DUCA has a concentration of approximately 0.32% U 3 O 8 , which makes interesting the development of a process for extracting that metal. One of the processes that can be used is leaching. For this study, it was decided to evaluate the alkaline leaching to extract the uranium present in the residue. It is necessary to optimize operational parameters for the process: percentage of solids, concentration of leaching agent in solution, temperature and reaction time. With these parameters, it is possible to improve the leaching so that the largest amount of uranium is extracted from the sample, to help solve the environmental impact caused by the wastewater from the treatment of acid waters and, in addition, to give an economical destination for this metal that is contained in the deposited DUCA

The complement system in age-related macular degeneration: A review of rare genetic variants and implications for personalized treatment

NARCIS (Netherlands)

Geerlings, M.J.; Jong, E.K.; Hollander, A.I. den

2017-01-01

Age-related macular degeneration (AMD) is a progressive retinal disease and the major cause of irreversible vision loss in the elderly. Numerous studies have found both common and rare genetic variants in the complement pathway to play a role in the pathogenesis of AMD. In this review we provide an

Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers.

Science.gov (United States)

Laíns, Inês; Kelly, Rachel S; Miller, John B; Silva, Rufino; Vavvas, Demetrios G; Kim, Ivana K; Murta, Joaquim N; Lasky-Su, Jessica; Miller, Joan W; Husain, Deeba

2018-02-01

that the most significant metabolites map to the glycerophospholipid pathway. These findings have the potential to improve our understanding of AMD pathogenesis, to support the development of plasma-based metabolomics biomarkers of AMD, and to identify novel targets for treatment of this blinding disease. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Endophenotypes for Age-Related Macular Degeneration: Extending Our Reach into the Preclinical Stages of Disease.

Science.gov (United States)

Gorin, Michael B; Weeks, Daniel E; Baron, Robert V; Conley, Yvette P; Ortube, Maria C; Nusinowitz, Steven

2014-11-28

The key to reducing the individual and societal burden of age-related macular degeneration (AMD)-related vision loss, is to be able to initiate therapies that slow or halt the progression at a point that will yield the maximum benefit while minimizing personal risk and cost. There is a critical need to find clinical markers that, when combined with the specificity of genetic testing, will identify individuals at the earliest stages of AMD who would benefit from preventive therapies. These clinical markers are endophenotypes for AMD, present in those who are likely to develop AMD, as well as in those who have clinical evidence of AMD. Clinical characteristics associated with AMD may also be possible endophenotypes if they can be detected before or at the earliest stages of the condition, but we and others have shown that this may not always be valid. Several studies have suggested that dynamic changes in rhodopsin regeneration (dark adaptation kinetics and/or critical flicker fusion frequencies) may be more subtle indicators of AMD-associated early retinal dysfunction. One can test for the relevance of these measures using genetic risk profiles based on known genetic risk variants. These functional measures may improve the sensitivity and specificity of predictive models for AMD and may also serve to delineate clinical subtypes of AMD that may differ with respect to prognosis and treatment.

Endophenotypes for Age-Related Macular Degeneration: Extending Our Reach into the Preclinical Stages of Disease

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Michael B. Gorin

2014-11-01

Full Text Available The key to reducing the individual and societal burden of age-related macular degeneration (AMD-related vision loss, is to be able to initiate therapies that slow or halt the progression at a point that will yield the maximum benefit while minimizing personal risk and cost. There is a critical need to find clinical markers that, when combined with the specificity of genetic testing, will identify individuals at the earliest stages of AMD who would benefit from preventive therapies. These clinical markers are endophenotypes for AMD, present in those who are likely to develop AMD, as well as in those who have clinical evidence of AMD. Clinical characteristics associated with AMD may also be possible endophenotypes if they can be detected before or at the earliest stages of the condition, but we and others have shown that this may not always be valid. Several studies have suggested that dynamic changes in rhodopsin regeneration (dark adaptation kinetics and/or critical flicker fusion frequencies may be more subtle indicators of AMD-associated early retinal dysfunction. One can test for the relevance of these measures using genetic risk profiles based on known genetic risk variants. These functional measures may improve the sensitivity and specificity of predictive models for AMD and may also serve to delineate clinical subtypes of AMD that may differ with respect to prognosis and treatment.

Recent developments in age-related macular degeneration: a review

Science.gov (United States)

Al-Zamil, Waseem M; Yassin, Sanaa A

2017-01-01

Background Visual impairment in elderly people is a considerable health problem that significantly affects quality of life of millions worldwide. The magnitude of this issue is becoming more evident with an aging population and an increasing number of older individuals. Objective The objective of this article was to review the clinical and pathological aspects of age-related macular degeneration (AMD), diagnostic tools, and therapeutic modalities presently available or underway for both atrophic and wet forms of the disease. Methods An online review of the PubMed database was performed, searching for the key words. The search was limited to articles published since 1980 to date. Results Several risk factors have been linked to AMD, such as age (>60 years), lifestyle (smoking and diet), and family history. Although the pathogenesis of AMD remains unclear, genetic factors have been implicated in the condition. Treatment for atrophic AMD is mainly close observation, coupled with nutritional supplements such as zinc and antioxidants, whereas treatment of wet AMD is based on targeting choroidal neovascular membranes. Conclusion Identification of modifiable risk factors would improve the possibilities of preventing the progression of AMD. The role of anti-vascular endothelial growth factor (anti-VEGF) agents has transformed the therapeutic approach of the potentially blinding disease “wet AMD” into a more favorable outcome. PMID:28860733

Optimization of the operation of packed bed bioreactor to improve the sulfate and metal removal from acid mine drainage.

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Dev, Subhabrata; Roy, Shantonu; Bhattacharya, Jayanta

2017-09-15

The present study discusses the potentiality of using anaerobic Packed Bed Bioreactor (PBR) for the treatment of acid mine drainage (AMD). The multiple process parameters such as pH, hydraulic retention time (HRT), concentration of marine waste extract (MWE), total organic carbon (TOC) and sulfate were optimized together using Taguchi design. The order of influence of the parameters towards biological sulfate reduction was found to be pH > MWE > sulfate > HRT > TOC. At optimized conditions (pH - 7, 20% (v/v) MWE, 1500 mg/L sulfate, 48 h HRT and 2300 mg/L TOC), 98.3% and 95% sulfate at a rate of 769.7 mg/L/d. and 732.1 mg/L/d. was removed from the AMD collected from coal and metal mine, respectively. Efficiency of metal removal (Fe, Cu, Zn, Mg and Ni) was in the range of 94-98%. The levels of contaminants in the treated effluent were below the minimum permissible limits of industrial discharge as proposed by Bureau of Indian Standards (IS 2490:1981). The present study establishes the optimized conditions for PBR operation to completely remove sulfate and metal removal from AMD at high rate. The study also creates the future scope to develop an efficient treatment process for sulfate and metal-rich mine wastewater in a large scale. Copyright © 2017 Elsevier Ltd. All rights reserved.

Common variants in LEPR, IL6, AMD1, and NAMPT do not associate with risk of juvenile and childhood obesity in Danes

DEFF Research Database (Denmark)

Hollensted, Mette; Ahluwalia, Tarun Veer Singh; Have, Christian Theil

2015-01-01

BACKGROUND: Childhood obesity is a highly heritable disorder, for which the underlying genetic architecture is largely unknown. Four common variants involved in inflammatory-adipokine triggering (IL6 rs2069845, LEPR rs1137100, NAMPT rs3801266, and AMD1 rs2796749) have recently been associated...... with obesity and related traits in Indian children. The current study aimed to examine the effect of these variants on risk of childhood/juvenile onset obesity and on obesity-related quantitative traits in two Danish cohorts. METHODS: Genotype information was obtained for 1461 young Caucasian men from...... the Genetics of Overweight Young Adults (GOYA) study (overweight/obese: 739 and normal weight: 722) and the Danish Childhood Obesity Biobank (TDCOB; overweight/obese: 1022 and normal weight: 650). Overweight/obesity was defined as having a body mass index (BMI) ≥25 kg/m(2); among children and youths, this cut...

Towards Treatment of Stargardt Disease: Workshop Organized and Sponsored by the Foundation Fighting Blindness

OpenAIRE

Sears, Avery E.; Bernstein, Paul S.; Cideciyan, Artur V.; Hoyng, Carel; Issa, Peter Charbel; Palczewski, Krzysztof; Rosenfeld, Philip J.; Sadda, SriniVas; Schraermeyer, Ulrich; Sparrow, Janet R.; Washington, Ilyas; Scholl, Hendrik P.N.

2017-01-01

Accumulation of fluorescent metabolic byproducts of the visual (retinoid) cycle is associated with photoreceptor and retinal pigment epithelial cell death in both Stargardt disease and atrophic (nonneovascular) age-related macular degeneration (AMD). As a consequence of this observation, small molecular inhibitors of enzymes in the visual cycle were recently tested in clinical trials as a strategy to protect the retina and retinal pigment epithelium in patients with atrophic AMD. To address t...

Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development

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Agarwal, Aniruddha; Rhoades, William R; Hanout, Mostafa; Soliman, Mohamed Kamel; Sarwar, Salman; Sadiq, Mohammad Ali; Sepah, Yasir Jamal; Do, Diana V; Nguyen, Quan Dong

2015-01-01

Contemporary management of neovascular age-related macular degeneration (AMD) has evolved significantly over the last few years. The goal of treatment is shifting from merely salvaging vision to maintaining a high quality of life. There have been significant breakthroughs in the identification of viable drug targets and gene therapies. Imaging tools with near-histological precision have enhanced our knowledge about pathophysiological mechanisms that play a role in vision loss due to AMD. Visual, social, and vocational rehabilitation are all important treatment goals. In this review, evidence from landmark clinical trials is summarized to elucidate the optimum modern-day management of neovascular AMD. Therapeutic strategies currently under development, such as gene therapy and personalized medicine, are also described. PMID:26089632

Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study)

DEFF Research Database (Denmark)

Nguyen, Quan Dong; Schachar, Ronald A; Nduaka, Chudy I

2012-01-01

To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD).......To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD)....

Guidelines for the Management of Wet Age-Related Macular Degeneration: Recommendations from a Panel of Greek Experts.

Science.gov (United States)

Androudi, Sofia; Dastiridou, Anna; Pharmakakis, Nikolaos; Stefaniotou, Maria; Kalogeropoulos, Christos; Symeonidis, Chrysanthos; Charonis, Alexandros; Tsilimbaris, Miltiadis

2016-05-01

To propose guidelines for the management of patients with wet age-related macular degeneration (wAMD), taking into account the results of large multicenter studies and clinical experience of retina experts. A team of retina experts developed a consensus paper after three consecutive meetings. The group was focused on guidelines to help clinical decision-making around the definition of successful treatment and the definition of non-response to therapy. Parameters suggestive of a successful response to treatments included: any gain in best corrected visual acuity (BCVA) or vision loss that is less than 5-10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, reduction of central retinal thickness, partial or complete absorption of subretinal fluid (SRF), reduction of intraretinal fluid, reduction of pigment epithelial detachment or restoration of the anatomy of outer retinal layers. Non-response to current treatment was considered in the case of loss of BCVA greater than 10 ETDRS letters, increased retinal edema or increase of SRF as evidenced by optical coherence tomography or new bleeding in biomicroscopy. The introduction of anti-VEGF agents revolutionized the treatment of wAMD. Given the complexity of the disease, the emerging new agents and the difference of cases recruited in clinical trials compared to those appearing in every-day practice, it is essential to individualize treatment options taking into account the results of clinical trials.

New research progress on the epidemiology of age-related macular degeneration

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Ming-Xing Wu

2015-02-01

Full Text Available Age-related macular degeneration(AMDis a kind of age-related blinding degenerative fundus lesions, totally about 30 million patients suffering from AMD all over the world, with about 500 000 people blind for it yearly. As the development of economy and the aging of the population intensified, incidence of AMD indicates a trend of rising year by year, being the third major cause of blindness in our country. At present, the pathogenesis of AMD is not fully clear, as reported it may be related to oxidative stress, inflammatory immune response, VEGF and genetic manipulation. Clinical treatments mainly include photodynamic therapy, drug therapy, radiation therapy, laser photocoagulaory operation, the pupil warm treatments, Chinese medicine and intravitreous injection VEGF antagonists such as Ranibizumab, Conbercept and so on. In this issue, we mainly expound on the progress in the epidemiological studies of AMD, especially elaborate the progress made on genetic manipulation in recent years.

Targeting modifiable risk factors in age-related macular degeneration in optometric practice in Sweden

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Martin L

2017-04-01

Full Text Available Lene Martin1,2 1School of Health, Care and Social Welfare, Mälardalen University, Eskilstuna, Sweden; 2School of Health Sciences, City, University of London, London, UK Purpose: The purpose of this study was to investigate the extent to which ophthalmologists and optometrists in Sweden recommend the use of nutritional supplements, changes in diet, or smoking cessation to patients who are at risk of or with signs of age-related macular degeneration (AMD. In addition, this study also examined how these practitioners rate the strength of evidence for nutritional supplements in AMD management and which sources of information they consult to determine supplement recommendations for the prevention or treatment of AMD. Methods: This study implemented a cross-sectional design using data from a questionnaire. All Swedish optometrists and ophthalmologists who were registered in the membership databases of their respective professional organizations were invited to participate. The questionnaire contained 18 forced choice questions and one free text question and was organized into the following four sections: use of nutritional supplements, dietary advice, smoking and eye diseases, and strength of evidence and the sources of information regarding nutritional supplement interventions. Results: The response rate was 40.3% for optometrists and 5% for ophthalmologists. Optometrists were more likely than ophthalmologists to recommend nutritional supplements in AMD and provided significantly more advice about diet than did the ophthalmologists for both patients at risk for AMD and those with established disease. The ophthalmologists were more likely than the optometrists to rely on the findings from the age-related eye disease studies of AMD regarding treatment with and selection of supplements and to recommend smoking cessation. Conclusion: Common evidence-based strategies for AMD management among eye care professionals would presumably be beneficial for AMD

Comparison of Outcomes and Costs of Ranibizumab and Aflibercept Treatment in Real-Life.

