Absolute and estimated values of macular pigment optical density in young and aged Asian participants with or without age-related macular degeneration.

PubMed

Ozawa, Yoko; Shigeno, Yuta; Nagai, Norihiro; Suzuki, Misa; Kurihara, Toshihide; Minami, Sakiko; Hirano, Eri; Shinoda, Hajime; Kobayashi, Saori; Tsubota, Kazuo

2017-08-29

Lutein and zeaxanthin are suggested micronutrient supplements to prevent the progression of age-related macular degeneration (AMD), a leading cause of blindness worldwide. To monitor the levels of lutein/zeaxanthin in the macula, macular pigment optical density (MPOD) is measured. A commercially available device (MPSII®, Elektron Technology, Switzerland), using technology based on heterochromatic flicker photometry, can measure both absolute and estimated values of MPOD. However, whether the estimated value is applicable to Asian individuals and/or AMD patients remains to be determined. The absolute and estimated values of MPOD were measured using the MPSII® device in 77 participants with a best-corrected visual acuity (BCVA) > 0.099 (logMAR score). The studied eyes included 17 young (20-29 years) healthy, 26 aged (>50 years) healthy, 18 aged and AMD-fellow, and 16 aged AMD eyes. The mean BCVA among the groups were not significantly different. Both absolute and estimated values were measurable in all eyes of young healthy group. However, absolute values were measurable in only 57.7%, 66.7%, and 43.8%, of the aged healthy, AMD-fellow, and AMD groups, respectively, and 56.7% of the eyes included in the 3 aged groups. In contrast, the estimated value was measurable in 84.6%, 88.9% and 93.8% of the groups, respectively, and 88.3% of eyes in the pooled aged group. The estimated value was correlated with absolute value in individuals from all groups by Spearman's correlation coefficient analyses (young healthy: R 2  = 0.885, P = 0.0001; aged healthy: R 2  = 0.765, P = 0.001; AMD-fellow: R 2  = 0.851, P = 0.0001; and AMD: R 2  = 0.860, P = 0.013). Using the estimated value, significantly lower MPOD values were found in aged AMD-related eyes, which included both AMD-fellow and AMD eyes, compared with aged healthy eyes by Student's t-test (P = 0.02). Absolute, in contrast to estimated, value was measurable in a limited number of aged participants; however, it was correlated with estimated value both in young and aged Asian populations with or without AMD. These results may inform future clinical studies investigating the measurement of MPOD in understanding the role of macular pigments in the pathogenesis of AMD.

Reproducibility of Macular Thickness Measurements in Eyes Affected by Dry Age-Related Macular Degeneration From Two Different SD-OCT Instruments.

PubMed

Tepelus, Tudor C; Hariri, Amir H; Balasubramanian, Siva; Sadda, SriniVas R

2018-06-01

To compare macular thickness measurement algorithms of two different spectral-domain optical coherence tomography (SD-OCT) devices in eyes affected by dry age-related macular degeneration (AMD). Patients with dry AMD and healthy volunteers from the retina clinic of the Doheny Eye Center - UCLA were imaged using two different SD-OCT devices: the RS-3000 Advance (Nidek, Padova, Italy) and the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). All patients had been previously diagnosed with drusen or geographic atrophy due to AMD. The commercial instrument software was used to generate the macular retinal thickness measurements, and measurements were compared between devices. Eighty-five diseased eyes from 49 patients and 16 healthy control eyes from eight normal volunteers were included in this study. The macular thickness measurements generated by the two instruments in eyes with AMD differed significantly in mean retinal thickness in the foveal center subfield (257.34 μm ± 51.72 μm using the Nidek OCT vs. 238.20 μm ± 51.89 μm using the Cirrus OCT; P < .001). The mean difference in macular thickness between the two devices was 19.14 μm ± 5.84 μm for diseased eyes and 17.06 μm ± 5.28 μm in normal control eyes, and this was not statistically different between the two groups (P > .05). The macular thickness measurements in diseased eyes, as evaluated by the two different instruments, however, showed excellent correlation (r = 0.99; P < .001), with an intraclass correlation coefficient of 0.99 (95% confidence interval, 0.98-0.99). Post hoc evaluation of cases with larger differences also showed differences in foveal center selection and variabilities in boundary selection with specific pathology. Macular thickness measurements provided by the Nidek and Cirrus OCT instruments in eyes with dry AMD are highly correlated but show a consistent difference, which may allow the use of a standard correction factor to be applied to better interrelate measurements between the devices. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:410-415.]. Copyright 2018, SLACK Incorporated.

Optics education for machine operators in the semiconductor industry: moving beyond button pushing

NASA Astrophysics Data System (ADS)

Karakekes, Meg; Currier, Deborah

1995-10-01

In the competitive semiconductor manufacturing industry, employees who operate equipment are able to make greater contributions if they understand how the equipment works. By understanding the 'why' behind the 'what', the equipment operators can better partner with other technical staff to produce quality integrated circuits efficiently and effectively. This additional knowledge also opens equipment operators to job enrichment and enlargement opportunities. Advanced Micro Devices (AMD) is in the process of upgrading the skills of its equipment operators. This paper is an overview of a pilot program that employs optics education to upgrade stepper operators' skills. The paper starts with stepper tasks that require optics knowledge, examines teaching methods, reports both end-of-course and three months post-training knowledge retention, and summarizes how the training has impacted the production floor.

Electrostatic artificial eyelid actuator as an analog micromirror device

NASA Astrophysics Data System (ADS)

Goodwin, Scott H.; Dausch, David E.; Solomon, Steven L.; Lamvik, Michael K.

2005-05-01

An electrostatic MEMS actuator is described for use as an analog micromirror device (AMD) for high performance, broadband, hardware-in-the-loop (HWIL) scene generation. Current state-of-the-art technology is based on resistively heated pixel arrays. As these arrays drive to the higher scene temperatures required by missile defense scenarios, the power required to drive the large format resistive arrays will ultimately become prohibitive. Existing digital micromirrors (DMD) are, in principle, capable of generating the required scene irradiances, but suffer from limited dynamic range, resolution and flicker effects. An AMD would be free of these limitations, and so represents a viable alternative for high performance UV/VIS/IR scene generation. An electrostatic flexible film actuator technology, developed for use as "artificial eyelid" shutters for focal plane sensors to protect against damaging radiation, is suitable as an AMD for analog control of projection irradiance. In shutter applications, the artificial eyelid actuator contained radius of curvature as low as 25um and operated at high voltage (>200V). Recent testing suggests that these devices are capable of analog operation as reflective microcantilever mirrors appropriate for scene projector systems. In this case, the device would possess larger radius and operate at lower voltages (20-50V). Additionally, frame rates have been measured at greater than 5kHz for continuous operation. The paper will describe the artificial eyelid technology, preliminary measurements of analog test pixels, and design aspects related to application for scene projection systems. We believe this technology will enable AMD projectors with at least 5122 spatial resolution, non-temporally-modulated output, and pixel response times of <1.25ms.

Implantable miniature telescope (IMT) for vision loss due to end-stage age-related macular degeneration.

PubMed

Gupta, Amisha; Lam, Jessica; Custis, Peter; Munz, Stephen; Fong, Donald; Koster, Marguerite

2018-05-30

Age-related macular degeneration (AMD) causes progressive and irreversible damage to the retina, resulting in loss of central vision. AMD is the third leading cause of irreversible visual impairment worldwide and the leading cause of blindness in industrialized countries. Since AMD is more common in older individuals, the number of affected individuals will increase significantly as the population ages. The implantable miniature telescope (IMT) is an ophthalmic device developed to improve vision in individuals who have lost vision due to AMD. Once implanted, the IMT is used to enlarge objects in the central visual field and focus them onto healthy areas of the retina not affected by AMD, allowing individuals to recognize objects that they otherwise could not see. It is unclear whether and how much the IMT can improve vision in individuals with end-stage AMD. To assess the effectiveness and safety of the IMT in improving visual acuity and quality of life in people with late or advanced AMD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 11); Ovid MEDLINE; Embase.com; PubMed; LILACS; AMED; Web of Science Conference Proceedings Citation Index-Science; OpenSIGLE; the metaRegister of Controlled Trials (mRCT) (last searched 27 June 2014); ClinicalTrials.gov; the ICTRP and the US Food and Drug Administration (FDA) Medical Devices database. The date of the search was 2 November 2017, with the exception of mRCT which is no longer in service. We planned to include randomized controlled trials (RCTs) and quasi-randomized trials that compared the IMT versus no IMT. Two review authors independently assessed all studies for inclusion, using standard methodological procedures expected by Cochrane. Our search yielded 1042 unique records. We removed irrelevant studies after screening titles and abstracts, and evaluated five full-text reports from four studies; three were non-randomized studies. There was one ongoing RCT that compared the OriLens intraocular telescope with standard low vision training in eyes with end-stage AMD. Results for this study are expected in 2020. We found no RCT or quasi-RCT and can draw no conclusion about the effectiveness and safety of the IMT in improving visual acuity in individuals with late or advanced AMD. Since the IMT is typically implanted monocularly based upon which eye has better best-corrected distance visual acuity, randomization between eyes within an individual may not be acceptable. Studies are needed that compare outcomes between individuals randomized to the device versus individuals not implanted, at least during study follow-up, who serve as controls.

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

PubMed

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

2013-05-01

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]O₂-AMD3100 as a potential SPECT tracer for imaging of CXCR4. 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. AMD3100 was labelled with technetium-99m with a radiochemical yield of >98%. The tracer was stable in PBS and mouse plasma for at least 6h at 37 °C. Heterologous and homologous binding assays with AMD3100 showed IC50 values of 240 ± 10 μM, and 92 ± 5 μM for [(125)I]SDF-1α and [(99m)Tc]O₂-AMD3100 respectively, with negligible receptor internalisation. The tracer showed high uptake in liver, lungs, spleen, thymus, intestine and bone. Blocking dose of AMD3100.8HCl (20mg/kg) decreased the uptake in these organs (p<0.05). [(99m)Tc]O2-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<0.05). [(99m)Tc]O2-AMD3100 is readily labelled, is stable in plasma and displays a favourable binding affinity for the CXCR4 receptors. [(99m)Tc O₂-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 biomarker for the non-invasive imaging of CXCR4 receptors. Copyright © 2013 Elsevier Inc. All rights reserved.

Employing OpenCL to Accelerate Ab Initio Calculations on Graphics Processing Units.

PubMed

Kussmann, Jörg; Ochsenfeld, Christian

2017-06-13

We present an extension of our graphics processing units (GPU)-accelerated quantum chemistry package to employ OpenCL compute kernels, which can be executed on a wide range of computing devices like CPUs, Intel Xeon Phi, and AMD GPUs. Here, we focus on the use of AMD GPUs and discuss differences as compared to CUDA-based calculations on NVIDIA GPUs. First illustrative timings are presented for hybrid density functional theory calculations using serial as well as parallel compute environments. The results show that AMD GPUs are as fast or faster than comparable NVIDIA GPUs and provide a viable alternative for quantum chemical applications.

MicroRNA-processing Enzymes Are Essential for Survival and Function of Mature Retinal Pigmented Epithelial Cells in Mice.

PubMed

Sundermeier, Thomas R; Sakami, Sanae; Sahu, Bhubanananda; Howell, Scott J; Gao, Songqi; Dong, Zhiqian; Golczak, Marcin; Maeda, Akiko; Palczewski, Krzysztof

2017-02-24

Age-related macular degeneration (AMD) is a major cause of irreversible vision loss. The neovascular or "wet" form of AMD can be treated to varying degrees with anti-angiogenic drugs, but geographic atrophy (GA) is an advanced stage of the more prevalent "dry" form of AMD for which there is no effective treatment. Development of GA has been linked to loss of the microRNA (miRNA)-processing enzyme DICER1 in the mature retinal pigmented epithelium (RPE). This loss results in the accumulation of toxic transcripts of Alu transposable elements, which activate the NLRP3 inflammasome and additional downstream pathways that compromise the integrity and function of the RPE. However, it remains unclear whether the loss of miRNA processing and subsequent gene regulation in the RPE due to DICER1 deficiency also contributes to RPE cell death. To clarify the role of miRNAs in RPE cells, we used two different mature RPE cell-specific Cre recombinase drivers to inactivate either Dicer1 or DiGeorge syndrome critical region 8 ( Dgcr8 ), thus removing RPE miRNA regulatory activity in mice by disrupting two independent and essential steps of miRNA biogenesis. In contrast with prior studies, we found that the loss of each factor independently led to strikingly similar defects in the survival and function of the RPE and retina. These results suggest that the loss of miRNAs also contributes to RPE cell death and loss of visual function and could affect the pathology of dry AMD. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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

PubMed

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 <0.0001 cd/m 2 ) FCP. For the S-MAIA device, cyan (505 nm) and red (627 nm) scotopic FCP were performed. For both devices, a 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.

AdA Compiler Validation Summary Report: Certificate Number: 910920W1. 11214 Verdix Corporation, VADS VAX VMS= AMD 29K, VAda-110-03525, Version 6.04, MicroVAX 3600 (Host) to Ironics IV9001 Board (Target). MVME147 (Target)

DTIC Science & Technology

1991-09-20

Agreement Number: 91-07-16- VRX See section 3.1 for any additional information about the testing environment. As a result of this validation effort...Washington DC 20301 92-06991 AVF Control Number: AVF-VSR-511.0292 18 February 1992 91-07-16- VRX Ada COMPILER VALIDATION SUMMARY REPORT: Certificate Number...System: Ironics IV9001 board (AMD 29000) (Am29000 bare VME machine) Customer Agreement Number: 91-07-16- VRX See section 3.1 for any additional information

Regulator Loss Functions and Hierarchical Modeling for Safety Decision Making.

