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Sample records for amd trial mira-1

  1. Mira Soars Through the Sky

    Science.gov (United States)

    2007-01-01

    [figure removed for brevity, see original site] [figure removed for brevity, see original site] Figure 1Figure 2 New ultraviolet images from NASA's Galaxy Evolution Explorer shows a speeding star that is leaving an enormous trail of 'seeds' for new solar systems. The star, named Mira (pronounced my-rah) after the latin word for 'wonderful,' is shedding material that will be recycled into new stars, planets and possibly even life as it hurls through our galaxy. In figure 1, the upper panel shows Mira's full, comet-like tail as seen only in shorter, or 'far' ultraviolet wavelengths, while the lower panel is a combined view showing both far and longer, or 'near' ultraviolet wavelengths. The close-up picture at bottom gives a better look at Mira itself, which appears as a pinkish dot, and is moving from left to right in this view. Shed material appears in light blue. The dots in the picture are stars and distant galaxies. The large blue dot on the left side of the upper panel, and the large yellow dot in the lower panel, are both stars that are closer to us than Mira. The Galaxy Evolution Explorer discovered the strange tail during part of its routine survey of the entire sky at ultraviolet wavelengths. When astronomers first saw the picture, they were shocked because Mira has been studied for over 400 years yet nothing like this has ever been documented before. Mira's comet-like tail stretches a startling 13 light-years across the sky. For comparison, the nearest star to our sun, Proxima Centauri, is only about 4 light-years away. Mira's tail also tells a tale of its history -- the material making it up has been slowly blown off over time, with the oldest material at the end of the tail being released about 30,000 years ago (figure 2). Mira is a highly evolved, 'red giant' star near the end of its life. Technically, it is called an asymptotic giant branch star. It is red in color and bloated; for example, if a red giant were to replace our sun, it would engulf

  2. MiraLAX is not as effective as GoLytely in bowel cleansing before screening colonoscopies.

    Science.gov (United States)

    Hjelkrem, Michael; Stengel, Joel; Liu, Mark; Jones, David P; Harrison, Stephen A

    2011-04-01

    Successful colonoscopies require good bowel preparations-poor bowel preparations can increase medical costs, rates of missed lesions, and procedure duration. The combination of polyethylene glycol (PEG) 3350 without electrolytes (MiraLAX; Schering-Plough Healthcare Products, Inc, Kenilworth, NJ) and 64 oz of Gatorade (PepsiCo, Inc, Purchase, NY) has gained popularity as a bowel preparation regimen. However, the efficacy and tolerability of this approach has not been compared with standard bowel preparations in clinical trials. We compared split-dose (PEG) 3350 with electrolytes (GoLytely; Braintree Laboratories, Inc, Braintree, MA) with split-dose MiraLAX alone and in combination with pretreatment medications (bisacodyl or lubiprostone) to determine the efficacy and patient tolerability of MiraLAX as an agent for bowel preparation. We performed a prospective, randomized, blinded, controlled trial at a tertiary care center. Patients (n=403) were randomly assigned to groups given GoLytely, MiraLAX, MiraLAX with bisacodyl (10 mg), or MiraLAX with lubiprostone (24 μg). MiraLAX was combined with 64 oz of Gatorade. All patients were surveyed regarding preparation satisfaction and tolerability. The Ottawa bowel preparation scale was used to grade colon cleanliness. GoLytely was more effective at bowel cleansing (average Ottawa score, 5.1) than MiraLAX alone (average Ottawa score, 6.9) or in combination with lubiprostone (average Ottawa score, 6.8), or bisacodyl (average Ottawa score, 6.3) (P<.001). MiraLAX was associated with a trend toward longer procedure duration (P=.096). Groups given MiraLAX rated the overall experience as more satisfactory than those given GoLytely (P<.001). There were no differences between polyp detection rates (P=.346) or adverse events (P=.823). Split-dose MiraLAX in 64 oz of Gatorade is not as effective as 4 L split-dose GoLytely in bowel cleansing for screening colonoscopies. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All

  3. Symbiotic Miras

    International Nuclear Information System (INIS)

    Whitelock, P.A.

    1987-01-01

    This paper concerns interacting binary systems involving Mira variables. Twenty-six objects which potentially fall into this category are identified and observations of them covering the spectral regions from X-ray to radio are reviewed. Particular emphasis is given to near-infrared observations which are pertinent to establishing the presence of a Mira variable and also to new far-infrared data from IRAS. The majority of the objects under consideration have been classified as symbiotic stars. They are closely related to the well-known binary, o Cet, which might be described as mildly symbiotic. It is shown how the knowledge of normal Miras can contribute to the understanding of the evolutionary condition and luminosities of these binary Miras. Distances are derived for those objects with measured pulsation periods. The significance of the relatively long pulsation periods shown by these objects is also discussed. 165 references

  4. 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.

  5. Mira B Rejuvenated

    OpenAIRE

    Wood, Brian E.; Karovska, Margarita

    2006-01-01

    Recent ultraviolet spectra from the Hubble Space Telescope (HST) and Far Ultraviolet Spectroscopic Explorer (FUSE) satellites demonstrate that UV line and continuum fluxes observed from Mira B are increasing back towards the levels that the International Ultraviolet Explorer observed in 1979-1980 and 1990-1995, after having been found in a very low state by HST and FUSE in 1999-2001. The UV emission is associated with accretion of material onto Mira B from Mira A's massive wind, so the variab...

  6. Resolving the stellar activity of the Mira AB binary with ALMA

    Science.gov (United States)

    Vlemmings, W. H. T.; Ramstedt, S.; O'Gorman, E.; Humphreys, E. M. L.; Wittkowski, M.; Baudry, A.; Karovska, M.

    2015-05-01

    Aims: We present the size, shape, and flux densities at millimeter continuum wavelengths, based on ALMA science verification observations in Band 3 (~94.6 GHz) and Band 6 (~228.7 GHz), from the binary Mira A (o Ceti) and Mira B. Methods: The Mira AB system was observed with ALMA at a spatial resolution down to ~25 mas. The extended atmosphere of Mira A and the wind around Mira B sources were resolved, and we derived the sizes of Mira A and of the ionized region around Mira B. The spectral indices within Band 3 (between 89-100 GHz) and between Bands 3 and 6 were also derived. Results: The spectral index of Mira A is found to change from 1.71 ± 0.05 within Band 3 to 1.54 ± 0.04 between Bands 3 and 6. The spectral index of Mira B is 1.3 ± 0.2 in Band 3, in good agreement with measurements at longer wavelengths; however, it rises to 1.72 ± 0.11 between the bands. For the first time, the extended atmosphere of a star is resolved at these frequencies, and for Mira A the diameter is ~3.8 × 3.2 AU in Band 3 (with brightness temperature Tb ~ 5300 K) and ~4.0 × 3.6 AU in Band 6 (Tb ~ 2500 K). Additionally, a bright hotspot ~0.4 AU, with Tb ~ 10 000 K, is found on the stellar disk of Mira A. The size of the ionized region around the accretion disk of Mira B is found to be ~2.4 AU. Conclusions: The emission around Mira B is consistent with emission from a partially ionized wind of gravitationally bound material from Mira A close to the accretion disk of Mira B. The Mira A atmosphere does not fully match predictions with brightness temperatures in Band 3 significantly higher than expected, potentially owing to shock heating. The hotspot is very likely due to magnetic activity and could be related to the previously observed X-ray flare of Mira A. Appendices are available in electronic form at http://www.aanda.org

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. 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.

  10. Focused Wind Mass Accretion in Mira AB

    Science.gov (United States)

    Karovska, Margarita; de Val-Borro, M.; Hack, W.; Raymond, J.; Sasselov, D.; Lee, N. P.

    2011-05-01

    At a distance of about only 100pc, Mira AB is the nearest symbiotic system containing an Asymptotic Giant Branch (AGB) star (Mira A), and a compact accreting companion (Mira B) at about 0.5" from Mira A. Symbiotic systems are interacting binaries with a key evolutionary importance as potential progenitors of a fraction of asymmetric Planetary Nebulae, and SN type Ia, cosmological distance indicators. The region of interaction has been studied using high-angular resolution, multiwavelength observations ranging from radio to X-ray wavelengths. Our results, including high-angular resolution Chandra imaging, show a "bridge" between Mira A and Mira B, indicating gravitational focusing of the Mira A wind, whereby components exchange matter directly in addition to the wind accretion. We carried out a study using 2-D hydrodynamical models of focused wind mass accretion to determine the region of wind acceleration and the characteristics of the accretion in Mira AB. We highlight some of our results and discuss the impact on our understanding of accretion processes in symbiotic systems and other detached and semidetached interacting systems.

  11. Latest Surprises from Mira the Wonderful

    Science.gov (United States)

    Karovska, Margarita; Marengo, Massimo; Wood, Brian

    We report the latest results from our long-term study of Mira A and its companion Mira B. These include a study of the dust environment in mid-IR wavelengths (Marengo et al. 2001), and of the accretion processes in the Mira AB interacting system (Wood, Karovska, and Raymond 2002).

  12. 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

  13. Mid-IR Observations of Mira Circumstellar Environment

    OpenAIRE

    Marengo, Massimo; Karovska, Margarita; Fazio, Giovanni G.; Hora, Joseph L.; Hoffmann, William F.; Dayal, Aditya; Deutsch, Lynne K.

    2001-01-01

    This paper presents results from high-angular resolution mid-IR imaging of the Mira AB circumbinary environment using the MIRAC3 camera at the NASA Infrared Telescope Facility (IRTF). We resolved the dusty circumstellar envelope at 9.8, 11.7 and 18 micron around Mira A (o Ceti), and measured the size of the extended emission. Strong deviations from spherical symmetry are detected in the images of Mira AB system, including possible dust clumps in the direction of the companion (Mira B). These ...

  14. Multi-criteria Integrated Resource Assessment (MIRA)

    Science.gov (United States)

    MIRA is an approach that facilitates stakeholder engagement for collaborative multi-objective decision making. MIRA is designed to facilitate and support an inclusive, explicit, transparent, iterative learning-based decision process.

  15. X-ray Outburst in Mira A

    OpenAIRE

    Karovska, M.; Schlegel, E.; Hack, W.; Wood, B.

    2005-01-01

    We report here the Chandra ACIS-S detection of a bright soft X-ray transient in the Mira AB interacting symbiotic-like binary. We resolved the system for the first time in the X-rays. Using Chandra and HST images we determined that the unprecedented outburst is likely associated with the cool AGB star (Mira A), the prototype of Mira-type variables. X-rays have never before been detected from an AGB star, and the recent activity signals that the system is undergoing dramatic changes. The total...

  16. Outburst in Mira AB?

    Science.gov (United States)

    Karovska, Margarita

    2003-09-01

    The nearby system Mira AB composed of an aging AGB star (Mira A) and a WD companion (Mira B) offers a unique laboratory for studying wind accretion processes, a poorly understood phenomenon in many sources. Recent Chandra ACIS-S Obs.(70ks on 12/6/03; PI.M.Karovska) resolved for the first time the components (~0.6") in X-rays, and detected a new bright soft source (A. This is the first detection of X-rays from an AGB star. This source was not detected by ROSAT in 1993 or recently by XMM 8/03 (AAS/03,J.Kastner), and could be a transient phenomenon. Model fitting shows that the soft X-ray emission is likely several emission lines, rather then a continuum; with ACIS spectral resolution we cannot resolve or identify these lines. We propose a 40ks LETG+HRC-S obs. to identify the lines and determine the emission mechanism.

  17. 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.

  18. Monitoring of Mira (omi Cet) in support of HST Observations

    Science.gov (United States)

    Karovska, Margarita; Templeton, Matthew R.

    2007-09-01

    Dr. Margarita Karovska (Harvard-Smithsonian Center for Astrophysics) and collaborators are performing a comprehensive study of the Mira AB interacting system, using the HST WFPC2 camera. Mira AB is composed of the prototype Mira variable omi Cet and its companion VZ Cet, separated by about 0.5 arcsecond. As part of this project they plan to obtain a large number of high-angular resolution images at wavelengths ranging from UV to optical. The main objectives of the HST/WFPC2 observations are 1) to determine the properties of the material ejected in December 2004 as it flows throughout the binary and interacts with the Mira A (omi Cet, Mira) circumstellar material and wind; 2) to determine the physical characteristics of mass transfer in this system and especially the role of the accretion stream between Mira A and its accreting companion Mira B (VZ Cet); 3) to determine the response of the system to the increased accretion rate onto Mira B following the outburst. The HST observations are scheduled for September 23, 1900-2300 UT. Both visual and instrumental observers are requested to observe this object, currently at minimum around visual magnitude 9-9.5. Observations should be made approximately two weeks on either side of the September 23 observation date. Visual observer should observe as usual, making not more than 3 observations spaced about 10 days apart. PEP and CCD observers should use the bluest-wavelength filters they have, and should make nightly observations, with intensive observations during the HST observations themselves. UBV and RIJH observations would be very valuable. Please make sure to use an aperture that covers both omi Cet and VZ Cet when evaluating CCD images. Observations should be submitted to the AAVSO International Database as OMI CET.

  19. 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

  20. DISCOVERY OF MIRA VARIABLE STARS IN THE METAL-POOR SEXTANS DWARF SPHEROIDAL GALAXY

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, Tsuyoshi [Japan Spaceguard Association, 1716-3 Ookura, Bisei, Ibara, Okayama 714-1411 (Japan); Matsunaga, Noriyuki; Nakada, Yoshikazu [Kiso Observatory, Institute of Astronomy, School of Science, University of Tokyo, 10762-30 Mitake, Kiso-machi, Kiso-gun, Nagano 397-0101 (Japan); Hasegawa, Takashi, E-mail: sakamoto@spaceguard.or.jp [Gunma Astronomical Observatory, 6860-86 Nakayama, Takayama, Agatsuma, Gunma 377-0702 (Japan)

    2012-12-10

    We report the discovery of two Mira variable stars (Miras) toward the Sextans dwarf spheroidal galaxy (dSph). We performed optical long-term monitoring observations for two red stars in the Sextans dSph. The light curves of both stars in the I{sub c} band show large-amplitude (3.7 and 0.9 mag) and long-period (326 {+-} 15 and 122 {+-} 5 days) variations, suggesting that they are Miras. We combine our own infrared data with previously published data to estimate the mean infrared magnitudes. The distances obtained from the period-luminosity relation of the Miras (75.3{sup +12.8}{sub -10.9} and 79.8{sup +11.5}{sub -9.9} kpc, respectively), together with the radial velocities available, support memberships of the Sextans dSph (90.0 {+-} 10.0 kpc). These are the first Miras found in a stellar system with a metallicity as low as [Fe/H] {approx} -1.9 than any other known system with Miras.

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

    Science.gov (United States)

    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.

  2. NLRP3 Inflammasome and Pathobiology in AMD

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    Lucia Celkova

    2015-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of central vision loss and blindness in the elderly. It is characterized by a progressive loss of photoreceptors in the macula due to damage to the retinal pigment epithelium (RPE. Clinically, it is manifested by drusen deposition between the RPE and underlying choroid and accumulation of lipofuscin in the RPE. End-stage disease is characterized by geographic atrophy (dry AMD or choroidal neovascularization (wet AMD. The NLRP3 inflammasome has recently been implicated in the disease pathology. Here we review the current knowledge on the involvement of this multiprotein complex and its effector cytokines interleukin-1β (IL-1β and IL-18 in AMD progression. We also describe cell death mechanisms that have been proposed to underlie RPE degeneration in AMD and discuss the role of autophagy in the regulation of disease progression.

  3. A MODEL OF MIRA'S COMETARY HEAD/TAIL ENTERING THE LOCAL BUBBLE

    International Nuclear Information System (INIS)

    Esquivel, A.; Raga, A. C.; RodrIguez-Gonzalez, A.; Lopez-Camara, D.; Velazquez, P. F.; Canto, J.; De Colle, F.

    2010-01-01

    We model the cometary structure around Mira as the interaction of an asymptotic giant branch stellar wind from Mira A with a streaming environment. Our simulations introduce the following new element: we assume that after 200 kyr of evolution in a dense environment, Mira entered the Local Bubble (low-density coronal gas). As Mira enters the bubble, the head of the comet expands quite rapidly, while the tail remains well collimated for a >100 kyr timescale. The result is a broad-head/narrow-tail structure that resembles the observed morphology of Mira's comet. The simulations were carried out with our new adaptive grid code WALICXE, which is described in detail.

  4. Discovering Mira Ceti: Celestial Change and Cosmic Continuity

    Science.gov (United States)

    Hatch, Robert Alan

    In the short narrative that follows I introduce two new heroes. Although we begin with Fabricius's first sighting in 1596, the new pivot point in the drama is the collaboration between Hevelius and Boulliau that began around 1660. As it happens, Learned Europe paid little attention to Mira in the generation after the first scattered sightings of 1596, indeed, nearly 70 years passed before the New Star was given a working identity. Like Columbus discovering America, Fabricius and Holwarda saw different things - for convenience, I call them Fabricius's Star and Holwarda's Star. Hevelius's Historiola (Danzig, 1662) and Boulliau's Ad astronomos (Paris, 1667) presented a different vision. It made Mira famous. As I shall argue, if Hevelius gave Mira a history, Boulliau gave Mira a future.5 In the end, the New Star not only challenged the ancient cosmos, it became an enduring icon for the New Science, a returning reminder of celestial continuity and cosmic order.

  5. 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

  6. 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...

  7. Low-Frequency Temporal Variability in Mira and Semiregular Variables

    Science.gov (United States)

    Templeton, Matthew R.; Karovska, M.; Waagen, E. O.

    2012-01-01

    We investigate low-frequency variability in a large sample of Mira and semiregular variables with long-term visual light curves from the AAVSO International Database. Our aim is to determine whether we can detect and measure long-timescale variable phenomena in these stars, for example photometric variations that might be associated with supergranular convection. We analyzed the long-term light curves of 522 variable stars of the Mira and SRa, b, c, and d classes. We calculated their low-frequency time-series spectra to characterize rednoise with the power density spectrum index, and then correlate this index with other observable characteristics such as spectral type and primary pulsation period. In our initial analysis of the sample, we see that the semiregular variables have a much broader range of spectral index than the Mira types, with the SRb subtype having the broadest range. Among Mira variables we see that the M- and S-type Miras have similarly wide ranges of index, while the C-types have the narrowest with generally shallower slopes. There is also a trend of steeper slope with larger amplitude, but at a given amplitude, a wide range of slopes are seen. The ultimate goal of the project is to identify stars with strong intrinsic red noise components as possible targets for resolved surface imaging with interferometry.

  8. MIRA: An R package for DNA methylation-based inference of regulatory activity.

    Science.gov (United States)

    Lawson, John T; Tomazou, Eleni M; Bock, Christoph; Sheffield, Nathan C

    2018-03-01

    DNA methylation contains information about the regulatory state of the cell. MIRA aggregates genome-scale DNA methylation data into a DNA methylation profile for independent region sets with shared biological annotation. Using this profile, MIRA infers and scores the collective regulatory activity for each region set. MIRA facilitates regulatory analysis in situations where classical regulatory assays would be difficult and allows public sources of open chromatin and protein binding regions to be leveraged for novel insight into the regulatory state of DNA methylation datasets. R package available on Bioconductor: http://bioconductor.org/packages/release/bioc/html/MIRA.html. nsheffield@virginia.edu.

  9. Development of Age-Related Macular Degeneration (AMD) in the Fellow Eye of Patients with AMD Treated by Treat-and-Extend Intravitreal Therapy with Aflibercept.

    Science.gov (United States)

    Mimura, Kensuke; Matsumoto, Hidetaka; Morimoto, Masahiro; Akiyama, Hideo

    2018-01-01

    To evaluate the development of neovascular age-related macular degeneration (nAMD) in the fellow eye in patients with unilateral nAMD treated by a treat-and-extend (TAE) regimen with intravitreal aflibercept injections. We retrospectively studied 104 patients with treatment-naïve unilateral nAMD. We assessed best-corrected visual acuity (BCVA) and exudative changes in the treated eyes and development of nAMD in the fellow eye for 2 years. The subjects included 46 patients with typical AMD (tAMD), 44 with polypoidal choroidal vasculopathy (PCV), and 14 with retinal angiomatous proliferation (RAP). BCVA was significantly improved after the loading phase in all subtypes. Forty-six patients (44.2%) had no recurrence within 2 years after the loading phase, including 12 (26.1%) with tAMD, 23 (52.2%) with PCV, and 11 (78.6%) with RAP (p < 0.01). Eleven patients (10.6%) developed nAMD in the fellow eye within 2 years, including 4 (8.7%) with tAMD, 0 (0%) with PCV, and 7 (50.0%) with RAP (p < 0.001). Patients with RAP had significantly more frequent development of nAMD in the fellow eye compared to other subtypes, while they showed significantly less recurrence during the TAE regimen with intravitreal aflibercept injections. Development of nAMD in the fellow eye should be monitored in RAP when the injection interval is extended. © 2017 S. Karger AG, Basel.

  10. The bolometric, infrared and visual absolute magnitudes of Mira variables

    International Nuclear Information System (INIS)

    Robertson, B.S.C.; Feast, M.W.

    1981-01-01

    Statistical parallaxes, as well as stars with individually known distances are used to derive bolometric and infrared absolute magnitudes of Mira (Me) variables. The derived bolometric magnitudes are in the mean about 0.75 mag fainter than recent estimates. The problem of determining the pulsation constant is discussed. Miras with periods greater than 150 days probably pulsate in the first overtone. Those of shorter periods are anomalous and may be fundamental pulsators. It is shown that the absolute visual magnitudes at mean light of Miras with individually determined distances are consistent with values derived by Clayton and Feast from statistical parallaxes. (author)

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  14. Tapping Stem Cells to Target AMD: Challenges and Prospects

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

    Directory of Open Access Journals (Sweden)

    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

  16. Estimating the intrinsic properties of miras from observational data

    International Nuclear Information System (INIS)

    Cahn, J.H.; Wyatt, S.P.

    1978-01-01

    We explore several of the consequences of the model of late stellar evolution recently investigated by Wood and Cahn. As stars ascend the asymptotic giant branch in the H-R plane, they evolve from left to right in the (M, log L) -plane, and also sink downward as they suffer a steady stellar-wind mass loss of the Reimers type. Stars in the approximate range of 1--2 M/sub sun/ eventually evolve to the point where they apparently begin first-overtone oscillation; during this phase they are Mira variables for a few hundred thousand years. At the end of their Mira stage, many of these stars evolve directly to white dwarfs; the rest of them eject one or more planetary nebulae before entering white-dwarf territory. Higher-mass stars evolve across the (M, log L) -plane without ever penetrating the Mira region and go on directly to give rise to planetary nebulae and eventually become white dwarfs. Stars of even greater mass presumably end their migration across the (M, logL) -domain by becoming supernovae. We adopt this broad picture and go on first to the Mira variables, seeking to establish an empirical diagram of period of light variation against mean spectral type at maximum light. Curves of constant period and constant spectral type are superposed on the (M, logL) -plane, along with evolutionary tracks and time scales. Thus a knowlege of the observed mean spectral type at maximum light and the period of a star permits approximate estimates to be made of its mean bolometric luminosity and present mass and gives a bird's-eve view of its past and future evolutionary track

  17. Pulsation properties of Mira long period variables

    International Nuclear Information System (INIS)

    Cahn, J.H.

    1980-01-01

    A matter of great interest to variable star students concerns the mode of pulsation of Mira long period variables. In this report we first give observational evidence for the pulsation constant Q. We then compare the observations with calculations. Next, we review two interesting groups of papers dealing with hydrodynamic properties of long period variables. In the first, a fully dynamic nonlinear calculation maps out the Mira instability domain. In the second, special attention is paid to shock propagation beyond the photosphere which in large measure accounts for the complex spectra from this region. (orig./WL)

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Long-Term Variability in o Ceti and Other Mira Variables: Signs of Supergranular Convection?

    Science.gov (United States)

    Templeton, Matthew R.; Karovska, Margarita

    2009-09-01

    We describe our study of long-term variability of o Ceti (Mira A), the prototype of the Mira-type pulsating stars. Our study was originally undertaken to search for coherent long-period variability, but the results of our analysis didn't uncover this. However, we detected a low-frequency ``red noise'' in the Fourier spectrum of the o Ceti century-long light curve. We have since found similar behavior in other Miras and pulsating giant stars and have begun a study of a large sample of Mira variables. Similar red noise has been previously detected in red supergiants and attributed to supergranular convection. Its presence in Miras suggests the phenomenon may be ubiquitous in cool giant pulsators. These results support high-angular resolution observations of Miras and supergiants showing asymmetries in their surface brightness distributions, which may be due to large supergranular convection cells. Theoretical modeling, and numerical simulations of pulsation processes in late-type giants and supergiants should therefore take into account the effects of deep convection and large supergranular structures, which in turn may provide important insights into the behavior of Miras and other giant and supergiant pulsators. In this work, we summarize our results for o Ceti, present preliminary results of our broader study of Mira variables, and discuss how the results of this study may be used by future studies of AGB variables.

  20. 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

  1. Blood Pressure Drugs and AMD

    Science.gov (United States)

    ... 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 ...

  2. 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

  3. Colour relations for Mira and Semiregular (SR) type stars

    International Nuclear Information System (INIS)

    Guney, Yavuz; Yesilyaprak, Cahit

    2016-01-01

    In this study, the period-colour relations, the colour-colour relations and the effective temperature were examined for Semiregular (SR) and Mira type variable stars. SR variables show an obvious period-colour relations, especially in infrared (IR). There are differences between SR and Mira type variable stars with respect to their colour relations. It has been thought that these differencies are caused by their mass loss rates and their effective temperatures. (paper)

  4. The complex model of risk and progression of AMD estimation

    Directory of Open Access Journals (Sweden)

    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.

  5. Aflibercept in wet AMD: specific role and optimal use

    Directory of Open Access Journals (Sweden)

    Semeraro F

    2013-08-01

    performed using the following terms (or combination of terms: vascular endothelial growth factors, VEGF, age-related macular degeneration, VEGF-Trap eye in wet AMD, VEGF-Trap eye in diabetic retinopathy, VEGF-Trap eye in retinal vein occlusions, aflibercept. Studies were limited to those published in English.Results and conclusion: Two Phase III clinical trials, VEGF Trap-eye Investigation of Efficacy and Safety in Wet AMD (VIEW 1 and 2, comparing VEGF Trap-eye to ranibizumab demonstrated the noninferiority of this novel compound. The clinical equivalence of this compound against ranibizumab is maintained even when the injections are administered at 8-week intervals, which indicates the potential to reduce the risk of monthly intravitreal injections and the burden of monthly monitoring.Keywords: aflibercept, AMD, neovascularization, VEGF, VEGF inhibition, VEGF-Trap eye

  6. 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

  7. Age-Related Macular Degeneration: New Paradigms for Treatment and Management of AMD

    Directory of Open Access Journals (Sweden)

    Luis Fernando Hernández-Zimbrón

    2018-01-01

    Full Text Available Age-related macular degeneration (AMD is a well-characterized and extensively studied disease. It is currently considered the leading cause of visual disability among patients over 60 years. The hallmark of early AMD is the formation of drusen, pigmentary changes at the macula, and mild to moderate vision loss. There are two forms of AMD: the “dry” and the “wet” form that is less frequent but is responsible for 90% of acute blindness due to AMD. Risk factors have been associated with AMD progression, and they are taking relevance to understand how AMD develops: (1 advanced age and the exposition to environmental factors inducing high levels of oxidative stress damaging the macula and (2 this damage, which causes inflammation inducing a vicious cycle, altogether causing central vision loss. There is neither a cure nor treatment to prevent AMD. However, there are some treatments available for the wet form of AMD. This article will review some molecular and cellular mechanisms associated with the onset of AMD focusing on feasible treatments for each related factor in the development of this pathology such as vascular endothelial growth factor, oxidative stress, failure of the clearance of proteins and organelles, and glial cell dysfunction in AMD.

  8. Age-Related Macular Degeneration: New Paradigms for Treatment and Management of AMD.

    Science.gov (United States)

    Hernández-Zimbrón, Luis Fernando; Zamora-Alvarado, Ruben; Ochoa-De la Paz, Lenin; Velez-Montoya, Raul; Zenteno, Edgar; Gulias-Cañizo, Rosario; Quiroz-Mercado, Hugo; Gonzalez-Salinas, Roberto

    2018-01-01

    Age-related macular degeneration (AMD) is a well-characterized and extensively studied disease. It is currently considered the leading cause of visual disability among patients over 60 years. The hallmark of early AMD is the formation of drusen, pigmentary changes at the macula, and mild to moderate vision loss. There are two forms of AMD: the "dry" and the "wet" form that is less frequent but is responsible for 90% of acute blindness due to AMD. Risk factors have been associated with AMD progression, and they are taking relevance to understand how AMD develops: (1) advanced age and the exposition to environmental factors inducing high levels of oxidative stress damaging the macula and (2) this damage, which causes inflammation inducing a vicious cycle, altogether causing central vision loss. There is neither a cure nor treatment to prevent AMD. However, there are some treatments available for the wet form of AMD. This article will review some molecular and cellular mechanisms associated with the onset of AMD focusing on feasible treatments for each related factor in the development of this pathology such as vascular endothelial growth factor, oxidative stress, failure of the clearance of proteins and organelles, and glial cell dysfunction in AMD.

  9. Mass Transfer in Mira-Type Binaries

    Directory of Open Access Journals (Sweden)

    Mohamed S.

    2012-06-01

    Full Text Available Detached, symbiotic binaries are generally assumed to interact via Bondi-Hoyle-Littleton (BHL wind accretion. However, the accretion rates and outflow geometries that result from this mass-transfer mechanism cannot adequately explain the observations of the nearest and best studied symbiotic binary, Mira, or the formation of some post-AGB binaries, e.g. barium stars. We propose a new mass-transfer mode for Mira-type binaries, which we call ‘wind Roche-lobe overflow’ (WRLOF, and which we demonstrate with 3D hydrodynamic simulations. Importantly, we show that the circumstellar outflows which result from WRLOF tend to be highly aspherical and strongly focused towards the binary orbital plane. Furthermore, the subsequent mass-transfer rates are at least an order of magnitude greater than the analogous BHL values. We discuss the implications of these results for the shaping of bipolar (proto-planetary nebulae and other related systems.

  10. Treatment of combined acid mine drainage (AMD)--flotation circuit effluents from copper mine via Fenton's process.

    Science.gov (United States)

    Mahiroglu, Ayse; Tarlan-Yel, Esra; Sevimli, Mehmet Faik

    2009-07-30

    The treatability of a copper mine wastewater, including heavy metals, AMD, as well as flotation chemicals, with Fenton process was investigated. Fenton process seems advantageous for this treatment, because of Fe(2+) content and low pH of AMD. First, optimum Fe(2+) condition under constant H(2)O(2) was determined, and initial Fe(2+) content of AMD was found sufficient (120 mg/L for removal of chemical oxygen demand (COD) of 6125 mg/L). In the second step, without any additional Fe(2+), optimum H(2)O(2) dosage was determined as 40 mg/L. Fe(2+)/H(2)O(2) molar ratio of 1.8 was enough to achieve the best treatment performance. In all trials, initial pH of AMD was 4.8 and pH adjustment was not performed. Utilization of existing pH and Fe(2+), low H(2)O(2) requirements, and up to 98% treatment performances in COD, turbidity, color, Cu(2+), Zn(2+) made the proposed treatment system promising. Since the reaction occurs stepwise, a two-step kinetic model was applied and calculated theoretical maximum removal rate was consistent to experimental one, which validates the applied model. For the optimum molar ratio (1.8), 140 mL/L sludge of high density (1.094 g/mL), high settling velocity (0.16 cm/s) with low specific resistance (3.15 x 10(8)m/kg) was obtained. High reaction rates and easily dewaterable sludge characteristics also made the proposed method advantageous.

  11. 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.).

  12. Large Magellanic Cloud Near-infrared Synoptic Survey. V. Period–Luminosity Relations of Miras

    International Nuclear Information System (INIS)

    Yuan, Wenlong; Macri, Lucas M.; He, Shiyuan; Huang, Jianhua Z.; Kanbur, Shashi M.; Ngeow, Chow-Choong

    2017-01-01

    We study the near-infrared properties of 690 Mira candidates in the central region of the Large Magellanic Cloud, based on time-series observations at JHK s . We use densely sampled I -band observations from the OGLE project to generate template light curves in the near-infrared and derive robust mean magnitudes at those wavelengths. We obtain near-infrared Period–Luminosity relations for oxygen-rich Miras with a scatter as low as 0.12 mag at K s . We study the Period–Luminosity–Color relations and the color excesses of carbon-rich Miras, which show evidence for a substantially different reddening law.

  13. MIRA: review of inputs from updated results of the phobos mission

    Science.gov (United States)

    Moroz, V. I.; Korablev, O. I.; Rodin, A. V.; Titov, D. V.

    1999-01-01

    The future Mars International Reference Atmosphere (MIRA) is intended to replace the present COSPAR Mars Reference Model compiled in 1979 on the basis of Mariner 9 and Viking 1,2 missions results. At the moment, several sources of the post-Viking data potentially useful for MIRA are available. Among them is a data set obtained during Phobos mission in 1989. The interpretation of these data has undergone thorough refinement, so final recommendations for MIRA can be made. The principal points are: 1) vertical profile of water vapor with a ``knee'' at the height about 25 km retrieved in the spring equinox season near equator; 2) variations of water vapor column density including peculiarities on the slopes of high mountains; 3) vertical profiles of ozone; 4) new estimates of CO abundance; 5) surface pressure/height mapping (CO2 altimetry) in selected regions; 6) optical depths of aerosols; 7) vertical profiles of aerosol between surface and 40 km; 8) properties of high altitude ice layers and clouds above mountains; 9) microphysical properties of aerosol particles (size, composition, and number density estimates). The data have been obtained by means of instruments AUGUSTE (UV and NIR spectrometers for limb sounding of the atmosphere using solar occultations), ISM (NIR scanning spectrometer), TERMOSKAN (thermal IR scanning radiometer), KRFM (near-UV and visible multi-band photometer). The observations were performed in equatorial regions during northern spring (solar aerocentric longitudes 8° < Ls < 18°).

  14. Large Magellanic Cloud Near-infrared Synoptic Survey. V. Period–Luminosity Relations of Miras

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Wenlong; Macri, Lucas M. [George P. and Cynthia W. Mitchell Institute for Fundamental Physics and Astronomy, Department of Physics and Astronomy, Texas A and M University, College Station, TX 77843 (United States); He, Shiyuan; Huang, Jianhua Z. [Department of Statistics, Texas A and M University, College Station, TX 77843 (United States); Kanbur, Shashi M. [Department of Physics, The State University of New York at Oswego, Oswego, NY 13126 (United States); Ngeow, Chow-Choong, E-mail: lmacri@tamu.edu [Graduate Institute of Astronomy, National Central University, Jhongli 32001, Taiwan (China)

    2017-10-01

    We study the near-infrared properties of 690 Mira candidates in the central region of the Large Magellanic Cloud, based on time-series observations at JHK{sub s}. We use densely sampled I -band observations from the OGLE project to generate template light curves in the near-infrared and derive robust mean magnitudes at those wavelengths. We obtain near-infrared Period–Luminosity relations for oxygen-rich Miras with a scatter as low as 0.12 mag at K{sub s}. We study the Period–Luminosity–Color relations and the color excesses of carbon-rich Miras, which show evidence for a substantially different reddening law.

  15. Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD

    Directory of Open Access Journals (Sweden)

    Miltiadis K. Tsilimbaris

    2016-01-01

    Full Text Available Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF therapy in the treatment of neovascular age-related macular degeneration (nAMD and to identify baseline characteristics that might predict response. Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology. Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review. Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response.

  16. Can shoulder range of movement be measured accurately using the Microsoft Kinect sensor plus Medical Interactive Recovery Assistant (MIRA) software?

    Science.gov (United States)

    Wilson, James D; Khan-Perez, Jennifer; Marley, Dominic; Buttress, Susan; Walton, Michael; Li, Baihua; Roy, Bibhas

    2017-12-01

    This study compared the accuracy of measuring shoulder range of movement (ROM) with a simple laptop-sensor combination vs. trained observers (shoulder physiotherapists and shoulder surgeons) using motion capture (MoCap) laboratory equipment as the gold standard. The Microsoft Kinect sensor (Microsoft Corp., Redmond, WA, USA) tracks 3-dimensional human motion. Ordinarily used with an Xbox (Microsoft Corp.) video game console, Medical Interactive Recovery Assistant (MIRA) software (MIRA Rehab Ltd., London, UK) allows this small sensor to measure shoulder movement with a standard computer. Shoulder movements of 49 healthy volunteers were simultaneously measured by trained observers, MoCap, and the MIRA device. Internal rotation was assessed with the shoulder abducted 90° and external rotation with the shoulder adducted. Visual estimation and MIRA measurements were compared with gold standard MoCap measurements for agreement using Bland-Altman methods. There were 1670 measurements analyzed. The MIRA evaluations of all 4 cardinal shoulder movements were significantly more precise, with narrower limits of agreement, than the measurements of trained observers. MIRA achieved ±11° (95% confidence interval [CI], 8.7°-12.6°) for forward flexion vs. ±16° (95% CI, 14.6°-17.6°) by trained observers. For abduction, MIRA showed ±11° (95% CI, 8.7°-12.8°) against ±15° (95% CI, 13.4°-16.2°) for trained observers. MIRA attained ±10° (95% CI, 8.1°-11.9°) during external rotation measurement, whereas trained observers only reached ±21° (95% CI, 18.7°-22.6°). For internal rotation, MIRA achieved ±9° (95% CI, 7.2°-10.4°), which was again better than TOs at ±18° (95% CI, 16.0°-19.3°). A laptop combined with a Microsoft Kinect sensor and the MIRA software can measure shoulder movements with acceptable levels of accuracy. This technology, which can be easily set up, may also allow precise shoulder ROM measurement outside the clinic setting. Copyright © 2017

  17. AMD genetics in India: The missing links

    Directory of Open Access Journals (Sweden)

    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.

  18. Comparison of colour curves of Mira stars of spectrum M and S

    International Nuclear Information System (INIS)

    Payne-Gaposchkin, C.

    1976-01-01

    Colour variations for Mira stars of Me and Se are deduced from the two micron survey of Neugebauer and Leighton and concurrent visual observations of the same stars. The colours change cyclically during the periodic change of brightness. Colour is a function of maximal spectrum and also of period. Mira stars of class Se are bluer than those of Me of similar period. (Auth.)

  19. Community interventions to reduce child mortality in Dhanusha, Nepal: study protocol for a cluster randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Costello Anthony

    2011-06-01

    Full Text Available Abstract Background Neonatal mortality remains high in rural Nepal. Previous work suggests that local women's groups can effect significant improvement through community mobilisation. The possibility of identification and management of newborn infections by community-based workers has also arisen. Methods/Design The objective of this trial is to evaluate the effects on newborn health of two community-based interventions involving Female Community Health Volunteers. MIRA Dhanusha community groups: a participatory intervention with women's groups. MIRA Dhanusha sepsis management: training of community volunteers in the recognition and management of neonatal sepsis. The study design is a cluster randomized controlled trial involving 60 village development committee clusters allocated 1:1 to two interventions in a factorial design. MIRA Dhanusha community groups: Female Community Health Volunteers (FCHVs are supported in convening monthly women's groups. Nine groups per cluster (270 in total work through two action research cycles in which they (i identify local issues around maternity, newborn health and nutrition, (ii prioritise key problems, (iii develop strategies to address them, (iv implement the strategies, and (v evaluate their success. Cycle 1 focuses on maternal and newborn health and cycle 2 on nutrition in pregnancy and infancy and associated postpartum care practices. MIRA Dhanusha sepsis management: FCHVs are trained to care for vulnerable newborn infants. They (i identify local births, (ii identify low birth weight infants, (iii identify possible newborn infection, (iv manage the process of treatment with oral antibiotics and referral to a health facility to receive parenteral gentamicin, and (v follow up infants and support families. Primary outcome: neonatal mortality rates. Secondary outcomes: MIRA Dhanusha community group: stillbirth, infant and under-two mortality rates, care practices and health care seeking behaviour, maternal

  20. Phase-dependent Photometric and Spectroscopic Characterization of the MASTER-Net Optical Transient J212444.87+321738.3: An Oxygen-rich Mira

    Science.gov (United States)

    Ghosh, Supriyo; Mondal, Soumen; Das, Ramkrishna; Banerjee, D. P. K.; Ashok, N. M.; Hambsch, Franz-Josef; Dutta, Somnath

    2018-05-01

    We describe the time-dependent properties of a new spectroscopically confirmed Mira variable, which was discovered in 2013 as MASTER-Net Optical Transient J212444.87+321738.3 toward the Cygnus constellation. We have performed long-term optical/near-infrared (NIR) photometric and spectroscopic observations to characterize the object. From the optical/NIR light curves, we estimate a variability period of 465 ± 30 days. The wavelength-dependent amplitudes of the observed light curves range from ΔI ∼ 4 mag to ΔK ∼ 1.5 mag. The (J ‑ K) color index varies from 1.78 to 2.62 mag over phases. Interestingly, a phase lag of ∼60 days between optical and NIR light curves is also seen, as in other Miras. Our optical/NIR spectra show molecular features of TiO, VO, CO, and strong water bands that are a typical signature of oxygen-rich Mira. We rule out S- or C-type as ZrO bands at 1.03 and 1.06 μm and C2 band at 1.77 μm are absent. We estimate the effective temperature of the object from the Spectral Energy Distribution, and distance and luminosity from standard Period–Luminosity relations. The optical/NIR spectra display time-dependent atomic and molecular features (e.g., TiO, Na I, Ca I, H2O, CO), as commonly observed in Miras. Such spectroscopic observations are useful for studying pulsation variability in Miras.

  1. R Aquarii - the large-scale optical nebula and the Mira variable position

    International Nuclear Information System (INIS)

    Michalitsianos, A.G.; Oliversen, R.J.; Hollis, J.M.; Kafatos, M.; Crull, H.E.

    1988-01-01

    The R Aquarii symbiotic star system is surrounded by a large-scale optical nebula. Observations of the nebular forbidden O III structure are presented and its morphological significance are discussed in context with previously observed small-scale radio-continuum features, which may be related. It is suggested that a precessing accretion disk may explain the global features of both the large-scale optical emission and the small-scale radio emission. Moreover, an accurate position has been determined of the system's Mira, which suggests that a recent theoretical model, yielding an egg-shaped central H II region for symbiotic systems with certain physical parameters, may apply to R Aquarii. The optical position of the 387 d period Mira variable is consistent with previous findings in the radio, that SiO maser emission is far removed from the Mira photosphere. 25 references

  2. 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.

  3. Detection of new southern SiO maser sources associated with Mira and symbiotic stars

    International Nuclear Information System (INIS)

    Allen, D.A.; Hall, P.J.; Norris, R.P.; Troup, E.R.; Wark, R.M.; Wright, A.E.

    1989-01-01

    In 1987 July the Parkes radio telescope was used to search for 43.12 GHz SiO maser emission from southern late-type stars. We report the discovery of such emission from 12 Mira-like systems, including the symbiotic star H1-36, and discuss the implications of our data for the symbiotic stars. We identify several M-type Mira variables with unusually low SiO/infrared flux ratios, but with present data are not able to discredit the correlation between the two parameters. In addition, we present line profiles for the only other known symbiotic maser, R Aqr, at unprecedented signal-to-noise ratio; these profiles show linearly polarized emission from several components of the source. (author)

  4. 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)

  5. 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)

  6. [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.