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Martin K Schmid

Full Text Available Treatment efficacy and costs of anti-VEGF drugs have not been studied in clinical routine.To compare treatment costs and clinical outcomes of the medications when adjusting for patients' characteristics and clinical status.Comparative study.The largest public ophthalmologic clinic in Switzerland.Health care claims data of patients with age-related macular degeneration, diabetic macula edema and retinal vein occlusion were matched to clinical and outcome data.Patients' underlying condition, gender, age, visual acuity and retinal thickness at baseline and after completing the loading phase, the total number of injections per treatment, the visual outcome and vital status was secured.We included 315 patients (19595 claims with a follow-up time of 1 to 99 months (mean 32.7, SD 25.8 covering the years 2006-2014. Mean age was 78 years (SD 9.3 and 200 (63.5% were female. At baseline, the mean number of letters was 55.6 (SD 16.3 and the central retinal thickness was 400.1 μm (SD 110.1. Patients received a mean number of 15.1 injections (SD 13.7; range 1 to 85. Compared to AMD, adjusted cost per month were significantly higher (+2174.88 CHF, 95%CI: 1094.50-3255.27; p<0.001 for patients with DME, while cost per month for RVO were slightly but not significantly higher. (+284.71 CHF, 95% CI: -866.73-1436.15; p = 0.627.Patients with DME are almost twice as expensive as AMD and RVO patients. Cost excess occurs with non-ophthalmologic interventions. The currently licensed anti-VEGF medications did not differ in costs, injection frequency and clinical outcomes. Linking health care claims to clinical data is a useful tool to examine routine clinical care.

Altered bioenergetics and enhanced resistance to oxidative stress in human retinal pigment epithelial cells from donors with age-related macular degeneration

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Deborah A. Ferrington

2017-10-01

Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness among older adults. It has been suggested that mitochondrial defects in the retinal pigment epithelium (RPE underlies AMD pathology. To test this idea, we developed primary cultures of RPE to ask whether RPE from donors with AMD differ in their metabolic profile compared with healthy age-matched donors. Analysis of gene expression, protein content, and RPE function showed that these cultured cells replicated many of the cardinal features of RPE in vivo. Using the Seahorse Extracellular Flux Analyzer to measure bioenergetics, we observed RPE from donors with AMD exhibited reduced mitochondrial and glycolytic function compared with healthy donors. RPE from AMD donors were also more resistant to oxidative inactivation of these two energy-producing pathways and were less susceptible to oxidation-induced cell death compared with cells from healthy donors. Investigation of the potential mechanism responsible for differences in bioenergetics and resistance to oxidative stress showed RPE from AMD donors had increased PGC1α protein as well as differential expression of multiple genes in response to an oxidative challenge. Based on our data, we propose that cultured RPE from donors phenotyped for the presence or absence of AMD provides an excellent model system for studying “AMD in a dish”. Our results are consistent with the ideas that (i a bioenergetics crisis in the RPE contributes to AMD pathology, and (ii the diseased environment in vivo causes changes in the cellular profile that are retained in vitro.

Massive choroidal hemorrhage after intravitreal administration of bevacizumab (Avastin® for AMD followed by controlateral sympathetic ophthalmia

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Dimitrios Brouzas

2009-08-01

Full Text Available Dimitrios Brouzas, Chryssanthi Koutsandrea, Marilita Moschos, Spiros Papadimitriou, Ioannis Ladas, Michael Apostolopoulos1st Eye Department , University of Athens, Athens, GreecePurpose: To report a severe ocular complication initiated ten days after intravitreal administration of bevacizumab (Avastin®, in a patient with exudative age-related macular degeneration (AMD.Patients and method: Case report.Results: Ten days after intravitreal injection of 1.25 mg Avastin®, the patient manifested acute loss of vision with excruciating pain. An extensive choroidal detachment was evident in close contact with the lens, which necessitated an emergency sclerotomy with reconstruction of the anterior chamber. Four months later, the eye proceeded to phthisis bulbi. Five months after the injection, the patient complained of mild pain, photophobia, and visual acuity deterioration from the fellow eye. The diagnosis of sympathetic ophthalmia was suggested and treated with intravitreal injections of triamcinolone acetonide every three months with good response, complicated by elevation of intraocular pressure which we managed with Ahmet valve implantation.Conclusion: Serious ocular complications after intravitreal of Avastin® can not be excluded, including massive choroidal hemorrhage and sympathetic ophthalmia of the fellow eye.Keywords: Avastin® complication, intravitreal injection, choroidal detachment, Phthisis bulbi, sympathetic ophthalmia

Passive aerobic treatment of net-alkaline, iron-laden drainage from a flooded underground anthracite mine, Pennsylvania, USA

Science.gov (United States)

Cravotta, C.A.

2007-01-01

This report evaluates the results of a continuous 4.5-day laboratory aeration experiment and the first year of passive, aerobic treatment of abandoned mine drainage (AMD) from a typical flooded underground anthracite mine in eastern Pennsylvania, USA. During 1991-2006, the AMD source, locally known as the Otto Discharge, had flows from 20 to 270 L/s (median 92 L/s) and water quality that was consistently suboxic (median 0.9 mg/L O2) and circumneutral (pH ??? 6.0; net alkalinity >10) with moderate concentrations of dissolved iron and manganese and low concentrations of dissolved aluminum (medians of 11, 2.2, and aeration experiment demonstrated rapid oxidation of ferrous iron (Fe 2+) without supplemental alkalinity; the initial Fe2+ concentration of 16.4 mg/L decreased to less than 0.5 mg/L within 24 h; pH values increased rapidly from 5.8 to 7.2, ultimately attaining a steady-state value of 7.5. The increased pH coincided with a rapid decrease in the partial pressure of carbon dioxide (PCO2) from an initial value of 10 -1.1atm to a steady-state value of 10-3.1atm. From these results, a staged aerobic treatment system was conceptualized consisting of a 2 m deep pond with innovative aeration and recirculation to promote rapid oxidation of Fe2+, two 0.3 m deep wetlands to facilitate iron solids removal, and a supplemental oxic limestone drain for dissolved manganese and trace-metal removal. The system was constructed, but without the aeration mechanism, and began operation in June 2005. During the first 12 months of operation, estimated detention times in the treatment system ranged from 9 to 38 h. However, in contrast with 80-100% removal of Fe2+ over similar elapsed times during the laboratory aeration experiment, the treatment system typically removed less than 35% of the influent Fe2+. Although concentrations of dissolved CO2 decreased progressively within the treatment system, the PCO2 values for treated effluent remained elevated (10-2.4 to 10-1.7atm). The

Sulfate reduction at low pH to remediate acid mine drainage

International Nuclear Information System (INIS)

Sánchez-Andrea, Irene; Sanz, Jose Luis; Bijmans, Martijn F.M.; Stams, Alfons J.M.

2014-01-01

Highlights: • Acid mine drainage (AMD) is an important environmental concern. • Remediation through biological sulfate reduction and metal recovery can be applied for AMD. • Microbial community composition has a major impact on the performance of bioreactors to treat AMD. • Acidophilic SRB are strongly influenced by proton, sulfide and organic acids concentration. - Abstract: Industrial activities and the natural oxidation of metallic sulfide-ores produce sulfate-rich waters with low pH and high heavy metals content, generally termed acid mine drainage (AMD). This is of great environmental concern as some heavy metals are highly toxic. Within a number of possibilities, biological treatment applying sulfate-reducing bacteria (SRB) is an attractive option to treat AMD and to recover metals. The process produces alkalinity, neutralizing the AMD simultaneously. The sulfide that is produced reacts with the metal in solution and precipitates them as metal sulfides. Here, important factors for biotechnological application of SRB such as the inocula, the pH of the process, the substrates and the reactor design are discussed. Microbial communities of sulfidogenic reactors treating AMD which comprise fermentative-, acetogenic- and SRB as well as methanogenic archaea are reviewed

Sulfate reduction at low pH to remediate acid mine drainage

Energy Technology Data Exchange (ETDEWEB)

Sánchez-Andrea, Irene, E-mail: irene.sanchezandrea@wur.nl [Departamento de Biología Molecular, Universidad Autónoma de Madrid, 28049 Madrid (Spain); Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen (Netherlands); Sanz, Jose Luis [Departamento de Biología Molecular, Universidad Autónoma de Madrid, 28049 Madrid (Spain); Bijmans, Martijn F.M. [Wetsus, Centre of Sustainable Water Technology, P.O. Box 1113, 8900 CC Leeuwarden (Netherlands); Stams, Alfons J.M. [Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen (Netherlands); IBB – Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, University of Minho, 4710-057 Braga (Portugal)

2014-03-01

Highlights: • Acid mine drainage (AMD) is an important environmental concern. • Remediation through biological sulfate reduction and metal recovery can be applied for AMD. • Microbial community composition has a major impact on the performance of bioreactors to treat AMD. • Acidophilic SRB are strongly influenced by proton, sulfide and organic acids concentration. - Abstract: Industrial activities and the natural oxidation of metallic sulfide-ores produce sulfate-rich waters with low pH and high heavy metals content, generally termed acid mine drainage (AMD). This is of great environmental concern as some heavy metals are highly toxic. Within a number of possibilities, biological treatment applying sulfate-reducing bacteria (SRB) is an attractive option to treat AMD and to recover metals. The process produces alkalinity, neutralizing the AMD simultaneously. The sulfide that is produced reacts with the metal in solution and precipitates them as metal sulfides. Here, important factors for biotechnological application of SRB such as the inocula, the pH of the process, the substrates and the reactor design are discussed. Microbial communities of sulfidogenic reactors treating AMD which comprise fermentative-, acetogenic- and SRB as well as methanogenic archaea are reviewed.

The role of preventive topical antibiotic treatment prior to intravitreal injection

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Elena Vladimirovna Ageeva

2015-06-01

Full Text Available Treatment of wet age-related macular degeneration (AMD requires frequent intravitreal injections of anti-VEGF agents, sometimes on monthly basis during a long period of time. Endophthalmitis is a rare but extremely severe complication of intravitreal injections. As it has been proven before, the flora from the conjunctival surface is the main source for endophthalmitis. Using Povidone-iodine solution (Betadine10 % Povidone-iodine, EGIS PHARMACEUTICALS is the only way to prevent endophthalmitis. The efficacy of it was proven by numerous studies. No evidence exists that topical antibiotiotics prior and after injections could be effective for prevention of endophthalmitis. Purpose: To study the advisability of topical antibiotic application before intravitreal injection. Materials and methods: Under investigation, there were 25 eyes of 25 patients with wet AMD treated by anti-VEGF intravitreal injections. All patients used topical antibiotics 3 days before injection. Conjunctival culture from injection eye was collected three times: before topical antibiotic use; after topical antibiotic use, and after Betadine 5 % application. Results: The rates of Staphylococcus epidermidis before and after topical antibiotic use were approximately equal. However there was no Staphylococcus epidermidis found after Betadine 5 % application. Conclusion: Our study showed the effectiveness of Betadine 5 % solution in conjunctival flora reduction. Use of topical antibiotics 3 days prior intravitreal injections is not effective. Key words: age-related macular degeneration; endophthalmitis; intravitreal injection; topical antibiotics; endophthalmitis prevention.

Prevalence and incidence of blindness and other degrees of sight impairment in patients treated for neovascular age-related macular degeneration in a well-defined region of the United Kingdom.

Science.gov (United States)

Buckle, M; Lee, A; Mohamed, Q; Fletcher, E; Sallam, A; Healy, R; Stratton, I; Tufail, A; Johnston, R L

2015-03-01

This study aimed to evaluate the incidence and prevalence of blindness, sight impairment, and other visual acuity (VA) states in patients receiving ranibizumab for neovascular age-related macular degeneration (nAMD) in Gloucestershire. Serial VA and injection data for all treatment-naive patients receiving their first intravitreal injections of ranibizumab for nAMD in the Gloucestershire National Health Service Ophthalmology department between 2008 and 2010 were extracted from an electronic medical record system. The prevalence of blindness (VA in the better-seeing eye ≤25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters) at the time of first intravitreal injection was 0.8%, increasing to 3.5% after 3 years. The prevalence of sight impairment (VA in the better-seeing eye 26-39 ETDRS letters) increased from 4.1% at baseline to 5.5% after 3 years. The incidence of initiating ranibizumab treatment for nAMD in people aged ≥50 years in Gloucestershire was 111 people per 100 000 population in 2009, and 97 people in 2010. The incidence of patients meeting the visual criteria for blindness and sight impairment registration from treated nAMD in people aged ≥50 years in Gloucestershire was 3.5 and 9.7 people, respectively per 100 000 population in 2010. This is the first real-world study on the incidence and prevalence of eligibility for blindness and sight impairment registration in treated nAMD in the UK based on VA data. The incidence and prevalence of eligibility for certification of blindness or sight impairment in patients treated with ranibizumab for nAMD is low in Gloucestershire, with only 3.6% of the incident population progressing to blindness in 2010.

OPTIMAL MANAGEMENT OF PIGMENT EPITHELIAL DETACHMENTS IN EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

Science.gov (United States)

Khanani, Arshad M; Eichenbaum, David; Schlottmann, Patricio G; Tuomi, Lisa; Sarraf, David

2018-04-24

This review aimed to determine the optimal management of retinal pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration (nAMD) based on review of available evidence in the literature. A comprehensive literature review evaluates previous retrospective and prospective studies that assessed the treatment of PEDs in nAMD. Studies illustrated that anti-vascular endothelial growth factor (VEGF) therapy can be effective in eyes with PED secondary to nAMD. Similar visual outcomes are associated with different anti-VEGF treatments. Higher anti-VEGF doses may improve anatomical response, without correlation with vision improvement. Fibrovascular PEDs may be difficult to treat, but even these eyes can gain vision with anti-VEGF therapy. A retinal pigment epithelial tear may develop in 15% to 20% of eyes with PEDs after anti-VEGF therapy, especially in PEDs greater than 500 µm to 600 µm in height; however, vision may stabilize with continued therapy. Atrophy may complicate eyes with PED and nAMD after anti-VEGF therapy, especially in association with complete PED resolution. Available literature suggests that anti-VEGF therapy is safe and efficacious for PED and nAMD. Treatment should focus on vision gains rather than PED resolution because there is no apparent correlation between anatomical and functional improvement in most eyes with PED and nAMD.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Limited availability of childhood overweightand obesity treatment programmes in Danish paediatric departments

DEFF Research Database (Denmark)

Eg, Marianne; Cortes, Dina; Johansen, Anders

2016-01-01

controlled and less demanding of sharp central vision. CONCLUSION: Patients with late AMD may still be physically active even when the disease progresses and vision is lost, but activities may change into more controlled and less central vision-demanding ones. FUNDING: The Lundbeck Foundation. TRIAL...... best-corrected visual acuity in the best-seeing and the worse-seeing eye was associated with less engagement in physical activities that would work up sweat and a lower number of steps taken daily. Patients with bilateral vision loss from late AMD engaged in physical activities that were more...