PubMed

Hatfield, Laura A; Baugh, Christine M; Azzone, Vanessa; Normand, Sharon-Lise T

2017-07-01

Regulators must act to protect the public when evidence indicates safety problems with medical devices. This requires complex tradeoffs among risks and benefits, which conventional safety surveillance methods do not incorporate. To combine explicit regulator loss functions with statistical evidence on medical device safety signals to improve decision making. In the Hospital Cost and Utilization Project National Inpatient Sample, we select pediatric inpatient admissions and identify adverse medical device events (AMDEs). We fit hierarchical Bayesian models to the annual hospital-level AMDE rates, accounting for patient and hospital characteristics. These models produce expected AMDE rates (a safety target), against which we compare the observed rates in a test year to compute a safety signal. We specify a set of loss functions that quantify the costs and benefits of each action as a function of the safety signal. We integrate the loss functions over the posterior distribution of the safety signal to obtain the posterior (Bayes) risk; the preferred action has the smallest Bayes risk. Using simulation and an analysis of AMDE data, we compare our minimum-risk decisions to a conventional Z score approach for classifying safety signals. The 2 rules produced different actions for nearly half of hospitals (45%). In the simulation, decisions that minimize Bayes risk outperform Z score-based decisions, even when the loss functions or hierarchical models are misspecified. Our method is sensitive to the choice of loss functions; eliciting quantitative inputs to the loss functions from regulators is challenging. A decision-theoretic approach to acting on safety signals is potentially promising but requires careful specification of loss functions in consultation with subject matter experts.

Note: Development of a small maglev-type antirolling system.

PubMed

Park, Cheol Hoon; Park, Hee Chang; Cho, Han Wook; Moon, Seok Jun; Chung, Tae Young

2010-05-01

Various passive and/or active antirolling devices have been used for suppressing the rolling motion of ships in the ocean. In this study, a maglev-type active mass driver (AMD) is developed for controlling the rolling motion of a shiplike structure. No friction is generated during the motion of this maglev-type AMD, as the moving mass is floated by the magnetic levitation force and displaced by the propulsion force generated by the linear motor. For verifying the feasibility of the proposed method, a small AMD having a moving mass of approximately 4.0 kg is constructed and used in a small-scale model of a catamaran. This paper presents the detailed design procedures and obtained experimental results. Our results show that the developed maglev-type AMD has the potential for use in controlling the rolling motion of ships and other oceanographic vessels.

SU-E-T-16: A Comparison of Expected Dwell Times and Dose Variations for NAMD Patients Treated with An Episcleral Brachytherapy Device

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamilton, R; Patel, P; Balaggan, K

2015-06-15

Purpose: To evaluate the variations in dwell times and doses expected when using an episcleral brachytherapy device for treatment of neovascular agerelated macular degeneration (n-AMD) based on accurate imaging modalities Methods: Data from 40 eyes from 40 subjects with known n- AMD acquired through the Distance of Choroid Study (DOCS) conducted at Moorfields Eye Hospital was used to determine the target depth; the distance from the outer scleral surface of the eye, through the choroid, to the apex of the choroidal neovascularization (CNV). Each subject underwent, in triplicate, enhanced-depth Spectral Domain Optical Coherence Tomography (SD-OCT), Swept Source Optical Coherence Tomography,more » (SS-OCT) and Ocular Ultrasound (O-US). These data are the most comprehensive and accurate measurements of the dimensions of the CNV and adjacent layers of the eye for this cohort of patients. During treatment of n-AMD, patients receive a dose of 24Gy to the apex at the target depth. Using the percentage depth dose for a Sr-90 episcleral brachytherapy device, dwell times and doses to the apex were computed to determine the expected variations. Results: The mean target depth and the 95% confidence interval (CI) determined by combining O-US with SD-OCT were 1326 (956,1696)µm and with SS-OCT were 1332 (970,1693)µm. The calculated corresponding mean dwell times and 95% (CI) were 334 (223,445)s and 335 (226,445)s for SD-OCT and SS-OCT determined depths, respectively. The corresponding mean apex dose and 95% (CI) were 24 (35.9,18.0)Gy (SD-OCT) and 24 (35.6,18.1)Gy (SS-OCT). Conclusion: For episcleral brachytherapy treatment of n-AMD, using a patient population average target depth for treatment planning is inadequate, resulting in dose variations of a factor of approximately two over the 95% CI and larger variations for a nontrivial segment of the population. Each patient should have individualized imaging studies to determine the target depth for use in the dwell time calculation. Study was sponsored by Salutaris Medical Devices, Ltd., a subsidiary of Salutaris Medical Devices, Inc. Hamilton and Marsteller are founders of Salutaris Medical Devices, Inc. Drew, McGovern and Vitali are minor equity holders in Salutaris Medical Devices, Inc.« less

Orientation Discrimination with Macular Changes Associated with Early AMD

PubMed Central

Bedell, Harold E.; Tong, Jianliang; Woo, Stanley Y.; House, Jon R.; Nguyen, Tammy

2010-01-01

Purpose Age-related macular degeneration (AMD) is a condition that progressively reduces central vision in elderly individuals, resulting in a reduced capacity to perform many daily activities and a diminished quality of life. Recent studies identified clinical treatments that can slow or reverse the progression of exudative (wet) AMD and ongoing research is evaluating earlier interventions. Because early diagnosis is critical for an optimal outcome, the goal of this study is to assess psychophysical orientation discrimination for randomly positioned short line segments as a potential indicator of subtle macular changes in eyes with early AMD. Methods Orientation discrimination was measured in a sample of 74 eyes of patients aged 47 to 82 years old, none of which had intermediate or advanced AMD. Amsler-grid testing was performed as well. A masked examiner graded each eye as level 0, 1, 2, or 3 on a streamlined version of the Age-Related Eye Disease Study (AREDS) scale for AMD, based on the presence and extent of macular drusen or retinal pigment epithelium (RPE) changes. Visual acuity in the 74 eyes ranged from 20/15 to 20/40+1, with no significant differences among the grading levels. Humphrey 10–2 and Nidek MP-1 micro-perimetry were used to assess retinal sensitivity at test locations 1° from the locus of fixation. Results Average orientation-discrimination thresholds increased systematically from 7.4° to 11.3° according to the level of macular changes. In contrast, only 3 of 74 eyes exhibited abnormalities on the Amsler grid and central-field perimetric defects occurred with approximately equal probability at all grading levels. Conclusions In contrast to Amsler grid and central-visual-field testing, psychophysical orientation discrimination has the capability to distinguish between eyes with and without subtle age-related macular changes. PMID:19319009

Population-based age group specific annual incidence rates of symptomatic age-related macular degeneration.

PubMed

Saari, Jukka M

2014-01-01

To study the population-based annual incidence rates of exudative, dry and all cases of symptomatic age-related macular degeneration (AMD) in different age and sex groups. This is a one year, prospective, population-based study on all consecutive new patients with AMD in the hospital district of Central Finland. The diagnosis was confirmed in all patients with slit lamp biomicroscopy, optical coherence tomography (OCT) using a Spectralis HRA + OCT device, and the Heidelberg Eye Explorer 1.6.2.0 program. Fluorescein angiograms were taken when needed. The population-based annual incidence rates of all cases of symptomatic AMD increased from 0.03% (95% CI, 0.01-0.05%) in the age group 50-59 years to 0.82% (95% CI, 0.55-1.09%) in the age group 85-89 years and were 0.2% (95% CI, 0.17-0.24%) in exudative, 0.11% (95% CI, 0.09-0.14%) in dry, and 0.32% (95% CI, 0.28-0.36%) in all cases of AMD in the age group 60 years and older. During the next 20 years in Central Finland the population-based annual incidence rates can be estimated to increase to 0.27% (95% CI, 0.24-0.30%) in exudative, to 0.13% (95% CI, 0.11-0.15%) in dry, and to 0.41% (95% CI, 0.37-0.45%) in all cases of AMD in the age group 60 years and older. The population-based annual incidence of AMD did not show statistically significant differences between males and females (p>0.1). The population-based age-group specific annual incidence rates of symptomatic AMD of this study may help to plan health care provision for patients of AMD.

A Discussion of Commercially Available Intra-ocular Telescopic Implants for Patients with Age-Related Macular Degeneration.

PubMed

Dunbar, Hannah M P; Dhawahir-Scala, Felipe E

2018-06-01

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the western world, causing significant reduction in quality of life. Despite treatment advances, the burden of visual impairment caused by AMD continues to rise. In addition to traditional low vision rehabilitation and support, optical and electronic aids, and strategies to enhance the use of peripheral vision, implantable telescopic devices have been indicated as a surgical means of enhancing vision. Here we examine the literature on commercially available telescopic devices discussing their design, mode of action, surgical procedure and published outcomes on visual acuity, quality of life, surgical complication rates and cost effectiveness data where available.Funding Article processing charges were funded by VisionCare Inc.

Autonomous mine detection system (AMDS) neutralization payload module

NASA Astrophysics Data System (ADS)

Majerus, M.; Vanaman, R.; Wright, N.

2010-04-01

The Autonomous Mine Detection System (AMDS) program is developing a landmine and explosive hazards standoff detection, marking, and neutralization system for dismounted soldiers. The AMDS Capabilities Development Document (CDD) has identified the requirement to deploy three payload modules for small robotic platforms: mine detection and marking, explosives detection and marking, and neutralization. This paper addresses the neutralization payload module. There are a number of challenges that must be overcome for the neutralization payload module to be successfully integrated into AMDS. The neutralizer must meet stringent size, weight, and power (SWaP) requirements to be compatible with a small robot. The neutralizer must be effective against a broad threat, to include metal and plastic-cased Anti-Personnel (AP) and Anti-Tank (AT) landmines, explosive devices, and Unexploded Explosive Ordnance (UXO.) It must adapt to a variety of threat concealments, overburdens, and emplacement methods, to include soil, gravel, asphalt, and concrete. A unique neutralization technology is being investigated for adaptation to the AMDS Neutralization Module. This paper will describe review this technology and how the other two payload modules influence its design for minimizing SWaP. Recent modeling and experimental efforts will be included.

Device for fluorescent control and photodynamic therapy of age-related macula degeneration

NASA Astrophysics Data System (ADS)

Loschenov, Victor B.; Meerovich, Gennadii A.; Budzinskaya, M. V.; Ermakova, N. A.; Shevchik, S. A.; Kharnas, Sergey S.

2004-07-01

Age-related macula degeneration (AMD) is a wide spread disease the appearance of which leads to poor eyesight and blindness. A method of treatment is not determined until today. Traditional methods, such as laser coagulation and surgical operations are rather traumatic for eye and often bring to complications. That's why recently a photodynamic method of AMD treatment is studied. Based on photodynamic occlusion of choroidal neovascularization (CNV) with minimal injury to overlying neurosensory retina what increases the efficiency.

GAS DISCHARGE DEVICES

DOEpatents

Arrol, W.J.; Jefferson, S.

1957-08-27

The construction of gas discharge devices where the object is to provide a gas discharge device having a high dark current and stabilized striking voltage is described. The inventors have discovered that the introduction of tritium gas into a discharge device with a subsequent electrical discharge in the device will deposit tritium on the inside of the chamber. The tritium acts to emit beta rays amd is an effective and non-hazardous way of improving the abovementioned discharge tube characteristics

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.

PubMed

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.

Optical coherence tomography-based decision making in exudative age-related macular degeneration: comparison of time- vs spectral-domain devices.

PubMed

Cukras, C; Wang, Y D; Meyerle, C B; Forooghian, F; Chew, E Y; Wong, W T

2010-05-01

To determine whether optical coherence tomography (OCT) device-type influences clinical grading of OCT imaging in the context of exudative age-related macular degeneration (AMD). Ninety-six paired OCT scans from 49 patients with active exudative AMD were obtained on both the time-domain Stratus OCT system and the spectral-domain Cirrus OCT system at the same visit. Three independent graders judged each scan for the presence of intraretinal fluid (IRF) or subretinal fluid (SRF). The degree of grader consensus was evaluated and the ability of the systems to detect the presence of disease activity was analysed. Cirrus OCT generated a higher degree of inter-grader consensus than Stratus OCT with higher intraclass correlation coefficients for all parameters analysed. A pair-wise comparison of Cirrus OCT with Stratus OCT systems revealed that Cirrus-based gradings more frequently reported the presence of SRF and IRF and detected overall neovascular activity at a higher rate (P<0.05) compared with Stratus-based gradings. The choice of time-domain (Stratus) vs spectra-domain (Cirrus) OCT systems has a measurable impact on clinical decision making in exudative AMD. Spectral-domain OCT systems may be able to generate more consensus in clinical interpretation and, in particular cases, detect disease activity not detected by time-domain systems. Clinical trials using OCT-based clinical evaluations of exudative AMD may need to account for these inter-system differences in planning and analysis.

Optical Coherence Tomography-Based Decision Making in Exudative Age-related Macular Degeneration: Comparison of Time- versus Spectral-Domain Devices

PubMed Central

Cukras, Catherine; Wang, Yunqing D.; Meyerle, Catherine B.; Forooghian, Farzin; Chew, Emily Y.; Wong, Wai T.

2010-01-01

Purpose To determine if optical coherence tomography (OCT) device-type influences clinical grading of OCT imaging in the context of exudative age-related macular degeneration (AMD). Methods Ninety-six paired OCT scans from 49 patients with active exudative AMD were obtained on both the time-domain Stratus™ OCT system and the spectral-domain Cirrus™ OCT system at the same visit. Three independent graders judged each scan for the presence of intraretinal fluid (IRF) or subretinal fluid (SRF). The degree of grader consensus was evaluated and the ability of the systems to detect the presence of disease activity was analyzed. Results Cirrus™ OCT generated a higher degree of inter-grader consensus than Stratus OCT with higher intraclass correlation coefficients (ICC) for all parameters analyzed. A pair-wise comparison of Cirrus™ OCT to Stratus™ OCT systems revealed that Cirrus™-based gradings more frequently reported the presence of SRF and IRF and detected overall neovascular activity at a higher rate (p<0.05) compared to Stratus™-based gradings Conclusions The choice of time-domain (Stratus™) versus spectra-domain (Cirrus™) OCT systems has a measurable impact on clinical decision making in exudative AMD. Spectral-domain OCT systems may be able to generate more consensus in clinical interpretation and, in particular cases, detect disease activity not detected by time-domain systems. Clinical trials employing OCT-based clinical evaluations of exudative AMD may need to account for these inter-system differences in planning and analysis. PMID:19696804

Microbial diversity and metabolic networks in acid mine drainage habitats

PubMed Central

Méndez-García, Celia; Peláez, Ana I.; Mesa, Victoria; Sánchez, Jesús; Golyshina, Olga V.; Ferrer, Manuel

2015-01-01

Acid mine drainage (AMD) emplacements are low-complexity natural systems. Low-pH conditions appear to be the main factor underlying the limited diversity of the microbial populations thriving in these environments, although temperature, ionic composition, total organic carbon, and dissolved oxygen are also considered to significantly influence their microbial life. This natural reduction in diversity driven by extreme conditions was reflected in several studies on the microbial populations inhabiting the various micro-environments present in such ecosystems. Early studies based on the physiology of the autochthonous microbiota and the growing success of omics-based methodologies have enabled a better understanding of microbial ecology and function in low-pH mine outflows; however, complementary omics-derived data should be included to completely describe their microbial ecology. Furthermore, recent updates on the distribution of eukaryotes and archaea recovered through sterile filtering (herein referred to as filterable fraction) in these environments demand their inclusion in the microbial characterization of AMD systems. In this review, we present a complete overview of the bacterial, archaeal (including filterable fraction), and eukaryotic diversity in these ecosystems, and include a thorough depiction of the metabolism and element cycling in AMD habitats. We also review different metabolic network structures at the organismal level, which is necessary to disentangle the role of each member of the AMD communities described thus far. PMID:26074887

The Evaluation of Reading Performance with Minnesota Low Vision Reading Charts in Patients with Age-related Macular Degeneration.