  7. A period-luminosity relation for Mira variables in globular clusters and its impact on the distance scale

    International Nuclear Information System (INIS)

    Menzies, J.W.; Whitelock, P.A.

    1985-01-01

    JHKL photometry is presented for 31 red variables in 15 galactic globular clusters. The photometry of the Mira variables is used to find absolute bolometric magnitudes and an Msub(bol)-log P relation which differs from the one found for LMC Miras. This can be understood only if there is some systematic error in the globular cluster and/or LMC distance scales or if there is some fundamental difference between the cluster Miras and those in the LMC. (author)

  8. Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics.

    Science.gov (United States)

    Sparrow, Janet R

    2016-04-26

    Although currently available treatment options for age-related macular degeneration (AMD) are limited, particularly for atrophic AMD, the identification of predisposing genetic variations has informed clinical studies addressing therapeutic options such as complement inhibitors and anti-inflammatory agents. To lower risk of early AMD, recommended lifestyle interventions such as the avoidance of smoking and the intake of low glycemic antioxidant-rich diets have largely followed from the identification of nongenetic modifiable factors. On the other hand, the challenge of understanding the complex relationship between aging and cumulative damage leading to AMD has fueled investigations of the visual cycle adducts that accumulate in retinal pigment epithelial (RPE) cells and are a hallmark of aging retina. These studies have revealed properties of these compounds that provide insights into processes that may compromise RPE and could contribute to disease mechanisms in AMD. This work has also led to the design of targeted therapeutics that are currently under investigation.

  9. Inherited Retinal Degenerative Clinical Trial Network. Addendum

    Science.gov (United States)

    2013-10-01

    inherited orphan retinal degenerative diseases and dry age-related macular degeneration (AMD) through the conduct of clinical trials and other...design and conduct of effective and efficient clinical trials for inherited orphan retinal degenerative diseases and dry AMD; • Limited number and...linica l trial in the NEER network for autosomal dominant retinitis pigmentosa, and the ProgSTAR studies for Stargardt disease ) . As new interventions b

  10. O corpo em mira: entrevista com Hermann Schmitz

    Directory of Open Access Journals (Sweden)

    Geraldo de Souza Dias

    2006-03-01

    Full Text Available Em meados da década de 1970, a artista plástica Mira Schendel toma conhecimento da fenomenologia de Hermann Schmitz, que influencia sobretudo seu último período de criação. As formulações de Schmitz negam tanto o dualismo platônico, que dividiu o ser humano em corpo e alma, como o entendimento positivista da ciência. Na entrevista transcrita abaixo, o filósofo apresenta os aspectos de seu pensamento que mais se aproximam da obra da artista.During the 1970's, artist Mira Schendel gets to know Hermann Schmitz' phenomenology, which becomes an important reference to her work. Schmitz' formulations deny not only platonic dualism, which divided the human being in body and soul, but also the Positivism in his understanding of science. In the following interview, he presents aspects of his thought that contribute to the understanding of Schendel's work.

  11. Mira – Artes Visuais Contemporâneas dos Povos Indígenas: Introdução

    Directory of Open Access Journals (Sweden)

    María Inês de Almeida

    2014-09-01

    Full Text Available O projeto Mira! Artes Visuais Contemporâneas dos Povos Indígenas nasceu com o intuito de trazer as muitas visões de mundo dos povos originários da imensa região pan-amazônica. O projeto Mira! com a exposição de 125 obras de artistas indígenas (pinturas, esculturas, arte digital quer mostrar ao público que, ao lado de estéticas ligadas ao mundo ocidental, há aquelas que se depuram em outros ambientes. Cinquenta e quatro artistas indígenas de Brasil, Bolívia, Colômbia, Equador e Peru estão participando da exposição Mira! Alguns artistas foram convidados a expor seus pensamentos e a debater sobre suas visões no seminário ocorrido em Belo Horizonte, em junho de 2013, quando a Mira! foi inaugurada.

  12. Genetic diversity and population structure of Prunus mira (Koehne from the Tibet plateau in China and recommended conservation strategies.

    Directory of Open Access Journals (Sweden)

    Wenquan Bao

    Full Text Available Prunus mira Koehne, an important economic fruit crop with high breeding and medicinal values, and an ancestral species of many cultivated peach species, has recently been declared an endangered species. However, basic information about genetic diversity, population structure, and morphological variation is still limited for this species. In this study, we sampled 420 P. mira individuals from 21 wild populations in the Tibet plateau to conduct a comprehensive analysis of genetic and morphological characteristics. The results of molecular analyses based on simple sequence repeat (SSR markers indicated moderate genetic diversity and inbreeding (A = 3.8, Ae = 2.5, He = 0.52, Ho = 0.44, I = 0.95, FIS = 0.17 within P. mira populations. STRUCTURE, GENELAND, and phylogenetic analyses assigned the 21 populations to three genetic clusters that were moderately correlated with geographic altitudes, and this may have resulted from significantly different climatic and environmental factors at different altitudinal ranges. Significant isolation-by-distance was detected across the entire distribution of P. mira populations, but geographic altitude might have more significant effects on genetic structure than geographic distance in partial small-scale areas. Furthermore, clear genetic structure, high genetic differentiation, and restricted gene flow were detected between pairwise populations from different geographic groups, indicating that geographic barriers and genetic drift have significant effects on P. mira populations. Analyses of molecular variance based on the SSR markers indicated high variation (83.7% and 81.7%, whereas morphological analyses revealed low variation (1.30%-36.17% within the populations. Large and heavy fruits were better adapted than light fruits and nutlets to poor climate and environmental conditions at high altitudes. Based on the results of molecular and morphological analyses, we classified the area into three conservation units

  13. Age-Related Macular Degeneration: New Paradigms for Treatment and Management of AMD

    OpenAIRE

    Hernández-Zimbrón, Luis Fernando; Zamora-Alvarado, Ruben; Ochoa-De la Paz, Lenin; Velez-Montoya, Raul; Zenteno, Edgar; Gulias-Cañizo, Rosario; Quiroz-Mercado, Hugo; Gonzalez-Salinas, Roberto

    2018-01-01

    Age-related macular degeneration (AMD) is a well-characterized and extensively studied disease. It is currently considered the leading cause of visual disability among patients over 60 years. The hallmark of early AMD is the formation of drusen, pigmentary changes at the macula, and mild to moderate vision loss. There are two forms of AMD: the “dry” and the “wet” form that is less frequent but is responsible for 90% of acute blindness due to AMD. Risk factors have been associated with AMD pro...

  14. AMD-stability in the presence of first-order mean motion resonances

    Science.gov (United States)

    Petit, A. C.; Laskar, J.; Boué, G.

    2017-11-01

    The angular momentum deficit (AMD)-stability criterion allows to discriminate between a priori stable planetary systems and systems for which the stability is not granted and needs further investigations. AMD-stability is based on the conservation of the AMD in the averaged system at all orders of averaging. While the AMD criterion is rigorous, the conservation of the AMD is only granted in absence of mean-motion resonances (MMR). Here we extend the AMD-stability criterion to take into account mean-motion resonances, and more specifically the overlap of first-order MMR. If the MMR islands overlap, the system will experience generalized chaos leading to instability. The Hamiltonian of two massive planets on coplanar quasi-circular orbits can be reduced to an integrable one degree of freedom problem for period ratios close to a first-order MMR. We use the reduced Hamiltonian to derive a new overlap criterion for first-order MMR. This stability criterion unifies the previous criteria proposed in the literature and admits the criteria obtained for initially circular and eccentric orbits as limit cases. We then improve the definition of AMD-stability to take into account the short term chaos generated by MMR overlap. We analyze the outcome of this improved definition of AMD-stability on selected multi-planet systems from the Extrasolar Planets Encyclopædia.

  15. VizieR Online Data Catalog: Mira stars discovered in LAMOST DR4 (Yao+, 2017)

    Science.gov (United States)

    Yao, Y.; Liu, C.; Deng, L.; de Grijs, R.; Matsunaga, N.

    2017-10-01

    By the end of 2016 March, the wide-field Large sky Area Multi-Object fiber Spectroscopic Telescope (LAMOST) DR4 catalog had accumulated 7681185 spectra (R=1800), of which 6898298 were of stars. We compiled a photometrically confirmed sample of Mira variables from the Kiso Wide-Field Camera (KWFC) Intensive Survey of the Galactic Plane (KISOGP; Matsunaga 2017, arXiv:1705.08567), the American Association of Variable Star Observers (AAVSO) International Database Variable Star Index (VSX; Watson 2006, B/vsx, version 2017-05-02; we selected stars of variability type "M"), and the SIMBAD Astronomical Database. We first cross-matched the KISOGP and VSX Miras with the LAMOST DR4 catalog. Finally, we cross-matched the DR4 catalog with the SIMBAD database. See section 2. (1 data file).

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

    Science.gov (United States)

    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.

  17. Results from the Astronomy Diagnostic Test: 3 Years at MiraCosta College

    Science.gov (United States)

    Sirbaugh French, Rica

    2007-12-01

    The Astronomy Diagnostic Test 2.0 (ADT) was administered to 26 sections of ASTR 101 at MiraCosta College (MCC) from fall 2004 through summer 2007. MiraCosta is a two-year community college located in Oceanside, CA, USA (roughly 40 miles north of San Diego) with an enrollment of approximately 11,000 students. ASTR 101 is MiraCosta's introductory astronomy survey course for non-science majors and has no math prerequisite. Class sizes ranged from 10 to 38 students. Comparison with the ADT National Project results indicates similar pre- and post-course averages: 31.8% (MCC) vs. 32.4% (National) for pre-course tests and 49.3% (MCC) vs. 47.3% (National) for post-course tests. The sample sizes are 709 and 530 students for the pre- and post-tests, respectively. The normalized gain for the entire data set is 0.256 and the effect size (ES) is 1.04, meaning that approximately 85% of the post-test scores are above the average of the pre-test scores. Previous studies have shown the ADT to be a reliable indicator of pre-course misconceptions while post-course scores are useful for comparing modes of instruction and assessing student learning on a limited number of concepts. Additional analyses of the MCC data probe for trends with variables such as gender, class size, and implementation of materials designed for a more "learner-centered” approach (such as Lecture Tutorials, Ranking Tasks, and Think-Pair-Share questions), as well as gains for a particular subset of concepts.

  18. Inhomogeneities in Molecular Layers of Mira Atmospheres

    Science.gov (United States)

    2011-01-01

    star atmospheres. In particular, observations using the IOTA interferometer have uncovered the wavelength-dependence of Mira star diameters using a few...al. 1998; Ireland et al. 2004a,b). H-band interferometry at the IOTA interferometer in the broad band (Ragland et al. 2006), as well as in three...might possibly be caused by pulsation- and shock-induced chaotic motion in the extended atmosphere. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF

  19. [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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. On the Chemical Abundances of Miras in Clusters: V1 in the Metal-rich Globular NGC 5927

    Science.gov (United States)

    D’Orazi, V.; Magurno, D.; Bono, G.; Matsunaga, N.; Braga, V. F.; Elgueta, S. S.; Fukue, K.; Hamano, S.; Inno, L.; Kobayashi, N.; Kondo, S.; Monelli, M.; Nonino, M.; Przybilla, N.; Sameshima, H.; Saviane, I.; Taniguchi, D.; Thevenin, F.; Urbaneja-Perez, M.; Watase, A.; Arai, A.; Bergemann, M.; Buonanno, R.; Dall’Ora, M.; Da Silva, R.; Fabrizio, M.; Ferraro, I.; Fiorentino, G.; Francois, P.; Gilmozzi, R.; Iannicola, G.; Ikeda, Y.; Jian, M.; Kawakita, H.; Kudritzki, R. P.; Lemasle, B.; Marengo, M.; Marinoni, S.; Martínez-Vázquez, C. E.; Minniti, D.; Neeley, J.; Otsubo, S.; Prieto, J. L.; Proxauf, B.; Romaniello, M.; Sanna, N.; Sneden, C.; Takenaka, K.; Tsujimoto, T.; Valenti, E.; Yasui, C.; Yoshikawa, T.; Zoccali, M.

    2018-03-01

    We present the first spectroscopic abundance determination of iron, α-elements (Si, Ca, and Ti), and sodium for the Mira variable V1 in the metal-rich globular cluster NGC 5927. We use high-resolution (R ∼ 28,000), high signal-to-noise ratio (∼200) spectra collected with WINERED, a near-infrared (NIR) spectrograph covering simultaneously the wavelength range 0.91–1.35 μm. The effective temperature and the surface gravity at the pulsation phase of the spectroscopic observation were estimated using both optical (V) and NIR time-series photometric data. We found that the Mira is metal-rich ([Fe/H] = ‑0.55 ± 0.15) and moderately α-enhanced ([α/Fe] = 0.15 ± 0.01, σ = 0.2). These values agree quite well with the mean cluster abundances based on high-resolution optical spectra of several cluster red giants available in the literature ([Fe/H] = ‑ 0.47 ± 0.06, [α/Fe] = + 0.24 ± 0.05). We also found a Na abundance of +0.35 ± 0.20 that is higher than the mean cluster abundance based on optical spectra (+0.18 ± 0.13). However, the lack of similar spectra for cluster red giants and that of corrections for departures from local thermodynamical equilibrium prevents us from establishing whether the difference is intrinsic or connected with multiple populations. These findings indicate a strong similarity between optical and NIR metallicity scales in spite of the difference in the experimental equipment, data analysis, and in the adopted spectroscopic diagnostics. Based on spectra collected with the WINERED spectrograph available as a visitor instrument at the ESO New Technology Telescope (NTT), La Silla, Chile (ESO Proposal: 098.D-0878(A), PI: G. Bono).

  4. Transformation of Consciousness: Decoding Conceptual Metaphors in Mira Bai

    Science.gov (United States)

    Amrita; Anisha

    2016-01-01

    Mira Bai, a saint-poet of North India is an important figure in medieval Hindi literature. Her "bhajan"-s (songs) profoundly represent the transforming of consciousness working through conceptual metaphors which fall in the realm of religious poetry wherein target domains are generally abstract. Since, the working of the mind is more…

  5. Infrared properties of Mira-type variables and other cool stars as determined from JHKL photometry

    Energy Technology Data Exchange (ETDEWEB)

    Feast, M W; Robertson, B S.C.; Catchpole, R M; Evans, T L; Glass, I S; Carter, B S [South African Astronomical Observatory, Cape

    1982-11-01

    Extensive infrared photometry of Me(Mira) variables and of C, S, SC and related stars is used to establish two-colour diagrams and period-colour relations. The characteristic areas in these plots occupied by the different classes of objects are delineated. The main aim is to provide a norm with which other stars (e.g. red variables in the Galactic Center and in the Magellanic Clouds and peculiar stars) can be compared. The (J-H) versus period relation offers a method for determining the interstellar reddenings of Me variables. The strong concentration to the longer periods of Miras which are OH masers is probably due primarily to the fact that in the sample surveyed, these stars also have the brightest apparent bolometric magnitudes. Period-amplitude plots are shown for Me variables. The Mira components in symbiotic stars are found to have exceptionally large amplitudes.

  6. 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)

  7. 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

    significance despite a large number of participants. Only one out of two clinical studies looked at further impairment in late stages of AMD and could not find an interrelation with cataract extraction. Thus the available evidence was not sufficient to come to a conclusion on the contribution of cataract extractions to the first manifestation of AMD and to the further impairment in late stages. Discussion: The presentation of the evaluated literature made clear that only a small number of publications dealt with the development of age related macula degeneration in consequence of a cataract extraction. The overall scientific level of evidence of these articles was not very high. Therefore it was not possible to obtain a well-defined conclusion on the effect of a cataract extraction on the development or progression of an age related macula degeneration. Conclusion: Additional well conducted clinical trials, that offer a sufficient number of patients, length of study period and adequate control for confounding variables like age and severity of cataract, are urgently needed. Health economic, ethical, social and legal aspect of the problem could and should be investigated after clarification of the mentioned medical issues.

  8. A seeded ambient temperature ferrite process for treatment of AMD ...

    African Journals Online (AJOL)

    A seeded ambient temperature ferrite process for treatment of AMD waters: magnetite formation in the presence and absence of calcium ions under steady state operation. ... promising for AMD treatment. Keywords: Ferrite process, Magnetite seed, Calcium interference, Acid mine drainage (WaterSA: 2003 29(2): 117-124) ...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. High-angular-resolution stellar imaging with occultations from the Cassini spacecraft - III. Mira

    Science.gov (United States)

    Stewart, Paul N.; Tuthill, Peter G.; Nicholson, Philip D.; Hedman, Matthew M.

    2016-04-01

    We present an analysis of spectral and spatial data of Mira obtained by the Cassini spacecraft, which not only observed the star's spectra over a broad range of near-infrared wavelengths, but was also able to obtain high-resolution spatial information by watching the star pass behind Saturn's rings. The observed spectral range of 1-5 microns reveals the stellar atmosphere in the crucial water-bands which are unavailable to terrestrial observers, and the simultaneous spatial sampling allows the origin of spectral features to be located in the stellar environment. Models are fitted to the data, revealing the spectral and spatial structure of molecular layers surrounding the star. High-resolution imagery is recovered revealing the layered and asymmetric nature of the stellar atmosphere. The observational data set is also used to confront the state-of-the-art cool opacity-sampling dynamic extended atmosphere models of Mira variables through a detailed spectral and spatial comparison, revealing in general a good agreement with some specific departures corresponding to particular spectral features.

  11. 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.)

  12. 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.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  16. 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.)

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Removal of phosphorus from wastewater using ferroxysorb sorption media produced from amd sludge

    Science.gov (United States)

    Sibrell, P.L.; Tucker, T.W.; Kehler, T.; Fletcher, J.W.

    2008-01-01

    Treatment of acid mine drainage (AMD), whether with lime, limestone, caustic or simple aeration, nearly always results in generation of a metal hydroxide sludge. Disposal of the sludge often constitutes a significant fraction of the operating cost for the AMD treatment plant. Research at the USGS - Leetown Science Center has shown that AMD sludge, with its high content of aluminum and iron oxides, has a high affinity of phosphorus (P). Anthropogenic sources of P are associated with eutrophication and degradation of aquatic environments, resulting in anoxic dead zones in certain sensitive waterways. In this paper, we describe a method of converting the AMD sludge from a liability into an asset - Ferroxysorb P removal media - which can be used to remove excess P from wastewater. Three different Ferroxysorb media samples were produced from differing AMD sources and tested for P removal. Adsorption isotherms confirmed that the media had a high sorption capacity for P, as high as 19,000 mg/kg. The technology was demonstrated at an active fish hatchery, where the media remained in service for over three months without stripping or regeneration. Over that period of time, the calculated P removal was 50%, even at a very low influent P concentration of 60 parts per billion. In summary, use of the AMD-derived Ferroxysorb sorption media will reduce AMD treatment costs while at the same time helping to resolve the pressing environmental issue of eutrophication and degradation of sensitive waterways.

  19. Assessing the sustainability of acid mine drainage (AMD) treatment in South Africa.

    Science.gov (United States)

    Masindi, Vhahangwele; Chatzisymeon, Efthalia; Kortidis, Ioannis; Foteinis, Spyros

    2018-04-20

    The environmental sustainability of acid mine drainage (AMD) treatment at semi-industrial scale is examined by means of the life cycle assessment (LCA) methodology. An integrated process which includes magnesite, lime, soda ash and CO 2 bubbling treatment was employed to effectively treat, at semi-industrial scale, AMD originating from a coal mine in South Africa. Economic aspects are also discussed. AMD is a growing problem of emerging concern that cause detrimental effects to the environment and living organisms, including humans, and impose on development, health, access to clean water, thus also affect economic growth and cause social instability. Therefore, sustainable and cost effective treatment methods are required. A life cycle cost analysis (LCCA) revealed the viability of the system, since the levelized cost of AMD treatment can be as low as R112.78/m 3 (€7.60/m 3 or $9.35/m 3 ). Moreover, due to its versatility, the system can be used both at remote locales, at stand-alone mode (e.g. using solar energy), or can treat AMD at industrial scale, thus substantially improving community resilience at local and national level. In terms of environmental sustainability, 29.6 kg CO 2eq are emitted per treated m 3 AMD or its environmental footprint amount to 2.96 Pt/m 3 . South Africa's fossil-fuel depended energy mix and liquid CO 2 consumption were the main environmental hotspots. The total environmental footprint is reduced by 45% and 36% by using solar energy and gaseous CO 2 , respectively. Finally, AMD sludge valorisation, i.e. mineral recovery, can reduce the total environmental footprint by up to 12%. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. The genetics of age-related macular degeneration (AMD)--Novel targets for designing treatment options?

    Science.gov (United States)

    Grassmann, Felix; Fauser, Sascha; Weber, Bernhard H F

    2015-09-01

    Age-related macular degeneration (AMD) is a progressive disease of the central retina and the main cause of legal blindness in industrialized countries. Risk to develop the disease is conferred by both individual as well as genetic factors with the latter being increasingly deciphered over the last decade. Therapeutically, striking advances have been made for the treatment of the neovascular form of late stage AMD while for the late stage atrophic form of the disease, which accounts for almost half of the visually impaired, there is currently no effective therapy on the market. This review highlights our current knowledge on the genetic architecture of early and late stage AMD and explores its potential for the discovery of novel, target-guided treatment options. We reflect on current clinical and experimental therapies for all forms of AMD and specifically note a persisting lack of efficacy for treatment in atrophic AMD. We further explore the current insight in AMD-associated genes and pathways and critically question whether this knowledge is suited to design novel treatment options. Specifically, we point out that known genetic factors associated with AMD govern the risk to develop disease and thus may not play a role in its severity or progression. Treatments based on such knowledge appear appropriate rather for prevention than treatment of manifest disease. As a consequence, future research in AMD needs to be greatly focused on approaches relevant to the patients and their medical needs. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. The value of radiotherapy in the treatment of aged-related macular degeneration (AMD)

    International Nuclear Information System (INIS)

    Zarzycka, M.; Ziolkowska, E.; Slonina, A.

    2007-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in patients older then 65 years. There are two forms of AMD: exudative wet and nonexudative dry. Most of the lesions are not amenable to laser therapy because of their vicinity to the fovea. Earlier studies suggested that radiotherapy may inhibit further loss of visual acuity but following studies rendered contradictory results. In recent years, treatment of benign disease has again attracted the interest of the radiation oncology community in the Western part of the world. Radiotherapy has been given successfully to patients suffering from a wide variety diseases and AMD is one of them. The present article extensively reviews the clinical studies to define the role of radiotherapy in the treatment of AMD. (authors)

  2. 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.

  3. 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...

  4. 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.

  5. 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.

  6. 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 %.

  7. 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)

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

    Science.gov (United States)

    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.

  9. 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

  10. Method for environmental risk analysis (MIRA) revision 2007; Metode for miljoerettet risikoanalyse (MIRA) revisjon 2007

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-04-15

    OLF's instruction manual for carrying out environmental risk analyses provides a united approach and a common framework for environmental risk assessments. This is based on the best information available. The manual implies standardizations of a series of parameters, input data and partial analyses that are included in the environmental risk analysis. Environmental risk analyses carried out according to the MIRA method will thus be comparable between fields and between companies. In this revision an update of the text in accordance with today's practice for environmental risk analyses and prevailing regulations is emphasized. Moreover, method adjustments for especially protected beach habitats have been introduced, as well as a general method for estimating environmental risk concerning fish. Emphasis has also been put on improving environmental risk analysis' possibilities to contribute to a better management of environmental risk in the companies (ml)

  11. The M33 Synoptic Stellar Survey. II. Mira Variables

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Wenlong; Macri, Lucas M. [George P. and Cynthia W. Mitchell Institute for Fundamental Physics and Astronomy, Department of Physics and Astronomy, Texas A and M University, College Station, TX 77843 (United States); He, Shiyuan; Long, James; Huang, Jianhua Z., E-mail: lmacri@tamu.edu [Department of Statistics, Texas A and M University, College Station, TX 77843 (United States)

    2017-04-01

    We present the discovery of 1847 Mira candidates in the Local Group galaxy M33 using a novel semi-parametric periodogram technique coupled with a random forest classifier. The algorithms were applied to ∼2.4 × 10{sup 5} I -band light curves previously obtained by the M33 Synoptic Stellar Survey. We derive preliminary period–luminosity relations at optical, near-infrared, and mid-infrared wavelengths and compare them to the corresponding relations in the Large Magellanic Cloud.

  12. [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

  13. PERIOD ESTIMATION FOR SPARSELY SAMPLED QUASI-PERIODIC LIGHT CURVES APPLIED TO MIRAS

    Energy Technology Data Exchange (ETDEWEB)

    He, Shiyuan; Huang, Jianhua Z.; Long, James [Department of Statistics, Texas A and M University, College Station, TX (United States); Yuan, Wenlong; Macri, Lucas M., E-mail: lmacri@tamu.edu [George P. and Cynthia W. Mitchell Institute for Fundamental Physics and Astronomy, Department of Physics and Astronomy, Texas A and M University, College Station, TX (United States)

    2016-12-01

    We develop a nonlinear semi-parametric Gaussian process model to estimate periods of Miras with sparsely sampled light curves. The model uses a sinusoidal basis for the periodic variation and a Gaussian process for the stochastic changes. We use maximum likelihood to estimate the period and the parameters of the Gaussian process, while integrating out the effects of other nuisance parameters in the model with respect to a suitable prior distribution obtained from earlier studies. Since the likelihood is highly multimodal for period, we implement a hybrid method that applies the quasi-Newton algorithm for Gaussian process parameters and search the period/frequency parameter space over a dense grid. A large-scale, high-fidelity simulation is conducted to mimic the sampling quality of Mira light curves obtained by the M33 Synoptic Stellar Survey. The simulated data set is publicly available and can serve as a testbed for future evaluation of different period estimation methods. The semi-parametric model outperforms an existing algorithm on this simulated test data set as measured by period recovery rate and quality of the resulting period–luminosity relations.

  14. Update on Clinical Trials in Dry Age-related Macular Degeneration

    Science.gov (United States)

    Taskintuna, Ibrahim; Elsayed, M. E. A. Abdalla; Schatz, Patrik

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future. PMID:26957835

  15. MIRAS characterization and monitoring during the SMOS In-Orbit Commissioning Phase

    Science.gov (United States)

    Corbella, I.; Torres, F.; Martin-Neira, M.; Duffo, N.; González-Gambau, V.; Camps, A.; Vall-Llossera, M.

    2009-04-01

    1 Introduction The Microwave Imaging Radiometer with Aperture Synthesis (MIRAS) is the single payload of the Soil Moisture and Ocean Salinity (SMOS) mission. The instrument was completed in early 2007 and thoroughly tested both in anechoic chamber and vacuum thermal chamber during 2007. It was integrated to the platform in early 2008 and re-tested, including compatibility, during 2008. At present, the whole satellite is stowed and waiting to be launched during 2009. In two weeks after launch, the satellite will be in the final orbit with all deployments completed. Then the In-Orbit Commissioning Phase will start, having an estimated duration of 5.5 months. During this phase, the instrument modes of operation will be systematically checked and the calibration parameters will be fully characterized in real conditions. Also, the first brightness temperature images will be obtained in order to assess the overall retrieval procedures including inversion. In the end, the objective of the In-Orbit Commissioning Phase is to provide verification that the payload meets the scientific requirements of the mission. The general design and planning of the In-Orbit Commissioning Phase is given in [1]. This abstract presents the foreseen activities to be performed during this phase by the UPC team. Just after the start of the In-Orbit Commissioning Phase, the instrument will be commanded to perform a sequence of operations oriented at providing a full characterization in terms of calibration parameters. The idea is to reproduce the results obtained during the tests carried out on ground [2]. In particular, the following issues will be covered: Thermal Stability: To provide understanding of both the intra-orbit and inter-orbit temperature variations. The instrument will be continuously operating during a number of orbits while all temperature sensors being monitored. Electrical Stability: To re-compute all internal calibration parameters (gains, offsets, receiver noise temperatures

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

    Directory of Open Access Journals (Sweden)

    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

  17. Vision Rehabilitation is Part of AMD Care

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. IR photometry results and dust envelope model for symbiotic Mira star candidate V 335 Vul

    Science.gov (United States)

    Bogdanov, M. B.; Taranova, O. G.; Shenavrin, V. I.

    2017-10-01

    We present the results of JHKLM-photometry for the symbiotic Mira star candidate V 335 Vul. Based on the average flux data, supplemented by IRAS, MSX, AKARI, and WISE mid-IR observations, we calculated a model of a spherically symmetric dust envelope of the star, made up of amorphous carbon and silicon carbide particles. The optical depth of the envelope in the visible range with a dust temperature at the inner boundary of T 1 = 1300 K is τ V = 0.58. For an envelope expansion velocity of 26.5 km s-1, the estimated mass loss rate is equal to 5.7 × 10-7 M ⊙ yr-1.

  1. 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...

  2. Revealing the importance of meristems and roots for the development of hypersensitive responses and full foliar resistance to Phytophthora infestans in the resistant potato cultivar Sarpo Mira

    DEFF Research Database (Denmark)

    Orlowska, Elzbieta Zofia; Basile, Alessio; Kandzia, Izabela

    2012-01-01

    The defence responses of potato against Phytophthora infestans were studied using the highly resistant Sarpo Mira cultivar. The effects of plant integrity, meristems, and roots on the hypersensitive response (HR), plant resistance, and the regulation of PR genes were analysed. Sarpo Mira shoots a...

  3. 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)

  4. 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)

  5. 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.

  6. [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

  7. 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

    Directory of Open Access Journals (Sweden)

    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

  8. 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...

  9. First Resolved Images of the Mira AB Symbiotic Binary at Centimeter Wavelengths

    OpenAIRE

    Matthews, Lynn D.; Karovska, Margarita

    2005-01-01

    We report the first spatially resolved radio continuum measurements of the Mira AB symbiotic binary system, based on observations obtained with the Very Large Array (VLA). This is the first time that a symbiotic binary has been resolved unambiguously at centimeter wavelengths. We describe the results of VLA monitoring of both stars over a ten month period, together with constraints on their individual spectral energy distributions, variability, and radio emission mechanisms. The emission from...

  10. Variable dust obscuration in the symbiotic Mira and very slow Nova, HM Sge

    International Nuclear Information System (INIS)

    Munari, U.; Whitelock, P.A.

    1989-01-01

    New infrared photometry is presented for the symbiotic Mira, HM Sge. Using this and published data a pulsation period of 527 day is derived. In addition to the normal pulsational modulation, the light curve for HM Sge has shown a distinct fading and reddening, starting in 1985. This is interpreted as a dust-obscuration event, and its possible association with the binary orbit is discussed. (author)

  11. 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

  12. 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)

  13. 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...

  14. 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...

  15. 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.

  16. 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

  17. The Role of mf-ERG in the Diagnosis and Treatment of Age-Related Macular Degeneration: Electrophysiological Features of AMD.

    Science.gov (United States)

    Moschos, Marilita M; Nitoda, Eirini

    2018-01-01

    Age-related macular cegeneration (AMD) is the leading cause of visual dysfunction worldwide, affecting 9-25% of individuals between 65 and 75 years old. We have reviewed the published articles investigating the role of multifocal electroretinogram (mf-ERG) in the diagnosis and treatment of AMD. Visual evoked potentials have revealed decreased amplitudes and higher latencies in patients with AMD, while the degeneration of photoreceptors and abnormalities of retinal pigment epithelium can be identified by electro-oculogram recordings. Moreover, ERG can detect the functional abnormalities observed in AMD and evaluate each therapeutic approach. The record of local electrophysiological responses coming from different retinal areas can be accurately performed by mfERG. The accuracy of mfERG in detecting the degeneration of photoreceptors, as well the disturbances of macular function, could be useful both in the early diagnosis of AMD and the assessment of treatment efficacy.

  18. 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...

  19. Method for environmental risk analysis (MIRA) revision 2007

    International Nuclear Information System (INIS)

    2007-04-01

    OLF's instruction manual for carrying out environmental risk analyses provides a united approach and a common framework for environmental risk assessments. This is based on the best information available. The manual implies standardizations of a series of parameters, input data and partial analyses that are included in the environmental risk analysis. Environmental risk analyses carried out according to the MIRA method will thus be comparable between fields and between companies. In this revision an update of the text in accordance with today's practice for environmental risk analyses and prevailing regulations is emphasized. Moreover, method adjustments for especially protected beach habitats have been introduced, as well as a general method for estimating environmental risk concerning fish. Emphasis has also been put on improving environmental risk analysis' possibilities to contribute to a better management of environmental risk in the companies (ml)

  20. DEMONSTRATION OF AN INTEGRATED, PASSIVE BIOLOGICAL TREATMENT PROCESS FOR AMD

    Science.gov (United States)

    An innovative, cost-effective, biological treatment process has been designed by MSE Technology Applications, Inc. to treat acid mine drainage (AMD). A pilot-scale demonstration is being conducted under the Mine Waste Technology Program using water flowing from an abandoned mine ...

  1. Arsenic in an alkaline AMD treatment sludge: Characterization and stability under prolonged anoxic conditions

    International Nuclear Information System (INIS)

    Beauchemin, Suzanne; Fiset, Jean-Francois; Poirier, Glenn; Ablett, James

    2010-01-01

    Lime treatment of acid mine drainage (AMD) generates large volumes of neutralization sludge that are often stored under water covers. The sludge consists mainly of calcite, gypsum and a widespread ferrihydrite-like Fe phase with several associated species of metal(loid) contaminants. The long-term stability of metal(loid)s in this chemically ill-defined material remains unknown. In this study, the stability and speciation of As in AMD sludge subjected to prolonged anoxic conditions is determined. The total As concentration in the sludge is 300 mg kg -1 . In the laboratory, three distinct water cover treatments were imposed on the sludge to induce different redox conditions (100%N 2 , 100%N 2 + glucose, 95%N 2 :5%H 2 ). These treatments were compared against a control of oxidized, water-saturated sludge. Electron micro-probe (EMP) analysis and spatially resolved synchrotron X-ray fluorescence (SXRF) results indicate that As is dominantly associated with Fe in the sludge. In all treatments and throughout the experiment, measured concentrations of dissolved As were less than 5 μg L -1 . Dissolved Mn concentration in the N 2 + glucose treatment increased significantly compared to other treatments. Manganese and As K-edge X-ray absorption near edge structure spectroscopy (XANES) analyses showed that Mn was the redox-active element in the solid-phase, while As was stable. Arsenic(V) was still the dominant species in all water-covered sludges after 9 months of anoxic treatments. In contrast, Mn(IV) in the original sludge was partially reduced into Mn(II) in all water-covered sludges. The effect was most pronounced in the N 2 + glucose treatment, suggesting microbial reduction. Micro-scale SXRF and XANES analysis of the treated sludge showed that Mn(II) accumulated in areas already enriched in Fe and As. Overall, the study shows that AMD sludges remain stable under prolonged anoxic conditions. External sources of chemical reductants or soluble C were needed to induce

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

    Directory of Open Access Journals (Sweden)

    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

  3. Effect of In Vitro Exposure of Corticosteroid Drugs, Conventionally Used in AMD Treatment, on Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Raffaele Nuzzi

    2012-01-01

    Full Text Available Age-related macular degeneration (AMD is a leading cause of legal blindness in individuals over 60 years of age, characterized by the dysfunction of retinal pigmented epithelium cells, specifically in the macular area. Despite several treatment options, AMD therapy remains difficult, especially for exudative AMD. Multipotent mesenchymal stem cells (MSCs, with great plasticity and immunomodulant properties, are a promising cell source for cellular therapy and tissue engineering. We evaluated the effects of steroid drugs, often used to treat AMD, in association with MSCs, in view of a possible application together to treat AMD. Morphology, viability, growth kinetics, and immunophenotype were evaluated on healthy donors’ MSCs, treated with triamcinolone acetonide, alcohol-free triamcinolone acetonide, micronized intravitreal triamcinolone and dexamethasone at different concentrations, and in a human retinal pigment epithelial cell line supernatant (ARPE-19. The morphological analysis of MSCs in their standard medium showed a negative correlation with drug concentrations, due to the numerous crystals. Dexamethasone was the least toxic corticosteroid used in this study. ARPE-19 seemed to help cells preserve the typical MSC morphology. In conclusion, this in vitro study demonstrated that high doses of corticosteroid drugs have a negative effect on MSCs, reduced in the presence of a conditioned media.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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...

  6. 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...

  7. Computer program of iodine removal in the LWR containment vessel under LOCA conditions, MIRA-PB

    International Nuclear Information System (INIS)

    Nishio, Gunji; Tanaka, Mitsugu; Tamura, Tomohiko.

    1978-03-01

    LWR plants have a containment system for reactor safety consisting of spray and air cleaning filter. R.L.Ritzman of Battele Columbus Lab. developed computer code MIRAP/MIRAB for predicting iodine removal by containment system for PWR and BWR; which has some problem, however. The computer code MIRA-PB prepared by the authors is a modification of MIRAP/MIRAB. (auth.)

  8. A new approach to the analysis of Mira light curves

    International Nuclear Information System (INIS)

    Mennessier, M.O.; Barthes, D.; Mattei, J.A.

    1990-01-01

    Two different but complementary methods for predicting Mira luminosities are presented. One method is derived from a Fourier analysis, it requires performing deconvolution, and its results are not certain due to the inherent instability of deconvolution problems. The other method is a learning method utilizing artificial intelligence techniques where a light curve is presented as an ordered sequence of pseudocycles, and rules are learned by linking the characteristics of several consecutive pseudocycles to one characteristic of the future cycle. It is observed that agreement between these methods is obtainable when it is possible to eliminate similar false frequencies from the preliminary power spectrum and to improve the degree of confidence in the rules

  9. The use of collaborative digital platforms in the perspective of shared administration. The MiraMap project in Turin

    Directory of Open Access Journals (Sweden)

    Cristina Coscia

    2016-06-01

    Full Text Available The paper intends to illustrate an innovative approach to urban planning and shared Administration based on the use of collaborative digital platforms involving the Public Administration / citizen. This perspective is expressed in the MiraMap pilot project in Turin, in the District of Mirafiori Sud, which has been drawn up by a research group of the Politecnico di Torino. The project implements and develops a previous experience carried out in 2013 (Crowdmapping Mirafiori Sud, the main purpose of which was to determine whether the use of ICT could generate and support processes of social inclusion. Through the reading of the MiraMap process, of its objectives, of the methodology adopted, of its phases and lines of action, are highlighted the interdisciplinary and technical reasoning relative to: the structuring of relations with the institutions, in particular with the Public Administration, in the processes of planning and management of public space; the triggering of the processes of inclusion, participation and civic engagement; the identification of contributions that these trials can generate in the construction of a renewed urban governance. Lastly, this contribution outlines a possible methodology for monitoring and evaluation of ex-post impact, based on Community Impact Assessment/Evaluation (CIA/CIE, that evaluates in a descriptive manner the impacts - monetary and non-monetary - that have derived from the project in relation to the various actors involved. The use of ICT can foster the process of transparency and strengthen the accountability of the Public Administration, provided that the technology is an enabling factor and one of exclusion. The detailed analysis of the case provides ideas for reflection on this innovative approach: the citizen/PA relationship can contribute in the medium-long term to conveying positive socio-economic impacts on the territory, making the citizen more informed and involved and the Administration more

  10. 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.

  11. 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)

  12. 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...

  13. 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.

  14. Reconstrucción de objetos por perfilometría interferométrica con sistema de posicionamiento de mira periódica

    Directory of Open Access Journals (Sweden)

    Néstor Alonso Arias-Hernández

    2015-01-01

    Full Text Available En este trabajo se presenta un método para extraer información 3D usando un microscopio interferométrico, sin la necesidad de utilizar un dispositivo transductor piezoeléctrico (PZT, por su siglas en inglés. En lugar de ello se utiliza un sistema de posicionamiento que aprovecha la sensibilidad a la fase de una mira periódica, que es registrada mediante el uso de un sistema de visión. El procesamiento de la mira permite calcular la distancia relativa entre el objetivo Mirau y el objeto. Reconstrucciones topográficas de algunas décimas de milímetros fueron calculadas con una precisión de aproximadamente 28 nanómetros. Se presenta un análisis teórico y algunos resultados experimentales.

  15. Low vision depression prevention trial in age-related macular degeneration: a randomized clinical trial.

    Science.gov (United States)

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Massof, Robert W; Leiby, Benjamin E; Ho, Allen C; Tasman, William S

    2014-11-01

    To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD). Single-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months. Patients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188). Before randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. The Diagnostic and Statistical Manual IV defined depressive disorder based on the Patient Health Questionnaire-9 (primary outcome), Activities Inventory, National Eye Institute Vision Function Questionnaire-25 plus Supplement (NEI-VFQ), and NEI-VFQ quality of life (secondary outcomes). At 4 months, 11 BA+LVR subjects (12.6%) and 18 ST+LVR subjects (23.4%) developed a depressive disorder (relative risk [RR], 0.54; 95% CI, 0.27-1.06; P = 0.067). In planned adjusted analyses the RR was 0.51 (95% CI, 0.27-0.98; P = 0.04). A mediational analysis suggested that BA+LVR prevented depression to the extent that it enabled subjects to remain socially engaged. In addition, BA+LVR was associated with greater improvements in functional vision than ST+LVR, although there was no significant between-group difference. There was no significant change or between-group difference in quality of life. An integrated mental health and low vision intervention halved the incidence of depressive disorders relative to standard outpatient LVR in patients with AMD. As the population ages, the number of persons with AMD and the adverse effects of comorbid depression will increase. Promoting interactions between ophthalmology, optometry

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

    Science.gov (United States)

    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.

  17. 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.

  18. MIRA: internet, democracy and participation. New technologies and re-connection of the citizen

    Directory of Open Access Journals (Sweden)

    Leydi Johanna Posada Amaya

    2011-06-01

    Full Text Available The deficit in the construction and consolidation of the Democratic Participation of citizens and, therefore, its continuos and constant distancing of the politics and politic affairs has led public institutions and political parties to own the tools that the Technologies of Communication offer with the main purpose of re-connecting the electorate with their representatives. The case study of the Movimiento Independiente de Renovación Absoluta (MIRA deals with identifying the type of participation and democracy that has constituted thanks to the tools offered by the Information and Comunication Tecnologies (TIC available in its web page.