Peripapillary Retinal Nerve Fiber Measurement with Spectral-Domain Optical Coherence Tomography in Age-Related Macular Degeneration

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Simon K. Law

2017-12-01

Full Text Available Purpose: To evaluate the relationship between the peripapillary retinal nerve fiber layer (RNFL measurements with Spectral-domain Optical Coherence Tomography (OCT and Age-related macular degeneration (AMD. Methods: Patients >60 years of age without glaucoma or record of intraocular pressure >21 mmHg and no systemic or intraocular diseases or treatment or surgical intervention that affected the RNFL underwent OCT measurement of the RNFL. The severity of AMD was staged with the Clinical Age-Related Maculopathy Staging System. The relationship between RNFL measurements and AMD stages of one eye per patient was analyzed. Results: Eighty-six eyes (46 patients with AMD and no glaucoma or other exclusion criteria received OCT RNFL measurements. Nine eyes (10.5% were excluded because of distorted peripapillary anatomy from exudative AMD (7 eyes or failure of the RNFL segmentation algorithm (2 eyes. Mean age ± S.D. of the 43 patients analyzed was 81.2 ± 7.3 years. The mean stage ± S.D. of AMD of the 77 eyes was 3.77 ± 1.05. Higher stages of AMD were statistically significantly associated with lower average RNFL and inferior sector RNFL (p = 0.049, 0 0015, respectively. The association of inferior sector RNFL and AMD stage remained statistically significant after adjusting for age. Conclusions: Spectral domain OCT is generally useful in measuring the peripapillary RNFL in eyes with different stages of AMD. Higher stage of AMD is associated with thinner peripapillary RNFL, which may masquerade as early glaucomatous damage.

Potential public health impact of Age-Related Eye Disease Study results: AREDS report no. 11.

Science.gov (United States)

Bressler, Neil M; Bressler, Susan B; Congdon, Nathan G; Ferris, Frederick L; Friedman, David S; Klein, Ronald; Lindblad, Anne S; Milton, Roy C; Seddon, Johanna M

2003-11-01

To estimate the potential public health impact of the findings of the Age-Related Eye Disease Study (AREDS) on reducing the number of persons developing advanced age-related macular degeneration (AMD) during the next 5 years in the United States. The AREDS clinical trial provides estimates of AMD progression rates and of reduction in risk of developing advanced AMD when a high-dose nutritional supplement of antioxidants and zinc is used. These results are applied to estimates of the US population at risk, to estimate the number of people who would potentially avoid advanced AMD during 5 years if those at risk were to take a supplement such as that used in AREDS. An estimated 8 million persons at least 55 years old in the United States have monocular or binocular intermediate AMD or monocular advanced AMD. They are considered to be at high risk for advanced AMD and are those for whom the AREDS formulation should be considered. Of these people, 1.3 million would develop advanced AMD if no treatment were given to reduce their risk. If all of these people at risk received supplements such as those used in AREDS, more than 300,000 (95% confidence interval, 158,000-487,000) of them would avoid advanced AMD and any associated vision loss during the next 5 years. If people at high risk for advanced AMD received supplements such as those suggested by AREDS results, the potential impact on public health in the United States would be considerable during the next 5 years.

Treatment Efficacy and Compliance in Patients with Diabetic Macular Edema Treated with Ranibizumab in a Real-Life Setting

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Anne-Laurence Best

2018-01-01

Full Text Available Purpose. To assess real-life efficacy of ranibizumab and treatment compliance of patients with vision loss secondary to diabetic macular edema (DME. Methods. A retrospective study was conducted in DME patients treated with ranibizumab. Patients were monitored every 4 weeks for visual acuity (VA and central retinal thickness (CRT by SD-OCT. All patients received a loading dose of 3 monthly injections followed by retreatments on an as-needed basis. The primary endpoint was the change in VA at M12. Patient compliance to the follow-up and the correlation between the injection number and VA were also investigated. Compliance was compared to that of neovascular age-related macular degeneration (nAMD patients. Results. Seventy-two eyes of 55 consecutive DME patients were included. At baseline, the mean VA was 56.5 letters and CRT was 470 μm. At M12, the mean VA was 63.4 letters (p 70 letters, the mean VA change was +6.9 letters, and the mean CRT was 361.9 μm (p=0.0001 after a mean number of 5.33 intravitreal injections. In patients who received ≥7 injections, the VA gain and final VA were significantly higher than in patients who received <7 injections. At M12, 25.45% of DME patients were lost to follow-up versus 16.8% of nAMD patients (n=55. Discussion/Conclusion. Our study confirms the real-life efficacy of ranibizumab in DME at M12 and the need for a large number of injections to achieve better visual outcomes. We also showed a trend to a lower compliance in diabetic versus nAMD patients.

Age-related macular degeneration with choroidal neovascularization in the setting of pre-existing geographic atrophy and ranibizumab treatment. Analysis of a case series and revision paper

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Miguel Hage Amaro

2012-12-01

Full Text Available PURPOSE: To report the response of choroidal neovascularization (CNV to intravitreal ranibizumab treatment in the setting of age-related macular degeneration (AMD with extensive pre-existing geographic atrophy (GA and a revision paper. METHODS: This is a revision paper and a retrospective case series of 10 eyes in nine consecutive patients from a photographic database. The patients were actively treated with ranibizumab for neovascular AMD with extensive pre-existing GA. Patients were included if they had GA at or adjacent to the foveal center that was present before the development of CNV. The best corrected visual acuity and optical coherence tomography (OCT analysis of the central macular thickness were recorded for each visit. Serial injections of ranibizumab were administered until there was resolution of any subretinal fluid clinically or on OCT. Data over the entire follow-up period were analyzed for overall visual and OCT changes. All patients had been followed for at least 2 years since diagnosis. RESULTS: The patients received an average of 6 ± 3 intravitreal injections over the treatment period. Eight eyes had reduced retinal thickening on OCT. On average, the central macular thickness was reduced by 94 ± 101 µm. Eight eyes had improvement of one or more lines of vision, where as one eye had dramatic vision loss and one had no change. The average treatment outcome for all patients was -0.07 ± 4.25 logMAR units, which corresponded to a gain of 0.6 ± 4.4 lines of Snellen acuity. The treatment resulted in a good anatomic response with the disappearance of the subretinal fluid, improved visual acuity, and stabilized final visual results. CONCLUSION: The results of this case series suggest that the use of an intravitreal anti-vascular endothelial growth factor (VEGF agent (ranibizumab for CNV in AMD with extensive pre-existing GA is effective. Our results are not as striking as published results from large-scale trials of anti

Right to refuse treatment in Turkey: a diagnosis and a slightly less than modest proposal for reform.

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Irmak, Nurbay

2016-07-01

This paper examines the current state of right to refuse medical treatment in Turkey. Even though there are only a few studies carried out with Turkish physicians on their attitude towards the right to refuse treatment, I argue that recent studies on physicians' views on informed consent and honest disclosure show that Turkish physicians do not tend to recognise their patients' right to decline treatment. This is because the refusal of treatment crucially requires that patients be properly informed and asked for their consent before the treatment. Turkish physicians and healthcare providers' tendency to ignore the right to decline medical treatment cannot be separated from their paternalistic approach to patients and their rights. I argue that part of the problem is the legal framework, which, in essence, is still paternalistic. More specifically, the frequent appearance of the phrase 'medical necessity' in the relevant legislation is conveniently used to justify medical intervention against a patient's will. I conclude the paper by proposing reforms in the legal documents defining and regulating patient rights, including the Constitution of the Turkish Republic, and I will argue that these reforms will help enhance patient rights in Turkey. Turkey has been discussing a new Constitution for the past several years, so my proposal should best be understood as contributing to public discussion of the new Constitution by initiating debate about medical paternalism and patient autonomy in Turkish medicine. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

New approaches and potential treatments for dry age-related macular degeneration

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Francisco Max Damico

2012-02-01

Full Text Available Emerging treatments for dry age-related macular degeneration (AMD and geographi c atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.

Preliminary results of ecotoxicological assessment of an Acid Mine Drainage (AMD) passive treatment system testing water quality of depurated lixiviates

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Miguel Sarmiento, Aguasanta; Bonnail, Estefanía; Nieto Liñán, José Miguel; Valls Casillas, Tomás Ángel del

2017-01-01

The current work reports on the preliminary results of a toxicity test using screening experiments to check the efficiency of an innovative passive treatment plant designed for acid mine drainage purification. Bioassays took place with water samples before and after the treatment system and in the river, once treated water is discharged. Due to the high toxicity of the water collected at the mouth of the mine (before the treatment plant), the bioassay was designed and developed with respect t...

Can innate and autoimmune reactivity forecast early and advance stages of age-related macular degeneration?

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Adamus, Grazyna

2017-03-01

Age-related macular degeneration (AMD) is a major cause of central vision loss in persons over 55years of age in developed countries. AMD is a complex disease in which genetic, environmental and inflammatory factors influence its onset and progression. Elevation in serum anti-retinal autoantibodies, plasma and local activation of complement proteins of the alternative pathway, and increase in secretion of proinflammatory cytokines have been seen over the course of disease. Genetic studies of AMD patients confirmed that genetic variants affecting the alternative complement pathway have a major influence on AMD risk. Because the heterogeneity of this disease, there is no sufficient strategy to identify the disease onset and progression sole based eye examination, thus identification of reliable serological biomarkers for diagnosis, prognosis and response to treatment by sampling patient's blood is necessary. This review provides an outline of the current knowledge on possible serological (autoantibodies, complement factors, cytokines, chemokines) and related genetic biomarkers relevant to the pathology of AMD, and discusses their application for prediction of disease activity and prognosis in AMD. Copyright © 2017 Elsevier B.V. All rights reserved.

Treatment strategies and regimens of graduated intensity for childhood acute lymphoblastic leukemia in low-income countries: A proposal.

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Hunger, Stephen P; Sung, Lillian; Howard, Scott C

2009-05-01

Cure rates for children with acute lymphoblastic leukemia (ALL) are 80-85% in high-income countries (HICs) in North America and Western Europe. However, cure rates are much lower in many low-income countries (LICs), where most cases of ALL occur. Over the past several decades partnerships ("twinning") between HIC and LIC pediatric oncology programs have led to major improvements in outcome for children with ALL in some LICs, often by developing time and resource intensive relationships that allow LIC centers to treat children with regimens similar or identical to those used in HICs. However, the resources are not available in most LICs to allow immediate introduction of intensive ALL treatment regimens similar to those used in HICs. With these thoughts in mind, we present a proposal for a systematic and graduated approach to ALL diagnosis, risk classification, and treatment in LICs. We have based the strategy and the proposed regimens on those developed by the Children's Cancer Group (CCG) and Children's Oncology Group (COG) over the past several decades, beginning with a first level regimen similar to CCG therapy of the early 1980s and then layering on successive treatment intensifications proven effective in randomized clinical trials. Simple monitoring rules are included to help centers decide when they are ready to add new treatment components. This proposal provides a framework that LIC centers can use to provide effective ALL therapy, particularly in regions of the world where few children are currently being cured. (c) 2009 Wiley-Liss, Inc.

AMIODARONE INDUCES THE SYNTHESIS OF HSPS IN SACCHAROMYCES CEREVISIAE AND ARABIDOPSIS THALIANA CELLS

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Pyatrikas D.V.

2012-08-01

Full Text Available Many biotic and abiotic stresses cause an increase of cytosolic Ca2+ level in cells. Calcium is one of the most important second messengers, regulating many various activities in the cell and was known to affect expression of stress activated genes. Mild heat shock induces the expression of heat shock proteins (Hsps which protect cell from drastic heat shock exposure. There are some literature data permitting to suggest that transient elevation of cytosolic Ca2+ level in plant cells is important for activation of Hsps expression. On the other hand mitochondria are known to regulate the intracellular calcium and reactive oxygen species signaling. It has been shown recently that mild heat shock induces hyperpolarization of inner mitochondrial membrane in plant and yeast cells and this event is critically important for activation of Hsps expression. To reveal the relationship between mitochondrial activity, intracellular calcium homeostasis and Hsps expression an antiarrhythmic drug amiodarone (AMD have been used. AMD is known to cause transient increase of cytosolic Ca2+ level in Saccharomyces cerevisiae. Obtained results have showed that AMD treatment induced the synthesis of Hsp104p in S. cerevisiae cells and Hsp101p in A. thaliana cell culture. Induction of Hsp104p synthesis leads to enhanced yeast capability to survive lethal heat shock exposure. Development of S. cerevisiae thermotolerance depended significantly on the presence of Hsp104p. Elevation of Hsp104p level in the result of AMD treatment was shown to be governed by activity of Msn2p and Msn4p transcription factors. Deletion of the MSN2 and MSN4 genes abrogated the AMD ability to induce Hsp104p synthesis. Mild heat shock and AMD treatment induced the hyperpolarization of the inner mitochondrial membrane in yeast and Arabidopsis cells which accompanied by HSP synthesis and development of thermotolerance. It was suggested that increase of cytosolic Ca2+ level after AMD treatment

Efficacy of the drug Vitalux Plus of patients with dry form of age-related macular degeneration

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I. R. Gazizova

2014-07-01

Full Text Available Purpose: To analyze the data, visometry and the thickness of the fovea, patients with dry form of age-related macular degeneration (AMD after dosing Vitalux Plus.Methods: We observed 25 patients with dry form of AMD. Visometry and optical coherence tomography of the macula was assessed at 1 and 3 months after treatment Vitalux Plus.Results: In the study group according to visometry and optical coherence tomography was found a positive trend. In the course of our research in 65.3 % of the thickness of the fovea increased, probably by increasing the layer of pigment epithelium. Improvement in the layer of pigment epithelium was observed mainly in patients with early-stage AMD, and in this group also found improvement in visual acuity and more motivated to treatment and further outpatient observation.Conclusion: During the observation period, all patients with dry form of AMD, the stabilization of visual acuity. In the main group on the background of the drug Vitalux Plus objective indicators showed improvement according to retinal optical coherence tomography.In the analysis of the results showed a positive therapeutic effect in patients Vitalux Plus, especially with early dry form of AMD.