PubMed

Altinbay, Deniz; Adibelli, Fatih Mehmet; Taskin, Ibrahim; Tekin, Adil

2016-01-01

To evaluate the reading performance using the Minnesota low vision reading (MNREAD) charts, of patients with age-related macular degeneration (AMD) who use low vision aid (LVA) devices. This prospective study enrolled 27 patients with AMD. Distance visual acuity (VA) was evaluated with a distance chart designed for patients with low vision. Near vision and reading performance were evaluated with the Turkish version of the MNREAD charts. Unaided vision and vision with LVA devices and high spherical add near glasses was measured. P <0.05 was considered statistically significant. The mean unaided near VA was 1.05 ± 0.27 log of the minimum angle of resolution (LogMAR). The mean VA with the LVA devices was 0.71 ± 0.41 LogMAR. Reading acuity ranged between 1.15 and 0.21 LogMAR, critical print size was between - 1.2 and 0.2 LogMAR. Maximum reading speeds were between 0 and 103 words/min. The cases are divided into groups in terms of reading speed according to age, gender, diagnosis, and education. Reading speed was negatively correlated to increasing age. MNREAD reading charts can be used to evaluate reading performance in patients with AMD with low vision. The outcomes of the present study indicate that optical correction is adequate for near VA requirements in this patient population. However, optical correction was inadequate for improving reading performance. Appropriate rehabilitation programs can be used to increase reading speed.

Evaluation of real-world mobility in age-related macular degeneration.

PubMed

Sengupta, Sabyasachi; Nguyen, Angeline M; van Landingham, Suzanne W; Solomon, Sharon D; Do, Diana V; Ferrucci, Luigi; Friedman, David S; Ramulu, Pradeep Y

2015-01-30

Previous research has suggested an association between poor vision and decreased mobility, including restricted levels of physical activity and travel away from home. We sought to determine the impact of age-related macular degeneration (AMD) on these measures of mobility. Fifty-seven AMD patients with bilateral, or severe unilateral, visual impairment were compared to 59 controls with normal vision. All study subjects were between the ages of 60 and 80. Subjects wore accelerometers and cellular network-based tracking devices over 7 days of normal activity. Number of steps taken, time spent in moderate-to-vigorous physical activity (MVPA), number of excursions from home, and time spent away from home were the primary outcome measures. In multivariate negative binomial regression models adjusted for age, gender, race, comorbidities, and education, AMD participants took fewer steps than controls (18% fewer steps per day, p = 0.01) and spent significantly less time in MVPA (35% fewer minutes, p < 0.001). In multivariate logistic regression models adjusting for age, sex, race, cognition, comorbidities, and grip strength, AMD subjects showed an increased likelihood of not leaving their home on a given day (odds ratio = 1.36, p = 0.04), but did not show a significant difference in the magnitude of time spent away from home (9% fewer minutes, p = 0.11). AMD patients with poorer vision engage in significantly less physical activity and take fewer excursions away from the home. Further studies identifying the factors mediating the relationship between vision loss and mobility are needed to better understand how to improve mobility among AMD patients.

Concordance of Macular Pigment Measurement Using Customized Heterochromatic Flicker Photometry and Fundus Autofluorescence in Age-Related Macular Degeneration.

PubMed

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

2015-12-01

We compared macular pigment (MP) measurements using customized heterochromatic flicker photometry (Macular Metrics Densitometer) and dual-wavelength fundus autofluorescence (Heidelberg Spectralis HRA + OCT MultiColor) in subjects with early age-related macular degeneration (AMD). Macular pigment was measured in 117 subjects with early AMD (age, 44-88 years) using the Densitometer and Spectralis, as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787). Baseline and 6-month study visits data were used for the analyses. Agreement was investigated at four different retinal eccentricities, graphically and using indices of agreement, including Pearson correlation coefficient (precision), accuracy coefficient, and concordance correlation coefficient (ccc). Agreement was poor between the Densitometer and Spectralis at all eccentricities, at baseline (e.g., at 0.25° eccentricity, accuracy = 0.63, precision = 0.35, ccc = 0.22) and at 6 months (e.g., at 0.25° eccentricity, accuracy = 0.52, precision = 0.43, ccc = 0.22). Agreement between the two devices was significantly greater for males at 0.5° and 1.0° of eccentricity. At all eccentricities, agreement was unaffected by cataract grade. In subjects with early AMD, MP measurements obtained using the Densitometer and Spectralis are not statistically comparable and should not be used interchangeably in either the clinical or research setting. Despite this lack of agreement, statistically significant increases in MP, following 6 months of supplementation with macular carotenoids, were detected with each device, confirming that these devices are capable of measuring change in MP within subjects over time. (http://www.controlled-trials.com number, ISRCTN13894787.).

The Effects of Low-Vision Rehabilitation on Reading Speed and Depression in Age Related Macular Degeneration: A Meta-Analysis.

PubMed

Hamade, Noura; Hodge, William G; Rakibuz-Zaman, Muhammad; Malvankar-Mehta, Monali S

2016-01-01

Age related macular degeneration (AMD) is a progressive eye disease that, as of 2015, has affected 11 million people in the U.S. and 1.5 million in Canada causing central vision blindness. By 2050, this number is expected to double to 22 million. Eccentric vision is the target of low-vision rehabilitation aids and programs for patients with AMD, which are thought to improve functional performance by improving reading speed and depression. This study evaluates the effect of various low-vision rehabilitation strategies on reading speed and depression in patients 55 and older with AMD. Computer databases including MEDLINE (OVID), EMBASE (OVID), BIOSIS Previews (Thomson-Reuters), CINAHL (EBSCO), Health Economic Evaluations Database (HEED), ISI Web of Science (Thomson-Reuters) and the Cochrane Library (Wiley) were searched from the year 2000 to January 2015. Included papers were research studies with a sample size of 20 eyes or greater focused on AMD in adults aged 55 or older with low vision (20/60 or lower). Two independent reviewers screened and extracted relevant data from the included articles. Standardized mean difference (SMD) was chosen as an effect size to perform meta-analysis using STATA. Fixed- and random-effect models were developed based on heterogeneity. Reading Speed and Depression Scores. A total of 9 studies (885 subjects) were included. Overall, a significant improvement in reading speed was found with a SMD of 1.01 [95% CI: 0.05 to 1.97]. Low-vision rehabilitation strategies including micro-perimetric biofeedback, microscopes teaching program significantly improved reading speed. Eccentric viewing training showed the maximum improvement in reading speed. In addition, a non-significant improvement in depression scores was found with a SMD of -0.44 [95% CI: -0.96 to 0.09]. A considerable amount of research is required in the area of low-vision rehabilitation strategies for patients with AMD. Based on current research, low-vision rehabilitation aids improve reading speed. However, they do not have a significant effect on depression scores in those 55 and older with AMD.

Method and apparatus for actively controlling a micro-scale flexural plate wave device

DOEpatents

Dohner, Jeffrey L.

2001-01-01

An actively controlled flexural plate wave device provides a micro-scale pump. A method of actively controlling a flexural plate wave device produces traveling waves in the device by coordinating the interaction of a magnetic field with actively controlled currents. An actively-controlled flexural plate wave device can be placed in a fluid channel and adapted for use as a micro-scale fluid pump to cool or drive micro-scale systems, for example, micro-chips, micro-electrical-mechanical devices, micro-fluid circuits, or micro-scale chemical analysis devices.

Advanced process control framework initiative

NASA Astrophysics Data System (ADS)

Hill, Tom; Nettles, Steve

1997-01-01

The semiconductor industry, one the world's most fiercely competitive industries, is driven by increasingly complex process technologies and global competition to improve cycle time, quality, and process flexibility. Due to the complexity of these problems, current process control techniques are generally nonautomated, time-consuming, reactive, nonadaptive, and focused on individual fabrication tools and processes. As the semiconductor industry moves into higher density processes, radical new approaches are required. To address the need for advanced factory-level process control in this environment, Honeywell, Advanced Micro Devices (AMD), and SEMATECH formed the Advanced Process Control Framework Initiative (APCFI) joint research project. The project defines and demonstrates an Advanced Process Control (APC) approach based on SEMATECH's Computer Integrated Manufacturing (CIM) Framework. Its scope includes the coordination of Manufacturing Execution Systems, process control tools, and wafer fabrication equipment to provide necessary process control capabilities. Moreover, it takes advantage of the CIM Framework to integrate and coordinate applications from other suppliers that provide services necessary for the overall system to function. This presentation discusses the key concept of model-based process control that differentiates the APC Framework. This major improvement over current methods enables new systematic process control by linking the knowledge of key process settings to desired product characteristics that reside in models created with commercial model development tools The unique framework-based approach facilitates integration of commercial tools and reuse of their data by tying them together in an object-based structure. The presentation also explores the perspective of each organization's involvement in the APCFI project. Each has complementary goals and expertise to contribute; Honeywell represents the supplier viewpoint, AMD represents the user with 'real customer requirements', and SEMATECH provides a consensus-building organization that widely disseminates technology to suppliers and users in the semiconductor industry that face similar equipment and factory control systems challenges.

Age related macular degeneration and visual disability.

PubMed

Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

2011-02-01

Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of substantial benefit in people with age-related macular degeneration. Prescription filters are one of the most beneficial visual aids that people with macular degeneration. In principle, one aims both at reducing short-wavelength light to reduce glare and at identifying light with specific wavelengths (colours) preferred by the patient for viewing. In both instances, such interventions result in apparent improved contrast sensitivity and better visual acuity. Although specific tests are performed to determine the best colour, tint, lens material, and type of frame for the patient's need, no scientific protocol has been developed so far to assist in prescribing tinted or selective transmission lenses . Magnifying optical lenses are available in a wide range of dioptric powers and are made from materials that correct for weight (plastic), thickness (high index), spherical aberrations (aspherical), and variable light intensities (photochromatic). These lenses can be used as loose lenses, mounted on optical frames, or used with a wide variety of attachments. As the dioptric power of plus lenses increases, the viewing distance of the target decreases, hence their usefulness mainly for tasks requiring near resolution acuity, like reading. Magnification can also be achieved with the use of telescopic devices that are built of two or more plus and (or) minus (minifying) optical lenses. Normal resolution acuity levels can be achieved with these devices for all viewing distances. Therefore, all telescopic devices are useful only for stationary patient tasks that do not require mobility and orientation. Electronic magnification has the great advantage over plus lenses of producing an acuity reserve enabling reading skills for almost all levels of visual acuity. The additional benefit provided is preservation of binocularity, even at high levels of visual disparity between the two eyes. Vision rehabilitation can help patients to maximize their remaining vision and adapt to activities of daily living. The support of the patient's social network is critical to patient's well-being as patients adjust to being partially sighted.

Complement inhibitors for age-related macular degeneration.

PubMed

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 parallel treatment groups which investigated either the prevention or treatment of advanced AMD by inhibition of the complement cascade. Two authors (MW and GMcK) independently evaluated all the titles and abstracts resulting from the searches. We contacted companies running clinical trials which had not yet reported results to request information. Since no trials met our inclusion criteria, we undertook no assessment of quality or meta-analysis. We identified and screened 317 references but there were no published RCTs that met the inclusion criteria. We identified two ongoing studies: one phase I study and one phase II study. There is insufficient information at present to generate evidence-based recommendations on the potential safety and efficacy of complement inhibitors for prevention or treatment of AMD. However we anticipate the results of ongoing trials.

Standardizing power monitoring and control at exascale

DOE PAGES

Grant, Ryan E.; Levenhagen, Michael; Olivier, Stephen L.; ...

2016-10-20

Power API-the result of collaboration among national laboratories, universities, and major vendors-provides a range of standardized power management functions, from application-level control and measurement to facility-level accounting, including real-time and historical statistics gathering. Here, support is already available for Intel and AMD CPUs and standalone measurement devices.

DETECTION OF TREATMENT-NAIVE CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION BY SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PubMed

Ahmed, Daniel; Stattin, Martin; Graf, Alexandra; Forster, Julia; Glittenberg, Carl; Krebs, Ilse; Ansari-Shahrezaei, Siamak

2017-09-04

To compare the detection rate of choroidal neovascularization (CNV) in treatment-naive neovascular age-related macular degeneration by swept source optical coherence tomography angiography (SS-OCTA, Topcon's DRI Triton) working at 1,050 nm wavelength versus fluorescence angiography. Cross-sectional analysis of 156 eyes (107 neovascular age-related macular degeneration and 49 dry AMD) in 98 patients, previously diagnosed by multimodal imaging using fluorescein (FA) and indocyanine green angiography (Heidelberg's Spectralis) in a tertiary retina center, evaluated by SS-OCTA 4.5 mm × 4.5 mm and 6 mm × 6 mm macular cubes. Main outcome measures were sensitivity and specificity of SS-OCTA in AMD. Potential factors influencing CNV detection rate were analyzed. Swept source optical coherence tomography angiography detected CNV in 81 of 107 eyes, resulting in a sensitivity of 75.7%. In 49 eyes with dry AMD, no CNV could be identified (specificity 100%). A statistical significance was calculated for nondetection of treatment-naive CNV by SS-OCTA in pigment epithelial detachment over 400 μm (P = 0.0238). Topcon's SS-OCTA was not able to detect all CNV lesions. Large pigment epithelial detachments were associated with signal loss. Fluorescence angiography still remains the gold standard, but the tested SS-OCTA device can be considered as a feasible additional diagnostic tool in AMD.