  19. Plantas, suelos y paisajes: ordenamientos de la naturaleza por los indígenas Miraña de la Amazonía colombiana Plants, soils and landscapes: sorting of nature by the Miraña Indians of Colombian Amazon

    Directory of Open Access Journals (Sweden)

    Mauricio Sánchez

    2007-01-01

    Full Text Available Con base en información obtenida sobre los nombres de todas las plantas con DAP > 2.5 cm (Diámetro a la Altura del Pecho, medido a una altura de 1.3 m dentro de 30 parcelas de 0.1 ha cada una, y sobre los suelos, la vegetación y el paisaje a lo largo de 8 transectos (entre 2 y 5 km de longitud cada uno, se describen los aspectos más importantes sobre la taxonomía botánica y el ordenamiento o jerarquización del medio ambiente desde la perspectiva de los Indígenas Miraña de la Amazonía central colombiana. A pesar de la pérdida cultural, algunos pocos ancianos guardan como parte de su tradición oral, los elementos básicos de un sistema complejo de conocimiento de su ambiente natural. Se detectó un alto grado de conocimiento sobre las especies vegetales silvestres, la existencia de sistemas nomenclaturales para éstas y para los suelos, y un reconocimiento organizado de paisajes fisiográficos y tipos de vegetación.We describe the most important aspects of Miraña's plant taxonomy, and landscape categorization. Data about plants' names (in 30 plots of 0.1 ha, was gathered from all individual plants with DBH > 2.5 cm (Diameter at Breast High, or 1.3 m above ground, and data about soils, forest types and landscapes was (in 8 transects of 2-5 km long each was gathered from 8 transects of 2-5 km long each. In spite of cultural lost, complex knowledge about natural environment classification, it is present into the oral tradition keep in some elders' mind. We detected a high level of knowledge about wild plants, the presence of nomenclatural systems for plants and soil types, and organized landscapes and forest types systems.

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

    Science.gov (United States)

    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.

  1. A randomised controlled trial of intravenous zoledronic acid in malignant pleural disease: a proof of principle pilot study.

    Science.gov (United States)

    Clive, Amelia O; Hooper, Clare E; Edey, Anthony J; Morley, Anna J; Zahan-Evans, Natalie; Hall, David; Lyburn, Iain; White, Paul; Braybrooke, Jeremy P; Sequeiros, Iara; Lyen, Stephen M; Milton, Tim; Kahan, Brennan C; Maskell, Nick A

    2015-01-01

    Animal studies have shown Zoledronic Acid (ZA) may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD). We performed a pilot study to evaluate its effects in humans. We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1) to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS) score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC) on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) from randomisation to week 5. Multiple secondary endpoints were also evaluated. Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline). At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD) 4.16 (95%CI -4.7 to 13.0)) or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3). Two of nine (22%) in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo). There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9)), side effects or serious adverse event rates. This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further. UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com.

  2. A randomised controlled trial of intravenous zoledronic acid in malignant pleural disease: a proof of principle pilot study.

    Directory of Open Access Journals (Sweden)

    Amelia O Clive

    Full Text Available Animal studies have shown Zoledronic Acid (ZA may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD. We performed a pilot study to evaluate its effects in humans.We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1 to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI from randomisation to week 5. Multiple secondary endpoints were also evaluated.Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline. At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD 4.16 (95%CI -4.7 to 13.0 or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3. Two of nine (22% in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo. There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9, side effects or serious adverse event rates.This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further.UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com.

  3. 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

  4. 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...

  5. 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...

  6. 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

  7. 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.

  8. 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

  9. 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)

  10. 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.

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

    Science.gov (United States)

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

    2016-12-20

    Study of age related macular degeneration (AMD) has been hampered by lack of human models that represent the complexity of the disease. Here we have developed a human in vitro disease model of AMD to investigate the underlying AMD disease mechanisms. Generation of iPSCs from retinal pigment epithelium (RPE) of AMD donors, age-matched normal donors, skin fibroblasts of a dry AMD patient, and differentiation of iPSCs into RPE (AMD RPE-iPSC-RPE, normal RPE-iPSC-RPE and AMD Skin-iPSC-RPE, respectively). Immunostaining, cell viability assay and reactive oxygen species (ROS) production under oxidative stress conditions, electron microscopy (EM) imaging, ATP production and glycogen concentration assays, quantitative real time PCR, western blot, karyotyping. The AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE present functional impairment and exhibit distinct disease phenotypes compared to RPE-iPSC-RPE generated from normal donors (Normal RPE-iPSC-RPE). The AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE show increased susceptibility to oxidative stress and produced higher levels of reactive oxygen species (ROS) under stress in accordance with recent reports. The susceptibility to oxidative stress-induced cell death in AMD RPE-iPSC-RPE and Skin-iPSC-RPE was consistent with inability of the AMD RPE-iPSC-RPE and Skin-iPSC-RPE to increase SOD2 expression under oxidative stress. Phenotypic analysis revealed disintegrated mitochondria, accumulation of autophagosomes and lipid droplets in AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE. Mitochondrial activity was significantly lower in AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE compared to normal cells and glycogen concentration was significantly increased in the diseased cells. Furthermore, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a regulator of mitochondrial biogenesis and function was repressed, and lower expression levels of NAD-dependent deacetylase sirtuin1 (SIRT1) were found in AMD RPE-iPSC-RPE and AMD Skin

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. 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)

  16. 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)

  17. 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

  18. Archaeology of the Afro-Ecuadorians in La Concepción, Ancestral Territory of the Chota-Mira Valley (Carchi-Ecuador)

    OpenAIRE

    Balanzategui , Daniela Catalina

    2017-01-01

    Historical Archaeology of the African Diaspora in the Americas urges for interdisciplinary, collaborative, and intercultural approaches to shed light on how the material culture reflects conditions of enslavement and racialization, but also process of resistance and historical reparation. This investigation is organized in five articles connected around the topic of the cultural construction of the African Diaspora identities in the Afro-Ecuadorian Ancestral Territory of the Chota-Mira Valley...

  19. 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.

  20. 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

  1. Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration.

    Science.gov (United States)

    Evans, Jennifer R; Lawrenson, John G

    2017-07-30

    available for a total of 55,614 participants. There was evidence that vitamin E supplements do not prevent the development of any AMD (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.90 to 1.06; high-certainty evidence), and may slightly increase the risk of late AMD (RR 1.22, 95% CI 0.89 to 1.67; moderate-certainty evidence) compared with placebo. Only one study (941 participants) reported data separately for neovascular AMD and geographic atrophy. There were 10 cases of neovascular AMD (RR 3.62, 95% CI 0.77 to 16.95; very low-certainty evidence), and four cases of geographic atrophy (RR 2.71, 95% CI 0.28 to 26.0; very low-certainty evidence). Two trials reported similar numbers of adverse events in the vitamin E and placebo groups. Another trial reported excess of haemorrhagic strokes in the vitamin E group (39 versus 23 events, hazard ratio 1.74, 95% CI 1.04 to 2.91, low-certainty evidence).Two studies reported the comparison of beta-carotene with placebo. These studies took place in Finland and the USA. Both trials enrolled men only. Average treatment and follow-up duration was 6 years and 12 years. Data were available for a total of 22,083 participants. There was evidence that beta-carotene supplements did not prevent any AMD (RR 1.00, 95% CI 0.88 to 1.14; high-certainty evidence) nor have an important effect on late AMD (RR 0.90, 95% CI 0.65 to 1.24; moderate-certainty evidence). Only one study (941 participants) reported data separately for neovascular AMD and geographic atrophy. There were 10 cases of neovascular AMD (RR 0.61, 95% CI 0.17 to 2.15; very low-certainty evidence) and 4 cases of geographic atrophy (RR 0.31 95% CI 0.03 to 2.93; very low-certainty evidence). Beta-carotene was associated with increased risk of lung cancer in people who smoked.One study reported the comparison of vitamin C with placebo, and multivitamin (Centrum Silver) versus placebo. This was a study in men in the USA with average treatment duration and follow-up of 8 years for

  2. Improved Adherence to Vision Self-monitoring with the Vision and Memory Stimulating (VMS) Journal for Non-neovascular Age-related Macular Degeneration during a Randomized Controlled Trial

    OpenAIRE

    Bittner, Ava K; Torr-Brown, Sheryl; Arnold, Ellen; Nwankwo, Antonia; Beaton, Patricia; Rampat, Radhika; Dagnelie, Gislin; Roser, Mark

    2014-01-01

    Objective An educational, interactive journal [Vision and Memory Stimulating (VMS) journal] was developed to boost patient confidence and promote long-term adherence with weekly vision self-monitoring in age-related macular degeneration (AMD) patients at risk for vision loss from new-onset neovascularization. Methods In a multicenter randomized controlled trial, 198 subjects with intermediate stage, non-neovascular AMD received the VMS journal or followed usual care (e.g. their doctor’s instr...

  3. 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.

  4. 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

  5. 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.

  6. A Mid-Infrared Study of the Circumstellar Dust Composition and Phase Behavior of Oxygen-rich Mira Variables

    Science.gov (United States)

    Guth, Tina

    2017-08-01

    identical data reduction process was applied to the dataset. To determine the dust composition in the circumstellar environment, the publically available 1-D radiative transfer modeling code, DUSTY (Ivezic et al., 1999), was implemented with key physical parameters, such as stellar temperature, inner dust boundary temperature, and optical depth, kept the same for all stars to help elucidate changes with phase. Because a simple blackbody fit does not adequately characterize the dust composition in the circumstellar environment, the 1-D hydrostatic, spherical local thermodynamic equilibrium (LTE) model grid code called MARCS was used (Gustafsson et al., 2008), which includes the molecular and atomic opacities that are characteristic of AGB spectra. MARCS only extends to a wavelength range of 20 micron, hence a power-law function is combined with the spectral energy distribution (SED) from MARCS to provide a reasonable source function for input in DUSTY. For the oxygen-rich Miras investigated, there are clear indications that the dust composition changes with phase over fairly short time scales, and that there are trends in the required dust species that correlate with the SE (silicate emission) classification (Sloan and Price, 1998) of the star. Iron oxide (FeO) is present in the dust composition of all stars, while aluminum oxide (Al2O3) shifts from being porous to compact for SE1-3 to SE7-8, respectively. The dust species pyroxene is only present in SE7-8 classes to account for a broad emission feature centered at 18 micron. The "13 micron feature", which is a well-known yet unidentified feature in the astronomical community is only present in SE1-4 classes, while completely absent in the other SE classes. In this work, the focus was not on identifying the 13 micron feature, though several constituents can be ruled out. Other dust constituents, such as water ice and sulfides, were considered but the shapes of their opacity curves do not fit with the observed features in the

  7. 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.

  8. 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...

  9. Effect of Dietary Supplementation With Lutein, Zeaxanthin, and ω-3 on Macular Pigment: A Randomized Clinical Trial.

    Science.gov (United States)

    Korobelnik, Jean-François; Rougier, Marie-Bénédicte; Delyfer, Marie-Noëlle; Bron, Alain; Merle, Bénédicte M J; Savel, Hélène; Chêne, Geneviève; Delcourt, Cécile; Creuzot-Garcher, Catherine

    2017-11-01

    Nutritional uptake of lutein, zeaxanthin, and ω-3 polyunsaturated fatty acids may increase macular pigment optical density (MPOD) and thereby protect against the development of age-related macular degeneration (AMD). To estimate the efficiency of dietary supplementation containing lutein, zeaxanthin, ω-3 polyunsaturated fatty acids, and vitamins to increase the density of macular pigment in first-generation offspring of parents with neovascular AMD. This study was a randomized clinical trial (Lutein Influence on Macula of Persons Issued From AMD Parents [LIMPIA]) with a 6-month treatment period, followed by a 6-month follow-up period. Analyses were based on the intent-to-treat principle. The setting was 2 university hospitals in France (at Bordeaux and Dijon) from January 2011 (first participant first visit) to February 2013 (last participant last visit). The analysis was conducted from January to November 2016. Participants were 120 individuals free of any retinal ocular disease. They were first-generation offspring of parents with neovascular AMD. Participants were randomized in a 1:1 ratio to receive either 2 daily dietary supplementation capsules or placebo for 6 months. The primary assessment criterion was the evolution of MPOD after 6 months of supplementation (value of both eligible eyes) measured using the modified MPD-Visucam 200 (Carl Zeiss Meditec) and the modified Heidelberg Retina Angiograph (Heidelberg Engineering) (HRA) at 0.98° eccentricity. The statistical analysis was adjusted for hospital and for risk factors. Overall, 120 participants (60 in each group) were included, and 239 eyes were analyzed (119 in the lutein plus zeaxanthin [L + Z] group and 120 in the placebo group). Their mean (SD) age was 56.7 (6.6) years, and 71.7% (n = 86) were female. A statistically significant increase in plasma lutein and zeaxanthin was shown in the L + Z group after 3 months and 6 months of treatment compared with the placebo group. However, the

  10. 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/

  11. 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.

  12. CARBON AND OXYGEN ISOTOPIC RATIOS FOR NEARBY MIRAS

    Energy Technology Data Exchange (ETDEWEB)

    Hinkle, Kenneth H. [National Optical Astronomy Observatory P.O. Box 26732, Tucson, AZ 85726 (United States); Lebzelter, Thomas [Department of Astrophysics, University of Vienna Türkenschanzstrasse 17, A-1180 Vienna (Austria); Straniero, Oscar, E-mail: khinkle@noao.edu, E-mail: thomas.lebzelter@univie.ac.at, E-mail: straniero@oa-teramo.inaf.it [INAF, Osservatorio Astronomico di Collurania I-64100 Teramo (Italy)

    2016-07-01

    Carbon and oxygen isotopic ratios are reported for a sample of 46 Mira and SRa-type variable asymptotic giant branch (AGB) stars. Vibration–rotation first and second-overtone CO lines in 1.5–2.5 μ m spectra were measured to derive isotopic ratios for {sup 12}C/{sup 13}C, {sup 16}O/{sup 17}O, and {sup 16}O/{sup 18}O. Comparisons with previous measurements for individual stars and with various samples of evolved stars, as available in the extant literature, are discussed. Models for solar composition AGB stars of different initial masses are used to interpret our results. We find that the majority of M-stars have main sequence masses ≤2 M {sub ⊙} and have not experienced sizable third dredge-up (TDU) episodes. The progenitors of the four S-type stars in our sample are slightly more massive. Of the six C-stars in the sample three have clear evidence relating their origin to the occurrence of TDU. Comparisons with O-rich presolar grains from AGB stars that lived before the formation of the solar system reveal variations in the interstellar medium chemical composition. The present generation of low-mass AGB stars, as represented by our sample of long period variables (LPVs), shows a large spread of {sup 16}O/{sup 17}O ratios, similar to that of group 1 presolar grains and in agreement with theoretical expectations for the composition of mass 1.2–2 M {sub ⊙} stars after the first dredge-up. In contrast, the {sup 16}O/{sup 18}O ratios of present-day LPVs are definitely smaller than those of group 1 grains. This is most probably a consequence of the the decrease with time of the {sup 16}O/{sup 18}O ratio in the interstellar medium due to the chemical evolution of the Milky Way. One star in our sample has an O composition similar to that of group 2 presolar grains originating in an AGB star undergoing extra-mixing. This may indicate that the extra-mixing process is hampered at high metallicity, or, equivalently, favored at low metallicity. Similarly to O

  13. Low Vision Depression Prevention Trial in Age-Related Macular Degeneration

    Science.gov (United States)

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Massof, Robert W.; Leiby, Benjamin E.; Ho, Allen C.; Tasman, William S.

    2014-01-01

    Purpose To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD). Design Single-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months. Participants Patients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188). Interventions Before randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. Main Outcome Measures The Diagnostic and Statistical Manual IV defined depressive disorder based on the Patient Health Questionnaire-9 (primary outcome), Activities Inventory, National Eye Institute Vision Function Questionnaire–25 plus Supplement (NEI-VFQ), and NEI-VFQ quality of life (secondary outcomes). Results At 4 months, 11 BA+LVR subjects (12.6%) and 18 ST+LVR subjects (23.4%) developed a depressive disorder (relative risk [RR], 0.54; 95% CI, 0.27–1.06; P = 0.067). In planned adjusted analyses the RR was 0.51 (95% CI, 0.27–0.98; P = 0.04). A mediational analysis suggested that BA+LVR prevented depression to the extent that it enabled subjects to remain socially engaged. In addition, BA+LVR was associated with greater improvements in functional vision than ST+LVR, although there was no significant between-group difference. There was no significant change or between-group difference in quality of life. Conclusions An integrated mental health and low vision intervention halved the incidence of depressive disorders relative to standard outpatient LVR in patients with AMD. As the population ages, the number of persons with AMD and the adverse effects of comorbid

  14. 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.

  15. 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.

  16. Incidence of choroidal neovascularization in the fellow eye in the comparison of age-related macular degeneration treatments trials.

    Science.gov (United States)

    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

  17. 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.

  18. 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)

  19. Superoxide Dismutase1 Levels in North Indian Population with Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Akshay Anand

    2013-01-01

    Full Text Available Aim. The aim of the study was to estimate the levels of superoxide dismutase1 (SOD1 in patients of age-related macular degeneration (AMD and examine the role of oxidative stress, smoking, hypertension, and other factors involved in the pathogenesis of AMD. Methods. 115 AMD patients and 61 healthy controls were recruited for this study. Serum SOD1 levels were determined by ELISA and were correlated to various risk factors. Logistic regression model of authenticity, by considering SOD1 as independent variable, has been developed along with ROC curve. Results. The SOD1 levels were significantly higher in AMD patients as compared to those of the controls. The difference was not significant for wet and dry AMD. However, the difference was significant between wet AMD subtypes. Nonsignificance of the Hosmer-Lemeshow goodness of fit statistic (χ2=10.516, df=8, P=0.231 indicates the appropriateness of logistic regression model to predict AMD. Conclusion. Oxidative stress in AMD patients may mount compensatory response resulting in increased levels of SOD1 in AMD patients. To predict the risk of AMD on the basis of SOD1, a logistic regression model shows authenticity of 78%, and area under the ROC curve (0.827, P=.0001 with less standard error of 0.033 coupled with 95% confidence interval of 0.762–0.891 further validates the model.

  20. Complement pathway biomarkers and age-related macular degeneration

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2016-01-01

    In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

  1. Association of HTRA1 polymorphism and bilaterality in advanced age-related macular degeneration.

    Science.gov (United States)

    Chen, Haoyu; Yang, Zhenglin; Gibbs, Daniel; Yang, Xian; Hau, Vincent; Zhao, Peiquan; Ma, Xiang; Zeng, Jiexi; Luo, Ling; Pearson, Erik; Constantine, Ryan; Kaminoh, Yuuki; Harmon, Jennifer; Tong, Zongzhong; Stratton, Charity A; Cameron, D Joshua; Tang, Shibo; Zhang, Kang

    2008-02-01

    Single nucleotide polymorphism (SNP), rs11200638, in the promoter of HTRA1 has recently been shown to increase the risk for AMD. In order to investigate the association of this HTRA1 polymorphism and the bilaterality of AMD, we genotyped rs11200638 in control, unilateral, and bilateral advanced AMD patients. The A allele for SNP rs11200638 in HTRA1, was significantly more prevalent in bilateral wet AMD and GA patients than in unilateral groups (p=.02 and p=.03, respectively). The homozygote odds ratios of bilateral wet AMD and GA are significantly greater than those seen in unilateral groups (twofold and threefold increase, respectively). This finding is consistent with the role of HTRA1 in AMD pathogenesis and will help aid in the clinical management and prognosis of AMD patients.

  2. 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...

  3. 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

  4. 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)

  5. HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration.

    Science.gov (United States)

    Cameron, D Joshua; Yang, Zhenglin; Gibbs, Daniel; Chen, Haoyu; Kaminoh, Yuuki; Jorgensen, Adam; Zeng, Jiexi; Luo, Ling; Brinton, Eric; Brinton, Gregory; Brand, John M; Bernstein, Paul S; Zabriskie, Norman A; Tang, Shibo; Constantine, Ryan; Tong, Zongzhong; Zhang, Kang

    2007-05-02

    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 (GA) and choroidal neovascularization (wet AMD), represent two types of degenerative processes in the macula that lead to loss of central vision. Soft confluent drusen, characterized by deposits in macula without visual loss are considered a precursor of advanced AMD. A single nucleotide polymorphism, rs11200638, in the promoter of HTRA1 has been shown to increases the risk for wet AMD. However, its impact on soft confluent drusen and GA or the relationship between them is unclear. To better understand the role the HTRA1 polymorphism plays in AMD subtypes, we genotyped an expanded Utah population with 658 patients having advanced AMD or soft confluent drusen and 294 normal controls and found that the rs11200638 was significantly associated with GA. This association remains significant conditional on LOC387715 rs10490924. In addition, rs11200638 was significantly associated with soft confluent drusen, which are strongly immunolabeled with HTRA1 antibody in an AMD eye with GA similar to wet AMD. Two-locus analyses were performed for CFH Y402H variant at 1q31 and the HTRA1 polymorphism. Together CFH and HTRA1 risk variants increase the odds of having AMD by more than 40 times. These findings expand the role of HTRA1 in AMD. Understanding the underlying molecular mechanism will provide an important insight in pathogenesis of AMD.

  6. 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.

  7. Type 1 Diabetes TrialNet--an international collaborative clinical trials network.

    Science.gov (United States)

    Skyler, Jay S; Greenbaum, Carla J; Lachin, John M; Leschek, Ellen; Rafkin-Mervis, Lisa; Savage, Peter; Spain, Lisa

    2008-12-01

    Type 1 Diabetes TrialNet is an international consortium of clinical research centers aimed at the prevention or delay of type 1 diabetes (T1D). The fundamental goal of TrialNet is to counter the T1D disease process by immune modulation and/or enhancement of beta cell proliferation and regeneration. To achieve this goal, TrialNet researchers are working to better understand the natural history of the disease, to identify persons at risk, and to clinically evaluate novel therapies that balance potential risks and benefits. The particular focus is on studies of preventive measures. In addition, TrialNet evaluates therapies in individuals with newly diagnosed T1D with preserved beta cell function to help determine the risk/benefit profile and gain an initial assessment of potential efficacy in preservation of beta cell function, so that promising agents can be studied in prevention trials. In addition, TrialNet evaluates methodologies that enhance the conduct of its clinical trials, which includes tests of outcome assessment methodology, the evaluation of surrogate markers, and mechanistic studies laying the foundation for future clinical trials.

  8. 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.

  9. Effect of a Multicomponent Behavioral Intervention in Adults Impaired by Psychological Distress in a Conflict-Affected Area of Pakistan: A Randomized Clinical Trial.

    Science.gov (United States)

    Rahman, Atif; Hamdani, Syed Usman; Awan, Naila Riaz; Bryant, Richard A; Dawson, Katie S; Khan, Muhammad Firaz; Azeemi, Mian Mukhtar-Ul-Haq; Akhtar, Parveen; Nazir, Huma; Chiumento, Anna; Sijbrandij, Marit; Wang, Duolao; Farooq, Saeed; van Ommeren, Mark

    2016-12-27

    The mental health consequences of conflict and violence are wide-ranging and pervasive. Scalable interventions to address a range of mental health problems are needed. To test the effectiveness of a multicomponent behavioral intervention delivered by lay health workers to adults with psychological distress in primary care settings. A randomized clinical trial was conducted from November 1, 2014, through January 28, 2016, in 3 primary care centers in Peshawar, Pakistan, that included 346 adult primary care attendees with high levels of both psychological distress and functional impairment according to the 12-item General Health Questionnaire and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Lay health workers administered 5 weekly 90-minute individual sessions that included empirically supported strategies of problem solving, behavioral activation, strengthening social support, and stress management. The control was enhanced usual care. Primary outcomes, anxiety and depression symptoms, were independently measured at 3 months with the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes were posttraumatic stress symptoms (Posttraumatic Stress Disorder Checklist for DSM-5), functional impairment (WHODAS 2.0), progress on problems for which the person sought help (Psychological Outcome Profiles), and symptoms of depressive disorder (9-item Patient Health Questionnaire). Among 346 patients (mean [SD] age, 33.0 [11.8] years; 78.9% women), 172 were randomly assigned to the intervention and 174 to enhanced usual care; among them, 146 and 160 completed the study, respectively. At baseline, the intervention and control groups had similar mean (SD) HADS scores on symptoms of anxiety (14.16 [3.17] vs 13.64 [3.20]; adjusted mean difference [AMD], 0.52; 95% CI, -0.22 to 1.27) and depression (12.67 [3.27] vs 12.49 [3.34]; AMD, 0.17, 95% CI, -0.54 to 0.89). After 3 months of treatment, the intervention group had significantly lower

  10. 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)

  11. 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)

  12. Arte y transformación: Experiencias e imágenes de los artistas de la Exposición ¡Mira!

    Directory of Open Access Journals (Sweden)

    Beatriz Matos

    2014-09-01

    Full Text Available A partir de una lectura de los textos del dossier ¡Mira! Artes Visuales Contemporáneas de los Pueblos Indígenas, las autoras señalan que los procesos creativos relatados por los artistas son actos de comunicación que no se reducen a una traducción cultural porque conllevan múltiples actos de transformación —de los cuerpos, las técnicas, las imágenes, y de los propios artistas—. Sus obras llaman al espectador a hacer parte de dicha transformabilidad creativa. 

  13. 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...

  14. 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

  15. 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:

  16. 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:

  17. Netrin-1 - DCC Signaling Systems and Age-Related Macular Degeneration.

    Directory of Open Access Journals (Sweden)

    John Paul SanGiovanni

    Full Text Available We conducted a nested candidate gene study and pathway-based enrichment analysis on data from a multi-national 77,000-person project on the molecular genetics of age-related macular degeneration (AMD to identify AMD-associated DNA-sequence variants in genes encoding constituents of a netrin-1 (NTN1-based signaling pathway that converges on DNA-binding transcription complexes through a 3'-5'-cyclic adenosine monophosphate-calcineurin (cAMP-CN-dependent axis. AMD-associated single nucleotide polymorphisms (SNPs existed in 9 linkage disequilibrium-independent genomic regions; these included loci overlapping NTN1 (rs9899630, P ≤ 9.48 x 10(-5, DCC (Deleted in Colorectal Cancer--the gene encoding a primary NTN1 receptor (rs8097127, P ≤ 3.03 x 10(-5, and 6 other netrin-related genes. Analysis of the NTN1-DCC pathway with exact methods demonstrated robust enrichment with AMD-associated SNPs (corrected P-value = 0.038, supporting the idea that processes driven by NTN1-DCC signaling systems operate in advanced AMD. The NTN1-DCC pathway contains targets of FDA-approved drugs and may offer promise for guiding applied clinical research on preventive and therapeutic interventions for AMD.

  18. Macular xanthophylls and ω-3 long-chain polyunsaturated fatty acids in age-related macular degeneration: a randomized trial.

    Science.gov (United States)

    Arnold, Christin; Winter, Lisa; Fröhlich, Kati; Jentsch, Susanne; Dawczynski, Jens; Jahreis, Gerhard; Böhm, Volker

    2013-05-01

    It has been shown that the functionality of the macula lutea depends on the nutritional uptake of lutein and zeaxanthin and that it is inversely associated with the risk of age-related macular degeneration (AMD). Additionally, ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) may also be protective. To investigate the effect of a 12-month intervention with macular xanthophylls and ω-3 LC-PUFAs on xanthophylls and fatty acids in plasma, antioxidant capacity, and optical density of the macular pigment of patients with nonexudative AMD. The LUTEGA study was a randomized, double-blind, placebo-controlled, parallel clinical trial that was conducted for 12 months. University Eye Hospital and Institute of Nutrition, Friedrich Schiller University Jena, Germany. A total of 172 individuals with nonexudative AMD. Individuals were enrolled and randomly divided as follows: placebo group, group 1 (a capsule containing 10 mg of lutein, 1 mg of zeaxanthin, 100 mg of docosahexaenoic acid, and 30 mg of eicosapentaenoic acid administered each day), and group 2 (same substances but twice the dose used in group 1). One hundred forty-five participants completed the study successfully. Plasma xanthophyll concentrations and fatty acid profiles, optical density of the macular pigment, and antioxidant capacity in plasma (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid [Trolox] equivalent antioxidant capacity and photochemiluminescence). The concentrations of the administered carotenoids in plasma as well as the optical density of the macular pigment increased significantly in the groups randomized to receive supplementary macular xanthophylls and ω-3 LC-PUFAs after 1 month of intervention and remained at this level through the end of the study. Use of the double dose resulted in a beneficial alteration of the fatty acid profile in the plasma of patients with AMD in comparison with the dose in group 1. The lipophilic antioxidant capacity in plasma was significantly elevated

  19. 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.

  20. 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

  1. MULTI-EPOCH IMAGING POLARIMETRY OF THE SiO MASERS IN THE EXTENDED ATMOSPHERE OF THE MIRA VARIABLE TX CAM

    International Nuclear Information System (INIS)

    Kemball, Athol J.; Diamond, Philip J.; Gonidakis, Ioannis; Mitra, Modhurita; Yim, Kijeong; Pan, K.-C.; Chiang, H.-F.

    2009-01-01

    We present a time series of synoptic images of the linearly polarized v = 1, J = 1-0 SiO maser emission toward the Mira variable, TX Cam. These data comprise 43 individual epochs at an approximate biweekly sampling over an optical pulsation phase range of φ = 0.68 to φ = 1.82. The images have an angular resolution of ∼500 μas and were obtained using the Very Long Baseline Array (VLBA), operating in the 43 GHz band in spectral-line, polarization mode. We have previously published the total intensity time series for this pulsation phase range; this paper serves to present the linearly polarized image sequence and an associated animation representing the evolution of the linear polarization morphology over time. We find a predominantly tangential polarization morphology, a high degree of persistence in linear polarization properties over individual component lifetimes, and stronger linear polarization in the inner projected shell than at larger projected shell radii. We present an initial polarization proper motion analysis examining the possible dynamical influence of magnetic fields in component motions in the extended atmospheres of late-type, evolved stars.

  2. 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

  3. Angiographic Cystoid Macular Edema and Outcomes in the Comparison of Age-Related Macular Degeneration Treatments Trials.

    Science.gov (United States)

    Shah, Neepa; Maguire, Maureen G; Martin, Daniel F; Shaffer, James; Ying, Gui-Shuang; Grunwald, Juan E; Toth, Cynthia A; Jaffe, Glenn J; Daniel, Ebenezer

    2016-04-01

    To describe morphologic and visual outcomes in eyes with angiographic cystoid macular edema (CME) treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration (nAMD). Prospective cohort study within a randomized clinical trial. A total of 1185 CATT study subjects. Baseline fluorescein angiography (FA) images of all CATT study eyes were evaluated for CME. Grading of other characteristics on optical coherence tomography (OCT) and photographic images at baseline and during 2-year follow-up was completed by readers at the CATT Reading Centers. Three groups were created on the basis of baseline CME and intraretinal fluid (IRF) status: (1) CME, (2) IRF without CME, (3) neither CME nor IRF. Visual acuity (VA) and total central retinal thickness (CRT) on OCT at baseline, year 1, and year 2. Among 1131 participants with images of sufficient quality for determining CME and IRF at baseline, 92 (8.1%) had CME, 766 (67.7%) had IRF without CME, and 273 (24.1%) had neither. At baseline, eyes with CME had worse mean VA (letters) than eyes with IRF without CME and eyes with neither CME nor IRF (52 vs. 60 vs. 66 letters, P macular edema seems to be a marker for poorer visual outcomes in nAMD because of underlying baseline retinal dysfunction and subsequent scarring. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  4. 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

  5. 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...

  6. 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

  7. 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

  8. Randomized trial of the ForeseeHome monitoring device for early detection of neovascular age-related macular degeneration. The HOme Monitoring of the Eye (HOME) study design - HOME Study report number 1.

    Science.gov (United States)

    Chew, Emily Y; Clemons, Traci E; Bressler, Susan B; Elman, Michael J; Danis, Ronald P; Domalpally, Amitha; Heier, Jeffrey S; Kim, Judy E; Garfinkel, Richard A

    2014-03-01

    To evaluate the effects of a home-monitoring device with tele-monitoring compared with standard care in detection of progression to choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), the leading cause of blindness in the US. Participants, aged 55 to 90 years, at high risk of developing CNV associated with AMD were recruited to the HOme Monitoring of Eye (HOME) Study, an unmasked, multi-center, randomized trial of the ForeseeHome (FH) device plus standard care vs. standard care alone. The FH device utilizes preferential hyperacuity perimetry and tele-monitoring to detect changes in vision function associated with development of CNV, potentially prior to symptom and visual acuity loss. After establishing baseline measurements, subsequent changes on follow-up are detected by the device, causing the monitoring center to alert the clinical center to recall participants for an exam. Standard care consists of instructions for self-monitoring visual changes with subsequent self-report to the clinical center. The primary objective of this study is to determine whether home monitoring plus standard care in comparison with standard care alone, results in earlier detection of incident CNV with better present visual acuity. The primary outcome is the decline in visual acuity at CNV diagnosis from baseline. Detection of CNV prior to substantial vision loss is critical as vision outcome following anti-angiogenic therapy is dependent on the visual acuity at initiation of treatment. HOME Study is the first large scale study to test the use of home tele-monitoring system in the management of AMD patients. Published by Elsevier Inc.

  9. 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.

  10. 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.

  11. Development of a risk score for geographic atrophy in complications of the age-related macular degeneration prevention trial.

    Science.gov (United States)

    Ying, Gui-Shuang; Maguire, Maureen G

    2011-02-01

    To develop a risk score for developing geographic atrophy (GA) involving easily obtainable information among patients with bilateral large drusen. Cohort study within a multicenter randomized clinical trial. We included 1052 participants with ≥ 10 large (>125 μm) drusen and visual acuity ≥ 20/40 in each eye. In the Complications of Age-related Macular Degeneration (AMD) Prevention Trial (CAPT), 1 eye of each participant was randomly assigned to laser treatment and the contralateral eye was assigned to observation to evaluate whether laser treatment of drusen could prevent vision loss. Gradings by a reading center were used to identify: CAPT end point GA (total area of GA [>250 μm] > 1 disc area), GA (>175 μm) involving the foveal center (CGA), and GA of any size and location (any GA). Established risk factors (age, smoking status, hypertension, Age-related Eye Disease Study simple severity scale score), both with and without a novel risk factor (night vision score), were used in assigning risk points. The risk scores were evaluated for the ability to discriminate and calibrate GA risk. Development of end point GA, CGA, and any GA. Among 942 CAPT participants who completed 5 years of follow-up and did not have any GA at baseline, 6.8% participants developed CAPT end point GA, 9.6% developed CGA, and 34.4% developed any GA. The 5-year incidence of end point GA in 1 or both eyes of a participant increased with the 15-point GA risk score, from 0.6% for prevention of GA and for clinical assessment of GA risk in early AMD patients. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  12. 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

  13. 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.

  14. 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

  15. Further mapping of 10q26 supports strong association of HTRA1 polymorphisms with age-related macular degeneration.

    Science.gov (United States)

    Gibbs, Daniel; Yang, Zhenglin; Constantine, Ryan; Ma, Xiang; Camp, Nicola J; Yang, Xian; Chen, Hayou; Jorgenson, Adam; Hau, Vincent; Dewan, Andrew; Zeng, Jiexi; Harmon, Jennifer; Buehler, Jeanette; Brand, John M; Hoh, Josephine; Cameron, D Joshua; Dixit, Manjusha; Tong, Zongzhong; Zhang, Kang

    2008-02-01

    Age-related macular degeneration (AMD) is a complex disorder with genetic and environmental influences. The genetic influences affecting AMD are not well understood and few genes have been consistently implicated and replicated for this disease. A polymorphism (rs11200638) in a transcription factor binding site of the HTRA1 gene has been described, in previous reports, as being most significantly associated with AMD. In this paper, we investigate haplotype association and individual polymorphic association by genotyping additional variants in the AMD risk-associated region of chromosome 10q26. We demonstrate that rs11200638 in the promoter region and rs2293870 in exon 1 of HTRA1, are among the most significantly associated variants for advanced forms of AMD.

  16. Increased Th1/Th17 Responses Contribute to Low-Grade Inflammation in Age-Related Macular Degeneration.

    Science.gov (United States)

    Chen, Jiajia; Wang, Wenzhan; Li, Qiuming

    2017-01-01

    Age-related macular degeneration (AMD) is the primary cause of senior blindness in developed countries. Mechanisms underlying initiation and development of AMD remained known. We examined the CD4+ T cell compartments and their functions in AMD patients. AMD patients presented significantly higher frequencies of interferon (IFN)-γ-expressing and interleukin (IL)-17-expressing CD4+ T cells than healthy controls. The levels of IFN-γ and IL-17 expression by CD4+ T cells were significantly higher in AMD patients. These IFN-γ-expressing Th1 cells and IL-17-expressing Th17 cells could be selectively enriched by surface CCR3+ and CCR4+CCR6+ expression, respectively. Th1 and Th17 cells from AMD patients promoted the differentiation of monocytes toward M1 macrophages, which were previously associated with retinal damage. Th1 and Th17 cells also increased the level of MHC class I expression in human retinal pigment epithelial (RPE)-1 cells, while Th1 cells increased the frequency of MHC class II-expressing RPE-1 cells. These proinflammatory effects were partly, but not entirely, induced by the secretion of IFN-γ and IL-17. This study demonstrated an enrichment of Th1 cells and Th17 cells in AMD patients. These Th1 and Th17 cells possessed proinflammatory roles in an IFN-γ- and IL-17-dependent fashion, and could potentially serve as therapeutic targets. © 2017 The Author(s). Published by S. Karger AG, Basel.

  17. Relationship Between Visual Acuity and Retinal Thickness During Anti-Vascular Endothelial Growth Factor Therapy for Retinal Diseases.

    Science.gov (United States)

    Ou, William C; Brown, David M; Payne, John F; Wykoff, Charles C

    2017-08-01

    To investigate the relationship between best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in eyes receiving ranibizumab for 3 common retinal diseases. Retrospective analysis of clinical trial data. Early Treatment Diabetic Retinopathy Study BCVA and spectral-domain optical coherence tomography-measured CRT of 387 eyes of 345 patients enrolled in 6 prospective clinical trials for management of neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) were evaluated by Pearson correlation and linear regression. At baseline, there was a small correlation between BCVA and CRT in pooled AMD trial data (r = -0.24). A medium correlation was identified in pooled DME trial data (r = -0.42). No correlation was found in pooled RVO trial data. At month 12, no correlation was found between changes from baseline in BCVA and CRT in pooled AMD trial data. Medium correlations were identified in both pooled DME (r = -0.45) and pooled RVO (r = -0.35) trial data at month 12. Changes in BCVA and CRT associated with edema recurrence upon transition from monthly to pro re nata (PRN) dosing were correlated in AMD (r = -0.27) and RVO (r = -0.72) trials, but not in DME trial data. DME demonstrated a convincing relationship between BCVA and CRT. Correlations appear to be more complex in AMD and RVO. At the inflection point between monthly and PRN dosing, when recurrence of edema is anticipated in many patients, CRT appears strongly correlated with loss of BCVA in RVO. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry; Kei Tze) in a food-based human supplementation trial.

    Science.gov (United States)

    Cheng, Chung Yuen; Chung, Wai Yuen; Szeto, Yim Tong; Benzie, Iris F F

    2005-01-01

    Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) micromol/l (P0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.

  19. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration.

    Science.gov (United States)

    Evans, Jennifer R; Lawrenson, John G

    2017-07-31

    one study of 108 participants (MD 1.48, 95% -5.53 to 8.49, moderate-certainty evidence). One study, conducted in Australia, compared vitamin E with placebo. This study randomised 1204 people to vitamin E or placebo, and followed up for four years. Participants were enrolled from the general population; 19% had AMD. The number of late AMD events was low (N = 7) and the estimate of effect was uncertain (RR 1.36, 95% CI 0.31 to 6.05, very low-certainty evidence). There were no data on neovascular AMD or geographic atrophy.There was no evidence of any effect of treatment on visual loss (RR 1.04, 95% CI 0.74 to 1.47, low-certainty evidence). There were no data on quality of life. Five studies compared zinc with placebo. The duration of supplementation and follow-up ranged from six months to seven years. People taking zinc supplements may be less likely to progress to late AMD (OR 0.83, 95% CI 0.70 to 0.98; 3790 participants; 3 RCTs; low-certainty evidence), neovascular AMD (OR 0.76, 95% CI 0.62 to 0.93; 2442 participants; 1 RCT; moderate-certainty evidence), geographic atrophy (OR 0.84, 95% CI 0.64 to 1.10; 2442 participants; 1 RCT; moderate-certainty evidence), or visual loss (OR 0.87, 95% CI 0.75 to 1.00; 3791 participants; 2 RCTs; moderate-certainty evidence). There were no data reported on quality of life.Very low-certainty evidence was available on adverse effects because the included studies were underpowered and adverse effects inconsistently reported. People with AMD may experience some delay in progression of the disease with multivitamin antioxidant vitamin and mineral supplementation. This finding was largely drawn from one large trial, conducted in a relatively well-nourished American population. We do not know the generalisability of these findings to other populations. Although generally regarded as safe, vitamin supplements may have harmful effects. A systematic review of the evidence on harms of vitamin supplements is needed. Supplements containing lutein

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Mutation of Asp(171) and Asp(262) of the chemokine receptor CXCR4 impairs its coreceptor function for human immunodeficiency virus-1 entry and abrogates the antagonistic activity of AMD3100

    DEFF Research Database (Denmark)

    Hatse, S; Princen, K; Gerlach, L O

    2001-01-01

    by mutational analysis. We established a set of stably transfected U87.CD4 cell lines expressing different mutant forms of CXCR4 (i.e., CXCR4[WT], CXCR4[D171N], CXCR4[D262N], CXCR4[D171N,D262N], and CXCR4[H281A]), to compare the activity of the compound against mutated versus wild-type CXCR4. We found...... by substitution of Asp(171) and/or Asp(262) by neutral asparagine residue(s). Both aspartates, but most particularly Asp(262), also proved essential for the anti-HIV-1 activity of AMD3100 against the viruses NL4.3, IIIB, and HE. In contrast, substitution of His(281) by a neutral alanine potentiated...

  2. 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...

  3. Relationship between HTRA1 polymorphism and genetic susceptibility of wet age-related macular degeneration in Han population

    Directory of Open Access Journals (Sweden)

    Nan Yang

    2018-05-01

    Full Text Available AIM: To investigate the relationship between high temperature essential factor A-1(HTRA1polymorphism and genetic susceptibility of wet age-related macular degeneration(AMDin Han population. METHODS: Totally 201 patients of wet AMD in Han population were selected from May 2014 to January 2017 in our hospital as disease group, and 201 healthy persons of Han were selected as health group. Blood samples of peripheral vein were collected and genomic DNA was extracted. HTRA1 polymorphism loci were detected, and the rs11200638 and rs2248799 loci of HTRA1 gene were detected by Sequenom mass spectrometry platform. Then the relationship between HTRA1 polymorphism and genetic susceptibility of wet AMD were analyzed. RESULTS: The grade distributions of the genotype of the rs11200638 and rs2248799 loci in the two groups subjects had significant differences(PPPOR values of rs11200638 genotype AA and AG were respectively 5.36 and 3.45, which were the risk factors of wet AMD(POR values of rs2248799 genotype TT and TC were respectively 2.36 and 1.98, which were the risk factors of wet AMD(PCONCLUSION: The rs11200638 and rs2248799 polymorphisms of HTRA1 gene are associated with the incidence of wet AMD, and the genotype AA and TT are closely related to the risk of wet AMD in Han population, of which the higher frequencies can increase the risk of wet AMD.