Efficacy of the drug Vitalux Plus of patients with dry form of age-related macular degeneration

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I. R. Gazizova

2013-01-01

Full Text Available Purpose: To analyze the data, visometry and the thickness of the fovea, patients with dry form of age-related macular degeneration (AMD after dosing Vitalux Plus.Methods: We observed 25 patients with dry form of AMD. Visometry and optical coherence tomography of the macula was assessed at 1 and 3 months after treatment Vitalux Plus.Results: In the study group according to visometry and optical coherence tomography was found a positive trend. In the course of our research in 65.3 % of the thickness of the fovea increased, probably by increasing the layer of pigment epithelium. Improvement in the layer of pigment epithelium was observed mainly in patients with early-stage AMD, and in this group also found improvement in visual acuity and more motivated to treatment and further outpatient observation.Conclusion: During the observation period, all patients with dry form of AMD, the stabilization of visual acuity. In the main group on the background of the drug Vitalux Plus objective indicators showed improvement according to retinal optical coherence tomography.In the analysis of the results showed a positive therapeutic effect in patients Vitalux Plus, especially with early dry form of AMD.

Real-Life Experience with Aflibercept and Ranibizumab in the Treatment of Newly Diagnosed Neovascular Age-Related Macular Degeneration over 24 Months.

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Garweg, Justus G; Gerhardt, Christin; Kodjikian, Laurent; Pfister, Isabel B

2017-09-01

Comparative data appertaining to the long-term effects of Aflibercept or Ranibizumab in newly diagnosed cases of neovascular age-related macular degeneration (nAMD) over follow-up periods exceeding 12 months in clinical routine are scarce. In this retrospective comparative analysis, a case series of patients with treatment-naïve nAMD and requiring anti-vascular endothelial growth factor (VEGF) therapy in a routine clinical setting were treated with either Aflibercept [Afl (n = 106)] or Ranibizumab [Ran (n = 47)]. During the drug-loading phase, 3 monthly injections were administered. Thereafter, a treat-and-extend protocol was pursued for a maximum of 24 months. Ran was administered predominantly in eyes with classical lesions; Afl was administered in all others. The primary outcome parameters included anatomical and functional stability after 24 months. Patients were comparable regarding age, gender distribution, and lens status. Fewer patients presented with intraretinal fluid in the Afl- than in the Ran group at diagnosis (46.2% vs. 67.4%; P = 0.02), but not after the drug-loading phase. After the drug-loading phase, visual acuity [-4.2 letters (Afl) vs. -4.5 letters (Ran); P = 0.78] and the central foveal thickness remained stable. Linked to the lesion type, the number of scheduled clinical visits during the course of 24 months was higher for the Ran- than for the Afl group [11.9 ± 4.7 visits (Ran) vs. 8.4 ± 3.1 visits (Afl); P = 0.0005]. However, the total number of injections was similar [10.5 ± 2.8 (Ran) vs. 11.7 ± 3.6 (Afl); P = 0.06]. Based on tailoring according to the lesion type in cases of nAMD, the anatomical and the functional outcomes of treatment with either Afl or Ran were comparable for a maximum of 2 years.

Age-Related Macular Degeneration.

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Mehta, Sonia

2015-09-01

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision. Copyright © 2015 Elsevier Inc. All rights reserved.

Research status of conbercept treating age-related macular degeneration

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Hai-Yan He

2015-08-01

Full Text Available Age-related macular degeneration(AMDis one of the major reasons of blindness among the elderly in the developed countries. As AMD patients are increasing year by year, AMD has become one of the important topics of ophthalmic research to prevent blindness. Its pathogenesis is not fully understood, but many studies have shown that vascular endothelial growth factor(VEGFplays an important role in the pathogenesis. With the development and application of anti-VEGF drugs, there are a variety of drugs applied to the disease. This article introduces conbercept for the treatment of AMD.

Note: Development of a small maglev-type antirolling system.

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Park, Cheol Hoon; Park, Hee Chang; Cho, Han Wook; Moon, Seok Jun; Chung, Tae Young

2010-05-01

Various passive and/or active antirolling devices have been used for suppressing the rolling motion of ships in the ocean. In this study, a maglev-type active mass driver (AMD) is developed for controlling the rolling motion of a shiplike structure. No friction is generated during the motion of this maglev-type AMD, as the moving mass is floated by the magnetic levitation force and displaced by the propulsion force generated by the linear motor. For verifying the feasibility of the proposed method, a small AMD having a moving mass of approximately 4.0 kg is constructed and used in a small-scale model of a catamaran. This paper presents the detailed design procedures and obtained experimental results. Our results show that the developed maglev-type AMD has the potential for use in controlling the rolling motion of ships and other oceanographic vessels.

Nutritional Modulation of Age-Related Macular Degeneration

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Weikel, Karen A; Taylor, Allen

2012-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30–50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 2011; Klein et al., 2011). Preventive interventions through dietary modulation are attractive strategies because many studies suggest a benefit of micro and macronutrients with respect to AMD, as well as other age-related debilities, and with few, if any, adverse effects (Chiu, 2011). Preservation of vision would enhance quality of life for millions of elderly people, and alleviate the personal and public health financial burden of AMD (Frick et al., 2007; Wood et al., 2011). Observational studies indicate that maintaining adequate levels of omega-3 fatty acids (i.e. with 2 servings/wk of fish) or a low glycemic index diet may be particularly beneficial for early AMD and that higher levels of carotenoids may be protective, most probably, against neovascular AMD. Intervention trials are needed to better understand the full effect of these nutrients and/or combinations of nutrients on retinal health. Analyses that describe effects of a nutrient on onset and/or progress of AMD are valuable because they indicate the value of a nutrient to arrest AMD at the early stages. This comprehensive summary provides essential information about the value of nutrients with regard to diminishing risk for onset or progress of AMD and can serve as a guide until data from ongoing intervention trials are available. PMID:22503690

Device for fluorescent control and photodynamic therapy of age-related macula degeneration

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Loschenov, Victor B.; Meerovich, Gennadii A.; Budzinskaya, M. V.; Ermakova, N. A.; Shevchik, S. A.; Kharnas, Sergey S.

2004-07-01

Age-related macula degeneration (AMD) is a wide spread disease the appearance of which leads to poor eyesight and blindness. A method of treatment is not determined until today. Traditional methods, such as laser coagulation and surgical operations are rather traumatic for eye and often bring to complications. That's why recently a photodynamic method of AMD treatment is studied. Based on photodynamic occlusion of choroidal neovascularization (CNV) with minimal injury to overlying neurosensory retina what increases the efficiency.

Radiotherapy of macular lesions in age-related macular degeneration (A.M.D.): preliminary results of a clinical study conducted in Lyon, France; Radiotherapie des degenerescences maculaires liees a l`age (DMLA): resultats preliminaires d`une etude lyonnaise

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Martin, P. [Centre oncologie radiotherapie Saint-Jean, 69 - Lyon (France); Mauget, M. [Centre ophtalmologique d`imagerie, laser, 69 - Lyon (France); Gerard, J.P. [Service de radiotherapie-oncologie, CHU Lyon Sud, 69 - Pierre-Benite (France) (and others)

1997-06-01

To evaluate irradiation effects on functional signs and choroidal neo-vascular lesions in age-related macular degeneration (AMD) that does not respond to laser therapy. Since 1994, 250 consecutive AMD patients were treated by two radiotherapy teams for sub-foveal neo-vascular lesions. At the end of september 1996, 52 patients were evaluable with a 1-year follow-up. Group 1 (Department de Radiotherapie Oncologie, Centre Hospitalo-Universitaire Lyon Sud) included 26 patients who were treated with a lateral beam of 6 MV photons. The irradiation dose were 20 Gy in five fractions for small lesions and 28.8 Gy in eight fractions for larger lesions. Group 2 (Centre Oncologie Radiotherapie Saint-Jean) was composed of 26 patients treated with a mini-beam of 25 MV photons via lateral arc-therapy. Beam diameters (14 and 18 mm) were adapted to the lesion size. The total dose was 16 Gy in four fractions or 20 Gy in five fractions. Functional and anatomical results were assessed at 3, 6, 9 months and 1 year after radiation therapy. Stable visual acuity was observed in 44 % (23/52) of the patients and visual acuity was improved in 35 % (18/52) of the patients at 6 months. Good functional results reached 79 % (41/52) at 6 months and 74 % (17/23) at 12 months. There was no statistical difference between the two groups and dose levels. All severe complications (1 cataract, 3 dilated choroidal vessels, and 2 papillitis) occurred in group 1. Though it is too early to conclude on the best dose level, radiotherapy of sub-foveal neo-vascular lesions of AMD that cannot be treated via laser therapy provides encouraging results. The technique used must be very precise to adequately irradiate the fovea and spare surrounding sensitive areas. Further studies and trials involving patients` randomization are necessary to confirm these preliminary results. (author) 13 refs.

Bacterial Oxidation and Reduction of Iron in the Processes of Creation and Treatment of Acid Mining Waters

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Daniel Kupka

2004-12-01

Full Text Available Acid mine drainages (AMDs arise at the weathering of sulphidic minerals. The occurrence of acidic streams is commonly associated with the human mining activities. Due to the disruption and excavation of sulphide deposits, the oxidation processes have initiated. Acidic products of sulphide oxidation accelerate the degradation of accompanying minerals. AMDs typically contain high concentrations of sulfuric acid and soluble metals and cause serious ecological problems due to the water pollution and the devastation of adjacent country. Microbial life in these extremely acidic environments may be considerably diverse. AMDs are abundant in bacteria capable to oxidize and/or to reduce iron. The rate of bacterial oxidation of ferrous iron released from pyrite surfaces is up to one million times faster than the chemical oxidation rate at low pH. Bacterial regeneration of ferric iron maintains the continuity of pyrite oxidation and the production of AMDs. Another group of microorganisms living in these environments are acidophilic ferric iron reducing bacteria. This group of microorganisms has been discovered only relatively recently. Acidophilic heterotrophic bacteria reduce ferric iron in either soluble or solid forms to ferrous iron. The reductive dissolution of ferric iron minerals brings about a mobilization of iron as well as associated heavy metals. The Bacterial oxidation and reduction of iron play an important role in the transformation of either crystalline or amorphous iron-containing minerals, including sulphides, oxides, hydroxysulfates, carbonates and silicates. This work discusses the role of acidophilic bacteria in the natural iron cycling and the genesis of acidic effluents. The possibilities of application of iron bacteria in the remediation of AMDs are also considered.

Incidence of choroidal neovascularization in the fellow eye in the comparison of age-related macular degeneration treatments trials.

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Maguire, Maureen G; Daniel, Ebenezer; Shah, Ankoor R; Grunwald, Juan E; Hagstrom, Stephanie A; Avery, Robert L; Huang, Jiayan; Martin, Revell W; Roth, Daniel B; Castellarin, Alessandro A; Bakri, Sophie J; Fine, Stuart L; Martin, Daniel F

2013-10-01

To assess the influence of drug; dosing regimen; and traditional, nontraditional, and genetic risk factors on the incidence of choroidal neovascularization (CNV) in the fellow eye of patients treated for CNV with ranibizumab or bevacizumab. Cohort study of patients enrolled in a multicenter, randomized clinical trial. Patients with no CNV in the fellow eye at the time of enrollment in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Eligibility criteria for the clinical trial required that study eyes have evidence on fluorescein angiography and optical coherence tomography of CNV secondary to age-related macular degeneration (AMD) and visual acuity between 20/25 and 20/320. Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different regimens for dosing over a 2-year period. The genotypes for 4 single nucleotide polymorphisms (SNPs) associated with risk of AMD were determined. Only patients without CNV in the fellow eye at baseline were considered at risk. The CATT ophthalmologists examined patients every 4 weeks through 2 years and recorded treatment for CNV in the fellow eye. Development of CNV in the fellow eye. Among 1185 CATT participants, 727 (61%) had no CNV in the fellow eye at enrollment. At 2 years, CNV had developed in 75 (20.6%) of 365 patients treated with ranibizumab and in 60 (16.6%) of 362 patients treated with bevacizumab (absolute difference, 4.0%; 95% confidence interval [CI], -1.7% to 9.6%; P = 0.17). The risk ratio for pro re nata dosing relative to monthly dosing was 1.1 (95% CI, 0.8-1.6). Greater elevation of the retinal pigment epithelium and fluid in the foveal center of the study eye were associated with increased incidence of CNV in the fellow eye. Incidence was not associated with genotype on rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3; P>0.35). Through 2 years, there was no statistically significant difference between ranibizumab and

The generation of induced pluripotent stem cells for macular degeneration as a drug screening platform: identification of curcumin as a protective agent for retinal pigment epithelial cells against oxidative stress

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Yun-Ching eChang

2014-08-01

Full Text Available Age-related macular degeneration (AMD is one retinal aging process that may lead to irreversible vision loss in the elderly. Its pathogenesis remains unclear, but oxidative stress inducing retinal pigment epithelial (RPE cells damage is perhaps responsible for the aging sequence of retina and may play an important role in macular degeneration. In this study, we have reprogrammed T cells from patients with dry type AMD into induced pluripotent stem cells (iPSCs via integration-free episomal vectors and differentiated them into RPE cells that were used as an expandable platform for investigating pathogenesis of the AMD and in-vitro drug screening. These patient-derived RPEs with the AMD-associated background (AMD-RPEs exhibited reduced antioxidant ability, compared with normal RPE cells. Among several screened candidate drugs, curcumin caused most significant reduction of ROS in AMD-RPEs. Pre-treatment of curcumin protected these AMD-RPEs from H2O2-induced cell death and also increased the cytoprotective effect against the oxidative stress of H2O2 through the reduction of ROS levels. In addition, curcumin with its versatile activities modulated the expression of many oxidative stress-regulating genes such as PDGF, VEGF, IGFBP-2, HO1, SOD2 and GPX1. Our findings indicated that the RPE cells derived from AMD patients have decreased antioxidative defense, making RPE cells more susceptible to oxidative damage and thereby leading to AMD formation. Curcumin represented an ideal drug that can effectively restore the neuronal functions in AMD patient-derived RPE cells, rendering this drug an effective option for macular degeneration therapy and an agent against aging-associated oxidative stress.

Tear film proteome in age-related macular degeneration.