Rehabilitation Approaches in Macular Degeneration Patients

PubMed Central

Maniglia, Marcello; Cottereau, Benoit R.; Soler, Vincent; Trotter, Yves

2016-01-01

Age related macular degeneration (AMD) is a visual disease that affects elderly population. It entails a progressive loss of central vision whose consequences are dramatic for the patient’s quality of life. Current rehabilitation programs are restricted to technical aids based on visual devices. They only temporarily improve specific visual functions such as reading skills. Considering the rapid increase of the aging population worldwide, it is crucial to intensify clinical research on AMD in order to develop simple and efficient methods that improve the patient’s visual performances in many different contexts. One very promising approach to face this challenge is based on perceptual learning (PL). Through intensive practice, PL can induce neural plasticity in sensory cortices and result in long-lasting enhancements for various perceptual tasks in both normal and visually impaired populations. A growing number of studies showed how appropriate PL protocols improve visual functions in visual disorders, namely amblyopia, presbyopia or myopia. In order to successfully apply these approaches to more severe conditions such as AMD, numerous challenges have to be overcome. Indeed, the overall elderly age of patients and the reduced cortical surface that is devoted to peripheral vision potentially limit neural plasticity in this population. In addition, ocular fixation becomes much less stable because patients have to rely on peripheral fixation spots outside the scotoma whose size keeps on evolving. The aim of this review article is to discuss the recent literature on this topic and to offer a unified approach for developing new rehabilitation programs of AMD using PL. We argue that with an appropriate experimental and training protocol that is adapted to each patient needs, PL can offer fascinating opportunities for the development of simple, non-expensive rehabilitation approaches a large spectrum of visual functions in AMD patients. PMID:28082876

Mineralogical and geochemical characterization of waste rocks from a gold mine in northeastern Thailand: application for environmental impact protection.

PubMed

Assawincharoenkij, Thitiphan; Hauzenberger, Christoph; Ettinger, Karl; Sutthirat, Chakkaphan

2018-02-01

Waste rocks from gold mining in northeastern Thailand are classified as sandstone, siltstone, gossan, skarn, skarn-sulfide, massive sulfide, diorite, and limestone/marble. Among these rocks, skarn-sulfide and massive sulfide rocks have the potential to generate acid mine drainage (AMD) because they contain significant amounts of sulfide minerals, i.e., pyrrhotite, pyrite, arsenopyrite, and chalcopyrite. Moreover, both sulfide rocks present high contents of As and Cu, which are caused by the occurrence of arsenopyrite and chalcopyrite, respectively. Another main concern is gossan contents, which are composed of goethite, hydrous ferric oxide (HFO), quartz, gypsum, and oxidized pyroxene. X-ray maps using electron probe micro-analysis (EPMA) indicate distribution of some toxic elements in Fe-oxyhydroxide minerals in the gossan waste rock. Arsenic (up to 1.37 wt.%) and copper (up to 0.60 wt.%) are found in goethite, HFO, and along the oxidized rim of pyroxene. Therefore, the gossan rock appears to be a source of As, Cu, and Mn. As a result, massive sulfide, skarn-sulfide, and gossan have the potential to cause environmental impacts, particularly AMD and toxic element contamination. Consequently, the massive sulfide and skarn-sulfide waste rocks should be protected from oxygen and water to avoid an oxidizing environment, whereas the gossan waste rocks should be protected from the formation of AMD to prevent heavy metal contamination.

Mobilization of bone marrow mesenchymal stem cells in vivo augments bone healing in a mouse model of segmental bone defect.

PubMed

Kumar, Sanjay; Ponnazhagan, Selvarangan

2012-04-01

Although the number of mesenchymal stem cells (MSC) in the bone marrow is sufficient to maintain skeletal homeostasis, in osteopenic pathology, aggravated osteoclast activity or insufficient osteoblast numbers ensue, affecting normal bone remodeling. Most of the currently available therapies are anti-resorptive with limited osteogenic potential. Since mobilization of stem/progenitors from the BM is a prerequisite for their participation in tissue repair, amplification of endogenous stem cells may provide an alternative approach in these conditions. The present study determined the potential of MSC mobilization in vivo, using combinations of different growth factors with the CXCR4 antagonist, AMD3100, in a mouse model of segmental bone defect. Results indicated that among several factors tested IGF1 had maximum proliferative ability of MSC in vitro. Results of the in vivo studies indicated that the combination of IGF1 and AMD3100 provided significant augmentation of bone growth as determined by DXA, micro-CT and histomorphometry in mice bearing segmental fractures. Further, characterization of MSC isolated from mice treated with IGF1 and AMD3100 indicated Akt/PI3K, MEK1/2-Erk1/2 and smad2/3 as key signaling pathways mediating this effect. These data indicate the potential of in vivo stem cell mobilization as a novel alternative for bone healing. Copyright © 2012 Elsevier Inc. All rights reserved.

Peripheral Retinal Changes Associated with Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report Number 12 by the Age-Related Eye Disease Study 2 Optos PEripheral RetinA (OPERA) Study Research Group.

PubMed

Domalpally, Amitha; Clemons, Traci E; Danis, Ronald P; Sadda, SriniVas R; Cukras, Catherine A; Toth, Cynthia A; Friberg, Thomas R; Chew, Emily Y

2017-04-01

To compare rates of peripheral retinal changes in Age-Related Eye Disease Study 2 (AREDS2) participants with at least intermediate age-related macular degeneration (AMD) with control subjects without intermediate age-related changes (large drusen). Cross-sectional evaluation of clinic-based patients enrolled in AREDS2 and a prospective study. Participants from prospective studies. The 200° pseudocolor and fundus autofluorescence (FAF) images were captured on the Optos 200 Tx Ultrawide-field device (Optos, Dunfermline, Scotland) by centering on the fovea and then steering superiorly and inferiorly. The montaged images were graded at a reading center with the images divided into 3 zones (zone 1 [posterior pole], zone 2 [midperiphery], and zone 3 [far periphery]) to document the presence of peripheral lesions. Peripheral retinal lesions: drusen, hypopigmentary/hyperpigmentary changes, reticular pseudodrusen, senile reticular pigmentary changes, cobblestone degeneration, and FAF abnormalities. A total of 484 (951 eyes) AREDS2 participants with AMD (cases) and 89 (163 eyes) controls without AMD had gradable color and FAF images. In zones 2 and 3, neovascularization and geographic atrophy (GA) were present, ranging from 0.4% to 6% in eyes of cases, respectively, and GA was present in 1% of eyes of controls. Drusen were detected in 97%, 78%, and 64% of eyes of cases and 48%, 21%, and 9% of eyes of controls in zones 2 and 3 superior and 3 inferior, respectively (P < 0.001 for all). Peripheral reticular pseudodrusen were seen in 15%. Senile reticular pigmentary change was the predominant peripheral change seen in 48% of cases and 16% of controls in zone 2 (P < 0.001). Nonreticular pigment changes were less frequent in the periphery than in the posterior pole (46% vs. 76%) and negligible in controls. Peripheral retinal changes are more prevalent in eyes with AMD than in control eyes. Drusen are seen in a majority of eyes with AMD in both the mid and far periphery, whereas pigment changes and features of advanced AMD are less frequent. Age-related macular degeneration may be more than a "macular" condition but one that involves the entire retina. Future longitudinal studies of peripheral changes in AMD and their impact on visual function may contribute to understanding AMD pathogenesis. Published by Elsevier Inc.

Cloning and analysis of the positively acting regulatory gene amdR from Aspergillus nidulans.

PubMed Central

Andrianopoulos, A; Hynes, M J

1988-01-01

The positively acting regulatory gene amdR of Aspergillus nidulans coordinately regulates the expression of four unlinked structural genes involved in acetamide (amdS), omega amino acid (gatA and gabA), and lactam (lamA) catabolism. By the use of DNA-mediated transformation of A. nidulans, the amdR regulatory gene was cloned from a genomic cosmid library. Southern blot analysis of DNA from various loss-of-function amdR mutants revealed the presence of four detectable DNA rearrangements, including a deletion, an insertion, and a translocation. No detectable DNA rearrangements were found in several constitutive amdRc mutants. Analysis of the fate of amdR-bearing plasmids in transformants showed that 10 to 20% of the transformation events were homologous integrations or gene conversions, and this phenomenon was exploited in developing a strategy by which amdRc and amdR- alleles can be readily cloned and analyzed. Examination of the transcription of amdR by Northern blot (RNA blot) analysis revealed the presence of two mRNAs (2.7 and 1.8 kilobases) which were constitutively synthesized at a very low level. In addition, amdR transcription did not appear to depend on the presence of a functional amdR product nor was it altered in amdRc mutants. The dosage effects of multiple copies of amdR in transformants were examined, and it was shown that such transformants exhibited stronger growth than did the wild type on acetamide and pyrrolidinone media, indicating increased expression of the amdS and lamA genes, respectively. These results were used to formulate a model for amdR-mediated regulation of gene expression in which the low constitutive level of amdR product sets the upper limits of basal and induced transcription of the structural genes. Multiple copies of 5' sequences from the amdS gene can result in reduced growth on substrates whose utilization is dependent on amdR-controlled genes. This has been attributed to titration of limiting amdR gene product. Strong support for this proposal was obtained by showing that multiple copies of the amdR gene can reverse this phenomenon (antititration). Images PMID:3062382

The reduction of serum soluble Flt-1 in patients with neovascular age-related macular degeneration.

PubMed

Uehara, Hironori; Mamalis, Christina; McFadden, Molly; Taggart, Michael; Stagg, Brian; Passi, Samuel; Earle, Phillip; Chakravarthy, Usha; Hogg, Ruth E; Ambati, Balamurali K

2015-01-01

To evaluate serum soluble Flt-1 (sFlt-1) in age-related macular degeneration (AMD) patients. Case-control study. Study involved 56 non-AMD participants, 53 early AMD patients, and 97 neovascular AMD patients from Belfast in Northern Ireland. Serum samples were collected from each patient. Serum sFlt-1 was measured by human sVEGFR1/sFlt-1 ELISA kit. The results were analyzed by Excel and SPSS. Serum sFlt-1 concentration of non-AMD, early AMD, and neovascular AMD were 90.8 ± 2.9 pg/mL (± standard error of the mean), 88.2 ± 2.6 pg/mL, and 79.9 ± 2.2 pg/mL. sFlt-1 from neovascular AMD patients was significantly decreased compared to non-AMD and early AMD patients (ANOVA, P < .01). For each 10-point increase in sFlt-1, the odds for having neovascular AMD compared with non-AMD and neovascular AMD decrease by 27.8%, odds ratio (OR) = 0.722 (95% confidence interval [CI]: 0.588-0.888, P = .002) and 27.0%, OR = 0.730 (95% CI: 0.594-0.898, P = .003), respectively. In patients over 73 years of age, serum sFlt-1 <80 pg/mL was associated with a >6-fold higher risk of neovascular AMD. Reduced serum sFlt-1 differentiates those patients with neovascular AMD from both early AMD and non-AMD participants. In those aged over 73, serum sFlt <80 pg/mL seems to indicate a particularly high risk of neovascular AMD. Our results indicate serum sFlt-1 could be a biomarker for development of neovascular AMD. Copyright © 2015 Elsevier Inc. All rights reserved.

Measurement of Retinal Sensitivity on Tablet Devices in Age-Related Macular Degeneration.

PubMed

Wu, Zhichao; Guymer, Robyn H; Jung, Chang J; Goh, Jonathan K; Ayton, Lauren N; Luu, Chi D; Lawson, David J; Turpin, Andrew; McKendrick, Allison M

2015-06-01

We compared measurements of central retinal sensitivity on a portable, low-cost tablet device to the established method of microperimetry in age-related macular degeneration (AMD). A customized test designed to measure central retinal sensitivity (within the central 1° radius) on a tablet device was developed using an open-source platform called PsyPad. A total of 30 participants with AMD were included in this study, and all participants performed a practice test on PsyPad, followed by four tests of one eye and one test of the other eye. Participants then underwent standardized microperimetry examinations in both eyes. The average test duration on PsyPad was 53.9 ± 7.5 seconds, and no significant learning effect was observed over the examinations performed ( P = 1.000). The coefficient of repeatability of central retinal sensitivity between the first two examinations on PsyPad was ±1.76 dB. The mean central retinal sensitivity was not significantly different between PsyPad (25.7 ± 0.4 dB) and microperimetry (26.1 ± 0.4 dB, P = 0.094), and the 95% limits of agreement between the two measures were between -4.12 and 4.92 dB. The measurements of central retinal sensitivity can be performed effectively using a tablet device, displaying reasonably good agreement with those obtained using the established method of microperimetry. These findings highlight the potential of tablet devices as low-cost and portable tools for developing and performing visual function measures that can be easily and widely implemented.

76 FR 13620 - Opportunity to Partner; Testing of Patient Compartment Seating and Restraints to Proposed Test...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-14

... current or comparable pre-test or pre-standard seat, seat retention device, and occupant restraint and its... Partner; Testing of Patient Compartment Seating and Restraints to Proposed Test Standard Authority: 29 U.S... proposed ambulance component test standards. One such standard, AMD STANDARD 026--Seat, Seat Mount and...

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

PubMed Central

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 higher sensitivity to B. cinerea infections in plants treated with amdS transformants as detected in greenhouse assays. These observations suggest that the increased plant development promoted by the amdS transformants was at expense of defenses. PMID:27536277

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

PubMed

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 higher sensitivity to B. cinerea infections in plants treated with amdS transformants as detected in greenhouse assays. These observations suggest that the increased plant development promoted by the amdS transformants was at expense of defenses.

Implementation of the DPM Monte Carlo code on a parallel architecture for treatment planning applications.