  4. DJ-1-dependent regulation of oxidative stress in the retinal pigment epithelium (RPE.

    Directory of Open Access Journals (Sweden)

    Karen G Shadrach

    Full Text Available DJ-1 is found in many tissues, including the brain, where it has been extensively studied due to its association with Parkinson's disease. DJ-1 functions as a redox-sensitive molecular chaperone and transcription regulator that robustly protects cells from oxidative stress.Retinal pigment epithelial (RPE cultures were treated with H2O2 for various times followed by biochemical and immunohistological analysis. Cells were transfected with adenoviruses carrying the full-length human DJ-1 cDNA and a mutant construct, which has the cysteine residues at amino acid 46, 53 and 106 mutated to serine (C to S prior to stress experiments. DJ-1 localization, levels of expression and reactive oxygen species (ROS generation were also analyzed in cells expressing exogenous DJ-1 under baseline and oxidative stress conditions. The presence of DJ-1 and oxidized DJ-1 was evaluated in human RPE total lysates. The distribution of DJ-1 was assessed in AMD and non-AMD cryosectionss and in isolated human Bruch's membrane (BM/choroid from AMD eyes.DJ-1 in RPE cells under baseline conditions, displays a diffuse cytoplasmic and nuclear staining. After oxidative challenge, more DJ-1 was associated with mitochondria. Increasing concentrations of H2O2 resulted in a dose-dependent increase in DJ-1. Overexpression of DJ-1 but not the C to S mutant prior to exposure to oxidative stress led to significant decrease in the generation of ROS. DJ-1 and oxDJ-1 intensity of immunoreactivity was significantly higher in the RPE lysates from AMD eyes. More DJ-1 was localized to RPE cells from AMD donors with geographic atrophy and DJ-1 was also present in isolated human BM/choroid from AMD eyes.DJ-1 regulates RPE responses to oxidative stress. Most importantly, increased DJ-1 expression prior to oxidative stress leads to decreased generation of ROS, which will be relevant for future studies of AMD since oxidative stress is a known factor affecting this disease.

  5. Improved Adherence to Vision Self-monitoring with the Vision and Memory Stimulating (VMS) Journal for Non-neovascular Age-related Macular Degeneration during a Randomized Controlled Trial.

    Science.gov (United States)

    Bittner, Ava K; Torr-Brown, Sheryl; Arnold, Ellen; Nwankwo, Antonia; Beaton, Patricia; Rampat, Radhika; Dagnelie, Gislin; Roser, Mark

    2014-01-22

    An educational, interactive journal [Vision and Memory Stimulating (VMS) journal] was developed to boost patient confidence and promote long-term adherence with weekly vision self-monitoring in age-related macular degeneration (AMD) patients at risk for vision loss from new-onset neovascularization. In a multicenter randomized controlled trial, 198 subjects with intermediate stage, non-neovascular AMD received the VMS journal or followed usual care (e.g. their doctor's instructions for vision monitoring; Amsler grid). At 6 and/or 12 months post-enrollment, 157 subjects completed a questionnaire on vision self-monitoring. At 6 and 12 months, respectively, 85% and 80% of the VMS journal subjects reported vision monitoring at least weekly, which represent statistically significant 7.1 and 4.2 times greater odds than the 50% of controls who monitored weekly at both follow-up times (pself-monitoring. At 6 and 12 months, respectively, only 15% and 13% of the VMS journal subjects vs. 53% and 44% of the controls reported that they did not feel confident that they were taking care of their sight by self-monitoring (pself-monitoring between the groups (p=0.68), with 81% of all subjects reporting no change in frequency between 6 and 12 months. These findings support the efficacy of the VMS journal for increasing vision self-monitoring adherence and confidence, in addition to promoting persistence in weekly monitoring over the course of a year in AMD subjects at risk for exudative retinal changes.

  6. Monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in exudative age-related macular degeneration.

    Science.gov (United States)

    Jonas, Jost B; Tao, Yong; Neumaier, Michael; Findeisen, Peter

    2010-10-01

    To examine intraocular concentrations of monocyte chemoattractant protein 1 (MCP-1), soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and vascular endothelial growth factor (VEGF) in eyes with exudative age-related macular degeneration (AMD). The investigation included a study group of 28 patients (28 eyes) with exudative AMD and a control group of 25 patients (25 eyes) with cataract. The concentrations of MCP-1, sICAM-1, sVCAM-1, and VEGF in aqueous humor samples obtained during surgery were measured using a solid-phase chemiluminescence immunoassay. The study group as compared with the control group had higher aqueous concentrations of sICAM-1 (mean [SD], 844 [2073] vs 246 [206] pg/mL, respectively; P < .001), sVCAM-1 (mean [SD], 7978 [7120] vs 2999 [1426] pg/mL, respectively; P < .001), and MCP-1 (mean [SD], 587 [338] vs 435 [221] pg/mL, respectively; P = .07). The concentration of VEGF did not vary significantly between the groups (P = .76). The MCP-1 concentration was significantly associated with macular thickness (r = 0.40; P = .004). It decreased significantly with the type of subfoveal neovascular membrane (classic membrane type, occult membrane, retinal pigment epithelium detachment) (P = .009). The concentrations of sICAM-1, sVCAM-1, and VEGF were not significantly associated with membrane type and macular thickness (P ≥ .18). Concentrations of MCP-1, sICAM-1, and sVCAM-1 are significantly associated with exudative AMD, even in the presence of normal VEGF concentrations. Intraocular MCP-1 concentrations are correlated with the subfoveal neovascular membrane type and the amount of macular edema. One may infer that MCP-1, sICAM-1, and sVCAM-1 could potentially be additional target molecules in therapy for exudative AMD.

  7. Statins for age-related macular degeneration.

    Science.gov (United States)

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2015-02-11

    . Both trials compared simvastatin versus placebo in older people (> 50 or 60 years) with high risk of developing AMD (drusen present on examination). The larger trial with 114 participants was conducted in Australia and used a higher dose (40 mg daily) of simvastatin for three years. Participants and study personnel in this trial were adequately masked; however, data were missing for 30% of participants at three years follow-up. The smaller trial of 30 participants was conducted in Italy and used a lower dose (20 mg) of simvastatin for three months. This trial reported insufficient details to assess the risk of bias.Neither trial reported data for change in visual acuity. Analysis of 30 participants in the smaller trial did not show a statistically significant difference between the simvastatin and placebo groups in visual acuity values at three months of treatment (decimal visual acuity 0.21 ± 0.56 in simvastatin group and 0.19 ± 0.40 in placebo group) or 45 days after the completion of treatment (decimal visual acuity 0.20 ± 0.50 in simvastatin group and 0.19 ± 0.48 in placebo group). The lack of a difference in visual acuity was not explained by lens or retina status, which remained unchanged during and after the treatment period for both groups.Preliminary analyses of 42 participants who had completed 12 months follow-up in the larger trial did not show a statistically significant difference between simvastatin and the placebo groups for visual acuity, drusen score, or visual function (effect estimates and confidence intervals were not available). Complete data for these outcomes at three years follow-up were not reported. At three years, the effect of simvastatin in slowing progression of AMD compared with placebo was uncertain (odds ratio 0.51, 95% confidence interval 0.23 to 1.09).One trial did not report adverse outcomes. The second trial reported no difference between groups in terms of adverse events such as death, muscle aches, and acute hepatitis

  8. THE PULSATION OF χ CYGNI IMAGED BY OPTICAL INTERFEROMETRY: A NOVEL TECHNIQUE TO DERIVE DISTANCE AND MASS OF MIRA STARS

    International Nuclear Information System (INIS)

    Lacour, S.; Perrin, G.; Haubois, X.; Poncelet, A.; Thiebaut, E.; Meimon, S.; Pedretti, E.; Ridgway, S. T.; Monnier, J. D.; Berger, J. P.; Schuller, P. A.; Woodruff, H.; Le Coroller, H.; Millan-Gabet, R.; Lacasse, M.; Traub, W.

    2009-01-01

    We present infrared interferometric imaging of the S-type Mira star χ Cygni. The object was observed at four different epochs in 2005-2006 with the Infrared-Optical Telescope Array optical interferometer (H band). Images show up to 40% variation in the stellar diameter, as well as significant changes in the limb darkening and stellar inhomogeneities. Model fitting gave precise time-dependent values of the stellar diameter, and reveals presence and displacement of a warm molecular layer. The star radius, corrected for limb darkening, has a mean value of 12.1 mas and shows a 5.1 mas amplitude pulsation. Minimum diameter was observed at phase 0.94 ± 0.01. Maximum temperature was observed several days later at phase 1.02 ± 0.02. We also show that combining the angular acceleration of the molecular layer with CO (Δv = 3) radial velocity measurements yields a 5.9 ± 1.5 mas parallax. The constant acceleration of the CO molecules-during 80% of the pulsation cycle-lead us to argument for a free-falling layer. The acceleration is compatible with a gravitational field produced by a 2.1 +1.5 -0.7 solar mass star. This last value is in agreement with fundamental mode pulsator models. We foresee increased development of techniques consisting in combining radial velocity with interferometric angular measurements, ultimately allowing total mapping of the speed, density, and position of the diverse species in pulsation-driven atmospheres.

  9. Complement inhibitors for age-related macular degeneration.

    Science.gov (United States)

    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

  10. Análise de crédito e risco: estágio no Banco Caixa Crédito Agrícola Cantanhede e Mira

    OpenAIRE

    Dias, Diana Carolina Duarte

    2017-01-01

    Este trabalho tem por objetivo descrever e analisar as atividades desenvolvidas ao longo do estágio curricular realizado na Caixa de Crédito Agrícola Mútuo de Cantanhede e Mira, que teve a duração de 7 meses e se focalizou essencialmente na área de análise de risco de crédito. Antes, porém, procuraremos explicar o funcionamento do circuito processual do crédito em todas as fases, identificar a documentação necessária e quais os tipos de produtos bancários disponíveis para em...

  11. Trial 1 versus Trial 2 of the Test of Memory Malingering: Evaluating accuracy without a "gold standard".

    Science.gov (United States)

    Mossman, Douglas; Wygant, Dustin B; Gervais, Roger O; Hart, Kathleen J

    2018-01-01

    This study examines the accuracy of the Test of Memory Malingering (TOMM), a frequently administered measure for evaluating effort during neurocognitive testing. In the last few years, several authors have suggested that the initial recognition trial of the TOMM (Trial 1) might be a more useful index for detecting feigned or exaggerated impairment than Trial 2, which is the source for inference recommended by the original instruction manual (Tombaugh, 1996). We used latent class modeling (LCM) implemented in a Bayesian framework to evaluate archival Trial 1 and Trial 2 data collected from 1,198 adults who had undergone outpatient forensic evaluations. All subjects were tested with 2 other performance validity tests (the Word Memory Test and the Computerized Assessment of Response Bias), and for 70% of the subjects, data from the California Verbal Learning Test-Second Edition Forced Choice trial were also available. Our results suggest that not even a perfect score on Trial 1 or Trial 2 justifies saying that an evaluee is definitely responding genuinely, although such scores imply a lower-than-base-rate probability of feigning. If one uses a Trial 2 cut-off higher than the manual's recommendation, Trial 2 does better than Trial 1 at identifying individuals who are almost certainly feigning while maintaining a negligible false positive rate. Using scores from both trials, one can identify a group of definitely feigning and very likely feigning subjects who comprise about 2 thirds of all feigners; only 1% of the members of this group would not be feigning. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  12. HIV-1 transmission linkage in an HIV-1 prevention clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Leitner, Thomas [Los Alamos National Laboratory; Campbell, Mary S [UNIV OF WASHINGTON; Mullins, James I [UNIV OF WASHINGTON; Hughes, James P [UNIV OF WASHINGTON; Wong, Kim G [UNIV OF WASHINGTON; Raugi, Dana N [UNIV OF WASHINGTON; Scrensen, Stefanie [UNIV OF WASHINGTON

    2009-01-01

    HIV-1 sequencing has been used extensively in epidemiologic and forensic studies to investigate patterns of HIV-1 transmission. However, the criteria for establishing genetic linkage between HIV-1 strains in HIV-1 prevention trials have not been formalized. The Partners in Prevention HSV/HIV Transmission Study (ClinicaITrials.gov NCT00194519) enrolled 3408 HIV-1 serodiscordant heterosexual African couples to determine the efficacy of genital herpes suppression with acyclovir in reducing HIV-1 transmission. The trial analysis required laboratory confirmation of HIV-1 linkage between enrolled partners in couples in which seroconversion occurred. Here we describe the process and results from HIV-1 sequencing studies used to perform transmission linkage determination in this clinical trial. Consensus Sanger sequencing of env (C2-V3-C3) and gag (p17-p24) genes was performed on plasma HIV-1 RNA from both partners within 3 months of seroconversion; env single molecule or pyrosequencing was also performed in some cases. For linkage, we required monophyletic clustering between HIV-1 sequences in the transmitting and seroconverting partners, and developed a Bayesian algorithm using genetic distances to evaluate the posterior probability of linkage of participants sequences. Adjudicators classified transmissions as linked, unlinked, or indeterminate. Among 151 seroconversion events, we found 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) to have indeterminate transmissions. Nine (8.3%) were linked by consensus gag sequencing only and 8 (7.4%) required deep sequencing of env. In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage

  13. Improved Adherence to Vision Self-monitoring with the Vision and Memory Stimulating (VMS) Journal for Non-neovascular Age-related Macular Degeneration during a Randomized Controlled Trial

    Science.gov (United States)

    Bittner, Ava K; Torr-Brown, Sheryl; Arnold, Ellen; Nwankwo, Antonia; Beaton, Patricia; Rampat, Radhika; Dagnelie, Gislin; Roser, Mark

    2014-01-01

    Objective An educational, interactive journal [Vision and Memory Stimulating (VMS) journal] was developed to boost patient confidence and promote long-term adherence with weekly vision self-monitoring in age-related macular degeneration (AMD) patients at risk for vision loss from new-onset neovascularization. Methods In a multicenter randomized controlled trial, 198 subjects with intermediate stage, non-neovascular AMD received the VMS journal or followed usual care (e.g. their doctor’s instructions for vision monitoring; Amsler grid). At 6 and/or 12 months post-enrollment, 157 subjects completed a questionnaire on vision self-monitoring. Results At 6 and 12 months, respectively, 85% and 80% of the VMS journal subjects reported vision monitoring at least weekly, which represent statistically significant 7.1 and 4.2 times greater odds than the 50% of controls who monitored weekly at both follow-up times (psight by self-monitoring (p<0.001). Usual care controls had statistically significant 6.7 and 5.0 times greater odds of reporting non-confidence at 6 and 12 months, respectively. There was no statistically significant change in weekly vs. less frequent self-monitoring between the groups (p=0.68), with 81% of all subjects reporting no change in frequency between 6 and 12 months. Conclusions These findings support the efficacy of the VMS journal for increasing vision self-monitoring adherence and confidence, in addition to promoting persistence in weekly monitoring over the course of a year in AMD subjects at risk for exudative retinal changes. PMID:24791222

  14. SAFARI 2000 Daily Rainfall Estimates, 0.1-Deg, Southern Africa, 1993-2001

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: The Microwave InfraRed Algorithm (MIRA) is used to produce an imagery data set of daily mean rain rates at 0.1 degree spatial resolution over southern...

  15. Nutritional Modulation of Age-Related Macular Degeneration

    Science.gov (United States)

    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

  16. El liderazgo carismático religioso como elemento fundamental en la permanencia del movimiento independiente de renovación absoluta (MIRA) en el panorama electoral colombiano (2000-2014)

    OpenAIRE

    Barros Acosta, Laura Milena

    2015-01-01

    El propósito de esta investigación es explorar los efectos del liderazgo carismático religioso sobre el desempeño electoral y la supervivencia del movimiento político MIRA en Colombia. Para ello, emplea una metodología cualitativa, que se vale principalmente de entrevistas a profundidad y observación no participante, para acercarse a las prácticas religiosas y a las actitudes políticas de los fieles de la Iglesia de Dios Ministerial de Jesucristo Internacional. A partir de la información reca...

  17. Sieve analysis in HIV-1 vaccine efficacy trials.

    Science.gov (United States)

    Edlefsen, Paul T; Gilbert, Peter B; Rolland, Morgane

    2013-09-01

    The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine. The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 (HIV Vaccine Trials Network-502) and RV144, led to numerous studies in the last 5 years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses. Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons, whereas correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. The Association of Statin Use with Age-Related Macular Degeneration Progression: The Age-Related Eye Disease Study 2 Report Number 9.

    Science.gov (United States)

    Al-Holou, Shaza N; Tucker, William R; Agrón, Elvira; Clemons, Traci E; Cukras, Catherine; Ferris, Frederick L; Chew, Emily Y

    2015-12-01

    To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50 to 85 years. Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke-all known to be associated with statin use-were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses adjusting for the competing risk of death were also performed. Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.83-1.41; P = 0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29). Furthermore, subgroup analyses of persons with or without late AMD at baseline and the various components of late AMD (neovascular AMD, central GA, or any GA) also showed no statistically significant association of statin use with progression to AMD. Statin use was not statistically significantly associated with progression to late AMD in the AREDS2 participants, and these findings are consistent with findings in the

  3. 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.

  4. Quality assurance of the SCOPE 1 trial in oesophageal radiotherapy.

    Science.gov (United States)

    Wills, Lucy; Maggs, Rhydian; Lewis, Geraint; Jones, Gareth; Nixon, Lisette; Staffurth, John; Crosby, Tom

    2017-11-15

    SCOPE 1 was the first UK based multi-centre trial involving radiotherapy of the oesophagus. A comprehensive radiotherapy trials quality assurance programme was launched with two main aims: 1. To assist centres, where needed, to adapt their radiotherapy techniques in order to achieve protocol compliance and thereby enable their participation in the trial. 2. To support the trial's clinical outcomes by ensuring the consistent planning and delivery of radiotherapy across all participating centres. A detailed information package was provided and centres were required to complete a benchmark case in which the delineated target volumes and organs at risk, dose distribution and completion of a plan assessment form were assessed prior to recruiting patients into the trial. Upon recruiting, the quality assurance (QA) programme continued to monitor the outlining and planning of radiotherapy treatments. Completion of a questionnaire was requested in order to gather information about each centre's equipment and techniques relating to their trial participation and to assess the impact of the trial nationally on standard practice for radiotherapy of the oesophagus. During the trial, advice was available for individual planning issues, and was circulated amongst the SCOPE 1 community in response to common areas of concern using bulletins. 36 centres were supported through QA processes to enable their participation in SCOPE1. We discuss the issues which have arisen throughout this process and present details of the benchmark case solutions, centre questionnaires and on-trial protocol compliance. The range of submitted benchmark case GTV volumes was 29.8-67.8cm 3 ; and PTV volumes 221.9-513.3 cm 3 . For the dose distributions associated with these volumes, the percentage volume of the lungs receiving 20Gy (V20Gy) ranged from 20.4 to 33.5%. Similarly, heart V40Gy ranged from 16.1 to 33.0%. Incidence of incorrect outlining of OAR volumes increased from 50% of centres at benchmark

  5. [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

  6. Functional Outcomes of the Low Vision Depression Prevention Trial in Age-Related Macular Degeneration.

    Science.gov (United States)

    Deemer, Ashley D; Massof, Robert W; Rovner, Barry W; Casten, Robin J; Piersol, Catherine V

    2017-03-01

    To compare the efficacy of behavioral activation (BA) plus low vision rehabilitation with an occupational therapist (OT-LVR) with supportive therapy (ST) on visual function in patients with age-related macular degeneration (AMD). Single-masked, attention-controlled, randomized clinical trial with AMD patients with subsyndromal depressive symptoms (n = 188). All subjects had two outpatient low vision rehabilitation optometry visits, then were randomized to in-home BA + OT-LVR or ST. Behavioral activation is a structured behavioral treatment aiming to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. Functional vision was assessed with the activity inventory (AI) in which participants rate the difficulty level of goals and corresponding tasks. Participants were assessed at baseline and 4 months. Improvements in functional vision measures were seen in both the BA + OT-LVR and ST groups at the goal level (d = 0.71; d = 0.56 respectively). At the task level, BA + OT-LVR patients showed more improvement in reading, inside-the-home tasks and outside-the-home tasks, when compared to ST patients. The greatest effects were seen in the BA + OT-LVR group in subjects with a visual acuity ≥20/70 (d = 0.360 reading; d = 0.500 inside the home; d = 0.468 outside the home). Based on the trends of the AI data, we suggest that BA + OT-LVR services, provided by an OT in the patient's home following conventional low vision optometry services, are more effective than conventional optometric low vision services alone for those with mild visual impairment. (ClinicalTrials.gov number, NCT00769015.).

  7. Lutein, Zeaxanthin, and meso-Zeaxanthin in the Clinical Management of Eye Disease

    Directory of Open Access Journals (Sweden)

    Nicole K. Scripsema

    2015-01-01

    Full Text Available Lutein, zeaxanthin, and meso-zeaxanthin are xanthophyll carotenoids found within the retina and throughout the visual system. The retina is one of the most metabolically active tissues in the body. The highest concentration of xanthophylls is found within the retina, and this selective presence has generated many theories regarding their role in supporting retinal function. Subsequently, the effect of xanthophylls in the prevention and treatment of various eye diseases has been examined through epidemiological studies, animal studies, and clinical trials. This paper attempts to review the epidemiological studies and clinical trials investigating the effects of xanthophylls on the incidence and progression of various eye diseases. Observational studies have reported that increased dietary intake and higher serum levels of lutein and zeaxanthin are associated with lower risk of age-related macular degeneration (AMD, especially late AMD. Randomized, placebo-controlled clinical trials have demonstrated that xanthophyll supplementation increases macular pigment levels, improves visual function, and decreases the risk of progression to late AMD, especially neovascular AMD. Current publications on the preventive and therapeutic effects of lutein and zeaxanthin on cataracts, diabetic retinopathy, and retinopathy of prematurity have reported encouraging results.

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

    Science.gov (United States)

    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.

  9. 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.

  10. Multicenter cohort association study of SLC2A1 single nucleotide polymorphisms and age-related macular degeneration

    Science.gov (United States)

    Baas, Dominique C.; Ho, Lintje; Tanck, Michael W.T.; Fritsche, Lars G.; Merriam, Joanna E.; van het Slot, Ruben; Koeleman, Bobby P.C.; Gorgels, Theo G.M.F.; van Duijn, Cornelia M.; Uitterlinden, André G.; de Jong, Paulus T.V.M.; Hofman, Albert; ten Brink, Jacoline B.; Vingerling, Johannes R.; Klaver, Caroline C.W.; Dean, Michael; Weber, Bernhard H. F.; Allikmets, Rando; Hageman, Gregory S.

    2012-01-01

    Purpose Age-related macular degeneration (AMD) is a major cause of blindness in older adults and has a genetically complex background. This study examines the potential association between single nucleotide polymorphisms (SNPs) in the glucose transporter 1 (SLC2A1) gene and AMD. SLC2A1 regulates the bioavailability of glucose in the retinal pigment epithelium (RPE), which might influence oxidative stress–mediated AMD pathology. Methods Twenty-two SNPs spanning the SLC2A1 gene were genotyped in 375 cases and 199 controls from an initial discovery cohort (the Amsterdam-Rotterdam-Netherlands study). Replication testing was performed in The Rotterdam Study (the Netherlands) and study populations from Würzburg (Germany), the Age Related Eye Disease Study (AREDS; United States), Columbia University (United States), and Iowa University (United States). Subsequently, a meta-analysis of SNP association was performed. Results In the discovery cohort, significant genotypic association between three SNPs (rs3754219, rs4660687, and rs841853) and AMD was found. Replication in five large independent (Caucasian) cohorts (4,860 cases and 4,004 controls) did not yield consistent association results. The genotype frequencies for these SNPs were significantly different for the controls and/or cases among the six individual populations. Meta-analysis revealed significant heterogeneity of effect between the studies. Conclusions No overall association between SLC2A1 SNPs and AMD was demonstrated. Since the genotype frequencies for the three SLC2A1 SNPs were significantly different for the controls and/or cases between the six cohorts, this study corroborates previous evidence that population dependent genetic risk heterogeneity in AMD exists. PMID:22509097

  11. 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

  12. The results of randomized controlled trial of low-dose radiation for wet-type age-related macular degeneration on a 1 year term basis

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-06-01

    Evaluation of low dose radiation therapy to the wet-type age-related macular degeneration (AMD) located at the fovea centralis. Patients were irradiated with 10 fractions of 2 Gy external beam or just observed. Between the treated (39) and untreated (31) cases, there was no significant difference in gender, age, initial visual acuity, or size of the neovascular membrane. With the follow-up of 12 months, the visual acuity was significantly well preserved and the size of the neovascular membrane was decreased. These results indicate that low dose irradiation is effective for the wet-type AMD of the stage we treated in the present study. (author)

  13. The Association of Statin Use with Age-Related Macular Degeneration Progression The Age-Related Eye Disease Study 2 Report Number 9

    Science.gov (United States)

    Al-Holou, Shaza N.; Tucker, William R.; Agrón, Elvira; Clemons, Traci E.; Cukras, Catherine; Ferris, Frederick L.; Chew, Emily Y.

    2015-01-01

    Objective/purpose To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Design Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Subjects Age-Related Eye Disease Study 2 participants, aged 50 to 85 years. Methods Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke, all known to be associated with statin use, were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses were also performed adjusting for the competing risk of death. Main Outcome Measures Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Results Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratios [HR] of 1.08, 95% confidence intervals [CI] of 0.83–1.41, P=0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant with HR: 0.81, 95% CI: 0.55–1.20, P=0.29. Further subgroup analyses of persons with or without late AMD at baseline to the various components of late AMD (neovascular, central geographic atrophy, or any geographic atrophy) also showed no statistically significant association of statin use with progression to AMD. Conclusions Statin use was not statistically significantly associated with the

  14. Genome-wide analysis of disease progression in age-related macular degeneration.

    Science.gov (United States)

    Yan, Qi; Ding, Ying; Liu, Yi; Sun, Tao; Fritsche, Lars G; Clemons, Traci; Ratnapriya, Rinki; Klein, Michael L; Cook, Richard J; Liu, Yu; Fan, Ruzong; Wei, Lai; Abecasis, Gonçalo R; Swaroop, Anand; Chew, Emily Y; Weeks, Daniel E; Chen, Wei

    2018-03-01

    Family- and population-based genetic studies have successfully identified multiple disease-susceptibility loci for Age-related macular degeneration (AMD), one of the first batch and most successful examples of genome-wide association study. However, most genetic studies to date have focused on case-control studies of late AMD (choroidal neovascularization or geographic atrophy). The genetic influences on disease progression are largely unexplored. We assembled unique resources to perform a genome-wide bivariate time-to-event analysis to test for association of time-to-late-AMD with ∼9 million variants on 2721 Caucasians from a large multi-center randomized clinical trial, the Age-Related Eye Disease Study. To our knowledge, this is the first genome-wide association study of disease progression (bivariate survival outcome) in AMD genetic studies, thus providing novel insights to AMD genetics. We used a robust Cox proportional hazards model to appropriately account for between-eye correlation when analyzing the progression time in the two eyes of each participant. We identified four previously reported susceptibility loci showing genome-wide significant association with AMD progression: ARMS2-HTRA1 (P = 8.1 × 10-43), CFH (P = 3.5 × 10-37), C2-CFB-SKIV2L (P = 8.1 × 10-10) and C3 (P = 1.2 × 10-9). Furthermore, we detected association of rs58978565 near TNR (P = 2.3 × 10-8), rs28368872 near ATF7IP2 (P = 2.9 × 10-8) and rs142450006 near MMP9 (P = 0.0006) with progression to choroidal neovascularization but not geographic atrophy. Secondary analysis limited to 34 reported risk variants revealed that LIPC and CTRB2-CTRB1 were also associated with AMD progression (P < 0.0015). Our genome-wide analysis thus expands the genetics in both development and progression of AMD and should assist in early identification of high risk individuals.

  15. 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.

  16. Drusen Volume and Retinal Pigment Epithelium Abnormal Thinning Volume Predict 2-Year Progression of Age-Related Macular Degeneration.

    Science.gov (United States)

    Folgar, Francisco A; Yuan, Eric L; Sevilla, Monica B; Chiu, Stephanie J; Farsiu, Sina; Chew, Emily Y; Toth, Cynthia A

    2016-01-01

    To analyze the value of novel measures of retinal pigment epithelium-drusen complex (RPEDC) volume to predict 2-year disease progression of intermediate age-related macular degeneration (AMD). Prospective, observational study. Three hundred forty-five AMD and 122 non-AMD participants enrolled in the Age Related Eye Disease Study 2 Ancillary Spectral-Domain (SD) Optical Coherence Tomography (OCT) study. High-density SD OCT macular volumes were obtained at yearly study visits. The RPEDC abnormal thickening (henceforth, OCT drusen) and RPEDC abnormal thinning (RAT) volumes were generated by semiautomated segmentation of total RPEDC within a 5-mm-diameter macular field. Volume change and odds ratio (OR) with 95% confidence intervals (CI) for progression to advanced AMD with choroidal neovascularization (CNV) or central geographic atrophy (GA). Complete volumes were obtained in 265 and 266 AMD eyes and in 115 and 97 control eyes at baseline and at year 2, respectively. In AMD eyes, mean (standard deviation) OCT drusen volume increased from 0.08 mm(3) (0.16 mm(3)) to 0.10 mm(3) (0.23 mm(3); P < 0.001), and RAT volume increased from 8.3 × 10(-4) mm(3) (20.8 × 10(-4) mm(3)) to 18.4 × 10(-4) mm(3) (46.6 × 10(-4) mm(3); P < 0.001). Greater baseline OCT drusen volume was associated with 2-year progression to CNV (P = 0.002). Odds of developing CNV increased by 31% for every 0.1-mm(3) increase in baseline OCT drusen volume (OR, 1.31; 95% CI, 1.06-1.63; P = 0.013). Greater baseline RAT volume was associated with significant 2-year increase in RAT volume (P < 0.001), noncentral GA (P < 0.001), and progression to central GA (P < 0.001). Odds of developing central GA increased by 32% for every 0.001-mm(3) increase in baseline RAT volume (OR, 1.32; 95% CI, 1.14-1.53; P < 0.001). In non-AMD eyes, all volumes were significantly lower than AMD eyes and showed no significant 2-year change. Macular OCT drusen and RAT volumes increased significantly in AMD eyes over 2 years

  17. THE NUCLEUS OF THE PLANETARY NEBULA EGB 6 AS A POST-MIRA BINARY

    Energy Technology Data Exchange (ETDEWEB)

    Bond, Howard E.; Ciardullo, Robin; Esplin, Taran L. [Department of Astronomy and Astrophysics, Pennsylvania State University, University Park, PA 16802 (United States); Hawley, Steven A. [Department of Physics and Astronomy, University of Kansas, Lawrence, KS 66045 (United States); Liebert, James [Steward Observatory, University of Arizona, Tucson, AZ 85721 (United States); Munari, Ulisse, E-mail: heb11@psu.edu [INAF Astronomical Observatory of Padova, via dell’Osservatorio 8, I-36012 Asiago (VI) (Italy)

    2016-08-01

    EGB 6 is a faint, large, ancient planetary nebula (PN). Its central star, a hot DAOZ white dwarf (WD), is a prototype of a rare class of PN nuclei associated with dense, compact emission-line knots. The central star also shows excess fluxes in both the near-infrared (NIR) and mid-infrared (MIR). In a 2013 paper, we used Hubble Space Telescope ( HST ) images to show that the compact nebula is a point-like source, located 0.″16 (∼118 AU) from the WD. We attributed the NIR excess to an M dwarf companion star, which appeared to coincide with the dense emission knot. We now present new ground-based NIR spectroscopy, showing that the companion is actually a much cooler source with a continuous spectrum, apparently a dust-enshrouded low-luminosity star. New HST images confirm common proper motion of the emission knot and red source with the WD. The I -band, NIR, and MIR fluxes are variable, possibly on timescales as short as days. We can fit the spectral energy distribution (SED) with four blackbodies (the WD, a ∼1850 K NIR component, and MIR dust at 385 and 175 K). Alternatively, we show that the NIR/MIR SED is very similar to that of Class 0/I young stellar objects. We suggest a scenario in which the EGB 6 nucleus is descended from a wide binary similar to the Mira system, in which a portion of the wind from an AGB star was captured into an accretion disk around a companion star; a remnant of this disk has survived to the present time and is surrounded by gas photoionized by UV radiation from the WD.

  18. THE NUCLEUS OF THE PLANETARY NEBULA EGB 6 AS A POST-MIRA BINARY

    International Nuclear Information System (INIS)

    Bond, Howard E.; Ciardullo, Robin; Esplin, Taran L.; Hawley, Steven A.; Liebert, James; Munari, Ulisse

    2016-01-01

    EGB 6 is a faint, large, ancient planetary nebula (PN). Its central star, a hot DAOZ white dwarf (WD), is a prototype of a rare class of PN nuclei associated with dense, compact emission-line knots. The central star also shows excess fluxes in both the near-infrared (NIR) and mid-infrared (MIR). In a 2013 paper, we used Hubble Space Telescope ( HST ) images to show that the compact nebula is a point-like source, located 0.″16 (∼118 AU) from the WD. We attributed the NIR excess to an M dwarf companion star, which appeared to coincide with the dense emission knot. We now present new ground-based NIR spectroscopy, showing that the companion is actually a much cooler source with a continuous spectrum, apparently a dust-enshrouded low-luminosity star. New HST images confirm common proper motion of the emission knot and red source with the WD. The I -band, NIR, and MIR fluxes are variable, possibly on timescales as short as days. We can fit the spectral energy distribution (SED) with four blackbodies (the WD, a ∼1850 K NIR component, and MIR dust at 385 and 175 K). Alternatively, we show that the NIR/MIR SED is very similar to that of Class 0/I young stellar objects. We suggest a scenario in which the EGB 6 nucleus is descended from a wide binary similar to the Mira system, in which a portion of the wind from an AGB star was captured into an accretion disk around a companion star; a remnant of this disk has survived to the present time and is surrounded by gas photoionized by UV radiation from the WD.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Age-related macular degeneration-associated silent polymorphisms in HtrA1 impair its ability to antagonize insulin-like growth factor 1.

    Science.gov (United States)

    Jacobo, Sarah Melissa P; Deangelis, Margaret M; Kim, Ivana K; Kazlauskas, Andrius

    2013-05-01

    Synonymous single nucleotide polymorphisms (SNPs) within a transcript's coding region produce no change in the amino acid sequence of the protein product and are therefore intuitively assumed to have a neutral effect on protein function. We report that two common variants of high-temperature requirement A1 (HTRA1) that increase the inherited risk of neovascular age-related macular degeneration (NvAMD) harbor synonymous SNPs within exon 1 of HTRA1 that convert common codons for Ala34 and Gly36 to less frequently used codons. The frequent-to-rare codon conversion reduced the mRNA translation rate and appeared to compromise HtrA1's conformation and function. The protein product generated from the SNP-containing cDNA displayed enhanced susceptibility to proteolysis and a reduced affinity for an anti-HtrA1 antibody. The NvAMD-associated synonymous polymorphisms lie within HtrA1's putative insulin-like growth factor 1 (IGF-1) binding domain. They reduced HtrA1's abilities to associate with IGF-1 and to ameliorate IGF-1-stimulated signaling events and cellular responses. These observations highlight the relevance of synonymous codon usage to protein function and implicate homeostatic protein quality control mechanisms that may go awry in NvAMD.

  1. Differential Disease Progression in Atrophic Age-Related Macular Degeneration and Late-Onset Stargardt Disease.

    Science.gov (United States)

    Lindner, Moritz; Lambertus, Stanley; Mauschitz, Matthias M; Bax, Nathalie M; Kersten, Eveline; Lüning, Anna; Nadal, Jennifer; Schmitz-Valckenberg, Steffen; Schmid, Matthias; Holz, Frank G; Hoyng, Carel B; Fleckenstein, Monika

    2017-02-01

    To compare the disease course of retinal pigment epithelium (RPE) atrophy secondary to age-related macula degeneratio (AMD) and late-onset Stargardt disease (STGD1). Patients were examined longitudinally by fundus autofluorescence, near-infrared reflectance imaging, and best-corrected visual acuity (BCVA). Areas of RPE atrophy were quantified using semi-automated software, and the status of the fovea was evaluated based on autofluorescence and near-infrared reflectance images. Mixed-effects models were used to compare atrophy progression rates. BCVA loss and loss of foveal integrity were analyzed using Turnbull's estimator. A total of 151 patients (226 eyes) with RPE atrophy secondary to AMD and 38 patients (66 eyes) with RPE atrophy secondary to late-onset STGD1 were examined for a median time of 2.3 years (interquartile range, 2.7). Mean baseline age was 74.2 years (SD, 7.6) in AMD and 63.4 (SD, 9.9) in late-onset STGD1 (P = 1.1 × 10-7). Square root atrophy progression was significantly faster in AMD when compared with late-onset STGD1 (0.28 mm/year [SE, 0.01] vs. 0.23 [SE, 0.03]; P = 0.030). In late-onset STGD1, the median survival of the fovea was significantly longer when compared with eyes with AMD (8.60 vs. 3.35 years; P = 0.005) with a trend to a later BCVA loss of ≥3 lines (5.97 vs. 4.37 years; P = 0.382). These natural history data indicate differential disease progression in AMD versus late-onset STGD1. The results underline the relevance of refined phenotyping in elderly patients presenting with RPE atrophy in regard to prognosis and design of interventional trials.

  2. Self-propelled pulse X-ray apparatus Sirena-1

    International Nuclear Information System (INIS)

    Danil'chenko, N.T.; Ershov, L.S.; Il'chenko, A.V.; Krasil'nikov, S.B.; Kristalinskij, A.L.; Lozovoj, L.N.; Markov, S.N.; Morgovskij, L.Ya.

    1984-01-01

    The structure and specifications of a self-propelled pulse X-ray apparatus ''Sirena-1'' for testing oilt and gas pipelines welded joints are described. The apparatus is designed on the base of pulse X-ray apparatus MIRA. Apparatus control is realized by means of the 137 Cs source or manual control desk. The apparatus ensures perfect control sensitivity

  3. Massive choroidal hemorrhage after intravitreal administration of bevacizumab (Avastin® for AMD followed by controlateral sympathetic ophthalmia

    Directory of Open Access Journals (Sweden)

    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

  4. Immunotherapy trials for type 1 diabetes: the contribution of George Eisenbarth.

    Science.gov (United States)

    Skyler, Jay S; Pugliese, Alberto

    2013-06-01

    Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic β-cells, and as such it should respond to immunotherapy. George Eisenbarth gave many significant contributions to this field. He has been involved at some level in most immunotherapy trials during the past three decades. He was among the pioneers who attempted immunotherapy approaches in patients with recent-onset T1D. In the early 1980s he began studying relatives of those with the disease, leading to the concept that T1D was a chronic autoimmune disease, in which islet autoimmune responses would silently destroy β-cells and cause progressive impairment of insulin secretion, years to months before a diagnosis was made. Consequently, he was one of the first to attempt immune intervention in people at high risk of T1D. Throughout his career he developed autoantibody assays and predictive models (which included metabolic testing and later genetics) to identify individuals at risk of T1D. He provided seminal intellectual contributions and critical tools for prevention trials. His focus on insulin as a critical autoantigen led to multiple prevention trials, including the Diabetes Prevention Trial-Type 1 (DPT-1), which studied both parenteral and oral insulin. In the DPT-1 Oral Insulin Trial, a cohort with higher levels of insulin autoantibodies was identified that appeared to have delayed disease progression. Type 1 Diabetes TrialNet is conducting a new trial to verify or refute this observation. Moreover, George identified and tested in the mouse small molecules that block or modulate presentation of a key insulin peptide and in turn prevent the activation of insulin-specific T-lymphocytes. Thus, we believe his greatest contribution is yet to come, as in the near future we should see this most recent work translate into clinical trials.

  5. Effect of integrin α5β1 inhibition on SDF-l/CXCR4- mediated choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Yang Lyu

    2018-05-01

    Full Text Available AIM: To investigate the roles of integrins in choroidal neovascularization (CNV and their associations with the stromal cell-derived factor-1 (SDF-1/CXCR4 axis. METHODS: CNV lesions were induced in mice using laser photocoagulation. After CNV induction, all animals were randomly assigned to: control, SDF-1, SDF-1+age-related macular degeneration (AMD 3100 (CXCR4 inhibitor, and SDF-1+ATN161 (integrin α5β1 inhibitor groups; their effects on CNV progression were observed using hematoxylin eosin (HE staining, fundus fluorescein angiography (FFA grading and optical coherence tomography (OCT, and their effects on CXCR4/integrin α5 expression were evaluated using Western blot and double immunofluorescence staining. Hypoxia-exposed endothelial cells (ECs were used to simulate CNV in vitro, they were treated with SDF-1, combined with CXCR4 siRNA/AMD3100 or ATN161, and expression of integrin α5, cell migration and tube formation were analyzed. RESULTS: Integrin subunit α5 increased at 3rd and 7th day and decreased at 14th day in CNV mice, with no significant change of β1-integrin. CXCR4 expression in CNV mice had persistent increase within 14d after induction. SDF-1 treatment significantly promoted the CNV progression during 3-14d. The mean CNV length in AMD3100 and ATN161 group at day 7 was 270.13 and 264.23 μm in HE images, significantly lower than the mean length in SDF-1 (345.70 μm group. AMD3100 and ATN161 also significantly reduced thickness and leakage of CNV induced by SDF-1. Mean integrin α5 positive area in SDF-1 group reached 2.31×104 μm2, significantly higher than control (1.25×104 μm2, which decreased to 1.78×104 μm2 after AMD3100 treatment. About 61.36% of ECs in CNV lesions expressed α5 in SDF-1 group, which significantly decreased to 43.12% after AMD3100 treatment. In vitro, integrin α5 peaked by 6 folds after 6h of hypoxia exposure and CXCR4 gradually increased by up to 2.3 folds after 24h of hypoxia. Approximately 25

  6. The effects of educating mothers and girls on the girls' attitudes toward puberty health: a randomized controlled trial.

    Science.gov (United States)

    Afsari, Atousa; Mirghafourvand, Mojgan; Valizadeh, Sousan; Abbasnezhadeh, Massomeh; Galshi, Mina; Fatahi, Samira

    2017-04-01

    The attitude of a girl toward her menstruation and puberty has a considerable impact on her role during motherhood, social adjustment, and future marital life. This study was conducted in 2014 with the aim of comparing the effects of educating mothers and girls on the attitudes of adolescent girls of Tabriz City, Iran, towards puberty health. This randomized control clinical trial was conducted on 364 adolescent girls who experienced menstruation. Twelve schools were selected randomly among 107 secondary schools for girls. One-third of the students of each school were selected randomly using a table of random numbers and socio-demographic and each participant was asked to answer the attitude questionnaires. The schools were randomly allocated to the groups of mother's education, girl's education, and no-intervention. The attitude questionnaire was filled out by the participants again 2 months after intervention. The general linear model, in which the baseline values were controlled, was employed to compare the scores of the three groups after the intervention. No significant differences were observed among the three groups in terms of the attitude score before intervention (p>0.05). Attitude score improvement after intervention in the girl's education group was significantly higher than the one of both mother's education (adjusted mean difference [AMD]: 1.8; [95% confidence interval (CI): 0.4-1.3]) and no-intervention groups (AMD: 1.3; [95% CI: 0.0-2.6]) by controlling the attitude score before intervention. Based on the findings, it is more effective to educate girls directly about puberty health to improve adolescent girls' attitudes than educating mothers and asking them to transfer information to the girls. Nevertheless, studies with longer training period and follow-up are proposed to determine the effects of educating girls (through their mothers) on their attitudes about puberty health.