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Winiarczyk, Mateusz; Kaarniranta, Kai; Winiarczyk, Stanisław; Adaszek, Łukasz; Winiarczyk, Dagmara; Mackiewicz, Jerzy

2018-06-01

Age-related macular degeneration (AMD) is the main reason for blindness in elderly people in the developed countries. Current screening protocols have limitations in detecting the early signs of retinal degeneration. Therefore, it would be desirable to find novel biomarkers for early detection of AMD. Development of novel biomarkers would help in the prevention, diagnostics, and treatment of AMD. Proteomic analysis of tear film has shown promise in this research area. If an optimal set of biomarkers could be obtained from accessible body fluids, it would represent a reliable way to monitor disease progression and response to novel therapies. Tear films were collected on Schirmer strips from a total of 22 patients (8 with wet AMD, 6 with dry AMD, and 8 control individuals). 2D electrophoresis was used to separate tear film proteins prior to their identification with matrix-assisted laser desorption/ionization time of flight spectrometer (MALDI-TOF/TOF) and matching with functional databases. A total of 342 proteins were identified. Most of them were previously described in various proteomic studies concerning AMD. Shootin-1, histatin-3, fidgetin-like protein 1, SRC kinase signaling inhibitor, Graves disease carrier protein, actin cytoplasmic 1, prolactin-inducible protein 1, and protein S100-A7A were upregulated in the tear film samples isolated from AMD patients and were not previously linked with this disease in any proteomic analysis. The upregulated proteins supplement our current knowledge of AMD pathogenesis, providing evidence that certain specific proteins are expressed into the tear film in AMD. As far we are aware, this is the first study to have undertaken a comprehensive in-depth analysis of the human tear film proteome in AMD patients.

Verteporfin: a milestone in opthalmology and photodynamic therapy.

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Brown, S B; Mellish, K J

2001-02-01

During the past year, a photosensitiser named benzoporphyrin derivative (BPD) has been approved in 26 countries under the generic name verteporfin (Visudynetrade mark, Novartis), for the treatment of patients with a certain type of the wet form of age-related macular degeneration (AMD) by photodynamic therapy (PDT). AMD is the leading cause of blindness in the developed world, with approximately half a million new cases of the wet form per year. The approval of Visudynetrade mark therapy represents a major milestone in ophthalmology since AMD was previously untreatable by any modality which would preserve existing vision. It was also a milestone in the development of PDT, not only because it represented the first breakthrough in the use of PDT to treat an otherwise untreatable condition, but also because it represented the first mass market for a PDT treatment where prospects of a substantial financial return on many years of investment appear to be likely. In this article, we look at the background to the development of BPD, primarily for its use in AMD, but also in other applications.

The proposed 'concordance-statistic for benefit' provided a useful metric when modeling heterogeneous treatment effects.

Science.gov (United States)

van Klaveren, David; Steyerberg, Ewout W; Serruys, Patrick W; Kent, David M

2018-02-01

Clinical prediction models that support treatment decisions are usually evaluated for their ability to predict the risk of an outcome rather than treatment benefit-the difference between outcome risk with vs. without therapy. We aimed to define performance metrics for a model's ability to predict treatment benefit. We analyzed data of the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial and of three recombinant tissue plasminogen activator trials. We assessed alternative prediction models with a conventional risk concordance-statistic (c-statistic) and a novel c-statistic for benefit. We defined observed treatment benefit by the outcomes in pairs of patients matched on predicted benefit but discordant for treatment assignment. The 'c-for-benefit' represents the probability that from two randomly chosen matched patient pairs with unequal observed benefit, the pair with greater observed benefit also has a higher predicted benefit. Compared to a model without treatment interactions, the SYNTAX score II had improved ability to discriminate treatment benefit (c-for-benefit 0.590 vs. 0.552), despite having similar risk discrimination (c-statistic 0.725 vs. 0.719). However, for the simplified stroke-thrombolytic predictive instrument (TPI) vs. the original stroke-TPI, the c-for-benefit (0.584 vs. 0.578) was similar. The proposed methodology has the potential to measure a model's ability to predict treatment benefit not captured with conventional performance metrics. Copyright © 2017 Elsevier Inc. All rights reserved.

Prevalence of age-related macular degeneration in Nakuru, Kenya: a cross-sectional population-based study.

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Wanjiku Mathenge

impairment and blindness in Kenya. Greater availability of low vision services and ophthalmologist training in diagnosis and treatment of AMD would be appropriate next steps. Please see later in the article for the Editors' Summary.

Treatment of retinal diseases with VEGF antagonists

NARCIS (Netherlands)

Schlingemann, R. O.; Witmer, A. N.

2009-01-01

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are the most prevalent causes of blindness in the Western world. The pathogenesis of neovascularization and vascular leakage, both hallmarks of these diseases, appears to have one common denominator: vascular endothelial growth

Complement inhibitors for age-related macular degeneration.

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Williams, Michael A; McKay, Gareth J; Chakravarthy, Usha

2014-01-15

Given the relatively high prevalence of age-related macular degeneration (AMD) and the increased incidence of AMD as populations age, the results of trials of novel treatments are awaited with much anticipation. The complement cascade describes a series of proteolytic reactions occurring throughout the body that generate proteins with a variety of roles including the initiation and promotion of immune reactions against foreign materials or micro-organisms. The complement cascade is normally tightly regulated, but much evidence implicates complement overactivity in AMD and so it is a logical therapeutic target in the treatment of AMD. To assess the effects and safety of complement inhibitors in the prevention or treatment of advanced AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2013), EMBASE (January 1980 to November 2013), Allied and Complementary Medicine Database (AMED) (January 1985 to November 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2013), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January 1990 to November 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 November 2013. We also performed handsearching of proceedings, from 2012 onwards, of meetings and conferences of specific professional organisations. We planned to include randomised controlled trials (RCTs) with

Preferential Hyperacuity Perimeter (PreView PHP) for detecting choroidal neovascularization study.

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Alster, Yair; Bressler, Neil M; Bressler, Susan B; Brimacombe, Judith A; Crompton, R Michael; Duh, Yi-Jing; Gabel, Veit-Peter; Heier, Jeffrey S; Ip, Michael S; Loewenstein, Anat; Packo, Kirk H; Stur, Michael; Toaff, Techiya

2005-10-01

To assess the ability of the Preferential Hyperacuity Perimeter (PreView PHP; Carl Zeiss Meditec, Dublin, CA) to detect recent-onset choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and to differentiate it from an intermediate stage of AMD. Prospective, comparative, concurrent, nonrandomized, multicenter study. Eligible participants' study eyes had a corrected visual acuity of 20/160 or better and either untreated CNV from AMD diagnosed within the last 60 days or an intermediate stage of AMD. After obtaining consent, visual acuity with habitual correction, masked PHP testing, stereoscopic color fundus photography, and fluorescein angiography were performed. Photographs and angiograms were evaluated by graders masked to diagnosis and PHP results. The reading center's diagnosis determined if the patient was categorized as having intermediate AMD or neovascular AMD. A successful study outcome was defined a priori as a sensitivity of at least 80% and a specificity of at least 80%. Of 185 patients who gave consent to be enrolled, 11 (6%) had PHP results judged to be unreliable. An additional 52 were not included because they did not meet all eligibility criteria. Of the remaining 122 patients, 57 had an intermediate stage of AMD and 65 had neovascular AMD. The sensitivity to detect newly diagnosed CNV using PHP testing was 82% (95% confidence interval [CI], 70%-90%). The specificity to differentiate newly diagnosed CNV from the intermediate stage of AMD using PHP testing was 88% (95% CI, 76%-95%). Preferential Hyperacuity Perimeter testing can detect recent-onset CNV resulting from AMD and can differentiate it from an intermediate stage of AMD with high sensitivity and specificity. These data suggest that monitoring with PHP should detect most cases of CNV of recent onset with few false-positive results at a stage when treatment usually would be beneficial. Thus, this monitoring should be considered in the management of the

A Simplified Method of Identifying the Trained Retinal Locus for Training in Eccentric Viewing

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Vukicevic, Meri; Le, Anh; Baglin, James

2012-01-01

In the typical human visual system, the macula allows for high visual resolution. Damage to this area from diseases, such as age-related macular degeneration (AMD), causes the loss of central vision in the form of a central scotoma. Since no treatment is available to reverse AMD, providing low vision rehabilitation to compensate for the loss of…

A novel bioelectrochemical system for chemical-free permanent treatment of acid mine drainage.

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Pozo, Guillermo; Pongy, Sebastien; Keller, Jürg; Ledezma, Pablo; Freguia, Stefano

2017-12-01

The mining sector is currently under unprecedented pressure due to stringent environmental regulations. As a consequence, a permanent acid mine drainage (AMD) treatment is increasingly being regarded as a desirable target with direct benefits for the environment and the operational and economic viability of the resources sector. In this study we demonstrate that a novel bioelectrochemical system (BES) can deliver permanent treatment of acid mine drainage without chemical dosing. The technology consists of a two-cell bioelectrochemical setup to enable the removal of sulfate from the ongoing reduction-oxidation sulfur cycle to less than 550 mg L -1 (85 ± 2% removal from a real AMD of an abandoned silver mine), thereby also reducing salinity at an electrical energy requirement of 10 ± 0.3 kWh kg -1 of SO 4 2- -S removed. In addition, the BES operation drove the removal and recovery of the main cations Al, Fe, Mg, Zn at rates of 151 ± 0 g Al m -3  d -1 , 179 ± 1 g Fe m -3  d -1 , 172 ± 1 g Mg m -3  d -1 and 46 ± 0 g Zn m -3  d -1 into a concentrate stream containing 263 ± 2 mg Al, 279 ± 2 mg Fe, 152 ± 0 mg Mg and 90 ± 0 mg Zn per gram of solid precipitated after BES fed-rate control treatment. The solid metal-sludge was twice less voluminous and 9 times more readily settleable than metal-sludge precipitated using NaOH. The continuous BES treatment also demonstrated the concomitant precipitation of rare earth elements together with yttrium (REY), with up to 498 ± 70 μg Y, 166 ± 27 μg Nd, 155 ± 14 μg Gd per gram of solid, among other high-value metals. The high-REY precipitates could be used to offset the treatment costs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Current knowledge and trends in age-related macular degeneration: today's and future treatments.

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Velez-Montoya, Raul; Oliver, Scott C N; Olson, Jeffrey L; Fine, Stuart L; Mandava, Naresh; Quiroz-Mercado, Hugo

2013-09-01

To address the most dynamic and current issues concerning today's treatment options and promising research efforts regarding treatment for age-related macular degeneration. This review is aimed to serve as a practical reference for more in-depth reviews on the subject. An online review of the database PubMed and Ovid were performed, searching for the key words age-related macular degeneration, AMD, VEGF, treatment, PDT, steroids, bevacizumab, ranibizumab, VEGF-trap, radiation, combined therapy, as well as their compound phrases. The search was limited to articles published since 1985. All returned articles were carefully screened, and their references were manually reviewed for additional relevant data. The web page www.clinicaltrials.gov was also accessed in search of relevant research trials. A total of 363 articles were reviewed, including 64 additional articles extracted from the references. At the end, only 160 references were included in this review. Treatment for age-related macular degeneration is a very dynamic research field. While current treatments are mainly aimed at blocking vascular endothelial growth factor, future treatments seek to prevent vision loss because of scarring. Promising efforts have been made to address the dry form of the disease, which has lacked effective treatment.

Pluripotent stem cells: A therapeutic source for age-related macular degeneration

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Sowmya Parameswaran

2017-01-01

Full Text Available Age-related macular degeneration (AMD leads to progressive loss of central vision in the elderly. At a cellular level, there is aging of the retinal pigment epithelial (RPE cells, and accumulation of lipofuscin that interferes with the proper functioning of RPE which eventually leads to apoptosis. Treatment depends on the stage of the disease. Wet AMD which has neovascularization is managed by local therapies such as laser photocoagulation and photodynamic therapy and is managed with injections of antivascular endothelial growth factor-based therapy. Unlike the wet AMD, an effective therapy does not exist for dry AMD and geographic atrophy. Cell replacement therapy has shown promise. This review discusses the opportunities in the various types of cell-based therapy, their limitations, and what is possible for India.

Overview of clinical trials for dry age-related macular degeneration

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Wen-Sheng Cheng

2017-01-01

Full Text Available The overall goal of treating age-related macular degeneration (AMD is to target the underlying cause of the disease and prevent, or at least slow down, the loss of vision, which requires the preservation of the choroid, retinal pigment epithelium (RPE, and photoreceptors. At present, there is no proven drug treatment for dry AMD; however, the cessation of smoking and treatments based on the age-related eye diseases study vitamin formula combined with a healthy diet are considered the only options for slowing disease progression. A number of pharmaceutical agents are currently under evaluation for the treatment of dry AMD using strategies such as reduction RPE and photoreceptor loss, neuroprotection, visual cycle modulators, suppression of inflammation, prevention of oxidative damage, and choroidal perfusion enhancers. The hope is that some of these therapies will achieve significant improvement to current management and prevent future loss of vision in this devastating eye condition.

Post electrical or lightning injury syndrome: a proposal for an American Psychiatric Association's Diagnostic and Statistical Manual formulation with implications for treatment.

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Andrews, Christopher J; Reisner, Andrew D; Cooper, Mary Ann

2017-09-01

In the past, victims of electrical and lightning injuries have been assessed in a manner lacking a systematic formulation, and against ad hoc criteria, particularly in the area of neuropsychological disability. In this manner patients have, for example, only been partially treated, been poorly or incorrectly diagnosed, and have been denied the full benefit of compensation for their injuries. This paper contains a proposal for diagnostic criteria particularly for the neuropsychological aspects of the post injury syndrome. It pays attention to widely published consistent descriptions of the syndrome, and a new cluster analysis of post electrical injury patients. It formulates a proposal which could be incorporated into future editions of the American Psychiatric Association's Diagnostic and Statistical Manual (DSM). The major neuropsychological consequences include neurocognitive dysfunction, and memory subgroup dysfunction, with ongoing consequences, and sometimes including progressive or delayed psychiatric, cognitive, and/or neurological symptoms. The proposed diagnostic criteria insist on a demonstrated context for the injury, both specifying the shock circumstance, and also physical consequences. It allows for a certain delay in onset of symptoms. It recognizes exclusory conditions. The outcome is a proposal for a DSM classification for the post electrical or lightning injury syndrome. This proposal is considered important for grounding patient treatment, and for further treatment trials. Options for treatment in electrical or lightning injury are summarised, and future trials are foreshadowed.