PubMed

Tyagi, Neelam; Bose, Abhijit; Chetty, Indrin J

2004-09-01

We have parallelized the Dose Planning Method (DPM), a Monte Carlo code optimized for radiotherapy class problems, on distributed-memory processor architectures using the Message Passing Interface (MPI). Parallelization has been investigated on a variety of parallel computing architectures at the University of Michigan-Center for Advanced Computing, with respect to efficiency and speedup as a function of the number of processors. We have integrated the parallel pseudo random number generator from the Scalable Parallel Pseudo-Random Number Generator (SPRNG) library to run with the parallel DPM. The Intel cluster consisting of 800 MHz Intel Pentium III processor shows an almost linear speedup up to 32 processors for simulating 1 x 10(8) or more particles. The speedup results are nearly linear on an Athlon cluster (up to 24 processors based on availability) which consists of 1.8 GHz+ Advanced Micro Devices (AMD) Athlon processors on increasing the problem size up to 8 x 10(8) histories. For a smaller number of histories (1 x 10(8)) the reduction of efficiency with the Athlon cluster (down to 83.9% with 24 processors) occurs because the processing time required to simulate 1 x 10(8) histories is less than the time associated with interprocessor communication. A similar trend was seen with the Opteron Cluster (consisting of 1400 MHz, 64-bit AMD Opteron processors) on increasing the problem size. Because of the 64-bit architecture Opteron processors are capable of storing and processing instructions at a faster rate and hence are faster as compared to the 32-bit Athlon processors. We have validated our implementation with an in-phantom dose calculation study using a parallel pencil monoenergetic electron beam of 20 MeV energy. The phantom consists of layers of water, lung, bone, aluminum, and titanium. The agreement in the central axis depth dose curves and profiles at different depths shows that the serial and parallel codes are equivalent in accuracy.

LINE-ABOVE-GROUND ATTENUATOR

DOEpatents

Wilds, R.B.; Ames, J.R.

1957-09-24

The line-above-ground attenuator provides a continuously variable microwave attenuator for a coaxial line that is capable of high attenuation and low insertion loss. The device consists of a short section of the line-above- ground plane type transmission lime, a pair of identical rectangular slabs of lossy material like polytron, whose longitudinal axes are parallel to and indentically spaced away from either side of the line, and a geared mechanism to adjust amd maintain this spaced relationship. This device permits optimum fineness and accuracy of attenuator control which heretofore has been difficult to achieve.

StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR): study protocol for a randomised controlled clinical trial.

PubMed

Neffendorf, James E; Desai, Riti; Wang, Yanzhong; Kelly, Joanna; Murphy, Caroline; Reeves, Barnaby C; Chakravarthy, Usha; Wordsworth, Sarah; Lewis, Cornelius; Peacock, Janet; Uddin, Shahir; O'Sullivan, Joe M; Jackson, Timothy L

2016-11-24

The standard of care for neovascular age-related macular degeneration (nAMD) involves ongoing intravitreal injections of anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF). The most commonly used anti-VEGF drugs are ranibizumab, bevacizumab and aflibercept. The main objective of the STAR trial is to determine if stereotactic radiotherapy can reduce the number of anti-VEGF injections that patients with nAMD require. STAR is a multicentre, double-masked, randomised, sham-controlled clinical trial. It evaluates a new device (manufactured by Oraya, Newark, CA, USA) designed to deliver stereotactic radiotherapy (SRT) to nAMD lesions. The trial enrols participants with chronic, active nAMD. Participants receive a single SRT treatment (16 Gy or sham) with a concomitant baseline intravitreal injection of 0.5 mg ranibizumab. Thereafter, they attend every month for 24 months, and ranibizumab is administered at the visit if retreatment criteria are met. The primary outcome is the number of pro re nata ranibizumab injections during the first 24 months. Secondary outcomes include visual acuity, lesion morphology, quality of life and safety. Additional visits occur at 36 and 48 months to inspect for radiation retinopathy. The target sample size of 411 participants (randomised 2:1 in favour of radiation) is designed to detect a reduction of 2.5 injections against ranibizumab monotherapy, at 90% power, and a significance level (alpha) of 0.025 (one-sided two-sample t test). This gives 97% power to detect non-inferiority of visual acuity at a five-letter margin. The primary analyses will be by intention to treat. The safety and efficacy outcomes will help determine the role of SRT in the management of chronic, active nAMD. International Standard Randomised Controlled Trial Number: ISRCTN12884465. Registered on 28 November 2014. ClinicalTrials.gov: NCT02243878 . Registered on 17 September 2014.

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

PubMed

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

Significant seasonal variations of microbial community in an acid mine drainage lake in Anhui Province, China.

PubMed

Hao, Chunbo; Wei, Pengfei; Pei, Lixin; Du, Zerui; Zhang, Yi; Lu, Yanchun; Dong, Hailiang

2017-04-01

Acid mine drainage (AMD),characterized by strong acidity and high metal concentrations, generates from the oxidative dissolution of metal sulfides, and acidophiles can accelerate the process significantly. Despite extensive research in microbial diversity and community composition, little is known about seasonal variations of microbial community structure (especially micro eukaryotes) in response to environmental conditions in AMD ecosystem. To this end, AMD samples were collected from Nanshan AMD lake, Anhui Province, China, over a full seasonal cycle from 2013 to 2014, and water chemistry and microbial composition were studied. pH of lake water was stable (∼3.0) across the sampling period, while the concentrations of ions varied dramatically. The highest metal concentrations in the lake were found for Mg and Al, not commonly found Fe. Unexpectedly, ultrahigh concentration of chlorophyll a was measured in the extremely acidic lake, reaching 226.43-280.95 μg/L in winter, even higher than those in most eutrophic freshwater lakes. Both prokaryotic and eukaryotic communities showed a strong seasonal variation. Among the prokaryotes, "Ferrovum", a chemolithotrophic iron-oxidizing bacterium was predominant in most sampling seasons, although it was a minor member prior to September, 2012. Fe 2+ was the initial geochemical factor that drove the variation of the prokaryotic community. The eukaryotic community was simple but varied more drastically than the prokaryotic community. Photoautotrophic algae (primary producers) formed a food web with protozoa or flagellate (top consumers) across all four seasons, and temperature appeared to be responsible for the observed seasonal variation. Ochromonas and Chlamydomonas (responsible for high algal bloom in winter) occurred in autumn/summer and winter/spring seasons, respectively, because of their distinct growth temperatures. The closest phylogenetic relationship between Chlamydomonas species in the lake and those in Arctic and Alpine suggested that the native Chlamydomonas species may have been both acidophilic and psychrophilic after a long acclimation time in this extreme environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed Central

Dong, Yonghui; Liu, Hui; Zhang, Xuejun; Xu, Fei; Qin, Liang; Cheng, Peng; Huang, Hui; Guo, Fengjing; Yang, Qing; Chen, Anmin

2016-01-01

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 degeneration in PTOA mice. PMID:27322244

Targeted Vision Function Goals and Use of Vision Resources in Ophthalmology Patients with Age-Related Macular Degeneration and Comorbid Depressive Symptoms

ERIC Educational Resources Information Center

Casten, Robin; Rovner, Barry W.; Fontenot, Joseph L.

2016-01-01

Introduction: This study characterizes self-reported functional vision goals and the use of low vision resources (for example, services and devices) in ophthalmology clinic patients with age-related macular degeneration (AMD) and comorbid depressive symptoms. Methods: From July 2009 to February 2013, we assessed 188 consecutive patients (age 65+;…

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

PubMed

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.

Tumor Necrosis Factor-alpha Potentiates the Cytotoxicity of Amiodarone in Hepa1c1c7 Cells: Roles of Caspase Activation and Oxidative Stress

PubMed Central

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. PMID:23042730

let-7 Contributes to Diabetic Retinopathy but Represses Pathological Ocular Angiogenesis

PubMed Central

Zhou, Qinbo; Frost, Robert J. A.; Anderson, Chastain; Zhao, Fangkun; Ma, Jing; Yu, Bo

2017-01-01

ABSTRACT The in vivo function of microRNAs (miRs) in diabetic retinopathy (DR) and age-related macular degeneration (AMD) remains unclear. We report here that let-7 family members are expressed in retinal and choroidal endothelial cells (ECs). In ECs, overexpression of let-7 by adenovirus represses EC proliferation, migration, and networking in vitro, whereas inhibition of the let-7 family with a locked nucleic acid (LNA)–anti-miR has the opposite effect. Mechanistically, silencing of the let-7 target HMGA2 gene mimics the phenotype of let-7 overexpression in ECs. let-7 transgenic (let-7-Tg) mice show features of nonproliferative DR, including tortuous retinal vessels and defective pericyte coverage. However, these mice develop significantly less choroidal neovascularization (CNV) compared to wild-type controls after laser injury. Consistently, silencing of let-7 in the eye increased laser-induced CNV in wild-type mice. Together, our data establish a causative role of let-7 in nonproliferative diabetic retinopathy and a repressive function of let-7 in pathological angiogenesis, suggesting distinct implications of let-7 in the pathogenesis of DR and AMD. PMID:28584193

Short-range correlation in high-momentum antisymmetrized molecular dynamics

NASA Astrophysics Data System (ADS)

Myo, Takayuki

2018-03-01

We propose a new variational method for treating short-range repulsion of bare nuclear force for nuclei in antisymmetrized molecular dynamics (AMD). In AMD, the short-range correlation is described in terms of large imaginary centroids of Gaussian wave packets of nucleon pairs in opposite signs, causing high-momentum components in the nucleon pairs. We superpose these AMD basis states and call this method "high-momentum AMD" (HM-AMD), which is capable of describing the strong tensor correlation [T. Myo et al., Prog. Theor. Exp. Phys., 2017, 111D01 (2017)]. In this letter, we extend HM-AMD by including up to two kinds of nucleon pairs in each AMD basis state utilizing the cluster expansion, which produces many-body correlations involving high-momentum components. We investigate how well HM-AMD describes the short-range correlation by showing the results for ^3H using the Argonne V4^' central potential. It is found that HM-AMD reproduces the results of few-body calculations and also the tensor-optimized AMD. This means that HM-AMD is a powerful approach to describe the short-range correlation in nuclei. In HM-AMD, the momentum directions of nucleon pairs isotropically contribute to the short-range correlation, which is different from the tensor correlation.

Interferon gamma-inducible protein-10 (IP-10) and eotaxin as biomarkers in age-related macular degeneration.

PubMed

Mo, Fong Ming; Proia, Alan D; Johnson, Walter H; Cyr, Desiree; Lashkari, Kameran

2010-08-01

To analyze serum cytokine levels in subjects with different stages of AMD and to study the expression of salient cytokines in postmortem eyes with AMD. A suspension array system was used to analyze sera (n = 18 to 20/group) from control subjects and those with early AMD (AREDS stage 1), intermediate dry AMD (AREDS stage 3), advanced AMD with geographic atrophy (GA), or neovascular AMD (CNV). Postmortem eyes with AMD or control eyes were examined immunohistochemically for expression of IP-10 and eotaxin (n = 4 to 8/group). Serum eotaxin and IP-10 levels were significantly elevated in all stages of AMD, except for eotaxin levels in neovascular AMD (P < 0.07). The peak of serum IP-10 concentration was at intermediate dry AMD. In donor eyes, IP-10 and eotaxin expressions were increased in the RPE of eyes with early AMD, GA, and CNV. Eotaxin accumulated within the layer of basal linear/laminar deposits in all stages of AMD, while IP-10 was mainly in eyes with GA and CNV. IP-10 was abundant in the connective tissue matrix associated with CNV, and eotaxin was usually present but more focally and with less intense staining. Both IP-10 and eotaxin were expressed by neovascular endothelial cells. Both IP-10 and eotaxin were expressed in the neurosensory retina, but there was no detectable difference in staining between eyes with or without AMD. IP-10 and eotaxin may be early biomarkers in AMD. The authors hypothesize that the relative balance between levels of IP-10 and eotaxin is critical in regulating the neovascular response.

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

PubMed

Rowan, Sheldon; Taylor, Allen

2018-03-21

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

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

PubMed

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.

On the impact of different approaches to classify age-related macular degeneration: Results from the German AugUR study.

PubMed

Brandl, Caroline; Zimmermann, Martina E; Günther, Felix; Barth, Teresa; Olden, Matthias; Schelter, Sabine C; Kronenberg, Florian; Loss, Julika; Küchenhoff, Helmut; Helbig, Horst; Weber, Bernhard H F; Stark, Klaus J; Heid, Iris M

2018-06-06

While age-related macular degeneration (AMD) poses an important personal and public health burden, comparing epidemiological studies on AMD is hampered by differing approaches to classify AMD. In our AugUR study survey, recruiting residents from in/around Regensburg, Germany, aged 70+, we analyzed the AMD status derived from color fundus images applying two different classification systems. Based on 1,040 participants with gradable fundus images for at least one eye, we show that including individuals with only one gradable eye (n = 155) underestimates AMD prevalence and we provide a correction procedure. Bias-corrected and standardized to the Bavarian population, late AMD prevalence is 7.3% (95% confidence interval = [5.4; 9.4]). We find substantially different prevalence estimates for "early/intermediate AMD" depending on the classification system: 45.3% (95%-CI = [41.8; 48.7]) applying the Clinical Classification (early/intermediate AMD) or 17.1% (95%-CI = [14.6; 19.7]) applying the Three Continent AMD Consortium Severity Scale (mild/moderate/severe early AMD). We thus provide a first effort to grade AMD in a complete study with different classification systems, a first approach for bias-correction from individuals with only one gradable eye, and the first AMD prevalence estimates from a German elderly population. Our results underscore substantial differences for early/intermediate AMD prevalence estimates between classification systems and an urgent need for harmonization.

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

PubMed

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.

Methods and Devices for Micro-Isolation, Extraction, and/or Analysis of Microscale Components

NASA Technical Reports Server (NTRS)

Wade, Lawrence A. (Inventor); Kartalov, Emil P. (Inventor); Taylor, Clive (Inventor); Shibata, Darryl (Inventor)

2014-01-01

Provided herein are devices and methods for the micro-isolation of biological cellular material. A micro-isolation apparatus described can comprise a photomask that protects regions of interest against DNA-destroying illumination. The micro-isolation apparatus can further comprise photosensitive material defining access wells following illumination and subsequent developing of the photosensitive material. The micro-isolation apparatus can further comprise a chambered microfluidic device comprising channels providing access to wells defined in photosensitive material. The micro-isolation apparatus can comprise a chambered microfluidic device without access wells defined in photosensitive material where valves control the flow of gases or liquids through the channels of the microfluidic device. Also included are methods for selectively isolating cellular material using the apparatuses described herein, as are methods for biochemical analysis of individual regions of interest of cellular material using the devices described herein. Further included are methods of making masking arrays useful for the methods described herein.