  7. Reducing the environmental impact of trials: a comparison of the carbon footprint of the CRASH-1 and CRASH-2 clinical trials

    Science.gov (United States)

    2011-01-01

    Background All sectors of the economy, including the health research sector, must reduce their carbon emissions. The UK National Institute for Health Research has recently prepared guidelines on how to minimize the carbon footprint of research. We compare the carbon emissions from two international clinical trials in order to identify where emissions reductions can be made. Methods We conducted a carbon audit of two clinical trials (the CRASH-1 and CRASH-2 trials), quantifying the carbon dioxide emissions produced over a one-year audit period. Carbon emissions arising from the coordination centre, freight delivery, trial-related travel and commuting were calculated and compared. Results The total emissions in carbon dioxide equivalents during the one-year audit period were 181.3 tonnes for CRASH-1 and 108.2 tonnes for CRASH-2. In total, CRASH-1 emitted 924.6 tonnes of carbon dioxide equivalents compared with 508.5 tonnes for CRASH-2. The CRASH-1 trial recruited 10,008 patients over 5.1 years, corresponding to 92 kg of carbon dioxide per randomized patient. The CRASH-2 trial recruited 20,211 patients over 4.7 years, corresponding to 25 kg of carbon dioxide per randomized patient. The largest contributor to emissions in CRASH-1 was freight delivery of trial materials (86.0 tonnes, 48% of total emissions), whereas the largest contributor in CRASH-2 was energy use by the trial coordination centre (54.6 tonnes, 30% of total emissions). Conclusions Faster patient recruitment in the CRASH-2 trial largely accounted for its greatly increased carbon efficiency in terms of emissions per randomized patient. Lighter trial materials and web-based data entry also contributed to the overall lower carbon emissions in CRASH-2 as compared to CRASH-1. Trial Registration Numbers CRASH-1: ISRCTN74459797 CRASH-2: ISRCTN86750102 PMID:21291517

  8. Reducing the environmental impact of trials: a comparison of the carbon footprint of the CRASH-1 and CRASH-2 clinical trials

    Directory of Open Access Journals (Sweden)

    Roberts Ian

    2011-02-01

    Full Text Available Abstract Background All sectors of the economy, including the health research sector, must reduce their carbon emissions. The UK National Institute for Health Research has recently prepared guidelines on how to minimize the carbon footprint of research. We compare the carbon emissions from two international clinical trials in order to identify where emissions reductions can be made. Methods We conducted a carbon audit of two clinical trials (the CRASH-1 and CRASH-2 trials, quantifying the carbon dioxide emissions produced over a one-year audit period. Carbon emissions arising from the coordination centre, freight delivery, trial-related travel and commuting were calculated and compared. Results The total emissions in carbon dioxide equivalents during the one-year audit period were 181.3 tonnes for CRASH-1 and 108.2 tonnes for CRASH-2. In total, CRASH-1 emitted 924.6 tonnes of carbon dioxide equivalents compared with 508.5 tonnes for CRASH-2. The CRASH-1 trial recruited 10,008 patients over 5.1 years, corresponding to 92 kg of carbon dioxide per randomized patient. The CRASH-2 trial recruited 20,211 patients over 4.7 years, corresponding to 25 kg of carbon dioxide per randomized patient. The largest contributor to emissions in CRASH-1 was freight delivery of trial materials (86.0 tonnes, 48% of total emissions, whereas the largest contributor in CRASH-2 was energy use by the trial coordination centre (54.6 tonnes, 30% of total emissions. Conclusions Faster patient recruitment in the CRASH-2 trial largely accounted for its greatly increased carbon efficiency in terms of emissions per randomized patient. Lighter trial materials and web-based data entry also contributed to the overall lower carbon emissions in CRASH-2 as compared to CRASH-1. Trial Registration Numbers CRASH-1: ISRCTN74459797 CRASH-2: ISRCTN86750102

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Thermal structure of the Martian atmosphere retrieved from the IR spectrometry in the 15 μm CO2 band: input to MIRA

    Science.gov (United States)

    Zasova, L. V.; Formisano, V.; Grassi, D.; Igantiev, N. I.; Moroz, V. I.

    This paper describes one of the sources of the data concerning the thermal structure of the Martian atmosphere, based on the thermal IR spectrometry method. It allows to investigate the Martian atmosphere below 55 km by retrieving the temperature profiles from the 15 μm CO2 band. This approach enables to reach the vertical resolution of several kilometers and the temperature accuracy of several Kelvins. An aerosol abundance, which influences the temperature profile, is obtained from the continuum of the same spectrum parallel with the temperature profile and is taken into account in the temperature retrieval procedure in a self consistent way. Although this method has the limited vertical resolution, it possesses a significant advantage: the thermal IR spectrometry allows to monitor the temperature profiles with a good coverage both in space and local time. The Planetary Fourier spectrometer on board of Mars Express has the spectral range from 250 to 8000 cm-1 and a high spectral resolution of about 2 cm-1. Vertical temperature profiles retrieval is one of the main scientific goals of the experiment. The important data are expected to be obtained on the vertical thermal structure of the atmosphere, and its dependence on latitude, longitude, season, local time, clouds and dust loadings. These results should give a significant input in the future MIRA, being included in the Chapter “Structure of the atmosphere from the surface to 100 km”.

  11. The role of free-radical processes in the pathogenesis of age-related macular degeneration. Review

    Directory of Open Access Journals (Sweden)

    A. V. Kolesnikov

    2012-01-01

    Full Text Available the modern ideas of the role of free radical processes in the pathogenesis of age-related macular degeneration (AMD are consid- ered. Data of large randomized clinical trials on application of antioxidants for prevention and therapy AMD are provided. Possibility of the differential application of antioxidants depending on the genetic status of patients is discussed.

  12. Heterogeneity in Recent Onset Type 1 Diabetes – A Clinical Trial Perspective

    Science.gov (United States)

    Bollyky, Jennifer B.; Xu, Ping; Butte, Atul J.; Wilson, Darrell M.; Beam, Craig A.; Greenbaum, Carla J.

    2015-01-01

    Background Type 1 Diabetes TrialNet is an NIH-sponsored clinical trial network aimed at altering the disease course of type 1 diabetes. The purpose of this study is to evaluate age-dependent heterogeneity in clinical, metabolic, and immunologic characteristics of individuals with recent-onset type 1 diabetes (T1D), to identify cohorts of interest and to aid in planning of future studies. Methods 883 individuals with recent onset T1D involved in five TrialNet studies were categorized by age as: ≥ 18, age 12-17, ages 8-12, and age TrialNet studies, including C-peptide >0.2 pmol/ml, varies by age. Lower C-peptide level requirements for younger participants should be considered in the design of future trials. These data also highlight subgroups of type 1 diabetes patients, such as those with abnormal WBC or who are overweight, which allow for targeted studies of etiopathology and interventions. PMID:25689602

  13. Heterogeneity in recent-onset type 1 diabetes - a clinical trial perspective.

    Science.gov (United States)

    Bollyky, Jennifer B; Xu, Ping; Butte, Atul J; Wilson, Darrell M; Beam, Craig A; Greenbaum, Carla J

    2015-09-01

    Type 1 diabetes (T1D) TrialNet is a National Institutes of Health-sponsored clinical trial network aimed at altering the disease course of T1D. The purpose of this study is to evaluate age-dependent heterogeneity in clinical, metabolic and immunologic characteristics of individuals with recent-onset T1D, to identify cohorts of interest and to aid in planning of future studies. Eight hundred eighty-three individuals with recent-onset T1D involved in five TrialNet studies were categorized by age as follows: ≥18 years, 12-17 years, 8-12 years and TrialNet studies, including C-peptide >0.2 pmol/mL, varies by age. Lower C-peptide level requirements for younger participants and other aspects of heterogeneity of recent-onset T1D patients, such as white blood cell count abnormalities and body mass index should be considered in the design of future clinical studies. Copyright © 2015 John Wiley & Sons, Ltd.

  14. 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.

  15. The PREEMPT study - evaluating smartphone-assisted n-of-1 trials in patients with chronic pain: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Barr, Colin; Marois, Maria; Sim, Ida; Schmid, Christopher H; Wilsey, Barth; Ward, Deborah; Duan, Naihua; Hays, Ron D; Selsky, Joshua; Servadio, Joseph; Schwartz, Marc; Dsouza, Clyde; Dhammi, Navjot; Holt, Zachary; Baquero, Victor; MacDonald, Scott; Jerant, Anthony; Sprinkle, Ron; Kravitz, Richard L

    2015-02-27

    Chronic pain is prevalent, costly, and clinically vexatious. Clinicians typically use a trial-and-error approach to treatment selection. Repeated crossover trials in a single patient (n-of-1 trials) may provide greater therapeutic precision. N-of-1 trials are the most direct way to estimate individual treatment effects and are useful in comparing the effectiveness and toxicity of different analgesic regimens. The goal of the PREEMPT study is to test the 'Trialist' mobile health smartphone app, which has been developed to make n-of-1 trials easier to accomplish, and to provide patients and clinicians with tools for individualizing treatments for chronic pain. A randomized controlled trial is being conducted to test the feasibility and effectiveness of the Trialist app. A total of 244 participants will be randomized to either the Trialist app intervention group (122 patients) or a usual care control group (122 patients). Patients assigned to the Trialist app will work with their clinicians to set up an n-of-1 trial comparing two pain regimens, selected from a menu of flexible options. The Trialist app provides treatment reminders and collects data entered daily by the patient on pain levels and treatment side effects. Upon completion of the n-of-1 trial, patients review results with their clinicians and develop a long-term treatment plan. The primary study outcome (comparing Trialist to usual care patients) is pain-related interference with daily functioning at 26 weeks. Trialist will allow patients and clinicians to conduct personalized n-of-1 trials. In prior studies, n-of-1 trials have been shown to encourage greater patient involvement with care, which has in turn been associated with better health outcomes. mHealth technology implemented using smartphones may offer an efficient means of facilitating n-of-1 trials so that more patients can benefit from this approach. ClinicalTrials.gov: NCT02116621 , first registered 15 April 2014.

  16. Validation of the Diabetes Prevention Trial-Type 1 Risk Score in the TrialNet Natural History Study.

    Science.gov (United States)

    Sosenko, Jay M; Skyler, Jay S; Mahon, Jeffrey; Krischer, Jeffrey P; Beam, Craig A; Boulware, David C; Greenbaum, Carla J; Rafkin, Lisa E; Cowie, Catherine; Cuthbertson, David; Palmer, Jerry P

    2011-08-01

    We assessed the accuracy of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS), developed from the Diabetes Prevention Trial-Type 1 (DPT-1), in the TrialNet Natural History Study (TNNHS). Prediction accuracy of the DPTRS was assessed with receiver-operating characteristic curve areas. The type 1 diabetes cumulative incidence within the DPTRS intervals was compared between the TNNHS and DPT-1 cohorts. Receiver-operating characteristic curve areas for the DPTRS were substantial in the TNNHS (P < 0.001 at both 2 and 3 years). The type 1 diabetes cumulative incidence did not differ significantly between the TNNHS and DPT-1 cohorts within DPTRS intervals. In the TNNHS, 2-year and 3-year risks were low for DPTRS intervals <6.50 (<0.10 and <0.20, respectively). Thresholds ≥7.50 were indicative of high risk in both cohorts (2-year risks: 0.49 in the TNNHS and 0.51 in DPT-1). The DPTRS is an accurate and robust predictor of type 1 diabetes in autoantibody-positive populations.

  17. The N-of-1 Clinical Trial: A Timely Research Opportunity in Homeopathy.

    Science.gov (United States)

    Ulbrich-Zürni, Susanne; Teut, Michael; Roll, Stephanie; Mathie, Robert T

    2018-02-01

     The randomised controlled trial (RCT) is considered the 'gold standard' for establishing treatment efficacy or effectiveness of an intervention, but its data do not infer response in an individual patient. Individualised clinical care, a fundamental principle in complementary and alternative medicine (CAM), including homeopathy, seems well disposed in principle to being researched by single-patient (N-of-1) study design. Guidelines for reporting N-of-1 trials have recently been developed.  To overview the current status in the literature of the N-of-1 method and its application in medicine, including CAM. To consider whether the N-of-1 trial design offers an opportunity for novel research in homeopathy. N-OF-1 TRIAL DESIGN:  The N-of-1 trial applies the principles of the conventional crossover, blinded, RCT design. The treatment under study and the comparator are repeated in a randomised order, and with suitable washout time, over a defined period. N-of-1 design is constrained for use in chronic stable conditions, and for interventions that have quick onset and cessation of effect, with modest or negligible carryover. Outcome data can be aggregated and interpreted for the individual subject; they can also be pooled with data from several similar N-of-1 trials, enabling more generalisable conclusions. THE N-OF-1 TRIAL IN CAM: The typical individualisation of patient care can be accommodated in N-of-1 study design if the patient and the specific therapeutic intervention are selected within the constraints of the method. Application of the N-of-1 method in CAM has been advocated but has been mainly limited, in practice, to a small number of studies in herbal and traditional Chinese medicine. THE N-OF-1 TRIAL IN HOMEOPATHY:  Individualised homeopathy can be accommodated for investigation within the same methodological constraints; less in-depth homeopathic approaches to prescribing are also amendable to investigation using the N-of-1 method. No such studies

  18. Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Zhenglin Yang

    2010-02-01

    Full Text Available A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits.

  19. 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.

  20. Association between SERPING1 rs2511989 polymorphism and age-related macular degeneration: Meta-analysis

    Directory of Open Access Journals (Sweden)

    Yi Dong

    2015-04-01

    Full Text Available AIM: To investigate the association between SERPING1 rs2511989 (G>A polymorphism and age-related macular degeneration (AMD. METHODS: A number of electronic databases (up to July 15, 2014 were searched independently by two investigators. A Meta-analysis was performed on the association between SERPING1 rs2511989 polymorphism and AMD. Pooled odds ratios (ORs with 95% confidence intervals (CIs were estimated. RESULTS: Eight studies with 16 cohorts consisting of 9163 cases and 6813 controls were included in this Meta-analysis. There was no significant association between rs2511989 polymorphism and AMD under all genetic models in overall estimates (A vs G: OR= 0.938, 95%CI =0.858-1.025; AA vs GG:OR =0.871, 95%CI =0.719-1.056; AG vs GG: OR =0.944, 95%CI =0.845-1.054; AA+AG vs GG: OR =0.927, 95% CI =0.823-1.044; AA vs AG+GG: OR =0.890, 95%CI =0.780-1.034. Cumulative Meta-analyses also showed a trend of no association between rs2511989 polymorphism and AMD as information accumulated by year. Subgroup analysis and Meta-regression analysis indicated that age-matching status was the main source of heterogeneity. Sensitivity analysis found the results in overall comparisons and subgroup comparisons of white subjects under the allele model were found to have significantly statistical differences after studies deviating from Hardy-Weinberg equilibrium (HWE were excluded (overall: OR=0.918, 95%CI = 0.844-0.999, P =0.049; whites: OR =0.901, 95%CI = 0.817-0.994, P =0.038. However, the results were not sufficiently robust for further sensitivity analysis and statistical differences disappeared on applying Bonferroni correction (with a significance level set at 0.05/25. CONCLUSION: This Meta-analysis indicates that SERPING1 rs2511989 polymorphism and AMD tend to have no association with each other. Age matching status is a big confounding factor, and more studies with subtle designs are warranted in future.

  1. 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

  2. Overview of clinical trials for dry age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    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.

  3. 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

  4. Crystal Structure of the Yeast Nicotinamidase Pnc1p

    OpenAIRE

    Hu, Gang; Taylor, Alexander B.; McAlister-Henn, Lee; Hart, P. John

    2007-01-01

    The yeast nicotinamidase Pnc1p acts in transcriptional silencing by reducing levels of nicotinamide, an inhibitor of the histone deacetylase Sir2p. The Pnc1p structure was determined at 2.9 Å resolution using MAD and MIRAS phasing methods after inadvertent crystallization during the pursuit of the structure of histidine-tagged yeast isocitrate dehydrogenase (IDH). Pnc1p displays a cluster of surface histidine residues likely responsible for its co-fractionation with IDH from Ni2+-coupled chro...

  5. Systemic frequencies of T helper 1 and T helper 17 cells in patients with age-related macular degeneration: A case-control study

    DEFF Research Database (Denmark)

    Singh, Amardeep; Subhi, Yousif; Nielsen, Marie Krogh

    2017-01-01

    Age-related macular degeneration (AMD) is a degenerative disease of the retina and a leading cause of irreversible vision loss. We investigated the systemic differences in the frequency of T helper (Th) 1 and Th17 cells in patients with non-exudative and exudative AMD and compared to age...

  6. 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.

  7. 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

  8. Type 1 Diabetes TrialNet: A Multifaceted Approach to Bringing Disease-Modifying Therapy to Clinical Use in Type 1 Diabetes.

    Science.gov (United States)

    Bingley, Polly J; Wherrett, Diane K; Shultz, Ann; Rafkin, Lisa E; Atkinson, Mark A; Greenbaum, Carla J

    2018-04-01

    What will it take to bring disease-modifying therapy to clinical use in type 1 diabetes? Coordinated efforts of investigators involved in discovery, translational, and clinical research operating in partnership with funders and industry and in sync with regulatory agencies are needed. This Perspective describes one such effort, Type 1 Diabetes TrialNet, a National Institutes of Health-funded and JDRF-supported international clinical trials network that emerged from the Diabetes Prevention Trial-Type 1 (DPT-1). Through longitudinal natural history studies, as well as trials before and after clinical onset of disease combined with mechanistic and ancillary investigations to enhance scientific understanding and translation to clinical use, TrialNet is working to bring disease-modifying therapies to individuals with type 1 diabetes. Moreover, TrialNet uses its expertise and experience in clinical studies to increase efficiencies in the conduct of trials and to reduce the burden of participation on individuals and families. Herein, we highlight key contributions made by TrialNet toward a revised understanding of the natural history of disease and approaches to alter disease course and outline the consortium's plans for the future. © 2018 by the American Diabetes Association.

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

    Science.gov (United States)

    Bloch, Sara Brandi

    2013-11-01

    comparing our results with other pro re nata regimens based on a monthly reassessment of disease activity that our patients could gain substantial vision if we optimized our frequency of re-examinations. The analysis demonstrated that we could discontinue treatment in patients who had a poor visual acuity during the first 3 months of treatment and that visual outcome could be improved by minimizing the delay from diagnosis of neovascular AMD to first administered ranibizumab injection. This study led to changes in departmental treatment procedures. In the second study, we found that type 2 CNV lesions had a higher hazard ratio as compared to type 1 CNV lesions in developing subfoveal fibrosis. Prominent subfoveal fibrous tissue and fibrous tissue with retinal atrophy led to poorer visual performances in eyes with neovascular AMD after 2 years of treatment as compared with eyes without subfoveal fibrous tissue. In the development of randomized clinical trials designed to address how treatment with VEGF inhibitors can be improved by limiting the growth of subfoveal fibrous tissue or neuroretinal atrophy, it is important to define subgroups of eyes at risk of these pathological changes. The second PhD study has contributed to identify this subgroup of eyes. The third study included in this PhD thesis revealed that the annual incidence rate of AMD-related legally blind persons registered in Denmark has halved during the last decade, with the bulk of the reduction observed after the introduction of ranibizumab for neovascular AMD.

  10. Lower cognitive function in patients with age-related macular degeneration: a meta-analysis

    Science.gov (United States)

    Zhou, Li-Xiao; Sun, Cheng-Lin; Wei, Li-Juan; Gu, Zhi-Min; Lv, Liang; Dang, Yalong

    2016-01-01

    Objective To investigate the cognitive impairment in patients with age-related macular degeneration (AMD). Methods Relevant articles were identified through a search of the following electronic databases through October 2015, without language restriction: 1) PubMed; 2) the Cochrane Library; 3) EMBASE; 4) ScienceDirect. Meta-analysis was conducted using STATA 12.0 software. Standardized mean differences with corresponding 95% confidence intervals were calculated. All of the included studies met the following four criteria: 1) the study design was a case–control or randomized controlled trial (RCT) study; 2) the study investigated cognitive function in the patient with AMD; 3) the diagnoses of AMD must be provided; 4) there were sufficient scores data to extract for evaluating cognitive function between cases and controls. The Newcastle–Ottawa Scale criteria were used to assess the methodological quality of the studies. Results Of the initial 278 literatures, only six case–control and one RCT studies met all of the inclusion criteria. A total of 794 AMD patients and 1,227 controls were included in this study. Five studies were performed with mini-mental state examination (MMSE), two studies with animal fluency, two studies with trail making test (TMT)-A and -B, one study with Mini-Cog. Results of the meta-analysis revealed lower cognitive function test scores in patients with AMD, especially with MMSE and Mini-Cog test (P≤0.001 for all). The results also showed that differences in the TMT-A (except AMD [total] vs controls) and TMT-B test had no statistical significance (P>0.01). The Newcastle–Ottawa Scale score was ≥5 for all of the included studies. Based on the sensitivity analysis, no single study influenced the overall pooled estimates. Conclusion This meta-analysis suggests lower cognitive function test scores in patients with AMD, especially with MMSE and Mini-Cog test. The other cognitive impairment screening tests, such as animal fluency test and

  11. Recent clinical trials in idiopathic pulmonary fibrosis and the BUILD-1 study

    Directory of Open Access Journals (Sweden)

    K. K. Brown

    2008-12-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF, the most common of the interstitial pneumonias, is a progressive, life-limiting disease for which there are no truly effective therapies. In patients with biopsy-confirmed IPF, median survival is still <3 yrs. Although potent immunosuppressive therapy has underpinned the treatment of IPF in recent years and remains the standard of care, there is little quality evidence to support the efficacy and safety of traditional therapeutic strategies. This has spurred the search for new treatments for IPF and has led to a series of clinical trials of new therapies, seven of which are reviewed herein. They include the Bosentan Use in Interstitial Lung Disease (BUILD-1 trial, the results of which are discussed in detail, the European Idiopathic Pulmonary Fibrosis International Group Exploring N-acetylcysteine 1 Annual (IFIGENIA trial, the interferon gamma (GIPF-001 trial and the INSPIRE trial, as well as trials of anticoagulant therapy, pirfenidone and etanercept. Treatment trials in IPF are hindered by difficulties in achieving a secure diagnosis of IPF and the lack of validated outcome measures that represent either improvement or progression of disease. These and other limitations are discussed in the present article, as well as how some of these problems might be addressed in future trials. Although few of the seven studies met their primary end-points, marginal trends either on primary end-points or statistically significant trends on exploratory end-points were a recurrent theme in most trials. In the BUILD-1 trial, for example, a trend in favour of bosentan was observed on time-to-disease progression or death.

  12. 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.

  13. Diminishing Risk for Age-Related Macular Degeneration with Nutrition: A Current View

    Directory of Open Access Journals (Sweden)

    Allen Taylor

    2013-07-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies, because they are more affordable than clinical therapies, do not require specialists for administration and many studies suggest a benefit of micro- and macro-nutrients with respect to AMD with few, if any, adverse effects. The goal of this review is to provide information from recent literature on the value of various nutrients, particularly omega-3 fatty acids, lower glycemic index diets and, perhaps, some carotenoids, with regard to diminishing risk for onset or progression of AMD. Results from the upcoming Age-Related Eye Disease Study (AREDS II intervention trial should be particularly informative.

  14. Diminishing Risk for Age-Related Macular Degeneration with Nutrition: A Current View

    Science.gov (United States)

    Schleicher, Molly; Weikel, Karen; Garber, Caren; Taylor, Allen

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies, because they are more affordable than clinical therapies, do not require specialists for administration and many studies suggest a benefit of micro- and macro-nutrients with respect to AMD with few, if any, adverse effects. The goal of this review is to provide information from recent literature on the value of various nutrients, particularly omega-3 fatty acids, lower glycemic index diets and, perhaps, some carotenoids, with regard to diminishing risk for onset or progression of AMD. Results from the upcoming Age-Related Eye Disease Study (AREDS) II intervention trial should be particularly informative. PMID:23820727

  15. El capital social y el acceso a tecnología agrícola en comunidades afro de los valles Chota y cuenca del río Mira e indígenas de Saquisilí

    OpenAIRE

    Mazón Ortiz, Nelson Gonzalo

    2011-01-01

    La presente investigación trata de entender, desde el paradigma del capital social; si el acceso a tecnología e información agrícola de las comunidades afro del valle del Río Chota – Mira e indígenas de Saquisilí tiene relación con las prácticas de confianza, cooperación, cohesión, asociatividad y redes presentes en los mencionados territorios. Para recuperar las dimensiones macro y micro del capital social se combinaron métodos cuantitativos y cualitativos, a través de una encuesta estructu...

  16. 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.

  17. 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.

  18. Entry inhibitor-based microbicides are active in vitro against HIV-1 isolates from multiple genetic subtypes

    International Nuclear Information System (INIS)

    Ketas, Thomas J.; Schader, Susan M.; Zurita, Juan; Teo, Esther; Polonis, Victoria; Lu Min; Klasse, Per Johan; Moore, John P.

    2007-01-01

    Inhibitors of viral entry are under consideration as topical microbicides to prevent HIV-1 sexual transmission. Small molecules targeting HIV-1 gp120 (BMS-378806) or CCR5 (CMPD167), and a peptide fusion inhibitor (C52L), each blocks vaginal infection of macaques by a SHIV. A microbicide, however, must be active against multiple HIV-1 variants. We therefore tested BMS-C (a BMS-378806 derivative), CMPD167, C52L and the CXCR4 ligand AMD3465, alone and in combination, against 25 primary R5, 12 X4 and 7 R5X4 isolates from subtypes A-G. At high concentrations (0.1-1 μM), the replication of most R5 isolates in human donor lymphocytes was inhibited by > 90%. At lower concentrations, double and triple combinations were more effective than individual inhibitors. Similar results were obtained with X4 viruses when AMD3465 was substituted for CMPD167. The R5X4 viruses were inhibited by combining AMD3465 with CMPD167, or by the coreceptor-independent compounds. Thus, combining entry inhibitors may improve microbicide effectiveness

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

    Directory of Open Access Journals (Sweden)

    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

  20. Medición de la concentración de sedimentos en suspensión mediante dispositivos ópticos y acústicos: aplicación en sistemas tropicales (Delta del río Mira, Colombia Measurement of suspended sediment concentration using optical and acoustic devices: application in tropical systems (Mira River Delta, Colombia

    Directory of Open Access Journals (Sweden)

    Juan Camilo Restrepo

    2012-03-01

    Full Text Available En los últimos años, la utilización de dispositivos ópticos (e.g. Optical Backscatter Sensor, OBS y acústicos (e.g. Acoustic Doppler Current Profiler-ADCP ha permitido monitorear con mayor resolución la variabilidad temporal y espacial de la concentración de sedimentos en suspensión (CSS en ambientes costeros y estuarinos. Sin embargo, la aplicación de estas técnicas en ambientes tropicales ha tenido un desarrollo incipiente. En el presente trabajo se implementó un procedimiento de calibración para un dispositivo OBS-3A, tomando como patrón de calibración sedimento seco y desagregado de la zona de estudio. Además, se presentan las correcciones a las que se debe someter la señal de respuesta del ADCP, debido a la dispersión geométrica, la atenuación del sonido por el agua y las partículas en suspensión, para que sea útil en la estimación de CSS. El ADCP y el OBS-3A se utilizaron para realizar mediciones de CSS en el sistema deltaico del río Mira (isla del Morro y desembocadura principal, ubicado sobre la costa del Pacífico colombiano, un ambiente costero tropical donde algunos factores oceanográficos y estuarinos son determinantes en la señal de respuesta de los equipos.In recent years, the use of optical (Optical Backscatter Sensor, OBS and acoustic (Acoustic Current Doppler Profiler, ADCP instruments has allowed monitoring the temporal and spatial variation of the suspended sediment concentration (SSC in coastal and estuarine environments with greater resolution. However, the development of the application of those techniques in tropical environments is incipient. For this study, an OBS-3A calibration procedure was implemented, taking dry and desegregated sediment from the study zone as a calibrating pattern. Moreover, we present the corrections required for the ADCP signal to be useful in the estimation of SSC due to geometrical spreading, the attenuation of sound by water, and the particles in suspension. The ADCP

  1. Nye muligheder på vej til behandling af aldersrelateret maculadegeneration

    DEFF Research Database (Denmark)

    Rafique, Irfan; Munch, Inger Christine

    2013-01-01

    Currently, age-related macular degeneration (AMD) is untreatable, except for its neovascular complications. We review the primary pathogenesis of AMD and the pipeline of experimental interventions currently under way in clinical trials. They focus on four mechanisms: suppression of inflammation......, visual cycle modification, prevention of oxidative damage and neuroprotection. Regulatory approval is years away, but the development may be accelerated by re-purposing of medications designed for systemic diseases....

  2. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration.

    Science.gov (United States)

    Evans, Jennifer R; Lawrenson, John G

    2012-11-14

    It has been proposed that antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of age-related macular degeneration (AMD). The objective of this review was to assess the effects of antioxidant vitamin or mineral supplementation on the progression of AMD in people with AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 8), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2012), EMBASE (January 1980 to August 2012), Allied and Complementary Medicine Database (AMED) (January 1985 to August 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), 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 20 August 2012. We searched the reference lists of identified reports and the Science Citation Index. We contacted investigators and experts in the field for details of unpublished studies. We also searched for systematic reviews of harms of vitamin supplements. We included randomised trials comparing antioxidant vitamin or mineral supplementation (alone or in combination) to placebo or no intervention in people with AMD. Two authors assessed risk of bias and extracted data from the included trials. Where appropriate, we pooled data using a random-effects model unless three or fewer trials were available in which case we used a fixed-effect model. Thirteen trials (6150 participants) were included in this review. Over

  3. Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset

    DEFF Research Database (Denmark)

    Cabrera, Susanne M; Wang, Xujing; Chen, Yi-Guang

    2016-01-01

    It was hypothesized that IL-1 antagonism would preserve β-cell function in new onset Type 1 diabetes (T1D). However, the Anti-Interleukin-1 in Diabetes Action (AIDA) and TrialNet Canakinumab (TN-14) trials failed to show efficacy of IL-1 receptor antagonist (IL-1Ra) or canakinumab, as measured...

  4. Strategies for improving early detection and diagnosis of neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Keane PA

    2015-02-01

    Full Text Available Pearse A Keane,1 Gabriella de Salvo,2 Dawn A Sim,1 Srini Goverdhan,2 Rupesh Agrawal,1 Adnan Tufail1 1NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, 2Department of Ophthalmology, University Hospital Southampton NHS Foundation Trust, Southampton, UK Abstract: Treatment of the neovascular form of age-related macular degeneration (AMD has been revolutionized by the introduction of such agents as ranibizumab, bevacizumab, and aflibercept. As a result, the incidence of legal blindness occurring secondary to AMD has fallen dramatically in recent years in many countries. While these agents have undoubtedly been successful in reducing visual impairment and blindness, patients with neovascular AMD typically lose some vision over time, and often lose the ability to read, drive, or perform other important activities of daily living. Efforts are therefore under way to develop strategies that allow for earlier detection and treatment of this disease. In this review, we begin by providing an overview of the rationale for, and the benefits of, early detection and treatment of neovascular AMD. To achieve this, we begin by providing an overview of the pathophysiology and natural history of choroidal neovascularization, before reviewing the evidence from both clinical trials and “real-world” outcome studies. We continue by highlighting an area that is often overlooked: the importance of patient education and awareness for early AMD detection. We conclude the review by reviewing an array of both established and emerging technologies for early detection of choroidal neovascularization, ranging from Amsler chart testing, to hyperacuity testing, to advanced imaging techniques, such as optical coherence tomography. Keywords: Amsler, detection, choroidal neovascularization, hyperacuity, optical coherence tomography

  5. HTRA1 promoter polymorphism predisposes Japanese to age-related macular degeneration.

    Science.gov (United States)

    Yoshida, Tsunehiko; DeWan, Andrew; Zhang, Hong; Sakamoto, Ryosuke; Okamoto, Haru; Minami, Masayoshi; Obazawa, Minoru; Mizota, Atsushi; Tanaka, Minoru; Saito, Yoshihiro; Takagi, Ikue; Hoh, Josephine; Iwata, Takeshi

    2007-04-04

    To study the effect of candidate single nucleotide polymorphisms (SNPs) on chromosome 10q26, recently shown to be associated with wet age-related macular degeneration (AMD) in Chinese and Caucasian cohorts, in a Japanese cohort. Using genomic DNA isolated from peripheral blood of wet AMD cases and age-matched controls, we genotyped two SNPs, rs10490924, and rs11200638, on chromosome 10q26, 6.6 kb and 512 bp upstream of the HTRA1 gene, respectively, using temperature gradient capillary electrophoresis (TGCE) and direct sequencing. Association tests were performed for individual SNPs and jointly with SNP complement factor H (CFH) Y402H. The two SNPs, rs10490924 and rs11200638, are in complete linkage disequilibrium (D'=1). Previous sequence comparisons among seventeen species revealed that the genomic region containing rs11200638 was highly conserved while the region surrounding rs10490924 was not. The allelic association test for rs11200638 yielded a p-value fashion: Odds ratio was 10.1 (95% CI 4.36, 23.06), adjusted for SNP CFH 402, for those carrying two copies of the risk allele, whereas indistinguishable from unity if carrying only one risk allele. The HTRA1 promoter polymorphism, rs11200638, is a strong candidate with a functional consequence that predisposes Japanese to develop neovascular AMD.

  6. A Canadian Critical Care Trials Group project in collaboration with the international forum for acute care trialists - Collaborative H1N1 Adjuvant Treatment pilot trial (CHAT: study protocol and design of a randomized controlled trial

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    Kruger Peter

    2011-03-01

    Full Text Available Abstract Background Swine origin influenza A/H1N1 infection (H1N1 emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes. Methods/Design A multi-national, pilot randomized controlled trial (RCT of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM, waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to

  7. Cluster randomised trial of a school-community child health promotion and obesity prevention intervention: findings from the evaluation of fun ‘n healthy in Moreland!

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    Elizabeth Waters

    2017-08-01

    Full Text Available Abstract Background Multi-level, longer-term obesity prevention interventions that focus on inequalities are scarce. Fun ‘n healthy in Moreland! aimed to improve child adiposity, school policies and environments, parent engagement, health behaviours and child wellbeing. Methods All children from primary schools in an inner urban, culturally diverse and economically disadvantaged area in Victoria, Australia were eligible for participation. The intervention, fun ‘n healthy in Moreland!, used a Health Promoting Schools Framework and provided schools with evidence, school research data and part time support from a Community Development Worker to develop health promoting strategies. Comparison schools continued as normal. Participants were not blinded to intervention status. The primary outcome was change in adiposity. Repeated cross-sectional design with nested longitudinal subsample. Results Students from twenty-four primary schools (clusters were randomised (aged 5–12 years at baseline. 1426 students from 12 intervention schools and 1539 students from 10 comparison schools consented to follow up measurements. Despite increased prevalence of healthy weight across all schools, after 3.5 years of intervention there was no statistically significant difference between trial arms in BMI z score post-intervention (Mean (sd: Intervention 0.68(1.16; Comparison: 0.72(1.12; Adjusted mean difference (AMD: -0.05, CI: -0.19 to 0.08, p = 0.44. Children from intervention schools consumed more daily fruit serves (AMD: 0.19, CI:0.00 to 0.37, p = 0.10, were more likely to have water (AOR: 1.71, CI:1.05 to 2.78, p = 0.03 and vegetables (AOR: 1.23, CI: 0.99 to 1.55, p = 0.07, and less likely to have fruit juice/cordial (AOR: 0.58, CI:0.36 to 0.93, p = 0.02 in school lunch compared to children in comparison schools. More intervention schools (8/11 had healthy eating and physical activity policies compared with comparison schools (2/9. Principals and

  8. Viral linkage in HIV-1 seroconverters and their partners in an HIV-1 prevention clinical trial.

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    Mary S Campbell

    2011-03-01

    Full Text Available Characterization of viruses in HIV-1 transmission pairs will help identify biological determinants of infectiousness and evaluate candidate interventions to reduce transmission. Although HIV-1 sequencing is frequently used to substantiate linkage between newly HIV-1 infected individuals and their sexual partners in epidemiologic and forensic studies, viral sequencing is seldom applied in HIV-1 prevention trials. The Partners in Prevention HSV/HIV Transmission Study (ClinicalTrials.gov #NCT00194519 was a prospective randomized placebo-controlled trial that enrolled serodiscordant heterosexual couples to determine the efficacy of genital herpes suppression in reducing HIV-1 transmission; as part of the study analysis, HIV-1 sequences were examined for genetic linkage between seroconverters and their enrolled partners.We obtained partial consensus HIV-1 env and gag sequences from blood plasma for 151 transmission pairs and performed deep sequencing of env in some cases. We analyzed sequences with phylogenetic techniques and developed a Bayesian algorithm to evaluate the probability of linkage. For linkage, we required monophyletic clustering between enrolled partners' sequences and a Bayesian posterior probability of ≥ 50%. Adjudicators classified each seroconversion, finding 108 (71.5% linked, 40 (26.5% unlinked, and 3 (2.0% indeterminate transmissions, with linkage determined by consensus env sequencing in 91 (84%. Male seroconverters had a higher frequency of unlinked transmissions than female seroconverters. The likelihood of transmission from the enrolled partner was related to time on study, with increasing numbers of unlinked transmissions occurring after longer observation periods. Finally, baseline viral load was found to be significantly higher among linked transmitters.In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner

  9. 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.

  10. Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages.

    Science.gov (United States)

    Schick, Tina; Altay, Lebriz; Viehweger, Eva; Hoyng, Carel B; den Hollander, Anneke I; Felsch, Moritz; Fauser, Sascha

    2016-01-01

    Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic factors and different AMD stages depending on unilateral and bilateral disease severity. In this case-control study, participants were assigned to nine AMD severity stages based on the characteristics of each eye. 18 single nucleotide polymorphisms (SNPs) were genotyped and attempted to correlate with AMD severity stages by uni- and multivariate logistic regression analyses and trend analyses. Area under the receiver operating characteristic curves (AUC) were calculated. Of 3444 individuals 1673 were controls, 379 had early AMD, 333 had intermediate AMD and 989 showed late AMD stages. With increasing severity of disease and bilateralism more SNPs with significant associations were found. Odds ratios, especially for the main risk polymorphisms in ARMS2 (rs10490924) and CFH (rs1061170), gained with increasing disease severity and bilateralism (exemplarily: rs1061170: unilateral early AMD: OR = 1.18; bilateral early AMD: OR = 1.20; unilateral intermediate AMD: OR = 1.28; bilateral intermediate AMD: OR = 1.39, unilateral geographic atrophy (GA): OR = 1.50; bilateral GA: OR = 1.71). Trend analyses showed pstages was lowest for unilateral early AMD (AUC = 0.629) and showed higher values in more severely and bilaterally affected individuals being highest for late AMD with GA in one eye and neovascular AMD in the other eye (AUC = 0.957). The association of known genetic risk factors with AMD became stronger with increasing disease severity, which also led to an increasing discriminative ability of AMD cases and controls. Genetic predisposition was also associated with the disease severity of the fellow-eye, highlighting the importance of both eyes in AMD patients.

  11. 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...

  12. Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset.

    Science.gov (United States)

    Cabrera, Susanne M; Wang, Xujing; Chen, Yi-Guang; Jia, Shuang; Kaldunski, Mary L; Greenbaum, Carla J; Mandrup-Poulsen, Thomas; Hessner, Martin J

    2016-04-01

    It was hypothesized that IL-1 antagonism would preserve β-cell function in new onset Type 1 diabetes (T1D). However, the Anti-Interleukin-1 in Diabetes Action (AIDA) and TrialNet Canakinumab (TN-14) trials failed to show efficacy of IL-1 receptor antagonist (IL-1Ra) or canakinumab, as measured by stimulated C-peptide response. Additional measures are needed to define immune state changes associated with therapeutic responses. Here, we studied these trial participants with plasma-induced transcriptional analysis. In blinded analyses, 70.2% of AIDA and 68.9% of TN-14 participants were correctly called to their treatment arm. While the transcriptional signatures from the two trials were distinct, both therapies achieved varying immunomodulation consistent with IL-1 inhibition. On average, IL-1 antagonism resulted in modest normalization relative to healthy controls. At endpoint, signatures were quantified using a gene ontology-based inflammatory index, and an inverse relationship was observed between measured inflammation and stimulated C-peptide response in IL-1Ra- and canakinumab-treated patients. Cytokine neutralization studies showed that IL-1α and IL-1β additively contribute to the T1D inflammatory state. Finally, analyses of baseline signatures were indicative of later therapeutic response. Despite the absence of clinical efficacy by IL-1 antagonist therapy, transcriptional analysis detected immunomodulation and may yield new insight when applied to other clinical trials. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Kültürel Miras için Zenginleştirilmiş Gerçeklik Uygulamaları

    Directory of Open Access Journals (Sweden)

    Erkan Bostancı

    2011-03-01

    Full Text Available Bu makale bilgisayar grafiği alanının iki ilgi çekici konusu üzerinde yapılan güncel çalışmaların bir incelemesini sunmaktadır. Geniş çalışma alanları olan Zenginleştirilmiş Gerçeklik ve İzleme alanlarında yapılan yeni çalışmalar incelenirken, özellikle de makalede bahsedilen sebeplerden dolayı kültürel miras üzerine yapılan çalışmalar vurgulanmıştır. Belirtilen uygulama türü için birçok kaynağa sahip olan ülkemizde yeni bir çalışma alanı başlamasına yardımcı olmak amacıyla bu iki çalışma alanından birçok yöntem ve örnek uygulama yüzeysel fakat açık bir dille anlatılmıştır. Bu uygulamalarda genel olarak karşılaşılan sorunlar ortaya konulup, olası çözüm önerileri sunulmuştur. Ülkemizde yapılan ilgili çalışmalardan da örnekler verildikten sonra geliştirilen örnek "Masaüstü Tarih" çalışmasıyla da anlatım pekiştirilerek somut bir örnek ortaya konmuştur.

  14. The design and implementation of a study to investigate the effectiveness of community vs hospital eye service follow-up for patients with neovascular age-related macular degeneration with quiescent disease.

    Science.gov (United States)

    Taylor, J; Scott, L J; Rogers, C A; Muldrew, A; O'Reilly, D; Wordsworth, S; Mills, N; Hogg, R; Violato, M; Harding, S P; Peto, T; Townsend, D; Chakravarthy, U; Reeves, B C

    2016-01-01

    IntroductionStandard treatment for neovascular age-related macular degeneration (nAMD) is intravitreal injections of anti-VEGF drugs. Following multiple injections, nAMD lesions often become quiescent but there is a high risk of reactivation, and regular review by hospital ophthalmologists is the norm. The present trial examines the feasibility of community optometrists making lesion reactivation decisions.MethodsThe Effectiveness of Community vs Hospital Eye Service (ECHoES) trial is a virtual trial; lesion reactivation decisions were made about vignettes that comprised clinical data, colour fundus photographs, and optical coherence tomograms displayed on a web-based platform. Participants were either hospital ophthalmologists or community optometrists. All participants were provided with webinar training on the disease, its management, and assessment of the retinal imaging outputs. In a balanced design, 96 participants each assessed 42 vignettes; a total of 288 vignettes were assessed seven times by each professional group.The primary outcome is a participant's judgement of lesion reactivation compared with a reference standard. Secondary outcomes are the frequency of sight threatening errors; judgements about specific lesion components; participant-rated confidence in their decisions about the primary outcome; cost effectiveness of follow-up by optometrists rather than ophthalmologists.DiscussionThis trial addresses an important question for the NHS, namely whether, with appropriate training, community optometrists can make retreatment decisions for patients with nAMD to the same standard as hospital ophthalmologists. The trial employed a novel approach as participation was entirely through a web-based application; the trial required very few resources compared with those that would have been needed for a conventional randomised controlled clinical trial.