A randomised, double-masked phase III/IV study of the efficacy and safety of Avastin® (Bevacizumab intravitreal injections compared to standard therapy in subjects with choroidal neovascularisation secondary to age-related macular degeneration: clinical trial design

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Bunce Catey

2008-10-01

Full Text Available Abstract Background The management of neovascular age-related macular degeneration (nAMD has been transformed by the introduction of agents delivered by intravitreal injection which block the action of vascular endothelial growth factor-A (anti-VEGF agents. One such agent in widespread use is bevacizumab which was initially developed for use in oncology. Most of the evidence supporting the use of bevacizumab for nAMD has come from interventional case series and this clinical trial was initiated because of the increasing and widespread use of this agent in the treatment of nAMD (an off-label indication despite a lack of definitive unbiased safety and efficacy data. Methods and design The Avastin® (bevacizumab for choroidal neovascularisation (ABC trial is a double-masked randomised controlled trial comparing intravitreal bevacizumab injections to standard therapy in the treatment of nAMD. Patients are randomised to intravitreal bevacizumab or standard therapy available at the time of trial initiation (verteporfin photodynamic therapy, intravitreal pegaptanib or sham treatment. Ranibizumab treatment was not included in the control arm as it had not been licensed for use at the start of recruitment for this trial. The primary outcome is the proportion of patients gaining ≥ 15 letters of visual acuity at 1 year and secondary outcomes include the proportion of patients with stable vision and mean visual acuity change. Discussion The ABC Trial is the first double-masked randomised control trial to investigate the efficacy and safety of intravitreal bevacizumab in the treatment of nAMD. This trial fully recruited in November 2007 and results should be available in early 2009. Important design issues for this clinical trial include (a defining the control group (b use of gain in vision as primary efficacy end-point and (c use of pro re nata treatment using intravitreal bevacizumab rather than continuous therapy. Trial registration Current controlled

Age-related macular degeneration

DEFF Research Database (Denmark)

la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

2002-01-01

Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

Clinical observations on the use of new anti-VEGF drug, conbercept, in age-related macular degeneration therapy: a meta-analysis

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Cui C

2017-12-01

Full Text Available Chunmei Cui, Hong Lu Department of Ophthalmology, Beijing Chao-Yang Hospital, Beijing, China Purpose: Conbercept is a new anti-vascular endothelial growth factor (VEGF drug approved for the treatment of age-related macular degeneration (AMD. Although this novel drug has been widely used in clinic, unlike other anti-VEGF drugs, validation and consensus on its method of clinical application and clinical safety have not yet been achieved.Methods: Relevant literature was searched on PubMed, Web of Science, China National Knowledge Internet, and Wanfang Data. Stata 12.0 was used for data analysis. Random- and fixed-effect models were employed to evaluate heterogeneity. Best-corrected visual acuity (BCVA and central retinal thickness (CRT were utilized to measure the improvement of AMD patients.Results: In this study, we analyzed conbercept administration and compared its application with other control clinical methods for AMD treatment. Ranibizumab, triamcinolone, and traditional transpupillary thermotherapy (TTT were administered in the control group. No differences were found in the BCVA and CRT improvement between the groups treated with conbercept and ranibizumab. However, the conbercept group had a lower serum VEGF level. After 3 months of treatment, conbercept led to a more significant BCVA and CRT improvement than triamcinolone. A more considerable BCVA improvement was observed in the group treated with conbercept than in the group treated with TTT. Moreover, even 6 months after the treatment, the effect of conbercept on CRT improvement was still more pronounced than that of TTT.Conclusion: In AMD patients, conbercept exerts considerably more positive effects on the long-term BCVA and CRT improvement than triamcinolone and TTT. The serum VEGF level in the conbercept group was lower than that in the ranibizumab group. Keywords: AMD, VEGF, conbercept, BCVA, CRT

Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT: Classification of Atrophy Report 3.

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Sadda, Srinivas R; Guymer, Robyn; Holz, Frank G; Schmitz-Valckenberg, Steffen; Curcio, Christine A; Bird, Alan C; Blodi, Barbara A; Bottoni, Ferdinando; Chakravarthy, Usha; Chew, Emily Y; Csaky, Karl; Danis, Ronald P; Fleckenstein, Monika; Freund, K Bailey; Grunwald, Juan; Hoyng, Carel B; Jaffe, Glenn J; Liakopoulos, Sandra; Monés, Jordi M; Pauleikhoff, Daniel; Rosenfeld, Philip J; Sarraf, David; Spaide, Richard F; Tadayoni, Ramin; Tufail, Adnan; Wolf, Sebastian; Staurenghi, Giovanni

2018-04-01

To develop consensus terminology and criteria for defining atrophy based on OCT findings in the setting of age-related macular degeneration (AMD). Consensus meeting. Panel of retina specialists, image reading center experts, retinal histologists, and optics engineers. As part of the Classification of Atrophy Meetings (CAM) program, an international group of experts surveyed the existing literature, performed a masked analysis of longitudinal multimodal imaging for a series of eyes with AMD, and reviewed the results of this analysis to define areas of agreement and disagreement. Through consensus discussions at 3 meetings over 12 months, a classification system based on OCT was proposed for atrophy secondary to AMD. Specific criteria were defined to establish the presence of atrophy. A consensus classification system for atrophy and OCT-based criteria to identify atrophy. OCT was proposed as the reference standard or base imaging method to diagnose and stage atrophy. Other methods, including fundus autofluorescence, near-infrared reflectance, and color imaging, provided complementary and confirmatory information. Recognizing that photoreceptor atrophy can occur without retinal pigment epithelium (RPE) atrophy and that atrophy can undergo an evolution of different stages, 4 terms and histologic candidates were proposed: complete RPE and outer retinal atrophy (cRORA), incomplete RPE and outer retinal atrophy, complete outer retinal atrophy, and incomplete outer retinal atrophy. Specific OCT criteria to diagnose cRORA were proposed: (1) a region of hypertransmission of at least 250 μm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 μm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear. A classification system and criteria for OCT-defined atrophy in the setting of AMD has been proposed based on an international consensus. This classification is a more complete

Hot Topics in Pharmacogenetics of Age-Related Macular Degeneration.

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Schwartz, Stephen G; Brantley, Milam A; Kovach, Jaclyn L; Grzybowski, Andrzej

2017-01-01

Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss and is primarily treated with nutritional supplementation as well as with anti-vascular endothelial growth factor (VEGF) agents for certain patients with neovascular disease. AMD is a complex disease with both genetic and environmental risk factors. In addition, treatment outcomes from nutritional supplementation and anti-VEGF agents vary considerably. Therefore, it is reasonable to suspect that there may be pharmacogenetic influences on these treatments. Many series have reported individual associations with variants in complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), and other loci. However, at this time there are no validated associations. With respect to AMD, pharmacogenetics remains an intriguing area of research but is not helpful for routine clinical management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Two-year functional and anatomical results after converting treatment resistant eyes with exudative age-related macular degeneration to aflibercept in accordance with a treat and extend protocol.

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Jørstad, Øystein Kalsnes; Faber, Rowan Thomas; Moe, Morten Carstens

2017-08-01

To study the effects of converting to aflibercept in accordance with a treat and extend (T&E) strategy in eyes with treatment resistant exudative age-related macular degeneration (AMD). Two-year prospective study of eyes with exudative AMD and persistent macular fluid despite monthly treatment with ranibizumab or bevacizumab. Eyes were converted to 2.0 mg aflibercept in accordance with a T&E protocol. Fifty eyes from 47 patients were included. At baseline, the mean central retinal thickness (CRT) was 273 μm and mean best-corrected visual acuity (BCVA) 0.25 logarithm of the minimal angle of resolution (logMAR). The mean number of aflibercept injections the first year was 9.2. After 1 year, there was a reduction in mean CRT to 228 μm (p < 0.001); 22 eyes (44%) had a dry macula; and the mean BCVA was 0.24 logMAR (p = 0.531). The mean number of aflibercept injections the second year was 8.0 (p = 0.013 compared to first year). After 2 years, 24 eyes (48%) received treatment more frequently than every eighth week. The mean CRT was 225 μm (p < 0.001 compared to baseline); 31 eyes (62%) had a dry macula; and mean BCVA was 0.32 logMAR (p = 0.005 compared to baseline). Five eyes did not complete 2 years of aflibercept treatment after failing to improve. A majority of eyes showed improved anatomic outcomes. There was a small decrease in mean BCVA after the second year of treatment. About half of the eyes required treatment more frequently than the recommended aflibercept label of an 8-week interval. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Current perspectives on ranibizumab

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Dedania VS

2015-03-01

Full Text Available Vaidehi S Dedania,1 Sophie J Bakri21Department of Ophthalmology, Albany Medical Center, Lions Eye Institute, Albany, NY, USA; 2Department of Ophthalmology, Mayo Clinic, Rochester, MN, USABackground: This review summarizes the Phase III studies addressing intravitreal ranibizumab treatment in patients with neovascular age-related macular degeneration (AMD, macular edema (ME from retinal vein occlusion (RVO, and diabetic ME (DME.Results: The data from 12 major Phase III studies: six studies in patients with neovascular AMD, two studies in patients with ME from RVO, and four studies in patients with DME demonstrate significant improvement in vision in patients undergoing treatment with intravitreal ranibizumab over patients receiving no treatment or receiving only grid laser. These effects are achieved with low incidences of ocular and nonocular adverse events.Conclusion: Intravitreal ranibizumab is a highly effective and safe therapy for improving vision and reducing vision loss in patients with neovascular AMD, ME from RVO, and DME. Patients generally require long-term treatment although some data show that frequency of treatment necessary to maintain visual outcomes decreases over time.Keywords: age-related macular degeneration, branch retinal vein occlusion, central retinal vein occlusion, diabetic macular edema, intravitreal, macular edema

[Results of the use of antioxidant and angioprotective agents in type 2 diabetes patients with diabetic retinopathy and age-related macular degeneration].

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Moshetova, L K; Vorob'eva, I V; Alekseev, I B; Mikhaleva, L G

2015-01-01

to investigate changes in clinical, functional, and morphological parameters of the retina in type 2 diabetes patients with diabetic retinopathy (DR) and those with combined fundus pathology (DR plus age-related macular degeneration (AMD)) before and after a course of antioxidants and angioprotectors in the form of mono- or combination therapy. The study included 180 patients (180 eyes) with type 2 diabetes divided into 6 groups of 30 each. DR was graded according to E. Kohner and M. Porta classification, AMD--AREDS classification. Thus, group 1 consisted of patients with DRO,; group 2--DR1 without DM, group 3--DR1 with DM, group 4--DRO and "dry" AMD (AREDS 1-3), group 5--DR1 with no DM but with AMD (AREDS 1-3), and group 6--DR1 with DM and AMD (AREDS 1-3). A drug containing lutein 6 mg, zeaxanthin 0.5 mg, vitamin C 60 mg, vitamin E 7 mg, vitamin A 1.5 mg, vitamin B2 1.2 mg, rutin 25 mg, zinc 5 mg, selenium 25 mcg, and bilberry extract 60 mg was used for antioxidative therapy. Ginkgo biloba leaf extract 60 mg was chosen as the angioprotector. In all patients visual acuity, macular thickness and morphology (OCT) as well as light sensitivity (microperimetry) were assessed before and after the treatment course. Analysis of baseline measurements demonstrated a significant decrease in best corrected visual acuity (p Macular thickness was increased in all groups, however, the changes were statistically significant only in groups 3 and 6 (pmacular thickness decreased in all groups, however, the changes were statistically significant (p prevention, and early treatment. Conservative treatment with antioxidant and angioprotective agents has been proved effective in type 2 diabetes patients with preclinical (DRO) and early (DR1) diabetic retinopathy and those with DR and "dry" AMD (AREDS 1-3) in terms of functional and morphological parameters of the retina. From all the regimens, a combined antioxidant and double-dose angioprotective (240 mg) therapy appeared to be the most

Age-related macular degeneration.

Science.gov (United States)

Cheung, Lily K; Eaton, Angie

2013-08-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease. © 2013 Pharmacotherapy Publications, Inc.

Bioremediation of acid mine drainage using algae strains: A review

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J.K. Bwapwa

2017-12-01

Full Text Available Acid mine drainage (AMD causes massive environmental concerns worldwide. It is highly acidic and contains high levels of heavy metals causing environmental damage. Conventional treatment methods may not be effective for AMD. The need for environmental remediation requires cost effective technologies for efficient removal of heavy metals. In this study, algae based systems were reviewed and analyzed to point out the potentials and gaps for future studies. Algae strains such as Spirulina sp., Chlorella, Scenedesmus, Cladophora, Oscillatoria, Anabaena, Phaeodactylum tricornutum have showed the capacity to remove a considerable volume of heavy metals from AMD. They act as “hyper-accumulators” and “hyper-adsorbents” with a high selectivity for different elements. In addition, they generate high alkalinity which is essential for precipitation of heavy metals during treatment. However, algae based methods of abating AMD are not the ultimate solution to the problem and there is room for more studies. : The bioremediation of acid mine drainage is achievable with the use of microalgae. Keywords: Acid mine drainage, Algae strains, Contamination, Heavy metals, Bioremediation

The modeling of contaminant flow during proposed treatment of U.S. Department of Energy low-level radioactive mixed wastes

International Nuclear Information System (INIS)

Dolak, D.A.; Wilkins, B.D.; Kotek, T.J.; Wang, Y.Y.; Meshkov, N.K.

1995-01-01

Estimations of waste materials throughput and the potential radiological and chemical releases resulting from the proposed treatment of US Department of Energy (DOE) low-level mixed wastes (LLMWs) were used to support analyses of risks and costs associated with various waste management alternatives outlined in the Office of Environmental Management Programmatic Environmental Impact Statement (EM PEIS). The modeling of material flow and contaminant releases through a consolidated waste management flowchart was performed by the WASTE MGMT computational model developed by Argonne National Laboratory. This paper (1) briefly describes the process used to model estimated material and contaminant flow through the proposed treatment scenarios for the EM PEIS, (2) discusses the key site- and/or waste-stream-dependent factors involved in the determination of radiological and chemical emissions, and (3) explains the assumptions used to integrate the available LLMW database with the computational model

Salmeterol/fluticasone stable-dose treatment compared with formoterol/budesonide adjustable maintenance dosing: impact on health-related quality of life

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Williams Angela E

2007-07-01

Full Text Available Abstract Background Improving patients' health-related quality of life (HRQoL is recognized as a fundamental part of asthma management. The aims of this study were to evaluate the long-term efficacy (including symptom-free days and exacerbations and impact on HRQoL of a stable-dose regimen of salmeterol/fluticasone propionate (SAL/FP and an adjustable maintenance dosing (AMD regimen of formoterol/budesonide (FOR/BUD where treatment is adjusted based on symptoms [SAM40056]. Methods A total of 688 outpatients with asthma receiving regular low-dose inhaled corticosteroids (ICS plus a long-acting β2-agonist, or medium dose ICS alone participated in this randomized, double-blind, double-dummy, parallel-group, 1-year trial, which was conducted in 91 centers in 15 countries. Patients were randomized to receive 1 inhalation of SAL/FP 50/250 μg BID or 2 inhalations of FOR/BUD 6/200 μg BID during Weeks 1–4. For Weeks 5–52, patients meeting strict continuation criteria for stable asthma at Week 4 received AMD with FOR/BUD or stable-dose SAL/FP. Results The percentage of symptom-free days was significantly greater (58.8% vs 52.1%; p = 0.034 and the annual exacerbation rate was significantly lower (47%; p = 0.008 with stable-dose SAL/FP compared with FOR/BUD AMD. A total of 568 patients completed the Asthma Quality of Life Questionnaire (AQLQ at least once during the study. The mean change from baseline in AQLQ overall score was numerically greater with SAL/FP than FOR/BUD at week 28 and week 52, but did not reach statistical significance (p = 0.121 at Week 52. However, in a post hoc logistic regression analyses for any AQLQ improvement, significant benefits with SAL/FP were seen at both time points (p = 0.038 and p = 0.009, respectively. The minimally important difference of ≥ 0.5-point improvement in AQLQ overall score was achieved by a significantly greater number of patients receiving SAL/FP at Week 28 (68% vs 60%; p = 0.049; a trend for this

Combining macula clinical signs and patient characteristics for age-related macular degeneration diagnosis: a machine learning approach.