Interfacing 3D micro/nanochannels with a branch-shaped reservoir enhances fluid and mass transport

NASA Astrophysics Data System (ADS)

Kumar, Prasoon; Gandhi, Prasanna S.; Majumder, Mainak

2017-01-01

Three-dimensional (3D) micro/nanofluidic devices can accelerate progress in numerous fields such as tissue engineering, drug delivery, self-healing and cooling devices. However, efficient connections between networks of micro/nanochannels and external fluidic ports are key to successful applications of 3D micro/nanofluidic devices. Therefore, in this work, the extent of the role of reservoir geometry in interfacing with vascular (micro/nanochannel) networks, and in the enabling of connections with external fluidic ports while maintaining the compactness of devices, has been experimentally and theoretically investigated. A statistical modelling suggested that a branch-shaped reservoir demonstrates enhanced interfacing with vascular networks when compared to other regular geometries of reservoirs. Time-lapse dye flow experiments by capillary action through fabricated 3D micro/nanofluidic devices confirmed the connectivity of branch-shaped reservoirs with micro/nanochannel networks in fluidic devices. This demonstrated a ~2.2-fold enhancement of the volumetric flow rate in micro/nanofluidic networks when interfaced to branch-shaped reservoirs over rectangular reservoirs. The enhancement is due to a ~2.8-fold increase in the perimeter of the reservoirs. In addition, the mass transfer experiments exhibited a ~1.7-fold enhancement in solute flux across 3D micro/nanofluidic devices that interfaced with branch-shaped reservoirs when compared to rectangular reservoirs. The fabrication of 3D micro/nanofluidic devices and their efficient interfacing through branch-shaped reservoirs to an external fluidic port can potentially enable their use in complex applications, in which enhanced surface-to-volume interactions are desirable.

Influence of ROBO1 and RORA on risk of age-related macular degeneration reveals genetically distinct phenotypes in disease pathophysiology.

PubMed

Jun, Gyungah; Nicolaou, Michael; Morrison, Margaux A; Buros, Jacqueline; Morgan, Denise J; Radeke, Monte J; Yonekawa, Yoshihiro; Tsironi, Evangelia E; Kotoula, Maria G; Zacharaki, Fani; Mollema, Nissa; Yuan, Yang; Miller, Joan W; Haider, Neena B; Hageman, Gregory S; Kim, Ivana K; Schaumberg, Debra A; Farrer, Lindsay A; DeAngelis, Margaret M

2011-01-01

ROBO1 is a strong candidate gene for age-related macular degeneration (AMD) based upon its location under a linkage peak on chromosome 3p12, its expression pattern, and its purported function in a pathway that includes RORA, a gene previously associated with risk for neovascular AMD. Previously, we observed that expression of ROBO1 and RORA is down-regulated among wet AMD cases, as compared to their unaffected siblings. Thus, we hypothesized that contribution of association signals in ROBO1, and interaction between these two genes may be important for both wet and dry AMD. We evaluated association of 19 single nucleotide polymorphisms (SNPs) in ROBO1 with wet and dry stages of AMD in a sibling cohort and a Greek case-control cohort containing 491 wet AMD cases, 174 dry AMD cases and 411 controls. Association signals and interaction results were replicated in an independent prospective cohort (1070 controls, 164 wet AMD cases, 293 dry AMD cases). The most significantly associated ROBO1 SNPs were rs1387665 under an additive model (meta P = 0.028) for wet AMD and rs9309833 under a recessive model (meta P = 6 × 10(-4)) for dry AMD. Further analyses revealed interaction between ROBO1 rs9309833 and RORA rs8034864 for both wet and dry AMD (interaction P<0.05). These studies were further supported by whole transcriptome expression profile studies from 66 human donor eyes and chromatin immunoprecipitation assays from mouse retinas. These findings suggest that distinct ROBO1 variants may influence the risk of wet and dry AMD, and the effects of ROBO1 on AMD risk may be modulated by RORA variants.

Vitreoretinal interface changes in geographic atrophy.

PubMed

Abdillahi, Hannan; Enzmann, Volker; Wittwer, Valéry V; Wolf, Sebastian; Wolf-Schnurrbusch, Ute E K

2014-09-01

Geographic atrophy (GA) is the end-stage manifestation of atrophic age-related macular degeneration (AMD). The disease progresses slowly over time, eventually causing loss of central vision. Its cause and pathomechanism are not fully known. Previous studies have suggested that vitreoretinal traction (VRT) may contribute to the progression of neovascular AMD. The aim of this study was to examine whether an association between changes at the vitreoretinal interface (VRI), in particular traction (VRT), and the characteristics and progression of GA in eyes with dry AMD can be established. Clinic-based prospective cohort study. A total of 97 patients (age range, 61-90 years; mean, 78.4 years) with GA secondary to dry AMD were enrolled. Patients exhibiting neovascular signs on fluorescein angiography in either eye were excluded. The VRI changes were examined using spectral-domain optical coherence tomography (SD-OCT). Characteristics of GA were examined using fundus autofluorescence (FAF) imaging. All imaging was performed using a Spectralis SLO+OCT device (Heidelberg Engineering, Heidelberg, Germany); GA area was measured using the Region Finder (Heidelberg Engineering) software native to the Spectralis platform. Area and increase in area of GA. A total of 97 eyes were examined. Vitreoretinal traction was found in 39 eyes (40%). The GA area at baseline was 6.65±5.64 mm(2) in eyes with VRT and 5.73±4.72 mm(2) in eyes with no VRT. The annual rate of progression of GA area progression was 2.99±0.66 mm(2) in eyes with VRT and 1.45±0.67mm(2) in eyes without VRT. Differences between groups in both parameters were statistically significant (n = 97 total number of eyes; P<0.001). Multiple regression analysis confirmed this finding (B = 0.714, P<0.001; F3,93 = 72.542, P<0.001; adjusted R(2) = 0.691) CONCLUSIONS: Our results indicate an association between VRT and an increased rate of progression of GA area in dry AMD. Monitoring VRT may contribute to an improved estimate of the prospective time of visual loss and to a better timing of emerging therapies in dry AMD. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Genetic factors of age-related macular degeneration

PubMed Central

Tuo, Jingsheng; Bojanowski, Christine M.; Chan, Chi-Chao

2007-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness in the United States and developed countries. Although the etiology and pathogenesis of AMD remain unknown, a complex interaction of genetic and environmental factors is thought to exist. The incidence and progression of all of the features of AMD are known to increase significantly with age. The tendency for familial aggregation and the findings of gene variation association studies implicate a significant genetic component in the development of AMD. This review summarizes in detail the AMD-related genes identified by studies on genetically engineered and spontaneously gene-mutated (naturally mutated) animals, AMD chromosomal loci identified by linkage studies, AMD-related genes identified through studies of monogenic degenerative retinal diseases, and AMD-related gene variation identified by association studies. PMID:15094132

Polymorphisms in ARMS2/HTRA1 and Complement Genes and Age-Related Macular Degeneration in India: Findings from the INDEYE Study

PubMed Central

Sundaresan, Periasamy; Vashist, Praveen; Ravindran, Ravilla D.; Shanker, Ashwini; Nitsch, Dorothea; Nonyane, Bareng A. S.; Smeeth, Liam; Chakravarthy, Usha; Fletcher, Astrid E.

2012-01-01

Purpose. Association between genetic variants in complement factor H (CFH), factor B (CFB), component 2 (C2), and in the ARMS2/HTRA1 region with age-related macular degeneration (AMD) comes mainly from studies of European ancestry and case-control studies of late-stage disease. We investigated associations of both early and late AMD with these variants in a population-based study of people aged 60 years and older in India. Methods. Fundus images were graded using the Wisconsin Age-Related Maculopathy Grading System and participants assigned to one of four mutually exclusive stages based on the worse affected eye (0 = no AMD, 1–3 = early AMD, 4 = late AMD). Multinomial logistic regression was used to derive risk ratios (RR) accounting for sampling method and adjusting for age, sex, and study center. Results. Of 3569 participants, 53.2% had no signs of AMD, 45.6% had features of early AMD, and 1.2% had late AMD. CFH (rs1061170), C2 (rs547154), or CFB (rs438999) was not associated with early or late AMD. In the ARMS2 locus, rs10490924 was associated with both early (adjusted RR 1.22, 95% confidence interval [CI]: 1.13–1.33, P < 0.0001) and late AMD (adjusted RR 1.81, 95% CI: 1.15–2.86; P = 0.01); rs2672598 was associated only with early AMD (adjusted RR 1.12, 95% CI: 1.02–1.23; P = 0.02); rs10490923 was not associated with early or late AMD. Conclusions. Two variants in ARMS2/HTRA1 were associated with increased risk of early AMD, and for one of these, the increased risk was also evident for late AMD. The study provides new insights into the role of these variants in early stages of AMD in India. PMID:23060141

Homocysteine and risk of age-related macular degeneration: a systematic review and meta-analysis.

PubMed

Pinna, Antonio; Zaccheddu, Francesco; Boscia, Francesco; Carru, Ciriaco; Solinas, Giuliana

2018-05-01

There is still no agreement on total plasma homocysteine (tHcy) role in age-related macular degeneration (AMD), the leading cause of new blindness in industrialized countries. We performed a systematic review and meta-analysis of the published data on the correlation between tHcy and AMD. MEDLINE/PubMed and ISI Web of Sciences searches were performed according to MOOSE guidelines. Case-control studies were eligible for inclusion. Participants and controls were AMD patients and subjects without AMD. The main outcome measure was wet AMD. Homocysteine level was the main exposure variable. Data were pooled using a random-effects model. Twelve case-control studies were identified: 10 assessed wet AMD, four dry AMD, one early AMD, one late AMD, and one any AMD. As for wet AMD, there was a total of 453 cases and 514 controls. Mean tHcy was on average 1.1 μmol/l (95% confidence interval [CI] = 0.96-1.25) greater in wet AMD cases, but there was evidence of extreme between-study heterogeneity (p < 0.001, I 2  = 91.8%). In a model homogenous for age, including six wet AMD studies (214 cases, 274 controls), mean tHcy was on average 0.58 μmol/l (95% CI = 0.35-0.73) greater in the case group, a not statistically significant result (p = 0.144) associated with moderate heterogeneity (I 2  = 39.2%). Our meta-analysis indicates that there is some weak evidence that increased tHcy might be associated with wet AMD; however, this result should be interpreted cautiously, because of a marked between-study heterogeneity and the possible effect of publication bias. Future studies, preferably of cohort design, are necessary before any firm conclusions on the putative role of increased tHcy on AMD can be drawn. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage.

PubMed

Nashine, Sonali; Cohen, Pinchas; Chwa, Marilyn; Lu, Stephanie; Nesburn, Anthony B; Kuppermann, Baruch D; Kenney, M Cristina

2017-07-20

Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated. In this study, we characterized mitochondrial and cellular damage in transmitochondrial cybrid cell lines that contain identical nuclei but possess mitochondria from either AMD or age-matched normal (Older-normal (NL)) subjects. AMD cybrids showed (1) reduced levels of cell viability, lower mtDNA copy numbers, and downregulation of mitochondrial replication/transcription genes and antioxidant enzyme genes; and (2) elevated levels of genes related to apoptosis, autophagy and ER-stress along with increased mtDNA fragmentation and higher susceptibility to amyloid-β-induced toxicity compared to NL cybrids. In AMD cybrids, HNG protected the AMD mitochondria, reduced pro-apoptosis gene and protein levels, upregulated gp130 (a component of the HN receptor complex), and increased the protection against amyloid-β-induced damage. In summary, in cybrids, damaged AMD mitochondria mediate cell death that can be reversed by HNG treatment. Our results also provide evidence of Humanin playing a pivotal role in protecting cells with AMD mitochondria. In the future, it may be possible that AMD patient's blood samples containing damaged mitochondria may be useful as biomarkers for this condition. In conclusion, HNG may be a potential therapeutic target for treatment of dry AMD, a debilitating eye disease that currently has no available treatment. Further studies are needed to establish HNG as a viable mitochondria-targeting therapy for dry AMD.

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

PubMed Central

Zamora-Alvarado, Ruben; Gulias-Cañizo, Rosario; Quiroz-Mercado, Hugo

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. PMID:29484106

Prospective study of plasma homocysteine level and risk of age-related macular degeneration in women.

PubMed

Christen, William G; Cook, Nancy R; Ridker, Paul M; Buring, Julie E

2015-04-01

Prospective data to examine the association of homocysteine with age-related macular degeneration (AMD) are limited. We examined the prospective relation of plasma homocysteine level and AMD in a large cohort of apparently healthy women. We evaluated the relationship between baseline levels of plasma homocysteine and incident AMD among 27,479 female health professionals aged 40 years or older. Main outcome measures were total AMD, defined as self-report documented by medical record evidence of an initial diagnosis after randomization, and visually significant AMD, defined as confirmed incident AMD with visual acuity 20/30 or worse attributable to this condition. During an average 10 years of follow-up, a total of 452 cases of AMD, including 182 cases of visually significant AMD, were documented. Women in the highest versus lowest quartile of plasma homocysteine had modestly, but statistically non-significant, increased risks of total AMD (hazard ratio, HR, 1.24, 95% confidence interval, CI, 0.95-1.63; p for trend 0.07) and visually significant AMD (HR 1.41, 95% CI 0.92-2.17; p for trend 0.052) in age- and treatment-adjusted analyses. These prospective data from a large cohort of apparently healthy women do not support a strong role for homocysteine in AMD occurrence.