  15. Communication skills training for mental health professionals working with people with severe mental illness.

    Science.gov (United States)

    Papageorgiou, Alexia; Loke, Yoon K; Fromage, Michelle

    2017-06-13

    estimates of the risk ratio (RR) and their 95% confidence intervals (CI) using a fixed-effect model. For continuous outcomes, we planned to estimate the mean difference (MD) between groups, or obtain the adjusted mean difference (aMD) where available for cluster-randomised trials. If heterogeneity had been identified, we would have explored this using a random-effects model. We used GRADE to create a 'Summary of findings' table and we assessed risk of bias for the one included study. We included one pilot cluster-RCT that recruited a total of 21 psychiatrists and 97 patients. The psychiatrists were randomised to a training programme in communication skills, compared to a no specific training (NST) programme. The trial provided useable data for only one of our prestated outcomes of interest, patient satisfaction. The trial did not report global state but did report mental state and, as global state data were not available, we included these mental state data in the 'Summary of findings' table. There was high risk of bias from attrition because of substantial losses to follow-up and incomplete outcome data.Patient satisfaction was measured as satisfaction with treatment and 'experience of therapeutic relationship' at medium term (five months). Satisfaction with treatment was similar between the CST and NST group using the Client Satisfaction Questionnaire (CSQ-8) (1 RCT, n = 66/97*, aMD 1.77 95% CI - 0.13 to 3.68, low-quality evidence). When comparing patient experience of the therapeutic relationship using the STAR-P scale, participants in the CST group rated the therapeutic relationship more positively than participants in the NST group (1 RCT, n = 63/97, aMD 0.21 95% CI 0.01 to 0.41, low-quality evidence).Mental state scores on the Positive and Negative Syndrome Scale (PANSS) were similar between treatment groups for general symptoms (1 RCT, n = 59/97, aMD 4.48 95% CI -2.10 to 11.06, low-quality evidence), positive symptoms (1 RCT, n = 59/97, aMD -0.23, 95% CI -2.91 to 2

  16. N-of-1 trials in the clinical care of patients in developing countries: a systematic review.

    Science.gov (United States)

    Alemayehu, Chalachew; Nikles, Jane; Mitchell, Geoffrey

    2018-04-23

    N-of-1 trials have a potential role in promoting patient-centered medicine in developing countries. However, there is limited academic literature regarding the use of N-of-1 trials in the clinical care of patients in resource-poor settings. To assess the extent of use, purpose and treatment outcome of N-of-1 trials in developing countries. A systematic review of clinical N-of-1 trials was conducted between 1985 and September 2015 using PubMed, Embase, CINAHL, Web of Science and the Cochrane Central Register of Controlled Trials. Grey literature databases and clinical trial registers were also searched. This review included randomized, multi-cycle, crossover within individual patient trials involving drug intervention. Quality assessment and data extraction were conducted by two independent reviewers. Out of 131 N-of-1 trials identified, only 6 (4.5%) were conducted in developing countries. The major reason that N-of-1 trials were used was to provide evidence on feasibility, effectiveness and safety of therapies. A total of 72 participants were involved in these trials. Five of the studies were conducted in China and all evaluated Chinese traditional medicine. The remaining study was conducted in Brazil. The completion rate was 93%. More than half, 46 (69%) of subjects made medication changes consistent with trial results after trial completion. A number of threats to the validity of the included evidence limited the validity of the evidence. In particular, the estimated overall effect in four of the included studies could have been affected by the "carry over" of the previous treatment effect as no adequate pharmacokinetic evidence regarding traditional medicines was presented. The prevalence and scope of N-of-1 trials in developing countries is low. A coordinated effort among government, clinicians, researchers and sponsor organizations is needed to increase their uptake and quality in developing countries. PROSPERO CRD42015026841 .

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  19. Omics in Ophthalmology: Advances in Genomics and Precision Medicine for Leber Congenital Amaurosis and Age-Related Macular Degeneration.

    Science.gov (United States)

    den Hollander, Anneke I

    2016-03-01

    The genomic revolution has had a huge impact on our understanding of the genetic defects and disease mechanisms underlying ophthalmic diseases. Two examples are discussed here. The first is Leber congenital amaurosis (LCA), a severe inherited retinal dystrophy leading to severe vision loss in children, and the second is age-related macular degeneration (AMD), the most common cause of vision loss in the elderly. Twenty years ago, the genetic causes of these diseases were unknown. Currently, more than 20 LCA genes have been identified, and genetic testing can now successfully identify the genetic defects in at least 75% of all LCA cases. Gene-specific treatments have entered the clinical trial phase for three LCA genes, and for seven LCA genes gene-specific therapies have been tested in model systems. Age-related macular degeneration is a multifactorial disease caused by a combination of genetic and environmental factors. Currently, more than 40 loci have been identified for AMD, accounting for 15%-65% of the total genetic contribution to AMD. Despite the progress that has been made so far, genetic testing is not yet recommended for AMD, but this may change if we move to clinical trials or treatments that are dependent on an individual's genotype. The identification of serum or plasma biomarkers using other "-omics" technologies may further improve predictive tests and our understanding of the disease mechanisms of AMD. Ultimately, it is anticipated that predictive tests will help to stratify patients for the most suitable therapy, which will enable the development of precision medicine, tailored to individual needs.

  20. Améjimínaa majcho: "La comida de nuestra gente". Etnografía de la alimentación entre los miraña

    Directory of Open Access Journals (Sweden)

    Carmensusana Tapia Morales

    2009-01-01

    Full Text Available Para los miraña, pueblo indígena que habita el medio y bajo río Caquetá (región amazónica colombiana, saber cocinar implica saber cultivar, cosechar, pescar y recolectar. Dicho conocimiento se enlaza, por tanto, con la dimensión tangible de su mundo, donde el río, la selva, el lugar de la plantación (o "chagra" y la casa comunal ancestral (o "maloca" se erigen como espacios culturales y microcosmos que representan la inmensidad del territorio ancestral. El propósito de este artículo es evidenciar el mundo existente en el saber culinario que envuelve a la práctica alimenticia de los indígenas de la región amazónica colombiana, haciendo énfasis en el interés en el conocimiento gastronómico de estos indígenas, grupo aborigen poco investigado en el campo antropológico y etnográfico, lo que hace aún más necesario reivindicar todo aquello que forma parte de su saber tradicional.

  1. Salmeterol/fluticasone stable-dose treatment compared with formoterol/budesonide adjustable maintenance dosing: impact on health-related quality of life

    Directory of Open Access Journals (Sweden)

    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

  2. A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy.

    Science.gov (United States)

    Dirksen, A; Dijkman, J H; Madsen, F; Stoel, B; Hutchison, D C; Ulrik, C S; Skovgaard, L T; Kok-Jensen, A; Rudolphus, A; Seersholm, N; Vrooman, H A; Reiber, J H; Hansen, N C; Heckscher, T; Viskum, K; Stolk, J

    1999-11-01

    We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha(1)-antitrypsin, can prevent the progression of pulmonary emphysema in patients with alpha(1)-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with alpha(1)-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV(1) between 30% and 80% of predicted) participated in a double-blind trial of alpha(1)-antitrypsin augmentation therapy. The patients were randomized to either alpha(1)-antitrypsin (250 mg/kg) or albumin (625 mg/kg) infusions at 4-wk intervals for at least 3 yr. Self-administered spirometry performed every morning and evening at home showed no significant difference in decline of FEV(1) between treatment and placebo. Each year, the degree of emphysema was quantified by the 15th percentile point of the lung density histogram derived from computed tomography (CT). The loss of lung tissue measured by CT (mean +/- SEM) was 2.6 +/- 0.41 g/L/yr for placebo as compared with 1.5 +/- 0.41 g/L/yr for alpha(1)-antitrypsin infusion (p = 0.07). Power analysis showed that this protective effect would be significant in a similar trial with 130 patients. This is in contrast to calculations based on annual decline of FEV(1) showing that 550 patients would be needed to show a 50% reduction of annual decline. We conclude that lung density measurements by CT may facilitate future randomized clinical trials of investigational drugs for a disease in which little progress in therapy has been made in the past 30 yr.

  3. How does age-related macular degeneration affect real-world visual ability and quality of life? A systematic review

    Science.gov (United States)

    Taylor, Deanna J; Hobby, Angharad E; Binns, Alison M; Crabb, David P

    2016-01-01

    Objectives To review systematically the evidence of age-related macular degeneration (AMD) affecting real-world visual ability and quality of life (QoL). To explore trends in specific topics within this body of the literature. Design Systematic review. Methods A systematic literature search was carried out using MEDLINE, EMBASE, CINAHL, PsycINFO, PsychARTICLES and Health and Psychosocial Instruments for articles published up to January 2015 for studies including people diagnosed with AMD, assessing real-world visual ability or QoL as an outcome. Two researchers screened studies for eligibility. Details of eligible studies including study design, characteristics of study population and outcomes measured were recorded in a data extraction table. All included studies underwent quality appraisal using the Mixed Methods Appraisal Tool 2011 Version (MMAT). Results From 5284 studies, 123 were eligible for inclusion. A range of approaches were identified, including performance-based methods, quantitative and qualitative patient-reported outcome measures (PROMs). AMD negatively affects tasks including mobility, face recognition, perception of scenes, computer use, meal preparation, shopping, cleaning, watching TV, reading, driving and, in some cases, self-care. There is evidence for higher rates of depression among people with AMD than among community dwelling elderly. A number of adaptation strategies have been associated with AMD of varying duration. Much of the research fails to report the type of AMD studied (59% of included studies) or the duration of disease in participants (74%). Of those that do report type studied, the breakdown is as follows: wet AMD 20%, dry AMD 4% and both types 17%. Conclusions There are many publications highlighting the negative effects of AMD in various domains of life. Future research should focus on delivering some of this research knowledge into patient management and clinical trials and differentiating between the types of AMD. PMID

  4. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials

    DEFF Research Database (Denmark)

    Chaturvedi, N.; Porta, M.; Klein, R.

    2008-01-01

    of retinopathy in type 1 diabetes. METHODS: Two randomised, double-blind, parallel-design, placebo-controlled trials were done in 309 centres worldwide. Participants with normotensive, normoalbuminuric type 1 diabetes without retinopathy were recruited to the DIRECT-Prevent 1 trial and those with existing...... retinopathy were recruited to DIRECT-Protect 1, and were assigned to candesartan 16 mg once a day or matching placebo. After 1 month, the dose was doubled to 32 mg. Investigators and participants were unaware of the treatment allocation status. The primary endpoints were incidence and progression......BACKGROUND: Results of previous studies suggest that renin-angiotensin system blockers might reduce the burden of diabetic retinopathy. We therefore designed the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme to assess whether candesartan could reduce the incidence and progression...

  5. Harvesting of freshwater microalgae Scenedesmus obliquus and Chlorella vulgaris using acid mine drainage as a cost effective flocculant for biofuel production

    International Nuclear Information System (INIS)

    Salama, El-Sayed; Jeon, Byong-Hun; Kurade, Mayur B.; Abou-Shanab, Reda A.I.; Govindwar, Sanjay P.; Lee, Sang-hun; Yang, Il-Seung; Lee, Dae Sung

    2016-01-01

    Graphical abstract: Schematic presentation of coagulation/flocculation of microalgal biomass using AMD. - Highlights: • AMDs containing high Fe"2"+/Al"3"+ improved the settling kinetics of microalgal biomass. • The highest k_2 value was 40 × 10"−"2 L mg"−"1 min"−"1 for C. vulgaris with AMD (1). • With AMD (2), k_2 was 4.0 × 10"−"2 L mg"−"1 min"−"1 for both C. vulgaris and S. obliquus. • The highest FE (93%) and CF (29) for C. vulgaris was achieved with AMD (1). • AMD (1) removed 99.80% of Fe"3"+ and 99.99% of Al"3"+ from the supernatant. - Abstract: Development of a low-cost harvesting technology could be an effective approach for making microalgal biofuel commercially feasible. The use of acid mine drainage (AMD) to coagulate/flocculate biomass is a cost-effective strategy for addressing this challenge. Here, settling kinetics, flocculation efficiency (FE), and concentration factor (CF) of two morphologically different microalgae species, Scenedesmus obliquus and Chlorella vulgaris, were investigated with respect to AMD dosage (5% and 10%) and medium pH (7 and 9). AMD was collected from two different sites, AMD (1) and AMD (2), and increasing its dosage to 10% improved the settling rate, FE, and CF of the floc. At 10% AMD (1) dosage and pH 9, the highest rate constants (k_2) for the second order equations were 6.65 × 10"−"2 and 40 × 10"−"2 L mg"−"1⋅min"−"1 for S. obliquus and C. vulgaris, respectively; at 10% AMD (2), k_2 values were 4.22 × 10"−"2 and 4.76 × 10"−"2 L mg"−"1 min"−"1, respectively. Similarly, FE/CF values were 89%/25 for S. obliquus and 93%/29 for C. vulgaris with 10% AMD (1); and 81%/17 and 79%/17, respectively, with 10% AMD (2). AMD effectively removed 99.80% of Fe"3"+, 99.99% of Al"3"+, 94% of Ca"2"+, 84% of Mg"2"+ and all of Na"+ and K"+ ions from the supernatant. The results of kinetics, EF, and CF measurements indicate that AMDs, naturally rich in iron and aluminum ions, could provide a feasible

  6. Cluster randomised trial of a school-community child health promotion and obesity prevention intervention: findings from the evaluation of fun 'n healthy in Moreland!

    Science.gov (United States)

    Waters, Elizabeth; Gibbs, Lisa; Tadic, Maryanne; Ukoumunne, Obioha C; Magarey, Anthea; Okely, Anthony D; de Silva, Andrea; Armit, Christine; Green, Julie; O'Connor, Thea; Johnson, Britt; Swinburn, Boyd; Carpenter, Lauren; Moore, Graham; Littlecott, Hannah; Gold, Lisa

    2017-08-03

    Multi-level, longer-term obesity prevention interventions that focus on inequalities are scarce. Fun 'n healthy in Moreland! aimed to improve child adiposity, school policies and environments, parent engagement, health behaviours and child wellbeing. All children from primary schools in an inner urban, culturally diverse and economically disadvantaged area in Victoria, Australia were eligible for participation. The intervention, fun 'n healthy in Moreland!, used a Health Promoting Schools Framework and provided schools with evidence, school research data and part time support from a Community Development Worker to develop health promoting strategies. Comparison schools continued as normal. Participants were not blinded to intervention status. The primary outcome was change in adiposity. Repeated cross-sectional design with nested longitudinal subsample. Students from twenty-four primary schools (clusters) were randomised (aged 5-12 years at baseline). 1426 students from 12 intervention schools and 1539 students from 10 comparison schools consented to follow up measurements. Despite increased prevalence of healthy weight across all schools, after 3.5 years of intervention there was no statistically significant difference between trial arms in BMI z score post-intervention (Mean (sd): Intervention 0.68(1.16); Comparison: 0.72(1.12); Adjusted mean difference (AMD): -0.05, CI: -0.19 to 0.08, p = 0.44). Children from intervention schools consumed more daily fruit serves (AMD: 0.19, CI:0.00 to 0.37, p = 0.10), were more likely to have water (AOR: 1.71, CI:1.05 to 2.78, p = 0.03) and vegetables (AOR: 1.23, CI: 0.99 to 1.55, p = 0.07), and less likely to have fruit juice/cordial (AOR: 0.58, CI:0.36 to 0.93, p = 0.02) in school lunch compared to children in comparison schools. More intervention schools (8/11) had healthy eating and physical activity policies compared with comparison schools (2/9). Principals and schools highly valued the approach as a catalyst

  7. Inherited Retinal Degenerative Disease Clinical Trial Network

    Science.gov (United States)

    2012-10-01

    diseases and dry AMD; • Established patient databases at the University of Utah and University of Medicine and Dentistry of New Jersey CTECs, classified...Scholl: Emily Fletcher, Rupert Strauss, Yulia Wolfson, Stacey Seabrook Wilmer Biostatistics Center: Ann Ervin, Beatriz Munoz Reading Center

  8. MicroRNA-381 Favors Repair of Nerve Injury Through Regulation of the SDF-1/CXCR4 Signaling Pathway via LRRC4 in Acute Cerebral Ischemia after Cerebral Lymphatic Blockage

    Directory of Open Access Journals (Sweden)

    Jian-Min Piao

    2018-04-01

    Full Text Available Background/Aims: Acute cerebral ischemia is a manifestation of cerebral vascular insufficiency and has a high mortality. However, the therapy for acute cerebral ischemia is still limited. This study aimed to investigate the effect of microRNA-381 (miR-381 on the repair of nerve injury in rats with acute cerebral ischemia after cerebral lymphatic blockage (CLB by targeting leucine-rich repeat C4 protein (LRRC4 through the Stromal cell-derived factor-1/CXC chemokine receptor-4 signaling pathway. Methods: Rat models of CLB and middle cerebral artery occlusion (MCAO were established, and 56 Wistar rats were divided into sham, MCAO, CLB + MCAO, CLB + MCAO + miR-381 inhibitor, CLB + MCAO + miR-381 mimic, CLB + MCAO + AMD3100 and CLB + MCAO + miR-381 mimic + AMD3100 groups. Modified neurological severity score (mNSS was used to determine nerve injury, TTC staining to measure infarction volume, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL staining and flow cytometry to evaluate cell apoptosis, immunofluorescence to measure BrdU-positive cell number, enzyme-linked immunosorbent assay (ELISA to determine contents of tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, interleukin-6 (IL-6, interleukin-10 (IL-10, nerve growth factor (NGF and neurite outgrowth inhibitor -A (Nogo-A, Reverse transcription quantitative polymerase chain reaction (RT-qPCR and Western blotting to evaluate expression of miR-381, LRRC4, SDF-1, CXCR4, pERK, Slit2 and vascular endothelial growth factor (VEGF. Results: LRRC4 was a target gene of miR-381. Compared with the results in the CLB + MCAO group, mNSS, infarction volume, apoptosis rate and TNF-α, IL-1β, IL-6 and Nogo-A contents as well as LRRC4 expression in the CLB + MCAO + miR-381 inhibitor and CLB + MCAO + AMD3100 groups were increased (those in the CLB + MCAO + AMD3100 group > those in the CLB + MCAO + miR-381 mimic + AMD3100 group, while BrdU-positive cell number, contents of NGF and

  9. Fatigue crack growth rates and fracture toughness of rapidly solidified Al-8.5 pct Fe-1.2 pct V-1.7 pct Si alloys

    International Nuclear Information System (INIS)

    Hariprasad, S.; Sastry, S.M.L.; Jerina, K.L.

    1994-01-01

    The room-temperature fatigue crack growth rates (FCGR) and fracture toughness were evaluated for different crack plane Orientations of an Al-8.5 pct Fe-1.2 pct V-1.7 pct Si alloy produced by planar flow casting (PFC) and atomized melt deposition (AMD) processes. For the alloy produced by the PFC process, properties were determined in six different orientations, including the short transverse directions S-T and S-L. Diffusion bonding and adhesive bonding methods were used to prepare specimens for determining FCGR and fracture toughness in the short transverse direction. Interparticle boundaries control fracture properties in the alloy produced by PFC. Fracture toughness of the PFC alloy varies from 13.4 MPa√ bar m to 30.8 MPa√ bar m, depending on the orientation of the crack plane relative to the interparticle boundaries. Fatigue crack growth resistance and fracture toughness are greater in the L-T, L-S, and T-S directions than in the T-L, S-T, and S-L orientations. The alloy produced by AMD does not exhibit anisotropy in fracture toughness and fatigue crack growth resistance in the as-deposited condition or in the extruded condition. The fracture toughness varies from 17.2 MPa√ bar m to 18.5 MPa√ bar m for the as-deposited condition and from 19.8 MPa√ bar m to 21.0 MPa√ bar m for the extruded condition. Fracture properties are controlled by intrinsic factors in the alloy produced by AMD. Fatigue crack growth rates of the AMD alloy are comparable to those of the PFC alloy in the L-T orientation. The crack propagation modes were studied by optical metallographic examination of crack-microstructure interactions and scanning electron microscopy of the fracture surfaces

  10. Mitochondrial recessive ataxia syndrome mimicking dominant spinocerebellar ataxia.

    Science.gov (United States)

    Palin, Eino J H; Hakonen, Anna H; Korpela, Mari; Paetau, Anders; Suomalainen, Anu

    2012-04-15

    We studied the genetic background of a family with SCA, showing dominant inheritance and anticipation. Muscle histology, POLG1 gene sequence, neuropathology and mitochondrial DNA analyses in a mother and a son showed typical findings for a mitochondrial disorder, and both were shown to be homozygous for a recessive POLG1 mutation, underlying mitochondrial recessive ataxia syndrome, MIRAS. The healthy father was a heterozygous carrier for the same mutation. Recessively inherited MIRAS mutations should be tested in dominantly inherited SCAs cases of unknown cause, as the high carrier frequency of MIRAS may result in two independent introductions of the mutant allele in the family and thereby mimic dominant inheritance. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. 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.

  12. Influence of UV and blue-light sun radiation to developing of age-related macular degeneration on Croatian Island Rab

    International Nuclear Information System (INIS)

    Vojnikovic, Bozo; Coklo, Miran; Ranogajec-Komor, Maria

    2008-01-01

    Full text: Croatian island Rab has one of the highest solar radiation in geographical area of Europe. The aim of this clinical trial was to estimate correlation between incidence of age-related macular degeneration (AMD) and the exposure to sunlight in different population on island Rab. In the first group agriculturists and fishermen were collected, in the second group members of the urban population were involved. 1753 individuals were investigated. The age in this population was between 40 and 73 years. The incidence of AMD in the first group was 19% while in the urban population only 2% showed AMD. It can be concluded that a very significant incidence exists between chronic exposure to sunlight and appearance of age-related macular degeneration. (author)

  13. A comparison of the baseline metabolic profiles between Diabetes Prevention Trial-Type 1 and TrialNet Natural History Study participants.

    Science.gov (United States)

    Sosenko, Jay M; Mahon, Jeffrey; Rafkin, Lisa; Lachin, John M; Krause-Steinrauf, Heidi; Krischer, Jeffrey P; Cuthbertson, David; Palmer, Jerry P; Thompson, Clinton; Greenbaum, Carla J; Skyler, Jay S

    2011-03-01

    We assessed whether differing autoantibody screening criteria for type 1 diabetes (T1D) prevention trials result in different baseline metabolic profiles of those who screen positive. Diabetes Prevention Trial-Type 1 (DPT-1) participants were screened for islet cell autoantibodies, whereas TrialNet Natural History Study (TNNHS) participants were screened for biochemical autoantibodies. In both studies, those determined to be autoantibody positive underwent baseline oral glucose tolerance tests (OGTTs) in which glucose and C-peptide were measured. The percentage of those with an OGTT in the diabetic range was higher among the DPT-1 participants (10.0% of 956 vs. 6.4% of 645, p < 0.01). In a logistic regression analysis with adjustments for age and gender, the difference persisted (p < 0.01). Among those in the non-diabetic range (n = 860 for DPT-1 and n = 604 for the TNNHS), glucose levels were similar at all time points, except for higher fasting glucose levels in the TNNHS participants (p < 0.001). There was a higher percentage of impaired fasting glucose (IFG) in the TNNHS participants (10.9 vs. 6.7%, p < 0.01); however, with adjustments for age and gender, there was no longer a significant difference. There was no significant difference in the percentages with impaired glucose tolerance. C-peptide levels were much lower in the DPT-1 cohort at all OGTT time points (p < 0.001 for all). Differing criteria for autoantibody screening can result in marked differences in the baseline metabolic profiles of prospective participants of T1D prevention trials. © 2010 John Wiley & Sons A/S.

  14. Inhibition of SDF-1α/CXCR4 Signalling in Subchondral Bone Attenuates Post-Traumatic Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Yonghui Dong

    2016-06-01

    Full Text Available Previous studies showed that SDF-1α is a catabolic factor that can infiltrate cartilage, decrease proteoglycan content, and increase MMP-13 activity. Inhibiting the SDF-1α/CXCR4 signalling pathway can attenuate the pathogenesis of osteoarthritis (OA. Recent studies have also shown that SDF-1α enhances chondrocyte proliferation and maturation. These results appear to be contradictory. In the current study, we used a destabilisation OA animal model to investigate the effects of SDF-1α/CXCR4 signalling in the tibial subchondral bone and the OA pathological process. Post-traumatic osteoarthritis (PTOA mice models were prepared by transecting the anterior cruciate ligament (ACLT, or a sham surgery was performed, in a total of 30 mice. Mice were treated with phosphate buffer saline (PBS or AMD3100 (an inhibitor of CXCR4 and sacrificed at 30 days post ACLT or sham surgery. Tibial subchondral bone status was quantified by micro-computed tomography (μCT. Knee-joint histology was analysed to examine the articular cartilage and joint degeneration. The levels of SDF-1α and collagen type I c-telopeptidefragments (CTX-I were quantified by ELISA. Bone marrow mononuclear cells (BMMCs were used to clarify the effects of SDF-1α on osteoclast formation and activity in vivo. μCT analysis revealed significant loss of trabecular bone from tibial subchondral bone post-ACLT, which was effectively prevented by AMD3100. AMD3100 could partially prevent bone loss and articular cartilage degeneration. Serum biomarkers revealed an increase in SDF-1α and bone resorption, which were also reduced by AMD3100. SDF-1α can promote osteoclast formation and the expression oftartrate resistant acid phosphatase (TRAP, cathepsin K (CK, and matrix metalloproteinase (MMP-9 in osteoclasts by activating the MAPK pathway, including ERK and p38, but not JNK. In conclusion, inhibition of SDF-1α/CXCR4signalling was able to prevent trabecular bone loss and attenuated cartilage

  15. Randomized Trial of 2 Versus 1 Dose of Measles Vaccine

    DEFF Research Database (Denmark)

    Brønd, Marie; Martins, Cesario L; Byberg, Stine

    2018-01-01

    Background: Two doses of measles vaccine (MV) might reduce the nonmeasles mortality rate more than 1 dose of MV does. The effect of 2 versus 1 dose on morbidity has not been examined. Within a randomized trial of the effect of 2 doses versus 1 dose of MV on mortality in Guinea-Bissau, we investig...

  16. The use of intermediate endpoints in the design of type 1 diabetes prevention trials.

    Science.gov (United States)

    Krischer, Jeffrey P

    2013-09-01

    This paper presents a rationale for the selection of intermediate endpoints to be used in the design of type 1 diabetes prevention clinical trials. Relatives of individuals diagnosed with type 1 diabetes were enrolled on the TrialNet Natural History Study and screened for diabetes-related autoantibodies. Those with two or more such autoantibodies were analysed with respect to increased HbA1c, decreased C-peptide following an OGTT, or abnormal OGTT values as intermediate markers of disease progression. Over 2 years, a 10% increase in HbA1c, and a 20% or 30% decrease in C-peptide from baseline, or progression to abnormal OGTT, occurred with a frequency between 20% and 41%. The 3- to 5-year risk of type 1 diabetes following each intermediate endpoint was high, namely 47% to 84%. The lower the incidence of the endpoint being reached, the higher the risk of diabetes. A diabetes prevention trial using these intermediate endpoints would require a 30% to 50% smaller sample size than one using type 1 diabetes as the endpoint. The use of an intermediate endpoint in diabetes prevention is based on the generally held view of disease progression from initial occurrence of autoantibodies through successive immunological and metabolic changes to manifest type 1 diabetes. Thus, these markers are suitable for randomised phase 2 trials, which can more rapidly screen promising new therapies, allowing them to be subsequently confirmed in definitive phase 3 trials.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Sensor-augmented pump therapy lowers HbA(1c) in suboptimally controlled Type 1 diabetes; a randomized controlled trial

    NARCIS (Netherlands)

    Hermanides, J.; Nørgaard, K.; Bruttomesso, D.; Mathieu, C.; Frid, A.; Dayan, C. M.; Diem, P.; Fermon, C.; Wentholt, I. M. E.; Hoekstra, J. B. L.; DeVries, J. H.

    2011-01-01

    To investigate the efficacy of sensor-augmented pump therapy vs. multiple daily injection therapy in patients with suboptimally controlled Type 1 diabetes. In this investigator-initiated multi-centre trial (the Eurythmics Trial) in eight outpatient centres in Europe, we randomized 83 patients with

  19. Mitochondrial DNA Variants Mediate Energy Production and Expression Levels for CFH, C3 and EFEMP1 Genes: Implications for Age-Related Macular Degeneration

    Science.gov (United States)

    Kenney, M. Cristina; Chwa, Marilyn; Atilano, Shari R.; Pavlis, Janelle M.; Falatoonzadeh, Payam; Ramirez, Claudio; Malik, Deepika; Hsu, Tiffany; Woo, Grace; Soe, Kyaw; Nesburn, Anthony B.; Boyer, David S.; Kuppermann, Baruch D.; Jazwinski, S. Michal; Miceli, Michael V.; Wallace, Douglas C.; Udar, Nitin

    2013-01-01

    Background Mitochondrial dysfunction is associated with the development and progression of age-related macular degeneration (AMD). Recent studies using populations from the United States and Australia have demonstrated that AMD is associated with mitochondrial (mt) DNA haplogroups (as defined by combinations of mtDNA polymorphisms) that represent Northern European Caucasians. The aim of this study was to use the cytoplasmic hybrid (cybrid) model to investigate the molecular and biological functional consequences that occur when comparing the mtDNA H haplogroup (protective for AMD) versus J haplogroup (high risk for AMD). Methodology/Principal Findings Cybrids were created by introducing mitochondria from individuals with either H or J haplogroups into a human retinal epithelial cell line (ARPE-19) that was devoid of mitochondrial DNA (Rho0). In cybrid lines, all of the cells carry the same nuclear genes but vary in mtDNA content. The J cybrids had significantly lower levels of ATP and reactive oxygen/nitrogen species production, but increased lactate levels and rates of growth. Q-PCR analyses showed J cybrids had decreased expressions for CFH, C3, and EFEMP1 genes, high risk genes for AMD, and higher expression for MYO7A, a gene associated with retinal degeneration in Usher type IB syndrome. The H and J cybrids also have comparatively altered expression of nuclear genes involved in pathways for cell signaling, inflammation, and metabolism. Conclusion/Significance Our findings demonstrate that mtDNA haplogroup variants mediate not only energy production and cell growth, but also cell signaling for major molecular pathways. These data support the hypothesis that mtDNA variants play important roles in numerous cellular functions and disease processes, including AMD. PMID:23365660

  20. Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    M Cristina Kenney

    Full Text Available Mitochondrial dysfunction is associated with the development and progression of age-related macular degeneration (AMD. Recent studies using populations from the United States and Australia have demonstrated that AMD is associated with mitochondrial (mt DNA haplogroups (as defined by combinations of mtDNA polymorphisms that represent Northern European Caucasians. The aim of this study was to use the cytoplasmic hybrid (cybrid model to investigate the molecular and biological functional consequences that occur when comparing the mtDNA H haplogroup (protective for AMD versus J haplogroup (high risk for AMD.Cybrids were created by introducing mitochondria from individuals with either H or J haplogroups into a human retinal epithelial cell line (ARPE-19 that was devoid of mitochondrial DNA (Rho0. In cybrid lines, all of the cells carry the same nuclear genes but vary in mtDNA content. The J cybrids had significantly lower levels of ATP and reactive oxygen/nitrogen species production, but increased lactate levels and rates of growth. Q-PCR analyses showed J cybrids had decreased expressions for CFH, C3, and EFEMP1 genes, high risk genes for AMD, and higher expression for MYO7A, a gene associated with retinal degeneration in Usher type IB syndrome. The H and J cybrids also have comparatively altered expression of nuclear genes involved in pathways for cell signaling, inflammation, and metabolism.Our findings demonstrate that mtDNA haplogroup variants mediate not only energy production and cell growth, but also cell signaling for major molecular pathways. These data support the hypothesis that mtDNA variants play important roles in numerous cellular functions and disease processes, including AMD.

  1. 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.

  2. Is Age-Related Macular Degeneration Associated with Stroke Among Elderly Americans?§

    Science.gov (United States)

    Liao, Duanping; Mo, Jingping; Duan, Yinkang; Klein, Ronald; Scott, Ingrid U; Huang, Kui A; Zhou, Haibo

    2008-01-01

    Objective: To investigate whether age-related macular degeneration (AMD) is associated with the development of ischemic and hemorrhagic stroke among elderly Americans. Design: Population-based cohort study. Participants: The five percent random sample of 2000-2003 Medicare enrollees was obtained. The cohort (n=1,519,086) consisted of enrollees who were aged 65 or older at the first two-year (January 1, 2000 to December 31, 2001). Methods: Baseline demographic variables and chronic conditions (AMD and type, history of myocardial infarction (MI), stroke, hypertension, and diabetes) were defined based on the occurrence of relevant ICD-9 codes in relevant diagnosis fields of the baseline Medicare Data. We excluded 215,900 persons who had a diagnosis of MI or stroke during baseline period to form a cohort of 1,303,186 individuals who were free of major cardio-cerebral vascular disease (CVD) at baseline. Main Outcome Measures: In two years of follow-up (January 1, 2002 to December 31, 2003), a total of 89,501 incident stroke cases were identified, including 80,018 ischemic, 7048 hemorrhagic, and 2,435 stroke cases of both types. Results: Baseline mean age was 75 years (Standard Divination=7.7), with 60% women and 88% whites. The prevalence of AMD was 10.6%, with 19.7% being neovascular AMD and 80.3% being non-neovascular AMD. Baseline age, gender, race, hypertension, and diabetes adjusted 2-year incident odds ratios and 95% confidence internal of stroke associated with AMD were 1.31 (1.26, 1.36) for neovascular AMD, 1.18 (1.15, 1.21) for non-neovascular AMD, and 1.21 (1.18, 1.23) for either neovascular or non-neovascular AMD. Conclusion: The findings are suggestive of an association between AMD, especially neovascular AMD, and incident stroke, independent of demographic factors and co-morbidity. These findings, if confirmed by other studies that control for smoking and other lifestyle covariables not measured in this study, suggest the possibility of shared common

  3. Is age-related macular degeneration associated with stroke among elderly americans?

    Science.gov (United States)

    Liao, Duanping; Mo, Jingping; Duan, Yinkang; Klein, Ronald; Scott, Ingrid U; Huang, Kui A; Zhou, Haibo

    2008-03-08

    To investigate whether age-related macular degeneration (AMD) is associated with the development of ischemic and hemorrhagic stroke among elderly Americans. Population-based cohort study. The five percent random sample of 2000-2003 Medicare enrollees was obtained. The cohort (n=1,519,086) consisted of enrollees who were aged 65 or older at the first two-year (January 1, 2000 to December 31, 2001). Baseline demographic variables and chronic conditions (AMD and type, history of myocardial infarction (MI), stroke, hypertension, and diabetes) were defined based on the occurrence of relevant ICD-9 codes in relevant diagnosis fields of the baseline Medicare Data. We excluded 215,900 persons who had a diagnosis of MI or stroke during baseline period to form a cohort of 1,303,186 individuals who were free of major cardio-cerebral vascular disease (CVD) at baseline. In two years of follow-up (January 1, 2002 to December 31, 2003), a total of 89,501 incident stroke cases were identified, including 80,018 ischemic, 7048 hemorrhagic, and 2,435 stroke cases of both types. Baseline mean age was 75 years (Standard Divination=7.7), with 60% women and 88% whites. The prevalence of AMD was 10.6%, with 19.7% being neovascular AMD and 80.3% being non-neovascular AMD. Baseline age, gender, race, hypertension, and diabetes adjusted 2-year incident odds ratios and 95% confidence internal of stroke associated with AMD were 1.31 (1.26, 1.36) for neovascular AMD, 1.18 (1.15, 1.21) for non-neovascular AMD, and 1.21 (1.18, 1.23) for either neovascular or non-neovascular AMD. The findings are suggestive of an association between AMD, especially neovascular AMD, and incident stroke, independent of demographic factors and co-morbidity. These findings, if confirmed by other studies that control for smoking and other lifestyle covariables not measured in this study, suggest the possibility of shared common antecedents between stroke and AMD.

  4. PPAR Agonists: Potential as Therapeutics for Neovascular Retinopathies

    Directory of Open Access Journals (Sweden)

    Harrihar A. Pershadsingh

    2008-01-01

    Full Text Available The angiogenic, neovascular proliferative retinopathies, proliferative diabetic retinopathy (PDR, and age-dependent macular degeneration (AMD complicated by choroidal neovascularization (CNV, also termed exudative or “wet” AMD, are common causes of blindness. The antidiabetic thiazolidinediones (TZDs, rosiglitazone, and troglitazone are PPAR agonists with demonstrable antiproliferative, and anti-inflammatory effects, in vivo, were shown to ameliorate PDR and CNV in rodent models, implying the potential efficacy of TZDs for treating proliferative retinopathies in humans. Activation of the angiotensin II type 1 receptor (AT1-R propagates proinflammatory and proliferative pathogenic determinants underlying PDR and CNV. The antihypertensive dual AT1-R blocker (ARB, telmisartan, recently was shown to activate PPAR and improve glucose and lipid metabolism and to clinically improve PDR and CNV in rodent models. Therefore, the TZDs and telmisartan, clinically approved antidiabetic and antihypertensive drugs, respectively, may be efficacious for treating and attenuating PDR and CNV humans. Clinical trials are needed to test these possibilities.

  5. Relationship between macular pigment and visual function in subjects with early age-related macular degeneration.

    Science.gov (United States)

    Akuffo, Kwadwo Owusu; Nolan, John M; Peto, Tunde; Stack, Jim; Leung, Irene; Corcoran, Laura; Beatty, Stephen

    2017-02-01

    To investigate the relationship between macular pigment (MP) and visual function in subjects with early age-related macular degeneration (AMD). 121 subjects with early AMD enrolled as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787) were assessed using a range of psychophysical measures of visual function, including best corrected visual acuity (BCVA), letter contrast sensitivity (CS), mesopic and photopic CS, mesopic and photopic glare disability (GD), photostress recovery time (PRT), reading performance and subjective visual function, using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). MP was measured using customised heterochromatic flicker photometry. Letter CS, mesopic and photopic CS, photopic GD and mean reading speed were each significantly (p0.05, for all). MP relates positively to many measures of visual function in unsupplemented subjects with early AMD. The CREST trial will investigate whether enrichment of MP influences visual function among those afflicted with this condition. ISRCTN13894787. 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/.

  6. 77 FR 42711 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-07-20

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-20] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This..., Amd 3). (v) Prior Related Cases, if any: FMS case ULJ-$46M-15Jan10. (vi) Sales Commission, Fee, etc...

  7. Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: phase 1 trial outcomes.

    Science.gov (United States)

    Feldman, Eva L; Boulis, Nicholas M; Hur, Junguk; Johe, Karl; Rutkove, Seward B; Federici, Thais; Polak, Meraida; Bordeau, Jane; Sakowski, Stacey A; Glass, Jonathan D

    2014-03-01

    The US Food and Drug Administration-approved trial, "A Phase 1, Open-Label, First-in-Human, Feasibility and Safety Study of Human Spinal Cord-Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis, Protocol Number: NS2008-1," is complete. Our overall objective was to assess the safety and feasibility of stem cell transplantation into lumbar and/or cervical spinal cord regions in amyotrophic lateral sclerosis (ALS) subjects. Preliminary results have been reported on the initial trial cohort of 12 ALS subjects. Here, we describe the safety and functional outcome monitoring results for the final trial cohort, consisting of 6 ALS subjects receiving 5 unilateral cervical intraspinal neural stem cell injections. Three of these subjects previously received 10 total bilateral lumbar injections as part of the earlier trial cohort. All injections utilized a novel spinal-mounted stabilization and injection device to deliver 100,000 neural stem cells per injection, for a dosing range up to 1.5 million cells. Subject assessments included detailed pre- and postsurgical neurological outcome measures. The cervical injection procedure was well tolerated and disease progression did not accelerate in any subject, verifying the safety and feasibility of cervical and dual-targeting approaches. Analyses on outcome data revealed preliminary insight into potential windows of stem cell biological activity and identified clinical assessment measures that closely correlate with ALS Functional Rating Scale-Revised scores, a standard assessment for ALS clinical trials. This is the first report of cervical and dual-targeted intraspinal transplantation of neural stem cells in ALS subjects. This approach is feasible and well-tolerated, supporting future trial phases examining therapeutic dosing and efficacy. © 2014 Child Neurology Society/American Neurological Association.

  8. 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...

  9. 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

  10. Direct Interferometric Imaging with IOTA Interferometer: Morphology of the Water Shell around U Ori

    Science.gov (United States)

    Pluzhnik, Eugene; Ragland, S.; Le Coroller, H.; Cotton, W.; Danchi, W.; Traub, W.; Willson, L.

    2007-12-01

    Optical interferometric observations of Mira stars with adequate resolution using the 3-telescope Infrared Optical Telescope Array (IOTA) interferometer have shown detectable asymmetry in several Mira stars. Several mechanisms have been proposed to explain the observed asymmetry. In this paper, we present subsequent IOTA observations of a Mira star, namely, U Ori taken at 1.51, 1.64 and 1.78 μm in 2005. The reconstructed images based on a model independent algorithm are also presented. These images show asymmetric structures of the water shell that is similar to the structure of 22 GHz masers obtained by Vlemmings et al. in 2003. We explore the possibility of the detection of molecular shell rotation with a period of about 30 years by comparing our results with radio observations and discuss a possible geometric structure of the shell.

  11. Epigenetic regulation of cardiac progenitor cells marker c-kit by stromal cell derived factor-1α.

    Directory of Open Access Journals (Sweden)

    Zhongpu Chen

    Full Text Available BACKGROUND: Cardiac progenitor cells (CPCs have been proven suitable for stem cell therapy after myocardial infarction, especially c-kit(+CPCs. CPCs marker c-kit and its ligand, the stem cell factor (SCF, are linked as c-kit/SCF axis, which is associated with the functions of proliferation and differentiation. In our previous study, we found that stromal cell-derived factor-1α (SDF-1α could enhance the expression of c-kit. However, the mechanism is unknown. METHODS AND RESULTS: CPCs were isolated from adult mouse hearts, c-kit(+ and c-kit(- CPCs were separated by magnetic beads. The cells were cultured with SDF-1α and CXCR4-selective antagonist AMD3100, and c-kit expression was measured by qPCR and Western blotting. Results showed that SDF-1α could enhance c-kit expression of c-kit(+CPCs, made c-kit(-CPCs expressing c-kit, and AMD3100 could inhibit the function of SDF-1α. After the intervention of SDF-1α and AMD3100, proliferation and migration of CPCs were measured by CCK-8 and transwell assay. Results showed that SDF-1α could enhance the proliferation and migration of both c-kit(+ and c-kit(- CPCs, and AMD3100 could inhibit these functions. DNA methyltransferase (DNMT mRNA were measured by qPCR, DNMT activity was measured using the DNMT activity assay kit, and DNA methylation was analyzed using Sequenom's MassARRAY platform, after the CPCs were cultured with SDF-1α. The results showed that SDF-1α stimulation inhibited the expression of DNMT1 and DNMT3β, which are critical for the maintenance of regional DNA methylation. Global DNMT activity was also inhibited by SDF-1α. Lastly, SDF-1α treatment led to significant demethylation in both c-kit(+ and c-kit(- CPCs. CONCLUSIONS: SDF-1α combined with CXCR4 could up-regulate c-kit expression of c-kit(+CPCs and make c-kit(-CPCs expressing c-kit, which result in the CPCs proliferation and migration ability improvement, through the inhibition of DNMT1 and DNMT3β expression and global DNMT

  12. A2E Suppresses Regulatory Function of RPE Cells in Th1 Cell Differentiation Via Production of IL-1β and Inhibition of PGE2.