Science.gov (United States)

Fraccaro, Paolo; Nicolo, Massimo; Bonetto, Monica; Giacomini, Mauro; Weller, Peter; Traverso, Carlo Enrico; Prosperi, Mattia; OSullivan, Dympna

2015-01-27

To investigate machine learning methods, ranging from simpler interpretable techniques to complex (non-linear) "black-box" approaches, for automated diagnosis of Age-related Macular Degeneration (AMD). Data from healthy subjects and patients diagnosed with AMD or other retinal diseases were collected during routine visits via an Electronic Health Record (EHR) system. Patients' attributes included demographics and, for each eye, presence/absence of major AMD-related clinical signs (soft drusen, retinal pigment epitelium, defects/pigment mottling, depigmentation area, subretinal haemorrhage, subretinal fluid, macula thickness, macular scar, subretinal fibrosis). Interpretable techniques known as white box methods including logistic regression and decision trees as well as less interpreitable techniques known as black box methods, such as support vector machines (SVM), random forests and AdaBoost, were used to develop models (trained and validated on unseen data) to diagnose AMD. The gold standard was confirmed diagnosis of AMD by physicians. Sensitivity, specificity and area under the receiver operating characteristic (AUC) were used to assess performance. Study population included 487 patients (912 eyes). In terms of AUC, random forests, logistic regression and adaboost showed a mean performance of (0.92), followed by SVM and decision trees (0.90). All machine learning models identified soft drusen and age as the most discriminating variables in clinicians' decision pathways to diagnose AMD. Both black-box and white box methods performed well in identifying diagnoses of AMD and their decision pathways. Machine learning models developed through the proposed approach, relying on clinical signs identified by retinal specialists, could be embedded into EHR to provide physicians with real time (interpretable) support.

Siderite formation in mining lakes. Sanitation strategy for the Spreetal Nordost lake; Sideritbildung in Tagebaurestseen. Moegliche Sanierungsstrategie des Restlochs Spreetal Nordost

Energy Technology Data Exchange (ETDEWEB)

Unger, Y.; Wolkersdorfer, C. [Technische Univ. Bergakademie Freiberg (Germany)

2006-07-01

The treatment of acid mine lakes is a worldwide problem. In this study, it will be investigated since the sludge from acid mine drainage (AMD) treatment plants combined with carbon dioxide injections may improve the water quality in such pit lakes. Simultaneously, the emissions of carbon dioxide into the atmosphere may be reduced. The CO{sub 2} will be sequestered in the lake sediments as siderite (FeCO{sub 3}). The acid mine lake Spreetal-Nordost (Lusatia/Germany) was chosen as a test site. Since 1998 iron hydroxide sludge from an AMD treatment plant was deposited into the lake. In preliminary tests the feasibility of this treatment scheme will be investigated. (orig.)

Attenuation of pyrite oxidation with a fly ash pre-barrier: Reactive transport modelling of column experiments

Energy Technology Data Exchange (ETDEWEB)

Perez-Lopez, R.; Cama, J.; Nieto, J.M.; Ayora, C.; Saaltink, M.W. [University of Huelva, Huelva (Spain). Dept. of Geology

2009-09-15

Conventional permeable reactive barriers (PRBs) for passive treatment of groundwater contaminated by acid mine drainage (AMD) use limestone as reactive material that neutralizes water acidity. However, the limestone-alkalinity potential ceases as inevitable precipitation of secondary metal-phases on grain surfaces occurs, limiting its efficiency. In the present study, fly ash derived from coal combustion is investigated as an alternative alkalinity generating material for the passive treatment of AMD using solution-saturated column experiments. Unlike conventional systems, the utilization of fly ash in a pre-barrier to intercept the non-polluted recharge water before this water reacts with pyrite-rich wastes is proposed. Chemical variation in the columns was interpreted with the reactive transport code RETRASO. In parallel, kinetics of fly ash dissolution at alkaline pH were studied using flow-through experiments and incorporated into the model. In a saturated column filled solely with pyritic sludge-quartz sand (1: 10), oxidation took place at acidic conditions (pH 3.7). According to SO{sub 4}{sup 2-} release and pH, pyrite dissolution occurred favourably in the solution-saturated porous medium until dissolved O{sub 2} was totally consumed. In a second saturated column, pyrite oxidation took place at alkaline conditions (pH 10.45) as acidity was neutralized by fly ash dissolution in a previous level. At this pH Fe release from pyrite dissolution was immediately depleted as Fe-oxy(hydroxide) phases that precipitated on the pyrite grains, forming Fe-coatings (microencapsulation). With time, pyrite microencapsulation inhibited oxidation in practically 97% of the pyritic sludge. Rapid pyrite-surface passivation decreased its reactivity, preventing AMD production in the relatively short term.

Injection of alkaline ashes into underground coal mines for acid mine drainage abatement

International Nuclear Information System (INIS)

Aljoe, W.W.

1996-01-01

The injection of alkaline coal combustion waste products into abandoned underground coal mines for acid mine drainage (AMD) abatement has obvious conceptual appeal. This paper summarizes the findings of the baseline hydrogeologic and water quality evaluations at two sites--one in West Virginia and one in Maryland--where field demonstrations of the technique are being pursued in cooperative efforts among State and Federal agencies and/or private companies. The West Virginia site produces severe AMD from three to seven AMD sources that are spaced over about a 1.2 km stretch of the down-dip side of the mine workings. By completely filling the most problematic portion of the mine workings with coal combustion ashes, the State expects that the costs and problems associated with AMD treatment will be greatly reduced. At the Maryland site, it is expected that the AMD from a relatively small target mine will be eliminated completely by filling the entire mine void with a grout composed of a mixture of fly ash, fluidized-bed combustion ash, and flue gas desulfurization sludge. This project will also demonstrate the potential cost-effectiveness of the technique at other sites, both for the purpose of AMD remediation and control of land subsidence

Comparison of Visual Function in Older Eyes in the Earliest Stages of Age-related Macular Degeneration to Those in Normal Macular Health.

Science.gov (United States)

Owsley, Cynthia; Huisingh, Carrie; Clark, Mark E; Jackson, Gregory R; McGwin, Gerald

2016-01-01

To compare the ability of several visual functional tests in terms of the strength of their associations with the earliest phases of age-related macular degeneration (AMD), which bears on their potential to serve as functional endpoints in evaluating treatments for early AMD and prevention strategies. Eyes from adults ≥60 years old were identified as being in normal macular health or in the earliest stages of AMD (steps 2, 3 or 4) through grading of color stereo-fundus photos by an experienced grader masked to all other study variables who used the 9-step Age-Related Eye Disease Study (AREDS) classification system for AMD severity. Visual function was assessed using the following tests: best-corrected visual acuity, low luminance visual acuity, spatial contrast sensitivity, macular cone-mediated light sensitivity and rod-mediated dark adaptation. A total of 1260 eyes were tested from 640 participants; 1007 eyes were in normal macular health (defined as step 1 in AREDS system) and 253 eyes had early AMD (defined as steps 2, 3 or 4). Adjusting for age and gender, early AMD eyes had two times the odds of having delayed rod-mediated dark adaptation than eyes in normal macular health (p = 0.0019). Visual acuity, low luminance acuity, spatial contrast sensitivity and macular light sensitivity did not differ between normal eyes and early AMD eyes. Eyes in the earliest phases of AMD were two times more likely to have delayed rod-mediated dark adaptation, as assessed by the rod-intercept, as compared to older eyes in normal macular health, whereas there was no difference in early AMD versus normal eyes in tests of visual acuity, low luminance acuity, macular light sensitivity and spatial contrast sensitivity.

Modelling the genetic risk in age-related macular degeneration.

Directory of Open Access Journals (Sweden)

Felix Grassmann

Full Text Available Late-stage age-related macular degeneration (AMD is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05 than patients aged 75 and above (1.45, 95% CI: 1.36-1.54. Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96 for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population. The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.

Clinical, legal and ethical implications of the intra-ocular (off-label) use of bevacizumab (avastin)--a South African perspective.

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Jansen, Rita-Marié; Gouws, Chris

2009-06-01

Choroidal neovascularisation is a potentially visually devastating element of various forms of eye pathology. Recent research has focused on neurovascular age-related macular degeneration (AMD) as a cause. AMD can be classified as being exudative (wet) or atrophic (dry). Wet AMD is characterised by a pathological process in which new blood vessels develop in the choroids, causing leakage of fluid and haemorrhage under the retina and leading to localised serous detachment and loss of central vision. Vascular endothelial growth factor (VEGF) stimulates growth of neovascular membranes. Treatments have until recently yielded disappointing results. Ophthalmologists are using intra-ocular injections of bevacizumab (Avastin), an anti-VEGF, to treat AMD. Avastin appears to be safe and effective in the short term, but its intra-ocular administration is entirely off-label. Avastin is registered for treating metastatic colorectal and breast cancer. The off-label use of medication is an important part of mainstream, legitimate medical practice worldwide. Lawyers representing plaintiffs injured by drugs increasingly encounter off-label use claims. From a legal/ethical point of view the off-label use of medication represents a delicate balance between the statutory regulation of medication and a physician's prerogative to prescribe medication that in his or her medical opinion will be beneficial to the patient. The main reason for the controversy created by the off-label use of Avastin is that there are anti-VEGF drugs on the market that have formal approval for the treatment of AMD (and other eye conditions). Lucentis, for example, is extremely expensive, with treatment cost approximately 50 times that of Avastin. Many patients suffering from AMD and macular oedema cannot afford the registered product. The off-label use of Avastin has passed the innovative or experimental stages, as ophthalmologists have used it regularly and openly for a long time, with good success. Such use

Heavy Metals and Radioactivity Reduction from Acid Mine Drainage Lime Neutralized Sludge

Science.gov (United States)

Mashifana, T.; Sithole, N.

2018-03-01

The worldwide known treatment processes of acid mine drainage result into the formation of hydrous ferric oxides that is amorphous, poorly crystalline and into the generation of hazardous voluminous sludge posing threat to the environment. Applicable treatment technologies to treat hazardous solid material and produce useful products are limited and in most cases nonexistence. A chemical treatment process utilizing different reagents was developed to treat hazardous acid mine drainage (AMD) sludge with the objectives to conduct radioactivity assessment of the sludge generated from lime treatment process and determine the reagent that provides the best results. Leaching with 0.5 M citric acid, 0.4 M oxalic acid, 0.5 M sodium carbonate and 0.5 M sodium bicarbonate was investigated. The leaching time applied was 24 hours at 25 °C. The characterization of the raw AMD revealed that the AMD sludge from lime treatment process is radioactive. The sludge was laden with radioactive elements namely, 238U, 214Pb, 226Ra, 232Th, 40K and 214Bi. 0.5 M citric acid provided the best results and the hazardous contaminants were significantly reduced. The constituents in the sludge after treatment revealed that there is a great potential for the sludge to be used for other applications such as building and construction.

Application of mine water leaching protocol on coal fly ash to assess leaching characteristics for suitability as a mine backfill material.

Science.gov (United States)

Madzivire, Godfrey; Ramasenya, Koena; Tlowana, Supi; Coetzee, Henk; Vadapalli, Viswanath R K

2018-04-16

Over the years, coal mining in the Mpumalanga Province of South Africa has negatively affected the environment by causing pollution of water resources, land subsidence and spontaneous coal combustion. Previous studies show that in-situ treatment of acid mine drainage (AMD) using coal fly ash (CFA) from local power stations was possible and sludge recovered out of such treatment can be used to backfill mines. In this article, the authors have attempted to understand the leaching characteristics of CFA when placed underground as a backfill material using the mine water leaching protocol (MWLP). The results show that the migration of contaminants between the coal fly ash and the AMD in the mine voids depends on the pH and quality of the mine water. While backfilling mine voids with CFA can neutralize and scavenge between 50% and 95% of certain environmentally sensitive elements from AMD such as Fe, Al, Zn, Cu, Ni, Co and Mn. At this moment, it is also important to point out that certain scavenged/removed contaminants from the AMD during initial phases of backfilling can be remobilized by the influx of acidic water into the mine voids. It has therefore been concluded that, while CFA can be used to backfill mine voids, the influx of fresh acidic mine water should be avoided to minimize the remobilization of trapped contaminants such as Fe, Al, Mn and As. However, the pozzolanic material resulting from the CFA-AMD interaction could prevent such influx.