Investigation of optical information for a single micro grating device combined with MATA by SMart process

NASA Astrophysics Data System (ADS)

Tsai, Chien-Chung; Huang, Yi-Chao; Yang, Tsa-Hsien; Chen, Jen-Chieh

2006-01-01

The concentric circles type and saw-tooth type of micro grating device based upon the diffraction theory are proposed in this study. The geometry dimension of micro optical device is 200 × 200 μm2, the interval of grating is 4 μm, and the depth is 0.75 μm. The Micro Array Thermal Actuator, MATA, is applied to drive the micro grating device, and the pre-elevating structure is designed to lift the micro grating device by the residual stress of polysilicon combined with metal. The micro grating device is fabricated by Surface Micromachining for applications and research technology platform, SMart, common process. The incident ray of He-Ne laser focused by a lens which focal length is 250 mm is applied to be the light source for the experiment, and then analyzes the optical information of the outgoing ray. From the experimental results, the basic optical features are examined based upon the concentric circles type and saw-tooth type of micro grating device, respectively. The outgoing ray angle of central spot is 60° in theory. The measurements are 59.475° for the concentric circles type and 59.88° for the saw-tooth type. The outgoing ray angle of the first stripe is 46.9° in theory, and 46.81° for the concentric circles type and 46.67° for the saw-tooth type are measured from the experiment. The variation of outgoing ray angle is smaller than 1% compared the measurement results with theory of diffraction on the central spot and first stripe characteristics. The work successfully demonstrates the micro grating device with highly accurate performance by the verification of optical information. All of the efforts will be contributed to Controlled Blazed Diffraction micro grating device, CBDMG, and that will be the main device of Integrate Opto-Electronics applied on display to develop in the future.

ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration.

PubMed

Wang, Jie; Zibetti, Cristina; Shang, Peng; Sripathi, Srinivasa R; Zhang, Pingwu; Cano, Marisol; Hoang, Thanh; Xia, Shuli; Ji, Hongkai; Merbs, Shannath L; Zack, Donald J; Handa, James T; Sinha, Debasish; Blackshaw, Seth; Qian, Jiang

2018-04-10

Age-related macular degeneration (AMD) is a significant cause of vision loss in the elderly. The extent to which epigenetic changes regulate AMD progression is unclear. Here we globally profile chromatin accessibility using ATAC-Seq in the retina and retinal pigmented epithelium (RPE) from AMD and control patients. Global decreases in chromatin accessibility occur in the RPE with early AMD, and in the retina of advanced disease, suggesting that dysfunction in the RPE drives disease onset. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs). Genes associated with DARs show altered expression in AMD. Cigarette smoke treatment of RPE cells recapitulates chromatin accessibility changes seen in AMD, providing an epigenetic link between a known risk factor for AMD and AMD pathology. Finally, overexpression of HDAC11 is partially responsible for the observed reduction in chromatin accessibility, suggesting that HDAC11 may be a potential new therapeutic target for AMD.

Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks

PubMed Central

2012-01-01

Background Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes. Methods RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort. Results We identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be involved in AMD pathogenesis. Conclusions We discovered new global biomarkers and gene expression signatures of AMD. These results are consistent with a model whereby cell-based inflammatory responses represent a central feature of AMD etiology, and depending on genetics, environment, or stochastic factors, may give rise to the advanced AMD phenotypes characterized by angiogenesis and/or cell death. Genes regulating these immunological activities, along with numerous other genes identified here, represent promising new targets for AMD-directed therapeutics and diagnostics. Please see related commentary: http://www.biomedcentral.com/1741-7015/10/21/abstract PMID:22364233

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

PubMed

Schick, Tina; Ersoy, Lebriz; Lechanteur, Yara T E; Saksens, Nicole T M; Hoyng, Carel B; den Hollander, Anneke I; Kirchhof, Bernd; Fauser, Sascha

2016-04-01

To evaluate effects of current and past sunlight exposure and iris color on early and late age-related macular degeneration (AMD). 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 about current and past sunlight exposure, former occupation type, subdivided in indoor working and outdoor working, and iris color were obtained by standardized interviewer-assisted questionnaires. Associations between environmental factors adjusted for age, gender, and smoking and early and late AMD were performed by multivariate regression analysis. Current sunlight exposure showed no association with early AMD or late AMD, but past sunlight exposure (≥8 hours outside daily) was significantly associated with early AMD (odds ratio: 5.54, 95% confidence interval 1.25-24.58, P = 0.02) and late AMD (odds ratio: 2.77, 95% confidence interval 1.25-6.16, P = 0.01). Outside working was found to be associated with late AMD (odds ratio: 2.57, 95% confidence interval 1.89-3.48, P = 1.58 × 10). No association was observed between iris color and early or late AMD. Sunlight exposure during working life is an important risk factor for AMD, whereas sunlight exposure after retirement seems to have less influence on the disease development. Therefore, preventive measures, for example, wearing sunglasses to minimize sunlight exposure, should start early to prevent development of AMD later in life.

Automatic age-related macular degeneration detection and staging

NASA Astrophysics Data System (ADS)

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

2013-03-01

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

Micro devices using shape memory polymer patches for mated connections

DOEpatents

Lee, Abraham P.; Fitch, Joseph P.

2000-01-01

A method and micro device for repositioning or retrieving miniature devices located in inaccessible areas, such as medical devices (e.g., stents, embolic coils, etc.) located in a blood vessel. The micro repositioning or retrieving device and method uses shape memory polymer (SMP) patches formed into mating geometries (e.g., a hoop and a hook) for re-attachment of the deposited medical device to a catheter or guidewire. For example, SMP or other material hoops are formed on the medical device to be deposited in a blood vessel, and SMP hooks are formed on the micro device attached to a guidewire, whereby the hooks on the micro device attach to the hoops on the medical device, or vice versa, enabling deposition, movement, re-deposit, or retrieval of the medical device. By changing the temperature of the SMP hooks, the hooks can be attached to or released from the hoops located on the medical device. An exemplary method for forming the hooks and hoops involves depositing a sacrificial thin film on a substrate, patterning and processing the thin film to form openings therethrough, depositing or bonding SMP materials in the openings so as to be attached to the substrate, and removing the sacrificial thin film.

Genetic association study of Age-Related Macular Degeneration in the Spanish population

PubMed Central

Brión, María; Sanchez-Salorio, Manuel; Cortón, Marta; de la Fuente, Maria; Pazos, Belen; Othman, Mohammad; Swaroop, Anand; Abecasis, Goncalo; Sobrino, Beatriz; Carracedo, Angel

2017-01-01

Purpose To investigate new genetic risk factors and replicate reported associations with advanced age related macular degeneration (AMD) in a prospective case - control study developed with a Spanish cohort. Methods Three hundred and fifty-three unrelated patients with advanced AMD (225 with atrophic AMD, 57 with neovascular AMD, and 71 with mixed AMD) and 282 age-matched controls were included. Functional and tagging SNPs in 55 candidate genes were genotyped using the SNPlex™ genotyping system. Single SNP and haplotype association analysis were performed to determine possible genetic associations; interaction effects between SNPs were also investigated. Results In agreement with previous reports, ARMS2 and CFH genes were strongly associated with AMD in the studied Spanish population. Moreover, both loci influenced risk independently giving support to different pathways implicated in AMD pathogenesis. No evidence for association of advanced AMD with other previous reported susceptibility genes, such as CST3, CX3CR1, FBLN5, HMCN1, PON1, SOD2, TLR4, VEGF and VLDLR, was detected. However, two additional genes appear to be candidate markers for the development of advanced AMD. A variant located at the 3´UTR of the FGF2 gene (rs6820411) was highly associated with atrophic AMD, and the functional SNP rs3112831 at ABCA4 showed a marginal association with the disease. Conclusion We performed a large gene association study in advanced AMD in a Spanish population. Our findings show that CFH and ARMS2 genes seem to be the principal risk loci contributing independently to AMD in our cohort. We report new significant associations that could also influence the development of advanced AMD. These findings should be confirmed in further studies with larger cohorts. PMID:21106043

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

PubMed

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.

FOUR-YEAR INCIDENCE AND PROGRESSION OF AGE-RELATED MACULAR DEGENERATION: THE LOS ANGELES LATINO EYE STUDY

PubMed Central

Varma, Rohit; Foong, Athena W.P.; Lai, Mei-Ying; Choudhury, Farzana; Klein, Ronald; Azen, Stanley P.

2011-01-01

Purpose To estimate 4-year incidence and progression of early and advanced age-related macular degeneration (AMD). Design Population-based cohort study. Methods A comprehensive ophthalmologic examination including stereoscopic fundus photography was performed on adult Latinos at baseline and follow-up. Photographs were graded using a modified Wisconsin Age-Related Maculopathy Grading System. For estimations of incidence and progression of AMD, the Age Related Eye Disease Study Scale was used. Main outcome measures are incidence and progression of early AMD (drusen type, drusen size, and retinal pigmentary abnormalities) and advanced AMD (exudative AMD and geographic atrophy). Results 4,658/6100 (76%) completed the follow-up examination. The 4-year incidence of early AMD was 7.5% (95%CI:6.6,8.4) and advanced AMD was 0.2% (95%CI:0.1,0.4). Progression of any AMD occurred in 9.3% (95%CI:8.4,10.3) of at-risk participants. Incidence and progression increased with age. Incidence of early AMD in the second eye (10.8%) was higher than incidence in the first eye (6.9%). Baseline presence of soft indistinct large drusen≥250μm in diameter was more likely to predict the 4-year incidence of pigmentary abnormalities, geographic atrophy, and exudative AMD than smaller or hard or soft distinct drusen. Conclusions Age-specific incidence and progression of AMD in Latinos are lower than in non-Hispanic whites. While incident early AMD is more often unilateral, the risk of its development in the second is higher than in the first eye. Older persons and those with soft indistinct large drusen had a higher risk of developing advanced AMD compared to those who were younger and did not have soft indistinct large drusen. PMID:20399926

Harmonizing the Classification of Age-related Macular Degeneration in the Three Continent AMD Consortium

PubMed Central

Klein, Ronald; Meuer, Stacy M.; Myers, Chelsea E.; Buitendijk, Gabriëlle H. S.; Rochtchina, Elena; Choudhury, Farzana; de Jong, Paulus T. V. M.; McKean-Cowdin, Roberta; Iyengar, Sudha K.; Gao, Xiaoyi; Lee, Kristine E.; Vingerling, Johannes R.; Mitchell, Paul; Klaver, Caroline C. W.; Wang, Jie Jin; Klein, Barbara E. K.

2014-01-01

Purpose To describe methods to harmonize the classification of age-related macular degeneration (AMD) phenotypes across four population-based cohort studies: the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES), Los Angeles Latino Eye Study (LALES), and Rotterdam Study (RS). Methods AMD grading protocols, definitions of categories, and grading forms from each study were compared to determine whether there were systematic differences in AMD severity definitions and lesion categorization among the three grading centers. Each center graded the same set of 60 images using their respective systems to determine presence and severity of AMD lesions. A common five-step AMD severity scale and definitions of lesion measurement cutpoints and early and late AMD were developed from this exercise. Results Applying this severity scale changed the age-sex adjusted prevalence of early AMD from 18.7% to 20.3% in BDES, from 4.7% to 14.4% in BMES, from 14.1% to 15.8% in LALES, and from 7.5% to 17.1% in RS. Age-sex adjusted prevalences of late AMD remained unchanged. Comparison of each center’s grades of the 60 images converted to the consortium scale showed that exact agreement of AMD severity among centers varied from 61.0% to 81.4%, and one-step agreement varied from 84.7% to 98.3%. Conclusion Harmonization of AMD classification reduced categorical differences in phenotypic definitions across the studies, resulted in a new 5-step AMD severity scale, and enhanced similarity of AMD prevalence among four cohorts. Despite harmonization it may still be difficult to remove systematic differences in grading, if present. PMID:24467558

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

PubMed Central

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

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

PubMed

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.

A front-end wafer-level microsystem packaging technique with micro-cap array

NASA Astrophysics Data System (ADS)

Chiang, Yuh-Min

2002-09-01

The back-end packaging process is the remaining challenge for the micromachining industry to commercialize microsystem technology (MST) devices at low cost. This dissertation presents a novel wafer level protection technique as a final step of the front-end fabrication process for MSTs. It facilitates improved manufacturing throughput and automation in package assembly, wafer level testing of devices, and enhanced device performance. The method involves the use of a wafer-sized micro-cap array, which consists of an assortment of small caps micro-molded onto a material with adjustable shapes and sizes to serve as protective structures against the hostile environments during packaging. The micro-cap array is first constructed by a micromachining process with micro-molding technique, then sealed to the device wafer at wafer level. Epoxy-based wafer-level micro cap array has been successfully fabricated and showed good compatibility with conventional back-end packaging processes. An adhesive transfer technique was demonstrated to seal the micro cap array with a MEMS device wafer. No damage or gross leak was observed while wafer dicing or later during a gross leak test. Applications of the micro cap array are demonstrated on MEMS, microactuators fabricated using CRONOS MUMPS process. Depending on the application needs, the micro-molded cap can be designed and modified to facilitate additional component functions, such as optical, electrical, mechanical, and chemical functions, which are not easily achieved in the device by traditional means. Successful fabrication of a micro cap array comprised with microlenses can provide active functions as well as passive protection. An optical tweezer array could be one possibility for applications of a micro cap with microlenses. The micro cap itself could serve as micro well for DNA or bacteria amplification as well.

Development and Validation of a Risk Score for Age-Related Macular Degeneration: The STARS Questionnaire.

PubMed

Delcourt, Cécile; Souied, Eric; Sanchez, Alice; Bandello, Francesco

2017-12-01

To develop and validate a risk score for AMD based on a simple self-administered questionnaire. Risk factors having shown the most consistent associations with AMD were included in the STARS (Simplified Théa AMD Risk-Assessment Scale) questionnaire. Two studies were conducted, one in Italy (127 participating ophthalmologists) and one in France (80 participating ophthalmologists). During 1 week, participating ophthalmologists invited all their patients aged 55 years or older to fill in the STARS questionnaire. Based on fundus examination, early AMD was defined by the presence of soft drusen and/or pigmentary abnormalities and late AMD by the presence of geographic atrophy and/or neovascular AMD. The Italian and French samples consisted of 12,639 and 6897 patients, respectively. All 13 risk factors included in the STARS questionnaire showed significant associations with AMD in the Italian sample. The area under the receiving operating characteristic curve for the STARS risk score, derived from the multivariate logistic regression in the Italian sample, was 0.78 in the Italian sample and 0.72 in the French sample. In both samples, less than 10% of patients without AMD were classified at high risk, and less than 13% of late AMD cases were classified as low risk, with a more intermediate situation in early AMD cases. STARS is a new, simple self-assessed questionnaire showing good discrimination of risk for AMD in two large European samples. It might be used by ophthalmologists in routine clinical practice or as a self-assessment for risk of AMD in the general population.