    Science.gov (United States)

    Shi, Qian; Wang, Qiu; Li, Jing; Zhou, Xiaohui; Fan, Huimin; Wang, Fenghua; Liu, Haiyun; Sun, Xiangjun; Sun, Xiaodong

    2015-12-01

    Inflammatory status of RPE cells induced by A2E is essential in the development of AMD. Recent research indicated T-cell immunity was involved in the pathological progression of AMD. This study was designed to investigate how A2E suppresses immunoregulatory function of RPE cells in T-cell immunity in vitro. Mouse RPE cells or human ARPE19 cells were stimulated with A2E, and co-cultured with naïve T cells under Th1, Th2, Th17, and regulatory T cell (Treg) polarization conditions. The intracellular cytokines or transcript factors of the induced T-cells subset were detected with flow cytometer and qRT-PCR. The ROS levels were detected, and the factors and possible pathways involved in the A2E-laden RPE cells were analyzed through neutralization antibody of IL-1β and inhibitors of related pathways. The A2E reduced regulatory function of RPE cells in Treg differentiation. The A2E-laden RPE cells promoted polarization of Th1 cells in vitro, but not Th2 or Th17 differentiation. The A2E induced RPE cells to release inflammatory cytokines and ROS, but PGE2 production was inhibited. Through neutralization of IL-1β or inhibition of COX2-PGE2 pathways, A2E-laden RPE cells expressed reduced effect in inducing Th1 cells. The A2E inhibited regulatory function of RPE cells in suppressing Th1 cell immunity in vitro through production of IL-1β and inhibition of PGE2. Our data indicate that A2E could suppress immunoregulatory function of RPE cells and adaptive immunity might play a role in the immune pathogenesis of AMD.

  13. 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

    The Muskau Arch is situated in the west of Poland and in the east of Germany. This region is a belt formed by push and frontal moraines during the Middle-Polish (Riss) glaciation, especially during the Wartanian glaciation. The occurrence of glacier caused folding and forming the glacitectonic type of lignit deposits which were mined for over 150 years. Both open pit and underground mining methods has exposed metal sulfides (mainly pyrite) to air and water causing bio-oxidation. Due to this process the acidity of many reservoirs have increased significantly (pH values between 2 and 4). As a consequence of changes in the environment, new mineral phases precipitated from highly acid waters rich in, among others, various forms of Fe and S. Precipitation of ochreous minerals such as schwertmannite, goethite and jarosite was partly catalyzed by many various acidophilic and acid-tolerant microorganisms: bacteria, archaea and probably yeasts. Jarosite KFe33+(OH)6(SO4)2 can be precipitated both in abiotic conditions and as a by-product of the activity of living organisms. The example of biomineralization induced by fungi Purpureocillium lilacinum in similar AMD environment of Rio Tinto is reported (Oggerin et al, 2014). Recently, jarosite is also considered as a possible biosignature of life on Mars. The assessment of microbial participation in formation of jarosite is an elementary step in geomicrobiological and astrobiological research. Isolated by us Rhodotorula sp. is an unicellular pigmented yeast. Fungi from the genus Rhodotorula F.C. Harrison belong to Sporidiobolalas part of phylum Basidiomycota. They are common environmental inhabitants. Some species, known from Rio Tinto, can live in extreme acidic soils at pH of about 2 (Lopez-Archila et al, 2004). For the first time, authors isolated strain Rhodotorula sp. from surface precipitates in Ł ęknica region (Muskau Arch). This ochreous precipitate contains jarosite. The yeast might be an important factor in indirect

  14. The anti-interleukin-1 in type 1 diabetes action trial--background and rationale

    DEFF Research Database (Denmark)

    Pickersgill, Linda M S; Mandrup-Poulsen, Thomas R

    2009-01-01

    Type 1 diabetes (T1D) is caused by an inflammatory destruction of pancreatic beta-cells. Pro-inflammatory cytokines, in particular interleukin-1 (IL-1), have been suggested to be effector molecules based on the observations that pro-inflammatory cytokines cause beta-cell apoptosis in vitro...... and aggravate diabetes in vivo, and that inhibition of the action of these cytokines reduce diabetes incidence in animal models of type 1 diabetes and islet graft destruction. This review presents the rationale for and design of a recently launched double-blind, multicenter, randomized clinical trial...... that investigates the effect of interleukin-1 antagonism on beta-cell function in subjects with T1D of recent-onset....

  15. Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up.

    Science.gov (United States)

    Wu, Juan; Cho, Eunyoung; Willett, Walter C; Sastry, Srinivas M; Schaumberg, Debra A

    2015-12-01

    Despite strong biological plausibility, evidence from epidemiologic studies and clinical trials on the relations between intakes of lutein and zeaxanthin and age-related macular degeneration (AMD) has been inconsistent. The roles of other carotenoids are less thoroughly investigated. To investigate the associations between intakes of carotenoids and AMD. Prospective cohort study, with cohorts from the Nurses' Health Study and the Health Professionals Follow-up Study in the United States. A total of 63,443 women and 38,603 men were followed up, from 1984 until May 31, 2010, in the Nurses' Health Study and from 1986 until January 31, 2010, in the Health Professionals Follow-up Study. All participants were aged 50 years or older and were free of diagnosed AMD, diabetes mellitus, cardiovascular disease, and cancer at baseline. Predicted plasma carotenoid scores were computed directly from food intake, assessed by repeated food frequency questionnaires at baseline and follow-up, using validated regression models to account for bioavailability and reporting validity of different foods, and associations between predicted plasma carotenoid scores and AMD were determined. We confirmed 1361 incident intermediate and 1118 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse by medical record review. Comparing extreme quintiles of predicted plasma lutein/zeaxanthin score, we found a risk reduction for advanced AMD of about 40% in both women and men (pooled relative risk comparing extreme quintiles = 0.59; 95% CI, 0.48-0.73; P for trend carotenoid scores for other carotenoids, including β-cryptoxanthin, α-carotene, and β-carotene, were associated with a 25% to 35% lower risk of advanced AMD when comparing extreme quintiles. The relative risk comparing extreme quintiles for the predicted plasma total carotenoid index was 0.65 (95% CI, 0.53-0.80; P for trend carotenoids, either as predicted plasma score or calculated intake, with

  16. 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.

  17. Nutritional and Lifestyle Interventions for Age-Related Macular Degeneration: A Review

    Directory of Open Access Journals (Sweden)

    Ângela Carneiro

    2017-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness in the developed world. In this narrative review, we will summarize the nutritional interventions evaluated in numerous observational studies and a few randomized clinical trials. The AREDS and AREDS2 studies demonstrated that supplements including vitamins C and E, beta-carotene, and zinc may reduce the progression to advanced AMD, in some patients, by 25% in five years. This is one of the few nutritional supplements known to have beneficial effects in any eye disease. Lutein/zeaxanthin supplementation may have beneficial effects in some individuals whereas omega-3 fatty acids supplementation needs to be further investigated and supported by more evidence. Genetic factors may explain the different patterns of response and explain differences found among individuals. More importantly, a combination of lifestyle behaviors such as the avoidance of smoking, physical activity, and the adoption of a healthy dietary pattern like the Mediterranean diet was associated with a lower prevalence of AMD. The adoption of these lifestyles may reduce the prevalence of the early stages of AMD and decrease the number of individuals who develop advanced AMD and consequently the onerous and climbing costs associated with the treatment of this disease.

  18. Risk assessment model for development of advanced age-related macular degeneration.

    Science.gov (United States)

    Klein, Michael L; Francis, Peter J; Ferris, Frederick L; Hamon, Sara C; Clemons, Traci E

    2011-12-01

    To design a risk assessment model for development of advanced age-related macular degeneration (AMD) incorporating phenotypic, demographic, environmental, and genetic risk factors. We evaluated longitudinal data from 2846 participants in the Age-Related Eye Disease Study. At baseline, these individuals had all levels of AMD, ranging from none to unilateral advanced AMD (neovascular or geographic atrophy). Follow-up averaged 9.3 years. We performed a Cox proportional hazards analysis with demographic, environmental, phenotypic, and genetic covariates and constructed a risk assessment model for development of advanced AMD. Performance of the model was evaluated using the C statistic and the Brier score and externally validated in participants in the Complications of Age-Related Macular Degeneration Prevention Trial. The final model included the following independent variables: age, smoking history, family history of AMD (first-degree member), phenotype based on a modified Age-Related Eye Disease Study simple scale score, and genetic variants CFH Y402H and ARMS2 A69S. The model did well on performance measures, with very good discrimination (C statistic = 0.872) and excellent calibration and overall performance (Brier score at 5 years = 0.08). Successful external validation was performed, and a risk assessment tool was designed for use with or without the genetic component. We constructed a risk assessment model for development of advanced AMD. The model performed well on measures of discrimination, calibration, and overall performance and was successfully externally validated. This risk assessment tool is available for online use.

  19. Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis.

    Directory of Open Access Journals (Sweden)

    Elizabeth G Holliday

    Full Text Available Genetic factors explain a majority of risk variance for age-related macular degeneration (AMD. While genome-wide association studies (GWAS for late AMD implicate genes in complement, inflammatory and lipid pathways, the genetic architecture of early AMD has been relatively under studied. We conducted a GWAS meta-analysis of early AMD, including 4,089 individuals with prevalent signs of early AMD (soft drusen and/or retinal pigment epithelial changes and 20,453 individuals without these signs. For various published late AMD risk loci, we also compared effect sizes between early and late AMD using an additional 484 individuals with prevalent late AMD. GWAS meta-analysis confirmed previously reported association of variants at the complement factor H (CFH (peak P = 1.5×10(-31 and age-related maculopathy susceptibility 2 (ARMS2 (P = 4.3×10(-24 loci, and suggested Apolipoprotein E (ApoE polymorphisms (rs2075650; P = 1.1×10(-6 associated with early AMD. Other possible loci that did not reach GWAS significance included variants in the zinc finger protein gene GLI3 (rs2049622; P = 8.9×10(-6 and upstream of GLI2 (rs6721654; P = 6.5×10(-6, encoding retinal Sonic hedgehog signalling regulators, and in the tyrosinase (TYR gene (rs621313; P = 3.5×10(-6, involved in melanin biosynthesis. For a range of published, late AMD risk loci, estimated effect sizes were significantly lower for early than late AMD. This study confirms the involvement of multiple established AMD risk variants in early AMD, but suggests weaker genetic effects on the risk of early AMD relative to late AMD. Several biological processes were suggested to be potentially specific for early AMD, including pathways regulating RPE cell melanin content and signalling pathways potentially involved in retinal regeneration, generating hypotheses for further investigation.

  20. 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

  1. Infrared variability and nature of symbiotic stars

    Energy Technology Data Exchange (ETDEWEB)

    Feast, M W; Robertson, B S.C.; Catchpole, R M [Royal Observatory, Cape Town (South Africa)

    1977-05-01

    Most symbiotic stars may be placed in one of two classes according to their infrared colours. In one group the systems contain an M type giant. In the other there is evidence for a star plus infrared emission from dust. JHKL photometry is given for three members of each class. Photometry of the VV Cephei system FR Sct is also given. No evidence for variability was found for systems without dust. The three systems with dust (RX Pup, RR Tel and PK 280-2/sup 0/.1) each show large variations of the stellar component (..delta..J, 1sup(m).6 to 2sup(m).7). It is concluded that these dusty systems contain Mira variables. For the systems without dust the mass transfer in the system is presumably through the inner Lagrangian point. For systems containing Miras it is possible that the companion accretes matter from a general stellar wind. Symbiotic systems containing Mira variables have more dust than average Mira variables. Either an unusually dense stellar wind is needed to produce a symbiotic system or such a system produces dust, perhaps in a high-density region resulting from the interaction of the stellar wind with the companion.

  2. Evaluation of Two Systems for Fundus-Controlled Scotopic and Mesopic Perimetry in Eye with Age-Related Macular Degeneration.

    Science.gov (United States)

    Steinberg, Julia S; Saßmannshausen, Marlene; Pfau, Maximilian; Fleckenstein, Monika; Finger, Robert P; Holz, Frank G; Schmitz-Valckenberg, Steffen

    2017-07-01

    The purpose of this study was to evaluate and compare the MP-1S (Nidek Technologies, Padova, Italy) and the S-MAIA (CenterVue, Padova, Italy) for mesopic and scotopic fundus-controlled perimetry (FCP) in age-related macular degeneration (AMD). Eleven eyes from 11 patients underwent mesopic and, after 30 minutes of dark adaptation, scotopic (MP-1S: Goldmann V, 200 ms, background luminance 0.0032 cd/m 2 ; S-MAIA: Goldman III, 200 ms, background luminance grid of 56 stimulus points covering 16° of the central macula was used. Examination time, fixation stability, and threshold values were analyzed. The upper end of the dynamic range (≤4 dB of lowest threshold) was frequently reached by the MP-1S for mesopic testing (median 34 of 56 stimuli), while threshold values within the lower 4 dB of the dynamic range were occasionally found with the S-MAIA for scotopic testing (median 3 for cyan, median 2 for red). After correction of the stimulus intensity for the S-MAIA results, the median difference for all stimuli between both devices for mesopic testing was -2.0 dB (interquartile range [-4;0], range -14 to 6). The results indicate that robust testing of mesopic and scotopic function is feasible with both devices in patients with AMD, although both devices are susceptible to floor and ceiling effects. The interpretation and particularly the comparison of both scotopic and mesopic FCP results between the MP-1S and the S-MAIA in AMD eyes need to consider variable susceptibility of floor and ceiling effects. Further software updates are desirable as FCP captures visual functional loss that is not noted with best-corrected central visual acuity and is important for clinical trials in AMD.

  3. Circulating vitamin D concentration and age-related macular degeneration: Systematic review and meta-analysis.

    Science.gov (United States)

    Annweiler, Cedric; Drouet, Morgane; Duval, Guillaume T; Paré, Pierre-Yves; Leruez, Stephanie; Dinomais, Mickael; Milea, Dan

    2016-06-01

    Vitamin D may be involved in ocular function in older adults, but there is no current consensus on a possible association between circulating concentrations of 25-hydroxyvitamin D (25OHD) and the occurrence of age-related macular degeneration (AMD). Our objective was to systematically review and quantitatively assess the association of circulating 25OHD concentration with AMD. A Medline search was conducted in November 2015, with no date limit, using the MeSH terms "Vitamin D" OR "Vitamin D deficiency" OR "Ergocalciferols" OR 'Cholecalciferol' combined with "Age-related macular degeneration" OR "Macular degeneration" OR "Retinal degeneration" OR "Macula lutea" OR "Retina". Fixed and random-effects meta-analyses were performed to compute (i) standard mean difference in 25OHD concentration between AMD and non-AMD patients; (ii) AMD risk according to circulating 25OHD concentration. Of the 243 retrieved studies, 11 observational studies-10 cross-sectional studies and 1 cohort study-met the selection criteria. The number of participants ranged from 65 to 17,045 (52-100% women), and the number with AMD ranged from 31 to 1440. Circulating 25OHD concentration was 15% lower in AMD compared with non-AMD on average. AMD was inversely associated with the highest 25OHD quintile compared with the lowest (summary odds ratio (OR)=0.83 [95%CI:0.71-0.97]), notably late AMD (summary OR=0.47 [95%CI:0.28-0.79]). Circulating 25OHD<50nmol/L was also associated with late-stage AMD (summary OR=2.18 [95%CI:1.34-3.56]), an association that did not persist when all categories of AMD were considered (summary OR=1.26 [95%CI:0.90-1.76]). In conclusion, this meta-analysis provides evidence that high 25OHD concentrations may be protective against AMD, and that 25OHD concentrations below 50nmol/L are associated with late AMD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Investigation into the Individualized Treatment of Traditional Chinese Medicine through a Series of N-of-1 Trials

    Science.gov (United States)

    Yang, Peilan; Wang, Jie; Wu, Yingen; Zi, Suna; Tang, Jie; Wang, Zhenwei

    2018-01-01

    Purpose To compare the efficacy of individualized herbal decoction with standard decoction for patients with stable bronchiectasis through N-of-1 trials. Methods We conducted a single center N-of-1 trials in 17 patients with stable bronchiectasis. Each N-of-1 trial contains three cycles. Each cycle is divided into two 4-week intervention including individualized decoction and fixed decoction (control). The primary outcome was patient self-reported symptoms scores on a 1–7 point Likert scale. Secondary outcomes were 24-hour sputum volume and CAT scores. Results Among 14 completed trials, five showed that the individualized decoction was statistically better than the control decoction on symptom scores (P traditional Chinese medicine individual diagnosis and treatment. PMID:29552084

  5. 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

  6. SieveSifter: a web-based tool for visualizing the sieve analyses of HIV-1 vaccine efficacy trials.

    Science.gov (United States)

    Fiore-Gartland, Andrew; Kullman, Nicholas; deCamp, Allan C; Clenaghan, Graham; Yang, Wayne; Magaret, Craig A; Edlefsen, Paul T; Gilbert, Peter B

    2017-08-01

    Analysis of HIV-1 virions from participants infected in a randomized controlled preventive HIV-1 vaccine efficacy trial can help elucidate mechanisms of partial protection. By comparing the genetic sequence of viruses from vaccine and placebo recipients to the sequence of the vaccine itself, a technique called 'sieve analysis', one can identify functional specificities of vaccine-induced immune responses. We have created an interactive web-based visualization and data access tool for exploring the results of sieve analyses performed on four major preventive HIV-1 vaccine efficacy trials: (i) the HIV Vaccine Trial Network (HVTN) 502/Step trial, (ii) the RV144/Thai trial, (iii) the HVTN 503/Phambili trial and (iv) the HVTN 505 trial. The tool acts simultaneously as a platform for rapid reinterpretation of sieve effects and as a portal for organizing and sharing the viral sequence data. Access to these valuable datasets also enables the development of novel methodology for future sieve analyses. Visualization: http://sieve.fredhutch.org/viz . Source code: https://github.com/nkullman/SIEVE . Data API: http://sieve.fredhutch.org/data . agartlan@fredhutch.org. © The Author(s) 2017. Published by Oxford University Press.

  7. "Me's me and you's you": Exploring patients' perspectives of single patient (n-of-1 trials in the UK

    Directory of Open Access Journals (Sweden)

    Woolhead Gillian

    2007-03-01

    Full Text Available Abstract Background The n-of-1 trial offers a more methodologically sound approach to determining optimum treatment for an individual patient than "trials of therapy" routinely conducted in clinical practice. However, such methodology is rarely used in the UK. This pilot study explores the acceptability of n-of-1 trials to patients in the UK. Methods Patients with osteoarthritis of the knee were recruited to their own 12-week n-of-1 trial comparing either two knee supports or an NSAID with simple analgesic. Patients were interviewed at the start and completion of their trial to explore reasons for participation, understanding of the trial design and experiences of participation. Daily diaries were completed to inform future treatment. Results Nine patients participated (5 supports, 4 drugs. Patients were keen to participate, believing that the trial may lead to personal gains such as improved symptom control and quality of life. However, recruitment to the pharmacological comparison was more difficult since this could also entail risk. All patients were eager to complete the trial, even when difficulties were encountered. Completing the daily diary provided some patients with greater insight into their condition, which allowed them to improve their self-management. The n-of-1 trial design was viewed as a 'logical' design offering an efficient method of reaching a personalised treatment decision tailored to suit individual needs and preferences. Conclusion This pilot study suggests that patients perceive the n-of-1 trial as an acceptable approach to the individualisation of treatment. In addition, further benefits over and above any gained from the interventions can be derived from involvement in such a study.

  8. 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...

  9. Prevalence of age-related macular degeneration in Nakuru, Kenya: a cross-sectional population-based study.

    Directory of Open Access Journals (Sweden)

    Wanjiku Mathenge

    Full Text Available Diseases of the posterior segment of the eye, including age-related macular degeneration (AMD, have recently been recognised as the leading or second leading cause of blindness in several African countries. However, prevalence of AMD alone has not been assessed. We hypothesized that AMD is an important cause of visual impairment among elderly people in Nakuru, Kenya, and therefore sought to assess the prevalence and predictors of AMD in a diverse adult Kenyan population.In a population-based cross-sectional survey in the Nakuru District of Kenya, 100 clusters of 50 people 50 y of age or older were selected by probability-proportional-to-size sampling between 26 January 2007 and 11 November 2008. Households within clusters were selected through compact segment sampling. All participants underwent a standardised interview and comprehensive eye examination, including dilated slit lamp examination by an ophthalmologist and digital retinal photography. Images were graded for the presence and severity of AMD lesions following a modified version of the International Classification and Grading System for Age-Related Maculopathy. Comparison was made between slit lamp biomicroscopy (SLB and photographic grading. Of 4,381 participants, fundus photographs were gradable for 3,304 persons (75.4%, and SLB was completed for 4,312 (98%. Early and late AMD prevalence were 11.2% and 1.2%, respectively, among participants graded on images. Prevalence of AMD by SLB was 6.7% and 0.7% for early and late AMD, respectively. SLB underdiagnosed AMD relative to photographic grading by a factor of 1.7. After controlling for age, women had a higher prevalence of early AMD than men (odds ratio 1.5; 95% CI, 1.2-1.9. Overall prevalence rose significantly with each decade of age. We estimate that, in Kenya, 283,900 to 362,800 people 50 y and older have early AMD and 25,200 to 50,500 have late AMD, based on population estimates in 2007.AMD is an important cause of visual

  10. Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials.

    Science.gov (United States)

    Gilbert, Peter B; Juraska, Michal; deCamp, Allan C; Karuna, Shelly; Edupuganti, Srilatha; Mgodi, Nyaradzo; Donnell, Deborah J; Bentley, Carter; Sista, Nirupama; Andrew, Philip; Isaacs, Abby; Huang, Yunda; Zhang, Lily; Capparelli, Edmund; Kochar, Nidhi; Wang, Jing; Eshleman, Susan H; Mayer, Kenneth H; Magaret, Craig A; Hural, John; Kublin, James G; Gray, Glenda; Montefiori, David C; Gomez, Margarita M; Burns, David N; McElrath, Julie; Ledgerwood, Julie; Graham, Barney S; Mascola, John R; Cohen, Myron; Corey, Lawrence

    2017-01-01

    Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions. The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark

  11. Characteristics of HIV-1 serodiscordant couples enrolled in a clinical trial of antiretroviral pre-exposure prophylaxis for HIV-1 prevention.

    Directory of Open Access Journals (Sweden)

    Andrew Mujugira

    Full Text Available Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort.HIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24-36 months.From July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758 of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners [IQR (28-40 and (26-39 respectively]. Most couples (98% were married, with a median duration of partnership of 7.0 years (IQR 3.0-14.0 and recent knowledge of their serodiscordant status [median 0.4 years (IQR 0.1-2.0]. During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2-8; 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log(10 copies/mL (IQR 3.31-4.53 and median CD4 count was 496 cells/µL (IQR 375-662; the majority (64% had WHO stage 1 HIV-1 disease.Couples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245.

  12. 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.

  13. 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

  14. AGB stellar evolution and symbiotic stars

    International Nuclear Information System (INIS)

    Schild, H.

    1989-01-01

    Published data on the mass loss rates and periods of Miras and OH/IR stars have been compiled. There is a good correlation between mass loss rate and period and a smooth transition from Miras to OH/IR sources. At periods below 600 d. the mass loss increases exponentially but at longer periods it remains constant. As a Mira evolves from short to longer periods, its mass loss rate increases dramatically. Phenomenologically, the object evolves from a classical Mira into a variable OH/IR source. Symbiotic stars cluster in the transition zone where Miras transform into OH/IR stars and mass loss increase is at its steepest. The red star in these symbiotic systems is in the same evolutionary status as short periodic OH/IR stars. (author)

  15. Effects of Amiodarone and N-Desethylamiodarone on Cardiac Voltage-gated Sodium Channels

    Directory of Open Access Journals (Sweden)

    Mohammad-Reza eGhovanloo

    2016-03-01

    Full Text Available Amiodarone (AMD is a potent antiarrhythmic drug with high efficacy for treating atrial fibrillation and tachycardia. The pharmacologic profile of AMD is complex. AMD possesses biophysical characteristics of all of class I, II, III, and IV agents. Despite its adverse side effects, AMD remains the most commonly prescribed antiarrhythmic drug. AMD was described to prolong the QT interval and can lead to torsades de pointes. Our goal was to study the effects of AMD on peak and late sodium currents (INa,P and INa,L and determine whether these effects change as AMD is metabolized into N-Desethylamiodarone (DES. We hypothesized that AMD and DES block both INa,P and INa,L with similar profiles due to structural similarities. Given the inherent small amounts of INa,L in NaV1.5, we screened AMD and DES against the Long QT-3-causing mutation, ∆KPQ, to better detect any drug-mediated effect on INa,L. Our results show that AMD and DES do not affect WT or ∆KPQ activation; however, both drugs altered the apparent valence of steady-state fast-inactivation. In addition, AMD and DES preferentially block ∆KPQ peak conductance compared to WT. Both compounds significantly increase INa,L and window currents. We conclude that both compounds have pro-arrhythmic effects on NaV1.5, especially ∆KPQ; however, DES seems to have a greater pro-arrhythmic effect than AMD.

  16. "Wonderful" Star Reveals its Hot Nature

    Science.gov (United States)

    2005-04-01

    For the first time an X-ray image of a pair of interacting stars has been made by NASA's Chandra X-ray Observatory. The ability to distinguish between the interacting stars - one a highly evolved giant star and the other likely a white dwarf - allowed a team of scientists to observe an X-ray outburst from the giant star and find evidence that a bridge of hot matter is streaming between the two stars. "Before this observation it was assumed that all the X-rays came from a hot disk surrounding a white dwarf, so the detection of an X-ray outburst from the giant star came as a surprise," said Margarita Karovska of the Harvard-Smithsonian Center for Astrophysics in Cambridge, Mass., and lead author article in the latest Astrophysical Journal Letters describing this work. An ultraviolet image made by the Hubble Space Telescope was a key to identifying the location of the X-ray outburst with the giant star. X-ray studies of this system, called Mira AB, may also provide better understanding of interactions between other binary systems consisting of a "normal" star and a collapsed star such as a white dwarf, black hole or a neutron star, where the stellar objects and gas flow cannot be distinguished in an image. HST Ultraviolet Image of Mira HST Ultraviolet Image of Mira The separation of the X-rays from the giant star and the white dwarf was made possible by the superb angular resolution of Chandra, and the relative proximity of the star system at about 420 light years from Earth. The stars in Mira AB are about 6.5 billion miles apart, or almost twice the distance of Pluto from the Sun. Mira A (Mira) was named "The Wonderful" star in the 17th century because its brightness was observed to wax and wane over a period of about 330 days. Because it is in the advanced, red giant phase of a star's life, it has swollen to about 600 times that of the Sun and it is pulsating. Mira A is now approaching the stage where its nuclear fuel supply will be exhausted, and it will collapse

  17. Novel grid combined with peripheral distortion correction for ultra-widefield image grading of age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Oellers P

    2017-11-01

    Full Text Available Patrick Oellers,1,* Inês Laíns,1,2,* Steven Mach,1 Shady Garas,1 Ivana K Kim,1 Demetrios G Vavvas,1 Joan W Miller,1 Deeba Husain,1 John B Miller1 1Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA; 2Faculty of Medicine, University of Coimbra, Coimbra, Portugal *These authors contributed equally to this work Purpose: Eyes with age-related macular degeneration (AMD often harbor pathological changes in the retinal periphery and perimacular region. These extramacular changes have not been well classified, but may be phenotypically and functionally relevant. The purpose of this study was to demonstrate a novel grid to systematically study peripheral retinal abnormalities in AMD using geometric distortion-corrected ultra-widefield (UWF imaging.Methods: This is a cross-sectional observational case series. Consecutive patients with AMD without any other coexisting vitreoretinal disease and control patients over age 50 without AMD or any other vitreoretinal disease were imaged using Optos 200 Tx. Captured 200° UWF images were corrected for peripheral geometric distortion using Optos transformation software. A newly developed grid to study perimacular and peripheral abnormalities in AMD was then projected onto the images.Results: Peripheral and perimacular changes such as drusen, retinal pigment epithelium changes and atrophy were found in patients with AMD. The presented grid in conjunction with geometric distortion-corrected UWF images allowed for systematic study of these peripheral changes in AMD.Conclusion: We present a novel grid to study peripheral and posterior pole changes in AMD. The grid is unique in that it adds a perimacular zone, which may be important in characterizing certain phenotypes in AMD. Our UWF images were corrected for geometric peripheral distortion to accurately reflect the anatomical dimensions of the retina. This grid offers a reliable and reproducible foundation

  18. Analysis of patient-reported outcomes from the LUME-Lung 1 trial

    DEFF Research Database (Denmark)

    Novello, Silvia; Kaiser, Rolf; Mellemgaard, Anders

    2015-01-01

    INTRODUCTION: The LUME-Lung 1 trial (NCT00805194; Study 1199.13) demonstrated a significant overall survival (OS) advantage for nintedanib plus docetaxel compared with placebo plus docetaxel as second-line therapy for patients with advanced non-small cell lung cancer (NSCLC) and adenocarcinoma...

  19. Autophagy Stimulus Promotes Early HuR Protein Activation and p62/SQSTM1 Protein Synthesis in ARPE-19 Cells by Triggering Erk1/2, p38MAPK, and JNK Kinase Pathways

    Directory of Open Access Journals (Sweden)

    Nicoletta Marchesi

    2018-01-01

    Full Text Available RNA-binding protein dysregulation and altered expression of proteins involved in the autophagy/proteasome pathway play a role in many neurodegenerative disease onset/progression, including age-related macular degeneration (AMD. HuR/ELAVL1 is a master regulator of gene expression in human physiopathology. In ARPE-19 cells exposed to the proteasomal inhibitor MG132, HuR positively affects at posttranscriptional level p62 expression, a stress response gene involved in protein aggregate clearance with a role in AMD. Here, we studied the early effects of the proautophagy AICAR + MG132 cotreatment on the HuR-p62 pathway. We treated ARPE-19 cells with Erk1/2, AMPK, p38MAPK, PKC, and JNK kinase inhibitors in the presence of AICAR + MG132 and evaluated HuR localization/phosphorylation and p62 expression. Two-hour AICAR + MG132 induces both HuR cytoplasmic translocation and threonine phosphorylation via the Erk1/2 pathway. In these conditions, p62 mRNA is loaded on polysomes and its translation in de novo protein is favored. Additionally, for the first time, we report that JNK can phosphorylate HuR, however, without modulating its localization. Our study supports HuR’s role as an upstream regulator of p62 expression in ARPE-19 cells, helps to understand better the early events in response to a proautophagy stimulus, and suggests that modulation of the autophagy-regulating kinases as potential therapeutic targets for AMD may be relevant.

  20. ADVANCES IN BIOTREATMENT OF ACID MINE DRAINAGE AND BIORECOVERY OF METALS: 1. METAL PRECIPITATION FOR RECOVERY AND RECYCLE

    Science.gov (United States)

    Acid-mine drainage (AMD) is a severe pollution problem attributed to past mining activities. AMD is an acidic, metal-bearing wastewater generated by the oxidation of metal sulfides to sulfates by Thiobacillus bacteria in both active and abandoned mining operations. The wastewater...

  1. Implementación del programa de reeducación psicomotriz con miras a mejorar las destrezas lecto-escritoras en niñas y niños de 6 a 12 años del Centro de Referencia Iñaquito Programa Acción Guambras, durante el periodo marzo-julio 2017.

    OpenAIRE

    Morales Yucaza, Diana Lizbeth

    2017-01-01

    The following systematization report describes the experience of the project called “Implementación del programa de reeducación psicomotriz con miras a mejorar las destrezas lecto-escritoras en niñas y niños de 6 a 12 años del centro de referencia Iñaquito Programa Acción Guambras, durante el periodo marzo-julio 2017”. According to the diagnosis made at the beginning of the intervention process, it is evident that the main need of the children of the Iñaquito reference center resides in th...

  2. Genetic mechanisms and age-related macular degeneration: common variants, rare variants, copy number variations, epigenetics, and mitochondrial genetics

    Directory of Open Access Journals (Sweden)

    Liu Melissa M

    2012-08-01

    Full Text Available Abstract Age-related macular degeneration (AMD is a complex and multifaceted disease involving contributions from both genetic and environmental influences. Previous work exploring the genetic contributions of AMD has implicated numerous genomic regions and a variety of candidate genes as modulators of AMD susceptibility. Nevertheless, much of this work has revolved around single-nucleotide polymorphisms (SNPs, and it is apparent that a significant portion of the heritability of AMD cannot be explained through these mechanisms. In this review, we consider the role of common variants, rare variants, copy number variations, epigenetics, microRNAs, and mitochondrial genetics in AMD. Copy number variations in regulators of complement activation genes (CFHR1 and CFHR3 and glutathione S transferase genes (GSTM1 and GSTT1 have been associated with AMD, and several additional loci have been identified as regions of potential interest but require further evaluation. MicroRNA dysregulation has been linked to the retinal pigment epithelium degeneration in geographic atrophy, ocular neovascularization, and oxidative stress, all of which are hallmarks in the pathogenesis of AMD. Certain mitochondrial DNA haplogroups and SNPs in mitochondrially encoded NADH dehydrogenase genes have also been associated with AMD. The role of these additional mechanisms remains only partly understood, but the importance of their further investigation is clear to elucidate more completely the genetic basis of AMD.

  3. Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

    Science.gov (United States)

    Jones, Melissa K.; Lu, Bin; Girman, Sergey; Wang, Shaomei

    2017-01-01

    Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments. PMID:28111323

  4. Mobilizing stem cells from normal donors: is it possible to improve upon G-CSF?

    Science.gov (United States)

    Cashen, A F; Lazarus, H M; Devine, S M

    2007-05-01

    Currently, granulocyte colony stimulating factor (G-CSF) remains the standard mobilizing agent for peripheral blood stem cell (PBSC) donors, allowing the safe collection of adequate PBSCs from the vast majority of donors. However, G-CSF mobilization can be associated with some significant side effects and requires a multi-day dosing regimen. The other cytokine approved for stem cell mobilization, granulocyte-macrophage colony stimulating factor (GM-CSF), alters graft composition and may reduce the development of graft-versus-host disease, but a significant minority of donors fails to provide sufficient CD34+ cells with GM-CSF and some experience unacceptable toxicity. AMD3100 is a promising new mobilizing agent, which may have several advantages over G-CSF for donor mobilization. As it is a direct antagonist of the interaction between the chemokine stromal-derived factor-1 and its receptor CXCR4, AMD3100 mobilizes PBSCs within hours rather than days. It is also well tolerated, with no significant side effects reported in any of the clinical trials to date. Studies of autologous and allogeneic transplantation of AMD3100 mobilized grafts have demonstrated prompt and stable engraftment. Here, we review the current state of stem cell mobilization in normal donors and discuss novel strategies for donor stem cell mobilization.

  5. Tear film proteome in age-related macular degeneration.

    Science.gov (United States)

    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.

  6. Risks of newly onset hemorrhagic stroke in patients with neovascular age-related macular degeneration.

    Science.gov (United States)

    Lee, Wan-Ju Annabelle; Cheng, Ching-Lan; Lee, Cheng-Han; Kao Yang, Yea-Huei; Lin, Swu-Jane; Hsieh, Cheng-Yang

    2017-10-01

    Age-related macular degeneration (AMD) is an eye disease causing blindness in the elderly. It shares many common possible pathogenic mechanisms with cardiovascular diseases. Many studies have discussed the association between AMD and stroke, but the results were inconsistent. Our aim was to determine the associations between neovascular AMD and the risk of stroke in the Taiwanese population. This is a retrospective cohort study. We used claims data from National Health Insurance Research Database. Patients aged more than 45 years without stroke, myocardial infarction, or any AMD were selected from 2001 to 2008 and followed until 2010. The index date was defined as the date of nAMD diagnosis (ICD-9 code, 362.52). The comparison group was patients without an nAMD diagnosis with age- and sex-matched to nAMD subjects at a ratio of up to 10 to 1. Kaplan-Meier survival analysis and Cox regression analysis were used. The incidence of stroke events (ICD-9 codes, 430-434) and their subtypes (hemorrhagic and ischemic) were primary outcomes. Secondary outcomes included acute myocardial infarction (AMI), composite AMI/stroke, and all-cause mortality. Patients with nAMD had a higher risk of developing stroke, with an adjusted HR of 1.30 (95% CI, 1.01-1.68). A higher risk for hemorrhagic stroke (HR, 1.70, 95% CI, 1.03-2.83) was also found. No significant differences were observed in ischemic stroke, the composite of AMI/stroke, and all-cause mortality. Patients with nAMD had a significantly higher risk of developing stroke, which was driven mainly by the increased risk of developing the hemorrhagic subtype. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Series: Pragmatic trials and real world evidence: Paper 1. Introduction.

    Science.gov (United States)

    Zuidgeest, Mira G P; Goetz, Iris; Groenwold, Rolf H H; Irving, Elaine; van Thiel, Ghislaine J M W; Grobbee, Diederick E

    2017-08-01

    This is the introductory paper in a series of eight papers. In this series, we integrate the theoretical design options with the practice of conducting pragmatic trials. For most new market-approved treatments, the clinical evidence is insufficient to fully guide physicians and policy makers in choosing the optimal treatment for their patients. Pragmatic trials can fill this gap, by providing evidence on the relative effectiveness of a treatment strategy in routine clinical practice, already in an early phase of development, while maintaining the strength of randomized controlled trials. Selecting the setting, study population, mode of intervention, comparator, and outcome are crucial in designing pragmatic trials. In combination with monitoring and data collection that does not change routine care, this will enable appropriate generalization to the target patient group in clinical practice. To benefit from the full potential of pragmatic trials, there is a need for guidance and tools in designing these studies while ensuring operational feasibility. This paper introduces the concept of pragmatic trial design. The complex interplay between pragmatic design options, feasibility, stakeholder acceptability, validity, precision, and generalizability will be clarified. In this way, balanced design choices can be made in pragmatic trials with an optimal chance of success in practice. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Therapeutic action of the mitochondria-targeted antioxidant SkQ1 on retinopathy in OXYS rats linked with improvement of VEGF and PEDF gene expression.

    Directory of Open Access Journals (Sweden)

    Anton M Markovets

    Full Text Available UNLABELLED: The incidence of age-related macular degeneration (AMD, the main cause of blindness in older patients in the developed countries, is increasing with the ageing population. At present there is no effective treatment for the prevailing geographic atrophy, dry AMD, whereas antiangiogenic therapies successful used in managing the wet form of AMD. Recently we showed that mitochondria-targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium (SkQ1 is able to prevent the development and moreover caused regression of pre-existing signs of the retinopathy in OXYS rats, an animal model of AMD. Here we examine the effects of SkQ1 on expression of key regulators of angiogenesis vascular endothelial growth factor A (VEGF and its antagonist pigment epithelium-derived factor (PEDF genes in the retina of OXYS rats as evidenced by real-time PCR and an ELISA test for VEGF using Wistar rats as control. Ophthalmoscopic examinations confirmed that SkQ1 supplementation (from 1.5 to 3 months of age, 250 nmol/kg prevented development while eye drops SkQ1 (250 nM, from 9 to 12 months caused some reduction of retinopathy signs in OXYS rats and did not reveal any negative effects on the control Wistar rat's retina. Prevention of premature retinopathy by SkQ1 was connected with an increase of VEGF mRNA and protein in OXYS rat's retina up to the levels corresponding to the Wistar rats, and did not involve changes in PEDF expression. In contrast the treatment with SkQ1 drops caused a decrease of VEGF mRNA and protein levels and an increase in the PEDF mRNA level in the middle-aged OXYS rats, but in Wistar rats the changes of gene expression were the opposite. CONCLUSIONS: The beneficial effects of SkQ1 on retinopathy connected with normalization of expression of VEGF and PEDF in the retina of OXYS rats and depended on age of the animals and the stage of retinopathy.

  9. HISTORY OF SUNLIGHT EXPOSURE IS A RISK FACTOR FOR AGE-RELATED MACULAR DEGENERATION

    NARCIS (Netherlands)

    Schick, T.; Ersoy, L.; Lechanteur, Y.T.; Saksens, N.T.; Hoyng, C.B.; Hollander, A.I. den; Kirchhof, B.; Fauser, S.

    2016-01-01

    PURPOSE: To evaluate effects of current and past sunlight exposure and iris color on early and late age-related macular degeneration (AMD). METHODS: Of 3,701 individuals from the EUGENDA database, 752 (20.3%) showed early AMD, 1,179 (31.9%) late AMD, and 1,770 (47.8%) were controls. Information

  10. Complement Factor H Y402H and LOC387715 A69S Polymorphisms in Association with Age-Related Macular Degeneration in Iran.

    Science.gov (United States)

    Nazari Khanamiri, Hossein; Ghasemi Falavarjani, Khalil; Sanati, Mohammad Hossein; Aryan, Hajar; Irani, Alireza; Hashemi, Masih; Modarres, Mehdi; Parvaresh, Mohammad Mehdi; Nikeghbali, Aminollah

    2014-04-01

    To determine the frequency of complement factor H (Y402H) and age related macular degeneration susceptibility gene 2 (A69S) single nucleotide polymorphisms in patients with age-related macular degeneration (AMD) and in matched non-AMD controls in an Iranian population. Seventy patients with AMD and 86 age- and sex-matched controls were recruited and examined. Peripheral blood sample was obtained from all subjects for DNA extraction and direct sequencing of Y402H and A69S genes. Odds ratios (ORs) with 95% confidence intervals (CIs) for the association of Y402H and A69S polymorphisms with AMD were determined. The frequencies of both homozygous and heterozygous genotypes were significantly higher in cases than controls for both Y402H and A69S polymorphisms. In comparison to the wild genotypes, OR for AMD associated with Y402H and A69S polymorphisms were 1.9 (95% CI, 1.1-3.2) and 2.2 (95%CI, 1.6-3.1), respectively. Joint risk analysis considering both genes revealed a higher risk of AMD when polymorphisms were present for both genes. Y402H and A69S polymorphisms were strongly associated with AMD in this Iranian population.