External beam radiation for retinoblastoma: Results, patterns of failure, and a proposal for treatment guidelines

International Nuclear Information System (INIS)

Hernandez, J. Carlos; Brady, Luther W.; Shields, Jerry A.; Shields, Carol L.; Potter, Patrick de; Karlsson, Ulf L.; Markoe, Arnold M.; Amendola, Beatriz E.; Singh, Arun

1996-01-01

Purpose: To analyze treatment results and patterns of failure following external beam radiation for retinoblastoma and propose treatment guidelines according to specific clinical variables. Methods and Materials: We analyzed 27 patients (34 eyes) with retinoblastoma who received external beam radiation as initial treatment at Hahnemann University Hospital from October 1980 to December 1991 and have been followed for at least 1 year. Of the 34 eyes, 14 were Groups I-II (Reese-Ellsworth classification), 7 were Group III, and 13 were Groups IV-V. Doses ranged from 34.5-49.5 Gy (mean 44.3 Gy, median 45 Gy) in 1.5-2.0 Gy fractions generally delivered through anterior and lateral wedged pair fields. Results: At a mean follow up of 35.2 months (range 12-93 months), local tumor control was obtained in 44% (15 out of 34) of eyes with external beam radiation alone. Salvage therapy (plaque brachytherapy, cryotherapy, and/or photocoagulation) controlled an additional 10 eyes (29.5%), so that overall ocular survival has been 73.5%. Local tumor control with external beam radiotherapy alone was obtained in 78.5% (11 out of 14) of eyes in Groups I-II, but in only 20% (4 out of 20) of eyes in Groups III-V. A total of 67 existing tumors were identified prior to treatment in the 34 treated eyes and local control with external beam radiation alone was obtained in 87% (46 out of 53) of tumors measuring 15 mm or less and in 50% (7 out of 14) of tumors measuring more than 15 mm. When analyzing patterns of failure in the 19 eyes that relapsed, a total of 28 failure sites were identified and consisted of progression of vitreous seeds in seven instances (25% of failure sites) recurrences from previously existing tumors in 10 instances (36% of failure sites) and development of new tumors in previously uninvolved retina in 11 instances (39% of failure sites). Conclusions: 1) We find that external beam radiation to a dose of 45 Gy in fractions of 1.5 to 2.0 Gy provides adequate tumor control

Crown and crown-root fractures: an evaluation of the treatment plans for management proposed by 154 specialists in restorative dentistry.

Science.gov (United States)

de Castro, Mara Antonio Monteiro; Poi, Wilson Roberto; de Castro, José Carlos Monteiro; Panzarini, Sônia Regina; Sonoda, Celso Koogi; Trevisan, Carolina Lunardelli; Luvizuto, Eloá Rodrigues

2010-06-01

Traumatic tooth injuries involve function and aesthetics and cause damage that range from minimal enamel loss to complex fractures involving the pulp tissue and even loss of the tooth crown. Technical knowledge and clinical experience are essential to establish an accurate diagnosis and provide a rational treatment. The purpose of this study was to evaluate the knowledge of Restorative Dentistry specialists about the management of crown and crown-root fractures based on treatment plans proposed by these professionals for these cases. A descriptive questionnaire was mailed to 245 Restorative Dentistry specialists with questions referring to their professional profile and the treatment plans they would propose for the management of crown and crow-root fractures resulting from dental trauma. One hundred and fifty-four questionnaires were returned properly filled. The data were subjected to descriptive statistics and the chi-square test was used to determine the frequency and the level of the significance among the variables. The analysis of data showed that in spite of having a specialist title, all interviewees had great difficulty in planning the treatments. As much as 42.8% of the participants were unable to treat all types of dental trauma. Complicated and uncomplicated crown-root fractures posed the greatest difficulties for the dentists to establish adequate treatment plans because these fractures require multidisciplinary knowledge and approach for a correct case planning and prognosis.

JNK inhibition reduces apoptosis and neovascularization in a murine model of age-related macular degeneration.

Science.gov (United States)

Du, Hongjun; Sun, Xufang; Guma, Monica; Luo, Jing; Ouyang, Hong; Zhang, Xiaohui; Zeng, Jing; Quach, John; Nguyen, Duy H; Shaw, Peter X; Karin, Michael; Zhang, Kang

2013-02-05

Age-related macular degeneration (AMD) is the leading cause of registered blindness among the elderly and affects over 30 million people worldwide. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in pathogenesis of AMD. In advanced wet AMD, although, most of the severe vision loss is due to bleeding and exudation of choroidal neovascularization (CNV), and it is well known that vascular endothelial growth factor (VEGF) plays a pivotal role in the growth of the abnormal blood vessels. VEGF suppression therapy improves visual acuity in AMD patients. However, there are unresolved issues, including safety and cost. Here we show that mice lacking c-Jun N-terminal kinase 1 (JNK1) exhibit decreased inflammation, reduced CNV, lower levels of choroidal VEGF, and impaired choroidal macrophage recruitment in a murine model of wet AMD (laser-induced CNV). Interestingly, we also detected a substantial reduction in choroidal apoptosis of JNK1-deficient mice. Intravitreal injection of a pan-caspase inhibitor reduced neovascularization in the laser-induced CNV model, suggesting that apoptosis plays a role in laser-induced pathological angiogenesis. Intravitreal injection of a specific JNK inhibitor decreased choroidal VEGF expression and reduced pathological CNV. These results suggest that JNK1 plays a key role in linking oxidative stress, inflammation, macrophage recruitment apoptosis, and VEGF production in wet AMD and pharmacological JNK inhibition offers a unique and alternative avenue for prevention and treatment of AMD.

Two-Year Outcomes of a Treat-and-Extend Regimen Using Intravitreal Aflibercept Injections for Typical Age-Related Macular Degeneration.

Science.gov (United States)

Ito, Arisa; Matsumoto, Hidetaka; Morimoto, Masahiro; Mimura, Kensuke; Akiyama, Hideo

2017-01-01

The aim of this study was to evaluate the efficacy of a treat-and-extend (TAE) regimen using intravitreal injection of aflibercept (IVA) for typical age-related macular degeneration (tAMD). We retrospectively studied 61 treatment-naïve eyes with tAMD. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), number of injections, and complications during 2 years were evaluated. BCVA significantly improved by on average 0.13 logMAR units, and CMT and CCT significantly decreased after 2 years. The number of injections was on average 13.6. In the second year, eyes with classic choroidal neovascularization (CNV) needed significantly fewer treatments than eyes with occult CNV. Fourteen eyes, which developed subfoveal fibrosis, showed significantly poorer BCVA after 2 years. Subfoveal fibrosis was significantly common in classic CNV. A TAE regimen using IVA for tAMD might be effective for improving BCVA and exudative changes. The exudation may be suppressed with fewer treatments in classic CNV compared to occult CNV. © 2017 S. Karger AG, Basel.

Sustainable Management of Flowback Water during Hydraulic Fracturing of Marcellus Shale for Natural Gas Production

Energy Technology Data Exchange (ETDEWEB)

Vidic, Radisav [Univ. of Pittsburgh, PA (United States)

2015-01-24

This study evaluated the feasibility of using abandoned mine drainage (AMD) as make- up water for the reuse of produced water for hydraulic fracturing. There is an abundance of AMD sources near permitted gas wells as documented in this study that can not only serve as makeup water and reduce the demand on high quality water resources but can also as a source of chemicals to treat produced water prior to reuse. The assessment of AMD availability for this purpose based on proximity and relevant regulations was accompanied by bench- and pilot-scale studies to determine optimal treatment to achieve desired water quality for use in hydraulic fracturing. Sulfate ions that are often present in AMD at elevated levels will react with Ba²⁺ and Sr²⁺ in produced water to form insoluble sulfate compounds. Both membrane microfiltration and gravity separation were evaluated for the removal of solids formed as a result of mixing these two impaired waters. Laboratory studies revealed that neither AMD nor barite formed in solution had significant impact on membrane filtration but that some produced waters contained submicron particles that can cause severe fouling of microfiltration membrane. Coagulation/flocculation was found to be an effective process for the removal of suspended solids and both bench- and pilot-scale studies revealed that optimal process conditions can consistently achieve the turbidity of the finished water below 5 NTU. Adjusting the blending ratio of AMD and produced water can achieve the desired effluent sulfate concentration that can be accurately predicted by chemical thermodynamics. Co-treatment of produced water and AMD will result in elevated levels of naturally occurring radioactive materials (NORM) in the solid waste generated in this process due to radium co-precipitation with barium sulfate. Laboratory studies revealed that the mobility of barite that may form in the subsurface due to the presence of sulfate in the fracturing fluid can be

Present and future treatment possibilities in macular degeneration

Science.gov (United States)

Fisher, E.; Wegner, A.; Pfeiler, T.; Mertz, M.

2005-11-01

Purpose: To discuss present and future treatment possibilities in different types of choroidal neovascularisation. Methods: Presented are angiographic- and OCT-findings in patients with macular degeneration of different origin. Choroidal neovascularisations, which are not likely to respond positively to established procedures like thermal laser coagulation or photodynamic therapy will be discussed. Results and conclusions: Present study-guidelines and new methods of pharmacological intervention are analysed in different patterns of macular degeneration. Conventional laser coagulation in the treatment of classic, extrafoveal CNV and photodynamic therapy of predominantly classic subfoveal CNV still represent a gold standard. There are new recommendations, loosening the tight criteria of the TAP and VIP-guidelines, which cover, for instance, wider visual acuity ranges and the treatment of juxtafoveally located choroidal neovascularisations. Positive findings in literature confirm the role of PDT in pathologic myopia and other non-AMD CNV. Studies about surgical procedures, like macula- or RPE-translocation after surgical removal or thermal laser destruction of the CNV are in progress and are expected to show promising results. Phase II/III studies will soon point out the effect of anti-VEGF agents. The application of intravitreal (triamcinolone) or peribulbar (anecortave acetat) steroids could be useful. The combination with surgical or laser techniques could bring further benefit to the patient.

New approaches in the management of choroidal neovascular membrane in age-related macular degeneration.

Directory of Open Access Journals (Sweden)

Verma Lalit

2000-01-01

Full Text Available Age-related macular degeneration (AMD is a leading cause of blindness in the elderly population. The prevalence is reported to be 1.2-1.4% in several population-based epidemiological studies. Currently 25-30 million people worldwide are blind due to AMD. With the aging world population it is bound to increase significantly, and could become a significant public health problem in next two decades, with serious socio-economic implications. Several strategies are today available to treat the wet form of AMD, which is responsible for significant visual loss. These were until recently confined to laser photocoagulation, and subretinal surgery, but today two other modalities, namely, radiation and photodynamic therapy, are available. These treatment modalities however, are aimed at preservation of vision only, and not at reversing the process of the disease. Further research on antiangiogenic drugs and gene therapy could significantly help AMD patients.

Preparation of metal-resistant immobilized sulfate reducing bacteria beads for acid mine drainage treatment.

Science.gov (United States)

Zhang, Mingliang; Wang, Haixia; Han, Xuemei

2016-07-01

Novel immobilized sulfate-reducing bacteria (SRB) beads were prepared for the treatment of synthetic acid mine drainage (AMD) containing high concentrations of Fe, Cu, Cd and Zn using up-flow anaerobic packed-bed bioreactor. The tolerance of immobilized SRB beads to heavy metals was significantly enhanced compared with that of suspended SRB. High removal efficiencies of sulfate (61-88%) and heavy metals (>99.9%) as well as slightly alkaline effluent pH (7.3-7.8) were achieved when the bioreactor was fed with acidic influent (pH 2.7) containing high concentrations of multiple metals (Fe 469 mg/L, Cu 88 mg/L, Cd 92 mg/L and Zn 128 mg/L), which showed that the bioreactor filled with immobilized SRB beads had tolerance to AMD containing high concentrations of heavy metals. Partially decomposed maize straw was a carbon source and stabilizing agent in the initial phase of bioreactor operation but later had to be supplemented by a soluble carbon source such as sodium lactate. The microbial community in the bioreactor was characterized by denaturing gradient gel electrophoresis (DGGE) and sequencing of partial 16S rDNA genes. Synergistic interaction between SRB (Desulfovibrio desulfuricans) and co-existing fermentative bacteria could be the key factor for the utilization of complex organic substrate (maize straw) as carbon and nutrients source for sulfate reduction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantitative autoradiography at electronic microscopy level of tobacco cells (Nicotiana tabacum L.) infected by pepper ringspot virus

International Nuclear Information System (INIS)

Lage, G.

1980-06-01

RNA replication of the pepper ringspot virus, its translocation and its association with mitochondria are studied. Some basic aspects of the research are first examined: actinomycin D (AMD) effects on parts of the nucleolus, nucleus and cytoplasm of healthy - and infected cells; comparative study between the circle method and the planimetry method to determine the cell areas; determination of the proportion between the silver grain densities of nucleulus, nucleus and cytoplasm of the cells treated with AMD; determination of the HD (Half-Distance) for the working conditions. Use of the mathemathical model proposed by NADLER gives basic information with respect to the translocation and association of the virus with the mitochondria in the host cells: in the mitochondria associated system the silver grains covering the two components are predominantly constituted by the RNA of the radioactive virus (78%); the time necessary for the RNA synthesis, the virus maturity and its translocation to the mitochondria, (checked by U-5- 3 H treatment) can be shorter than 5 hours. (M.A.) [pt

Assessment, water-quality trends, and options for remediation of acidic drainage from abandoned coal mines near Huntsville, Missouri, 2003-2004

Science.gov (United States)

Christensen, Eric D.

2005-01-01

Water from abandoned underground coal mines acidifies receiving streams in the Sugar Creek Basin and Mitchell Mine Basin near Huntsville, Missouri. A 4.35-kilometer (2.7-mile) reach of Sugar Creek has been classified as impaired based on Missouri's Water Quality Standards because of small pH values [mine drainage (AMD) from two mine springs as well as small and diffuse seeps were observed to have an effect on water quality in Sugar Creek. Metal and sulfate loads increased and pH decreased immediately downstream from Sugar Creek's confluence with the Calfee Slope and Huntsville Gob drainages that discharge AMD into Sugar Creek. Similar effects were observed in the Mitchell Mine drainage that receives AMD from a large mine spring. Comparisons of water-quality samples from this study and two previous studies by the U.S. Geological Survey in 1987-1988 and the Missouri Department of Natural Resources in 2000-2002 indicate that AMD generation in the Sugar Creek Basin and Mitchell Mine Basin is declining, but the data are insufficient to quantify any trends or time frame. AMD samples from the largest mine spring in the Calfee Slope subbasin indicated a modest but significant increase in median pH from 4.8 to 5.2 using the Wilcoxan rank-sum test (p mine spring in the Mitchell Mine Basin indicated an increase in median pH values from 5.6 to 6.0 and a decrease in median specific conductance from 3,050 to 2,450 ?S/cm during the same period. Remediation of AMD at or near the sites of the three largest mine springs is geochemically feasible based on alkalinity addition rates and increased pH determined by cubitainer experiments and geochemical mixing experiments using the computer model PHREEQCI. Alkalinity values for seven cubitainer experiments conducted to simulate anoxic treatment options exceeded the targeted value for alkalinity [90 mg/L as calcium carbonate (CaCO3)] specified in Missouri's Total Maximum Daily Load program by 18 percent or more, but maximum pH values were

Periodontics II: Course Proposal.

Science.gov (United States)

Dordick, Bruce

A proposal is presented for Periodontics II, a course offered at the Community College of Philadelphia to give the dental hygiene/assisting student an understanding of the disease states of the periodontium and their treatment. A standardized course proposal cover form is given, followed by a statement of purpose for the course, a list of major…