  11. Complement Factor H Y402H and LOC387715 A69S Polymorphisms in Association with Age-Related Macular Degeneration in Iran

    Directory of Open Access Journals (Sweden)

    Hossein Nazari Khanamiri

    2014-01-01

    Full Text Available Purpose: To determine the frequency of complement factor H (Y402H and age related macular degeneration susceptibility gene 2 (A69S single nucleotide polymorphisms in patients with age-related macular degeneration (AMD and in matched non-AMD controls in an Iranian population. Methods: Seventy patients with AMD and 86 age- and sex-matched controls were recruited and examined. Peripheral blood sample was obtained from all subjects for DNA extraction and direct sequencing of Y402H and A69S genes. Odds ratios (ORs with 95% confidence intervals (CIs for the association of Y402H and A69S polymorphisms with AMD were determined. Results: The frequencies of both homozygous and heterozygous genotypes were significantly higher in cases than controls for both Y402H and A69S polymorphisms. In comparison to the wild genotypes, OR for AMD associated with Y402H and A69S polymorphisms were 1.9 (95% CI, 1.1-3.2 and 2.2 (95%CI, 1.6-3.1, respectively. Joint risk analysis considering both genes revealed a higher risk of AMD when polymorphisms were present for both genes. Conclusion: Y402H and A69S polymorphisms were strongly associated with AMD in this Iranian population.

  12. Application of the SWAT model to an AMD-affected river (Meca River, SW Spain). Estimation of transported pollutant load

    Science.gov (United States)

    Galván, L.; Olías, M.; Fernandez de Villarán, R.; Domingo Santos, J. M.; Nieto, J. M.; Sarmiento, A. M.; Cánovas, C. R.

    2009-10-01

    SummaryThe Meca River is highly contaminated by acid mine drainage coming from the Tharsis mining district, belonging to the Iberian Pyrite Belt. This river is regulated by the Sancho reservoir (58 hm 3), with a pH close to 4.2. In this work, the load transported by the Meca River to the Sancho reservoir has been assessed. Due to the lack of streamflow data, the hydrological behaviour of the Meca River basin has been simulated using the SWAT model. The model has been calibrated against registered daily inflows of the Sancho reservoir (1982-2000), excluding the hydrological years 2000/2001 and 2001/2002 that were kept for the validation. The results were satisfactory; the evaluation coefficients for monthly calibration were: r = 0.85 (Pearson's correlation coefficient), NSE = 0.83 (Nash-Sutcliffe coefficient) and DV = 1.08 (runoff volume deviation). The main uncertainty was the calibration during low water because of the poor accuracy in the measurement of the inputs to the reservoir in these conditions. Discharge and dissolved concentration relationships for different elements were obtained from hydrochemical samplings, which allowed us to estimate the element pollutant load transported to the reservoir: 418 ton/year of Al, 8024 ton/year of SO 4, 121 ton/year of Zn, etc. Based on these loads, concentrations in the reservoir were calculated for some elements. Apart from Mn and Sr, good adjustment between calculated and measured values was observed (±20% for Ca, Co, Li, Mg, Na, Ni, Zn and SO 4). Capsule: Hydrological model combined with water quality data show how pollution by AMD can generate huge loads of contaminants acidifying streams and reservoirs.

  13. 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.

  14. Prevalence of anti-retinal autoantibodies in different stages of Age-related macular degeneration.

    Science.gov (United States)

    Adamus, Grazyna; Chew, Emily Y; Ferris, Frederick L; Klein, Michael L

    2014-12-08

    Age-related macular degeneration (AMD) is the leading cause of central vision loss in older adults. Anti-retinal autoantibodies (AAbs) have been found in individuals with AMD. The goal of the study was to determine the AAb specificity in different stages of AMD, and determine whether there is a prevalent AAb signature. Sera of 134 participants in the Age-related Eye Disease Study were analyzed for anti-retinal AAbs by western blotting. The subjects were classified by diagnostic subgroups based upon their clinical classification: No AMD, Intermediate AMD, and Late AMD - geographic atrophy (GA) and Late AMD - neovascular (NV). The presence of anti-retinal AAb was detected in 58% patients with Intermediate and Late AMD, and 54% of those with no AMD. AAbs bound to fifteen different retinal antigens. Most individuals had 1 specific AAbs (67%), with the remainder having 2 to 4 different AAbs. Over 40% of patients with Intermediate AMD, and 46% of those with GA had anti-enolase AAbs, compared with 29% of individuals with NV and 29% with no AMD. Different AAbs signatures related to NV as compared to GA and/or Intermediate AMD were distinguished. Anti-40-kDa (10%) and 42-kDa (16%) autoantibodies were associated with Intermediate AMD, while anti-30-kDa AAbs (23%) were primarily present in GA. Anti-32-kDa (12%), 35-kDa (21%), and 60-kDa (8%) AAbs were more frequent in NV AMD. A unique AAb pattern for each of the disease subgroups was present when AMD progressed from the intermediate to the late forms of severity. Differences in the frequency of specific AAbs between AMD subgroups suggested that they may participate in pathogenicity of AMD. Further studies are necessary to confirm these observations in the larger cohort and individual AMD patients over time.

  15. First Lessons From The Biarritz Trial Network [1

    Science.gov (United States)

    Touyarot, P.; Marc, B.; de Panafieu, A.

    1986-07-01

    Opened for commercial operation in 1984, the trial optical fiber network at Biarritz in south-west France gives 1,500 subscribers access to a whole range of broadband services - videophony, audiovisual databases, TV and stereo sound program distribution, and an on-line TV program library - in addition to conventional narrow-band services like telephony and videotex. The Biarritz network is an outstanding technology and engineering testbed. It is also a sociological testing ground for new services, unique in the world, with results of particular relevance to the interactive cable TV and visual communications networks of the future.

  16. Competitor presence reduces internal attentional focus and improves 16.1km cycling time trial performance.

    Science.gov (United States)

    Williams, Emily L; Jones, Hollie S; Andy Sparks, S; Marchant, David C; Midgley, Adrian W; Mc Naughton, Lars R

    2015-07-01

    Whilst the presence of a competitor has been found to improve performance, the mechanisms influencing the change in selected work rates during direct competition have been suggested but not specifically assessed. The aim was to investigate the physiological and psychological influences of a visual avatar competitor during a 16.1-km cycling time trial performance, using trained, competitive cyclists. Randomised cross-over design. Fifteen male cyclists completed four 16.1km cycling time trials on a cycle ergometer, performing two with a visual display of themselves as a simulated avatar (FAM and SELF), one with no visual display (DO), and one with themselves and an opponent as simulated avatars (COMP). Participants were informed the competitive avatar was a similar ability cyclist but it was actually a representation of their fastest previous performance. Increased performance times were evident during COMP (27.8±2.0min) compared to SELF (28.7±1.9min) and DO (28.4±2.3min). Greater power output, speed and heart rate were apparent during COMP trial than SELF (pperformance. Competitive cyclists performed significantly faster during a 16.1-km competitive trial than when performing maximally, without a competitor. The improvement in performance was elicited due to a greater external distraction, deterring perceived exertion. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  17. Recruitment and retention of participants for an international type 1 diabetes prevention trial

    DEFF Research Database (Denmark)

    Franciscus, Margaret; Nucci, Anita; Bradley, Brenda

    2014-01-01

    for long-term follow-up assessments. PURPOSE: Our purpose is to summarize the recruitment and retention strategies used to conduct TRIGR from the perspective of the study coordinators. METHODS: TRIGR was designed to test whether weaning to formula containing hydrolyzed versus intact cow's milk protein......BACKGROUND: The Trial to Reduce Insulin Dependent Diabetes Mellitus in the Genetically at Risk (TRIGR) is the first multicenter international type 1 diabetes (T1D) prevention trial to be undertaken. A unique feature of TRIGR has been recruitment of eligible pregnant women and enrollment of newborns......-year follow-up phases of this study. The TRIGR study met the accrual goal after 4.7 years of recruitment, 2.7 years longer than projected initially. Challenges included difficulty in finding fathers with T1D, a higher than expected rate of premature delivery among T1D mothers, and implementation of new...

  18. Environmental cadmium and lead exposures and age-related macular degeneration in U.S. adults: The National Health and Nutrition Examination Survey 2005 to 2008

    International Nuclear Information System (INIS)

    Wu, Erin W.; Schaumberg, Debra A.; Park, Sung Kyun

    2014-01-01

    Age-related macular degeneration (AMD) is a complex disease resulting from the interplay of genetic predisposition and environmental exposures, and has been linked to oxidative stress and inflammatory mechanisms. Lead and cadmium can accumulate in human retinal tissues and may damage the retina through oxidative stress, and may thereby play a role in the development of AMD. We examined associations between blood lead, blood cadmium, and urinary cadmium concentrations and the presence of AMD in 5390 participants aged 40 years and older with blood lead and blood cadmium measures and a subsample of 1548 with urinary cadmium measures in the 2005–2008 National Health and Nutrition Examination Surveys. AMD was identified by grading retinal photographs with a modification of the Wisconsin Age-Related Maculopathy Grading System. The weighted prevalence of AMD was 6.6% (n=426). Controlling for age, gender, race/ethnicity, education and body mass index, adults in the highest blood cadmium quartile had higher odds of AMD compared to the lowest quartile (odds ratio [OR], 1.56; 95% CI, 1.02–2.40), with a significant trend across quartiles (p-trend=0.02). After further adjustment for pack-years of cigarette smoking, estimates were somewhat attenuated (OR, 1.43; 95% CI, 0.91–2.27; p-trend=0.08). Similar associations were found with urinary cadmium. The association between urinary cadmium and AMD was stronger in non-Hispanic whites (NHW) than in non-Hispanic blacks (NHB) (OR, 3.31; 95% CI, 1.37–8.01 for levels above versus below the median among NHW; OR,1.45; 95% CI, 0.40–5.32 for levels above versus below the median among NHB; p-interaction=0.03). We found no association between blood lead levels and AMD. Higher cadmium body burden may increase risk of AMD, particularly among non-Hispanic white individuals; however, additional studies are needed before firm conclusions can be drawn. - Highlights: • We examined the association of cadmium and lead with age

  19. Environmental cadmium and lead exposures and age-related macular degeneration in U.S. adults: The National Health and Nutrition Examination Survey 2005 to 2008

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Erin W. [Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI (United States); Schaumberg, Debra A. [Division of Preventive Medicine, Brigham and Women' s Hospital, Harvard Medical School and Department of Epidemiology, Harvard School of Public Health, Boston, MA (United States); Center for Translational Medicine, Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT (United States); Park, Sung Kyun, E-mail: sungkyun@umich.edu [Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI (United States); Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI (United States)

    2014-08-15

    Age-related macular degeneration (AMD) is a complex disease resulting from the interplay of genetic predisposition and environmental exposures, and has been linked to oxidative stress and inflammatory mechanisms. Lead and cadmium can accumulate in human retinal tissues and may damage the retina through oxidative stress, and may thereby play a role in the development of AMD. We examined associations between blood lead, blood cadmium, and urinary cadmium concentrations and the presence of AMD in 5390 participants aged 40 years and older with blood lead and blood cadmium measures and a subsample of 1548 with urinary cadmium measures in the 2005–2008 National Health and Nutrition Examination Surveys. AMD was identified by grading retinal photographs with a modification of the Wisconsin Age-Related Maculopathy Grading System. The weighted prevalence of AMD was 6.6% (n=426). Controlling for age, gender, race/ethnicity, education and body mass index, adults in the highest blood cadmium quartile had higher odds of AMD compared to the lowest quartile (odds ratio [OR], 1.56; 95% CI, 1.02–2.40), with a significant trend across quartiles (p-trend=0.02). After further adjustment for pack-years of cigarette smoking, estimates were somewhat attenuated (OR, 1.43; 95% CI, 0.91–2.27; p-trend=0.08). Similar associations were found with urinary cadmium. The association between urinary cadmium and AMD was stronger in non-Hispanic whites (NHW) than in non-Hispanic blacks (NHB) (OR, 3.31; 95% CI, 1.37–8.01 for levels above versus below the median among NHW; OR,1.45; 95% CI, 0.40–5.32 for levels above versus below the median among NHB; p-interaction=0.03). We found no association between blood lead levels and AMD. Higher cadmium body burden may increase risk of AMD, particularly among non-Hispanic white individuals; however, additional studies are needed before firm conclusions can be drawn. - Highlights: • We examined the association of cadmium and lead with age

  20. Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Arabi, Yaseen M; Alothman, Adel; Balkhy, Hanan H; Al-Dawood, Abdulaziz; AlJohani, Sameera; Al Harbi, Shmeylan; Kojan, Suleiman; Al Jeraisy, Majed; Deeb, Ahmad M; Assiri, Abdullah M; Al-Hameed, Fahad; AlSaedi, Asim; Mandourah, Yasser; Almekhlafi, Ghaleb A; Sherbeeni, Nisreen Murad; Elzein, Fatehi Elnour; Memon, Javed; Taha, Yusri; Almotairi, Abdullah; Maghrabi, Khalid A; Qushmaq, Ismael; Al Bshabshe, Ali; Kharaba, Ayman; Shalhoub, Sarah; Jose, Jesna; Fowler, Robert A; Hayden, Frederick G; Hussein, Mohamed A

    2018-01-30

    It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.

  1. Thermal performance trials on the habitability of private bushfire shelters: part 1.

    Science.gov (United States)

    Taylor, Nigel A S; Haberley, Benjamin J; Hoyle, David J R

    2015-08-01

    This communication is the first of two in which specifications for private bushfire shelters were evaluated during human trials. The purpose of this investigation (series 1) was to test the hypothesis that shelters capable of maintaining the internal environment at, or below, a modified discomfort index of 39 °C would prevent a deep-body temperature elevation of >2 °C. This was tested over 96 trials during which eight men and eight women were exposed at rest (60 min) to three regulated shelter conditions satisfying that standard: 40 °C and 70 % relative humidity, 45 °C and 50 % relative humidity and 50 °C and 30 % relative humidity. Subjects were tested twice in each condition following exercise- and heat-induced dehydration (2 % body mass reduction) and pre-heating to each of two deep-body thermal states (37.5 and 38.5 °C). Participants presented well rested and euhydrated, and pre-treatments successfully achieved the thermal and hydration targets prior to exposure. Auditory canal temperatures declined as exposures commenced, with subsequent rises of >0.5 °C not evident within any trial. However, each increment in air temperature elicited a significant elevation in the respective within-trial mean auditory canal temperature (37.4, 37.7 and 37.9 °C) and heart rate (103, 116 and 122 beats.min(-1)) when subjects were moderately hyperthermic (all P < 0.05). Nevertheless, on average, subjects successfully defended deep-body temperature at levels significantly below those associated with heat illness, and it was concluded that this thermal specification for bushfire shelters appeared adequate, providing the physical characteristics of the internal air remained stable.

  2. Hip-Hop to Health Jr. Randomized Effectiveness Trial: 1-Year Follow-up Results.

    Science.gov (United States)

    Kong, Angela; Buscemi, Joanna; Stolley, Melinda R; Schiffer, Linda A; Kim, Yoonsang; Braunschweig, Carol L; Gomez-Perez, Sandra L; Blumstein, Lara B; Van Horn, Linda; Dyer, Alan R; Fitzgibbon, Marian L

    2016-02-01

    The preschool years provide a unique window of opportunity to intervene on obesity-related lifestyle risk factors during the formative years of a child's life. The purpose of this study was to assess the impact of a preschool-based obesity prevention effectiveness trial at 1-year follow-up. RCT. Primarily African American children (aged 3-5 years, N=618) attending Head Start preschool programs administered by Chicago Public Schools. Eighteen preschools were randomly assigned in 2007-2008 to receive either (1) a 14-week teacher-delivered intervention focused on healthy lifestyle behaviors or (2) a 14-week teacher-delivered general health curriculum (control group). The primary outcome, BMI, was measured at baseline, postintervention, and 1-year follow-up. Diet and screen time behaviors were also assessed at these time points. Multilevel mixed effects models were used to test for between-group differences. Data were analyzed in 2014. Significant between-group differences were observed in diet, but not in BMI z-score or screen time at 1-year follow-up. Diet differences favored the intervention arm over controls in overall diet quality (p=0.02) and in subcomponents of diet quality, as measured by the Healthy Eating Index-2005, and in fruit intake (servings/day, excludes juice) (p=0.02). Diet quality worsened more among controls than the intervention group at 1-year follow-up. The adaptation of Hip-Hop to Health Jr. produced modest benefits in diet quality but did not significantly impact weight gain trajectory. Not unlike other effectiveness trials, this real-world version delivered by Head Start teachers produced fewer benefits than the more rigorous efficacy trial. It is important to understand and build upon the lessons learned from these types of trials so that we can design, implement, and disseminate successful evidence-based programs more widely and effectively. This study is registered at www.clinicaltrials.gov NCT00241878. Copyright © 2016 American Journal of

  3. 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

  4. Understanding and preventing type 1 diabetes through the unique working model of TrialNet.

    Science.gov (United States)

    Battaglia, Manuela; Anderson, Mark S; Buckner, Jane H; Geyer, Susan M; Gottlieb, Peter A; Kay, Thomas W H; Lernmark, Åke; Muller, Sarah; Pugliese, Alberto; Roep, Bart O; Greenbaum, Carla J; Peakman, Mark

    2017-11-01

    Type 1 diabetes is an autoimmune disease arising from the destruction of pancreatic insulin-producing beta cells. The disease represents a continuum, progressing sequentially at variable rates through identifiable stages prior to the onset of symptoms, through diagnosis and into the critical periods that follow, culminating in a variable depth of beta cell depletion. The ability to identify the very earliest of these presymptomatic stages has provided a setting in which prevention strategies can be trialled, as well as furnishing an unprecedented opportunity to study disease evolution, including intrinsic and extrinsic initiators and drivers. This niche opportunity is occupied by Type 1 Diabetes TrialNet, an international consortium of clinical trial centres that leads the field in intervention and prevention studies, accompanied by deep longitudinal bio-sampling. In this review, we focus on discoveries arising from this unique bioresource, comprising more than 70,000 samples, and outline the processes and science that have led to new biomarkers and mechanistic insights, as well as identifying new challenges and opportunities. We conclude that via integration of clinical trials and mechanistic studies, drawing in clinicians and scientists and developing partnership with industry, TrialNet embodies an enviable and unique working model for understanding a disease that to date has no cure and for designing new therapeutic approaches.

  5. Trials in the prevention of type 1 diabetes: current and future.

    Science.gov (United States)

    Wherrett, Diane K

    2014-08-01

    A major thrust in type 1 diabetes research is stopping the destruction of beta cells that leads to type 1 diabetes. Research over the past 30 years has defined genetic factors and evidence of autoimmunity that have led to the development of robust prediction models in those at high risk for type 1 diabetes. The ability to identify those at risk and the development of new agents and of collaborative research networks has led to multiple trials aimed at preventing beta cell loss. Trials at all stages of beta cell loss have been conducted: primary prevention (prior to the development of autoimmunity); secondary prevention (after autoantibodies are found) and tertiary prevention (intervening after diagnosis to maintain remaining beta cells). Studies have shown mixed results; evidence of maintained insulin secretion after the time of diagnosis has been described in a number of studies, and primary and secondary prevention is proving to be elusive. Much has been learned from the increasing number of studies in the field in terms of network creation, study design and choice of intervention that will facilitate new avenues of investigation. Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  6. Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Tapia, Milagritos D; Sow, Samba O; Lyke, Kirsten E; Haidara, Fadima Cheick; Diallo, Fatoumata; Doumbia, Moussa; Traore, Awa; Coulibaly, Flanon; Kodio, Mamoudou; Onwuchekwa, Uma; Sztein, Marcelo B; Wahid, Rezwanul; Campbell, James D; Kieny, Marie-Paule; Moorthy, Vasee; Imoukhuede, Egeruan B; Rampling, Tommy; Roman, Francois; De Ryck, Iris; Bellamy, Abbie R; Dally, Len; Mbaya, Olivier Tshiani; Ploquin, Aurélie; Zhou, Yan; Stanley, Daphne A; Bailer, Robert; Koup, Richard A; Roederer, Mario; Ledgerwood, Julie; Hill, Adrian V S; Ballou, W Ripley; Sullivan, Nancy; Graham, Barney; Levine, Myron M

    2016-01-01

    The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo). In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18-65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18-50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 10(10) viral particle units (pu), 2·5 × 10(10) pu, 5 × 10(10) pu, or 1 × 10(11) pu; US participants received 1 × 10(10) pu or 1 × 10(11) pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 10(8) plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured

  7. Plasma long-chain omega-3 polyunsaturated fatty acids and macular pigment in subjects with family history of age-related macular degeneration: the Limpia Study.

    Science.gov (United States)

    Merle, Bénédicte M J; Buaud, Benjamin; Korobelnik, Jean-François; Bron, Alain; Delyfer, Marie-Noëlle; Rougier, Marie-Bénédicte; Savel, Hélène; Vaysse, Carole; Creuzot-Garcher, Catherine; Delcourt, Cécile

    2017-12-01

    In numerous epidemiological studies, omega-3 polyunsaturated fatty acids (PUFAs) have been associated with a decreased risk of age-related macular degeneration (AMD). Beyond their structural, functional and neuroprotective roles, omega-3 PUFAs may favour the retinal accumulation of lutein and zeaxanthin and thus increase macular pigment optical density (MPOD). We examined the associations of MPOD with plasma omega-3 PUFAs in subjects with family history of AMD. The Limpia study is a double-blind, placebo-controlled, prospective randomized clinical trial performed in 120 subjects. Subjects with at least one parent treated for neovascular AMD, aged 40-70, with a best corrected visual acuity (BCVA) >20/25, free of late AMD and other major eye conditions and with no use of supplement containing lutein or zeaxanthin the preceding year were recruited in Bordeaux and Dijon, France. At baseline, MPOD within 1° of eccentricity was measured by modified Heidelberg retinal analyser (Heidelberg, Germany) and plasma omega-3 PUFAs by gas chromatography. Medical history and lifestyle data were collected from a standardized questionnaire. Associations of MPOD with plasma omega-3 PUFAs were assessed at the baseline examination, using mixed linear models adjusted for age, gender, centre, body mass index, smoking, plasma high-density lipoprotein (HDL) cholesterol and lutein+zeaxanthin. After multivariate adjustment, high MPOD was significantly associated with higher level of plasma docosapentaenoic acid (DPA) (β = 0.029, 95% CI: 0.003, 0.055; p = 0.03). Plasma alpha linolenic, eicosapentaenoic and docosahexaenoic acids were not significantly associated with MPOD. In the Limpia study, high MPOD within 1° was significantly associated with higher plasma levels of omega-3 DPA. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  8. 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

  9. Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention.

    Science.gov (United States)

    Palanee-Phillips, Thesla; Schwartz, Katie; Brown, Elizabeth R; Govender, Vaneshree; Mgodi, Nyaradzo; Kiweewa, Flavia Matovu; Nair, Gonasagrie; Mhlanga, Felix; Siva, Samantha; Bekker, Linda-Gail; Jeenarain, Nitesha; Gaffoor, Zakir; Martinson, Francis; Makanani, Bonus; Naidoo, Sarita; Pather, Arendevi; Phillip, Jessica; Husnik, Marla J; van der Straten, Ariane; Soto-Torres, Lydia; Baeten, Jared

    2015-01-01

    Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges. ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial. Between August 2012 and June 2014, 5516 women were screened and 2629 HIV-1 seronegative women between 18-45 years of age were enrolled from 15 research sites in Malawi, South Africa, Uganda, and Zimbabwe. The median age was 26 years (IQR 22-31) and the majority (59%) were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64%) reported having disclosed to primary partners about planned vaginal ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis, 7% Trichomonas vaginalis, 4% Neisseria gonorrhoeae, and 1% syphilis. African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention.

  10. Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention.

    Directory of Open Access Journals (Sweden)

    Thesla Palanee-Phillips

    Full Text Available Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges.ASPIRE (A Study to Prevent Infection with a Ring for Extended Use is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial.Between August 2012 and June 2014, 5516 women were screened and 2629 HIV-1 seronegative women between 18-45 years of age were enrolled from 15 research sites in Malawi, South Africa, Uganda, and Zimbabwe. The median age was 26 years (IQR 22-31 and the majority (59% were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64% reported having disclosed to primary partners about planned vaginal ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis, 7% Trichomonas vaginalis, 4% Neisseria gonorrhoeae, and 1% syphilis.African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention.

  11. Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention

    Science.gov (United States)

    Palanee-Phillips, Thesla; Schwartz, Katie; Brown, Elizabeth R.; Govender, Vaneshree; Mgodi, Nyaradzo; Kiweewa, Flavia Matovu; Nair, Gonasagrie; Mhlanga, Felix; Siva, Samantha; Bekker, Linda-Gail; Jeenarain, Nitesha; Gaffoor, Zakir; Martinson, Francis; Makanani, Bonus; Naidoo, Sarita; Pather, Arendevi; Phillip, Jessica; Husnik, Marla J.; van der Straten, Ariane; Soto-Torres, Lydia; Baeten, Jared

    2015-01-01

    Introduction Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges. Methods ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial. Results Between August 2012 and June 2014, 5516 women were screened and 2629 HIV-1 seronegative women between 18–45 years of age were enrolled from 15 research sites in Malawi, South Africa, Uganda, and Zimbabwe. The median age was 26 years (IQR 22–31) and the majority (59%) were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64%) reported having disclosed to primary partners about planned vaginal ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis, 7% Trichomonas vaginalis, 4% Neisseria gonorrhoeae, and 1% syphilis. Conclusions African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention. PMID:26061040

  12. Compacted sewage sludge as a barrier for tailings: the heavy metal speciation and total organic carbon content in the compacted sludge specimen.

    Directory of Open Access Journals (Sweden)

    Huyuan Zhang

    Full Text Available Acid mine drainage (AMD was the main environmental problem facing the mining industry. For AMD had high heavy metals content and low pH, the compacted sewage sludge might be a barrier for tailings whose oxidation and weathering produced AMD, with its own carbon source, microorganism reduction ability and impermeability. To study the heavy metals environmental risk, under the simulate AMD, the deionized water (DW, and the pH 2.1 sulfuric acid water (SA seepage conditions, respectively, the changes of the chemical speciation of heavy metals Cd, Cu, Fe, Ni, Zn and total organic carbon (TOC content in the compacted sewage sludge were assessed in the different periods. The results indicated according to the distribution of heavy metals, the potential mobility was for Cd: 6.08 under AMD, 7.48 under SA, ∞ under DW; for Cu: 0.08 under AMD, 0.17 under SA, 0.59 under DW; for Fe: 0.15 under AMD, 0.22 under SA, 0.22 under DW; for Ni: 2.60 under AMD, 1.69 under SA, 1.67 under DW; and for Zn: 0.15 under AMD, 0.23 under SA and 0.21 under DW at the second checking time. TOC content firstly decreased from 67.62±0% to 66.29±0.35%, then increased to 67.74±0.65% under the AMD seepage while TOC decreased to 63.30±0.53%, then to 61.33±0.37% under the DW seepage, decreased to 63.86±0.41%, then to 63.28±0.49% under SA seepage. That indicated under the AMD seepage, the suitable microorganisms communities in the compacted sewage sludge were activated. And the heavy metals environmental risk of compacted sewage sludge was lower with AMD condition than with other two. So the compacted sewage sludge as a barrier for tailings was feasible as the aspect of environmental risk assessment.

  13. The Association between the Lipids Levels in Blood and Risk of Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Yafeng Wang

    2016-10-01

    Full Text Available Lipid metabolism may be involved in the pathogenic mechanism of age-related macular degeneration (AMD. However, conflicting results have been reported in the associations of AMD with blood lipids. We performed a meta-analysis including a total of 19 studies to evaluate associations between blood lipids and this disease. The result reported that the high level of high-density lipoprotein cholesterol (HDL-C obtained with an increment of 1 mmol/L could result in a significantly increase in the AMD risk of approximately 18% (relative risk (RR, 1.18; 95% confidence interval (CI, 1.01 to 1.35; I2 = 53.8%; p = 0.007. High levels of total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C, and triglycerides (TG were significantly associated with a decreased risk of AMD (RRs ranging from 0.92 to 0.95; all p < 0.05. The stratified analysis based on AMD subtypes showed that these blood lipids were only significantly associated with the risk of early AMD (all p < 0.05. The association between the blood lipids and AMD risk did not differ substantially based on the other characteristics of the participants. A high HDL-C level was associated with an increased AMD risk, whereas participants with high TC, LDL-C, and TG concentrations may show a decreased risk for this disease. Further well-designed large studies are warranted to confirm the conclusions.

  14. Clinical trials in dentistry in India: Analysis from trial registry.

    Science.gov (United States)

    Gowri, S; Kannan, Sridharan

    2017-01-01

    Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy

  15. Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

    Science.gov (United States)

    Agnandji, Selidji T; Huttner, Angela; Zinser, Madeleine E; Njuguna, Patricia; Dahlke, Christine; Fernandes, José F; Yerly, Sabine; Dayer, Julie-Anne; Kraehling, Verena; Kasonta, Rahel; Adegnika, Akim A; Altfeld, Marcus; Auderset, Floriane; Bache, Emmanuel B; Biedenkopf, Nadine; Borregaard, Saskia; Brosnahan, Jessica S; Burrow, Rebekah; Combescure, Christophe; Desmeules, Jules; Eickmann, Markus; Fehling, Sarah K; Finckh, Axel; Goncalves, Ana Rita; Grobusch, Martin P; Hooper, Jay; Jambrecina, Alen; Kabwende, Anita L; Kaya, Gürkan; Kimani, Domtila; Lell, Bertrand; Lemaître, Barbara; Lohse, Ansgar W; Massinga-Loembe, Marguerite; Matthey, Alain; Mordmüller, Benjamin; Nolting, Anne; Ogwang, Caroline; Ramharter, Michael; Schmidt-Chanasit, Jonas; Schmiedel, Stefan; Silvera, Peter; Stahl, Felix R; Staines, Henry M; Strecker, Thomas; Stubbe, Hans C; Tsofa, Benjamin; Zaki, Sherif; Fast, Patricia; Moorthy, Vasee; Kaiser, Laurent; Krishna, Sanjeev; Becker, Stephan; Kieny, Marie-Paule; Bejon, Philip; Kremsner, Peter G; Addo, Marylyn M; Siegrist, Claire-Anne

    2016-04-28

    The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa. We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo. No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants. In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials

  16. Diabetic subjects diagnosed through the Diabetes Prevention Trial-Type 1 (DPT-1) are often asymptomatic with normal A1C at diabetes onset.

    Science.gov (United States)

    Triolo, Taylor M; Chase, H Peter; Barker, Jennifer M

    2009-05-01

    Upon diagnosis of type 1 diabetes, patients are usually symptomatic, and many have ketoacidosis. Screening for islet autoantibodies (IAs) has been shown to decrease A1C level and rate of hospitalization at diabetes onset. Metabolic tests and the presence of symptoms were described at diabetes onset during the Diabetes Prevention Trial-Type 1 (DPT-1). The DPT-1 screened relatives of patients with type 1 diabetes for islet cell autoantiobodies (ICAs). Those with positive ICAs had intravenous and oral glucose tolerance tests (IVGTTs and OGTTs) and were randomized into one of two prevention trials. Throughout the DPT-1 parenteral and oral insulin study, 246 people were diagnosed with type 1 diabetes. Of the 246 subjects diagnosed with diabetes, 218 had data regarding the presence of symptoms, and 138 (63.3%) reported no symptoms suggestive of diabetes. Eight subjects (3.67%) presented with ketosis. Subjects presented with a mean +/- SD A1C of 6.41 +/- 1.15%. At diagnosis, 90 subjects (50.8%) had A1C in the normal range (IA followed by OGTT) may allow diagnosis of diabetes before severe metabolic decompensation. Screening with A1C will miss identifying many of the subjects with newly diagnosed type 1 diabetes in this cohort.

  17. The development, validation, and utility of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS).

    Science.gov (United States)

    Sosenko, Jay M; Skyler, Jay S; Palmer, Jerry P

    2015-08-01

    This report details the development, validation, and utility of the Diabetes Prevention Trial-Type 1 (DPT-1) Risk Score (DPTRS) for type 1 diabetes (T1D). Proportional hazards regression was used to develop the DPTRS model which includes the glucose and C-peptide sums from oral glucose tolerance tests at 30, 60, 90, and 120 min, the log fasting C-peptide, age, and the log BMI. The DPTRS was externally validated in the TrialNet Natural History Study cohort (TNNHS). In a study of the application of the DPTRS, the findings showed that it could be used to identify normoglycemic individuals who were at a similar risk for T1D as those with dysglycemia. The DPTRS could also be used to identify lower risk dysglycemic individuals. Risk estimates of individuals deemed to be at higher risk according to DPTRS values did not differ significantly between the DPT-1 and the TNNHS; whereas, the risk estimates for those with dysglycemia were significantly higher in DPT-1. Individuals with very high DPTRS values were found to be at such marked risk for T1D that they could reasonably be considered to be in a pre-diabetic state. The findings indicate that the DPTRS has utility in T1D prevention trials and for identifying pre-diabetic individuals.

  18. The national and subnational prevalence and burden of age-related macular degeneration in China.

    Science.gov (United States)

    Song, Peige; Du, Yuhang; Chan, Kit Yee; Theodoratou, Evropi; Rudan, Igor

    2017-12-01

    Age-related macular degeneration (AMD) is the third most common cause of blindness, and the fourth leading cause of visual impairment worldwide, but little is known about the burden of this disease in the most populous country-China. This study provides the first comprehensive estimates of the prevalence and burden of AMD in China from 1990 to 2015, with projections till 2050. In this study, a systematic review and meta-analysis was conducted to estimate the prevalence of AMD in China. China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedicine Literature Database (CBM-SinoMed), PubMed, Embase and Medline were searched before September 2016. Multilevel mixed-effect meta-regression was performed to define the prevalence rates of AMD and its subtypes. UN population data were used to estimate and project the number of people affected from 1990 to 2050. Based on different demographic and geographic features, the national burden of AMD in 2000 and 2010 was distributed to different regions in China. Our search returned 2016 citations, of which 25 met the inclusion criteria. The prevalence of any AMD ranged from 2.44% (95% CI = 1.85-3.22) in people aged 45-49 years to 18.98% (95% CI = 15.05-23.66) in people aged 85-89 years. Prevalence of early AMD ranged from 1.79% (95% CI = 1.05-3.02) to 10.05% (95% CI = 6.17-15.97), and, in the case of late AMD, from 0.38% (95% CI = 0.16-0.97) to 3.88% (95% CI = 1.68-9.13). In late AMD, the prevalence of geographic atrophy (GA) was 0.15% (95% CI = 0.05-0.47) in people aged 45-49 years and 1.09% (95% CI = 0.35-3.36) in those aged 85-89 years, and the prevalence of neovascular AMD (NVAMD) ranged between 0.24% (95% CI = 0.11-0.50) and 2.79% (95% CI = 1.33-5.77). The number of people with any AMD was 12.01 million (95% CI = 9.29-15.46) in 1990 and 26.65 million (95% CI = 20.62-34.27) in 2015. Within the same period, the number of people with early AMD increased from 9

  19. Random reward priming is task-contingent: The robustness of the 1-trial reward priming effect

    Directory of Open Access Journals (Sweden)

    Árni Gunnar Ásgeirsson

    2014-04-01

    Full Text Available Consistent financial reward of particular features influences the allocation of visual attention in many ways. More surprising are 1-trial reward priming effects on attention where reward schedules are random and reward on one trial influences attentional allocation on the next. Those findings are thought to reflect that rewarded features become more salient than unrewarded ones on the subsequent trial. Here we attempt to conceptually replicate this effect, testing its generalizability. In three versions of an analogous paradigm to the additional singleton paradigm involving singleton search for a Gabor patch of odd spatial frequency we found no evidence of reward priming, while we only partially replicate the reward priming in the exact original paradigm tested by Hickey and colleagues. The results cast doubt on the proposal that random reward enhances salience, suggested in the original papers, and highlight the need for a more nuanced account. In many other paradigms reward effects have been found to progress gradually, becoming stronger as they build up, and we argue that for robust reward priming, reward schedules need to be more consistent than in the original 1-trial reward priming paradigm.

  20. Recruitment to publicly funded trials--are surgical trials really different?

    Science.gov (United States)

    Cook, Jonathan A; Ramsay, Craig R; Norrie, John

    2008-09-01

    Good recruitment is integral to the conduct of a high-quality randomised controlled trial. It has been suggested that recruitment is particularly difficult for evaluations of surgical interventions, a field in which there is a dearth of evidence from randomised comparisons. While there is anecdotal speculation to support the inference that recruitment to surgical trials is more challenging than for medical trials we are unaware of any formal assessment of this. In this paper, we compare recruitment to surgical and medical trials using a cohort of publicly funded trials. Overall recruitment to trials was assessed using of a cohort of publicly funded trials (n=114). Comparisons were made by using the Recruitment Index, a simple measure of recruitment activity for multicentre randomised controlled trials. Recruitment at the centre level was also investigated through three example surgical trials. The Recruitment Index was found to be higher, though not statistically significantly, in the surgical group (n=18, median=38.0 IQR (10.7, 77.4)) versus (n=81, median=34.8 IQR (11.7, 98.0)) days per recruit for the medical group (median difference 1.7 (-19.2, 25.1); p=0.828). For the trials where the comparison was between a surgical and a medical intervention, the Recruitment Index was substantially higher (n=6, 68.3 (23.5, 294.8)) versus (n=93, 34.6 (11.7, 90.0); median difference 25.9 (-35.5, 221.8); p=0.291) for the other trials. There was no clear evidence that surgical trials differ from medical trials in terms of recruitment activity. There was, however, support for the inference that medical versus surgical trials are more difficult to recruit to. Formal exploration of the recruitment data through a modelling approach may go some way to tease out where important differences exist.

  1. Strength in Numbers: Opportunities for Enhancing the Development of Effective Treatments for Type 1 Diabetes-The TrialNet Experience.

    Science.gov (United States)

    Greenbaum, Carla J; Speake, Cate; Krischer, Jeffrey; Buckner, Jane; Gottlieb, Peter A; Schatz, Desmond A; Herold, Kevan C; Atkinson, Mark A

    2018-07-01

    The early to mid-1980s were an inflection point in the history of type 1 diabetes research. Two landmark events occurred: the initiation of immune-based interventions seeking to prevent type 1 diabetes and the presentation of an innovative model describing the disorder's natural history. Both formed the basis for hundreds of subsequent studies designed to achieve a dramatic therapeutic goal-a means to prevent and/or reverse type 1 diabetes. However, the need to screen large numbers of individuals and prospectively monitor them using immunologic and metabolic tests for extended periods of time suggested such efforts would require a large collaborative network. Hence, the National Institutes of Health formed the landmark Diabetes Prevention Trial-Type 1 (DPT-1) in the mid-1990s, an effort that led to Type 1 Diabetes TrialNet. TrialNet studies have helped identify novel biomarkers; delineate type 1 diabetes progression, resulting in identification of highly predictable stages defined by the accumulation of autoantibodies (stage 1), dysglycemia (stage 2), and disease meeting clinical criteria for diagnosis (stage 3); and oversee numerous clinical trials aimed at preventing disease progression. Such efforts pave the way for stage-specific intervention trials with improved hope that a means to effectively disrupt the disorder's development will be identified. © 2018 by the American Diabetes Association.

  2. Effects of organic matter application on methane emission from paddy fields adopting organic farming system

    Directory of Open Access Journals (Sweden)

    P Nungkat

    2015-01-01

    Full Text Available A study that was aimed to determine the effect of the use of organic manure and azolla on methane emission on paddy field of organic systems was conducted on paddy fields in the Gempol Village, Sambirejo District of Sragen Regency, Indonesia. The experimental design performed for this study was a completely randomized block design consisting of three factors; the factor I was rice cultivars (Mira-1; Mentik Wangi; Merah Putih; factor II was dose of organic manure (0 t/ha and 10 t/ha and factor III was Azolla inoculums dose (0 t/ha and 2 t/ha. Gas sampling was conducted 3 times in one growing season when the rice plants reached ages of 38, 66 and 90 days after planting. The results showed that there was no correlation between the uses of organic fertilizers for rice production on methane emission. The increase of methane emission was very much influenced by the redox potential. Methane emission from Mira-1 field was higher than that from Mentik Wangi and Merah Putih fields. Emission of methane gas from Mira-1 field ranged from -509.82 to 791.34 kg CH4/ha; that from Wangi ranged from -756.77 to d 547.50 kg CH4/ha and that from Merah Putih ranged from -399.63 to 459.94 kg CH4/ha. Application of 10 t organic manure /ha and 2 t azolla/ha in Mentik Wangi reduced methane emissions with a high rice production compared to Merah Putih and Mira-1.

  3. Repeat testing of low-level HIV-1 RNA: assay performance and implementation in clinical trials.

    Science.gov (United States)

    White, Kirsten; Garner, Will; Wei, Lilian; Eron, Joseph J; Zhong, Lijie; Miller, Michael D; Martin, Hal; Plummer, Andrew; Tran-Muchowski, Cecilia; Lindstrom, Kim; Porter, James; Piontkowsky, David; Light, Angela; Reiske, Heinz; Quirk, Erin

    2018-05-15

    Assess the performance of HIV-1 RNA repeat testing of stored samples in cases of low-level viremia during clinical trials. Prospective and retrospective analysis of randomized clinical trial samples and reference standards. To evaluate assay variability of the Cobas AmpliPrep/Cobas TaqMan HIV-1 Test, v2.0, three separate sources of samples were utilized: the World Health Organization (WHO) HIV reference standard (assayed using 50 independent measurements at six viral loads <200 copies/ml), retrospective analysis of four to six aliquots of plasma samples from four clinical trial participants, and prospective repeat testing of 120 samples from participants in randomized trials with low-level viremia. The TaqMan assay on the WHO HIV-1 RNA standards at viral loads <200 copies/ml performed within the expected variability according to assay specifications. However, standards with low viral loads of 36 and 18 copies/ml reported values of ≥ 50 copies/ml in 66 and 18% of tests, respectively. In participants treated with antiretrovirals who had unexpected viremia of 50-200 copies/ml after achieving <50 copies/ml, retesting of multiple aliquots of stored plasma found <50 copies/ml in nearly all cases upon retesting (14/15; 93%). Repeat testing was prospectively implemented in four clinical trials for all samples with virologic rebound of 50-200 copies/ml (n = 120 samples from 92 participants) from which 42% (50/120) had a retest result of less than 50 copies/ml and 58% (70/120) retested ≥ 50 copies/ml. The TaqMan HIV-1 RNA assay shows variability around 50 copies/ml that affects clinical trial results and may impact clinical practice. In participants with a history of viral load suppression, unexpected low-level viremia may be because of assay variability rather than low drug adherence or true virologic failure. Retesting a stored aliquot of the same sample may differentiate between assay variability and virologic failure as the source of viremia

  4. Dust around the Cool Component of D-Type Symbiotic Binaries

    Science.gov (United States)

    Jurkic, Tomislav; Kotnik-Karuza, Dubravka

    2018-04-01

    D type symbiotic binaries are an excellent astrophysical laboratory for investigation of the dust properties and dust formation under the influence of theMira stellar wind and nova activity and of the mass loss and mass transfer between components in such a widely separated system. We present a study of the properties of circumstellar dust in symbiotic Miras by use of long-term near-IR photometry and colour indices. The published JHKL magnitudes of o Ceti, RX Pup, KM Vel, V366 Car, V835 Cen, RR Tel, HM Sge and R Aqr have been collected, analyzed and corrected for short-term variations caused by Mira pulsations. Assuming spherical temperature distribution of the dust in the close neighbourhood of the Mira, the DUSTY code wa