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

PubMed

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.

Prevalence, racial variations, and risk factors of age-related macular degeneration in Singaporean Chinese, Indians, and Malays.

PubMed

Cheung, Chui Ming Gemmy; Li, Xiang; Cheng, Ching-Yu; Zheng, Yingfeng; Mitchell, Paul; Wang, Jie Jin; Wong, Tien Yin

2014-08-01

To describe the prevalence and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons. Population-based cross-sectional study. A total of 10 033 persons (3280 Malay, 3400 Indian, and 3353 Chinese; response rate, 75%) 40 years of age or older residing in Singapore. We performed comprehensive systemic and ocular examinations, retinal photography, and laboratory investigations for all participants. We graded early and late AMD signs from retinal photographs using the modified Wisconsin AMD grading scale. We calculated the age-standardized prevalence of AMD using the 2010 Singapore adult population and analyzed risk factors for AMD using logistic regression models. Early and late AMD. Of the 9799 participants with gradable photographs, 588 had early AMD and 60 had late AMD. The age-standardized prevalence was 5.1% (95% confidence interval [CI], 4.6-5.5) for early AMD and 0.5% (95% CI, 0.4-0.6) for late AMD. The prevalence of early AMD was similar between Chinese (5.7%) and Indian (4.5%; P = 0.27) persons and lower in Malays (3.5%; P = 0.002 compared with Chinese; P = 0.09 compared with Indians); in contrast, the prevalence for late AMD was similar across ethnic groups (Chinese, 0.6%; Indian, 0.3%; and Malay, 0.3%; P = 0.20). Risk factors for early AMD were older age (odds ratio [OR], 1.40 per 5-year increase in age; 95% CI, 1.33-1.47), male gender (OR, 1.81; 95% CI, 1.43-2.29), hypertension (OR, 1.28; 95% CI, 1.02-1.61), and hyperopic refraction (OR, 1.17 per 1-diopter increase in spherical equivalent; 95% CI, 1.11-1.24). Risk factors for late AMD include older age (OR, 1.87 per 5-year increase in age; 95% CI, 1.54-2.19), smoking more than 5 packs per week (OR, 3.63; 95% CI, 1.34-9.80), and presence of chronic kidney disease (OR, 2.17; 95% CI, 1.22-3.88). Early AMD is more common in Chinese and Indians than in Malays, but there were no racial variations in the prevalence of late AMD. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Role of diet and food intake in age-related macular degeneration: a systematic review.

PubMed

Chapman, Naoko A; Jacobs, Robert J; Braakhuis, Andrea J

2018-06-21

A systematic literature review was conducted to evaluate the role of diet and food intake in age-related macular degeneration (AMD). Eighteen high-quality studies were identified. Adherence to a Mediterranean diet had decreased risk of AMD progression. An Oriental diet pattern had decreased association with AMD prevalence, whereas a Western diet pattern had increased association with AMD prevalence. High consumption of vegetables rich in carotenoids, and fatty fish containing omega-3 fatty acids was beneficial for those at risk of AMD. Vegetable oils and animal fats containing omega-6 fatty acids, and red/processed meat should be consumed minimally to reduce the risk of AMD progression. High glycaemic index diets and alcohol consumption of greater than two drinks a day had increased association with AMD. As the quality of diet and food intake had a vital role in AMD, the provision of appropriate nutritional advice to those at risk of AMD is recommended. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Micro lens design for efficiency improvement of red organic light-emitting diode

NASA Astrophysics Data System (ADS)

Ki, Hyun-Chul; Kim, Doo-Gun; Kim, Seon-Hoon; Jung, U.-Ra; Kim, Sang-Gi; Hong, Kyung-Jin

2012-11-01

We have proposed a micro lens to improve the luminance of red organic light-emitting devices (ROLEDs). The micro lenses were applied on the glass/indium tin oxide (ITO)/OLED. The size, thickness and diameter of micro lenses were calculated by using FDTD (finite-difference timedomain) method. Simulations were performed for 5 µm and 10 µm sized. The thickness and the gap of the micro lens were both 1 µm. The material of the micro lenses was silicon dioxide. The highest luminance of an OLED applied with a micro lens was 11,185 cd/m2, at on approval voltage of 14.5 V, The efficiency of the device with a micro lens increased by 3 times compared to that of the device with no micro lens.

Inferring diagnosis and trajectory of wet age-related macular degeneration from OCT imagery of retina

NASA Astrophysics Data System (ADS)

Irvine, John M.; Ghadar, Nastaran; Duncan, Steve; Floyd, David; O'Dowd, David; Lin, Kristie; Chang, Tom

2017-03-01

Quantitative biomarkers for assessing the presence, severity, and progression of age-related macular degeneration (AMD) would benefit research, diagnosis, and treatment. This paper explores development of quantitative biomarkers derived from OCT imagery of the retina. OCT images for approximately 75 patients with Wet AMD, Dry AMD, and no AMD (healthy eyes) were analyzed to identify image features indicative of the patients' conditions. OCT image features provide a statistical characterization of the retina. Healthy eyes exhibit a layered structure, whereas chaotic patterns indicate the deterioration associated with AMD. Our approach uses wavelet and Frangi filtering, combined with statistical features that do not rely on image segmentation, to assess patient conditions. Classification analysis indicates clear separability of Wet AMD from other conditions, including Dry AMD and healthy retinas. The probability of correct classification of was 95.7%, as determined from cross validation. Similar classification analysis predicts the response of Wet AMD patients to treatment, as measured by the Best Corrected Visual Acuity (BCVA). A statistical model predicts BCVA from the imagery features with R2 = 0.846. Initial analysis of OCT imagery indicates that imagery-derived features can provide useful biomarkers for characterization and quantification of AMD: Accurate assessment of Wet AMD compared to other conditions; image-based prediction of outcome for Wet AMD treatment; and features derived from the OCT imagery accurately predict BCVA; unlike many methods in the literature, our techniques do not rely on segmentation of the OCT image. Next steps include larger scale testing and validation.

Plasma Protein Pentosidine and Carboxymethyllysine, Biomarkers for Age-related Macular Degeneration*

PubMed Central

Ni, Jiaqian; Yuan, Xianglin; Gu, Jiayin; Yue, Xiuzhen; Gu, Xiaorong; Nagaraj, Ram H.; Crabb, John W.

2009-01-01

Age-related macular degeneration (AMD) causes severe vision loss in the elderly; early identification of AMD risk could help slow or prevent disease progression. Toward the discovery of AMD biomarkers, we quantified plasma protein Nε-carboxymethyllysine (CML) and pentosidine from 58 AMD and 32 control donors. CML and pentosidine are advanced glycation end products that are abundant in Bruch membrane, the extracellular matrix separating the retinal pigment epithelium from the blood-bearing choriocapillaris. We measured CML and pentosidine by LC-MS/MS and LC-fluorometry, respectively, and found higher mean levels of CML (∼54%) and pentosidine (∼64%) in AMD (p < 0.0001) relative to normal controls. Plasma protein fructosyl-lysine, a marker of early glycation, was found by amino acid analysis to be in equal amounts in control and non-diabetic AMD donors, supporting an association between AMD and increased levels of CML and pentosidine independent of other diseases like diabetes. Carboxyethylpyrrole (CEP), an oxidative modification from docosahexaenoate-containing lipids and also abundant in AMD Bruch membrane, was elevated ∼86% in the AMD cohort, but autoantibody titers to CEP, CML, and pentosidine were not significantly increased. Compellingly higher mean levels of CML and pentosidine were present in AMD plasma protein over a broad age range. Receiver operating curves indicate that CML, CEP adducts, and pentosidine alone discriminated between AMD and control subjects with 78, 79, and 88% accuracy, respectively, whereas CML in combination with pentosidine provided ∼89% accuracy, and CEP plus pentosidine provided ∼92% accuracy. Pentosidine levels appeared slightly altered in AMD patients with hypertension and cardiovascular disease, indicating further studies are warranted. Overall this study supports the potential utility of plasma protein CML and pentosidine as biomarkers for assessing AMD risk and susceptibility, particularly in combination with CEP adducts and with concurrent analyses of fructosyl-lysine to detect confounding factors. PMID:19435712

Autophagy regulating kinases as potential therapeutic targets for age-related macular degeneration.

PubMed

Kaarniranta, Kai; Kauppinen, Anu; Blasiak, Janusz; Salminen, Antero

2012-11-01

Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly in the developed countries. The number of AMD patients will double during the next decades due to increasing number of aged people. Chronic oxidative stress, inflammation and accumulation of protein-rich deposits both in the retinal pigment epithelium lysosomes and under the retinal pigment epithelium herald the onset of AMD. The disease can be divided into dry and wet AMD forms. The dry form of the disease is more prevalent accounting for up to 90% of all cases. Continued intraocular injections are the current treatment strategy to prevent progression of wet AMD. It is a major challenge to develop new drugs that could prevent or at least ease the symptoms of the increasing population of AMD patients. Since AMD pathology is clearly associated with accumulated protein deposits, the autophagy clearance system might represent a potential future therapeutic target for AMD as is thoroughly discussed here.

Spatio-temporal variation of anthropogenic marine debris on Chilean beaches.

PubMed

Hidalgo-Ruz, Valeria; Honorato-Zimmer, Daniela; Gatta-Rosemary, Magdalena; Nuñez, Paloma; Hinojosa, Iván A; Thiel, Martin

2018-01-01

We examined the hypothesis that in an emerging economy such as Chile the abundances of Anthropogenic Marine Debris (AMD) on beaches are increasing over time. The citizen science program Científicos de la Basura ("Litter Scientists") conducted three national surveys (2008, 2012 and 2016) to determine AMD composition, abundance, spatial patterns and temporal trends. AMD was found on all beaches along the entire Chilean coast. Highest percentages of AMD in all surveys were plastics and cigarette butts, which can be attributed to local sources (i.e. beach users). The Antofagasta region in northern Chile had the highest abundance of AMD compared with all other zones. Higher abundances of AMD were found at the upper stations from almost all zones. No significant tendency of increasing or decreasing AMD densities was observed during the 8years covered by our study, which suggests that economic development alone cannot explain temporal trends in AMD densities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Do statins have a role in the prevention of age-related macular degeneration?

PubMed

Tsao, Sean W; Fong, Donald S

2013-04-01

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide for which preventative therapies are few. Evidence suggesting shared common risk factors and mirrored pathophysiology between cardiovascular disease and AMD led to the hypothesis that hydroxymethylglutaryl-CoA reductase inhibitors (statins) could be helpful in preventing AMD. For over a decade, observational studies have repeatedly investigated this hypothesis with conflicting conclusions. Although many reports conclude that statin use has no effect on the risk of AMD, no randomized controlled trial has yet been completed. Furthermore, relatively few studies factor characteristics of statin use into their analysis. A few studies have observed an incompletely explained protective effect against drusen, a funduscopic finding associated with AMD. Although there is insufficient evidence for a preventive effect of statins on dry AMD, there does seem to be stronger evidence against any effect on the development of exudative AMD. Overall, we find that there is insufficient evidence to conclude whether statin use is helpful in preventing AMD.

Manufacture of micro fluidic devices by laser welding using thermal transfer printing techniques

NASA Astrophysics Data System (ADS)

Klein, R.; Klein, K. F.; Tobisch, T.; Thoelken, D.; Belz, M.

2016-03-01

Micro-fluidic devices are widely used today in the areas of medical diagnostics and drug research, as well as for applications within the process, electronics and chemical industry. Microliters of fluids or single cell to cell interactions can be conveniently analyzed with such devices using fluorescence imaging, phase contrast microscopy or spectroscopic techniques. Typical micro-fluidic devices consist of a thermoplastic base component with chambers and channels covered by a hermetic fluid and gas tight sealed lid component. Both components are usually from the same or similar thermoplastic material. Different mechanical, adhesive or thermal joining processes can be used to assemble base component and lid. Today, laser beam welding shows the potential to become a novel manufacturing opportunity for midsize and large scale production of micro-fluidic devices resulting in excellent processing quality by localized heat input and low thermal stress to the device during processing. For laser welding, optical absorption of the resin and laser wavelength has to be matched for proper joining. This paper will focus on a new approach to prepare micro-fluidic channels in such devices using a thermal transfer printing process, where an optical absorbing layer absorbs the laser energy. Advantages of this process will be discussed in combination with laser welding of optical transparent micro-fluidic devices.

Clinical classification of age-related macular degeneration.

PubMed

Ferris, Frederick L; Wilkinson, C P; Bird, Alan; Chakravarthy, Usha; Chew, Emily; Csaky, Karl; Sadda, SriniVas R

2013-04-01

To develop a clinical classification system for age-related macular degeneration (AMD). Evidence-based investigation, using a modified Delphi process. Twenty-six AMD experts, 1 neuro-ophthalmologist, 2 committee chairmen, and 1 methodologist. Each committee member completed an online assessment of statements summarizing current AMD classification criteria, indicating agreement or disagreement with each statement on a 9-step scale. The group met, reviewed the survey results, discussed the important components of a clinical classification system, and defined new data analyses needed to refine a classification system. After the meeting, additional data analyses from large studies were provided to the committee to provide risk estimates related to the presence of various AMD lesions. Delphi review of the 9-item set of statements resulting from the meeting. Consensus was achieved in generating a basic clinical classification system based on fundus lesions assessed within 2 disc diameters of the fovea in persons older than 55 years. The committee agreed that a single term, age-related macular degeneration, should be used for the disease. Persons with no visible drusen or pigmentary abnormalities should be considered to have no signs of AMD. Persons with small drusen (<63 μm), also termed drupelets, should be considered to have normal aging changes with no clinically relevant increased risk of late AMD developing. Persons with medium drusen (≥ 63-<125 μm), but without pigmentary abnormalities thought to be related to AMD, should be considered to have early AMD. Persons with large drusen or with pigmentary abnormalities associated with at least medium drusen should be considered to have intermediate AMD. Persons with lesions associated with neovascular AMD or geographic atrophy should be considered to have late AMD. Five-year risks of progressing to late AMD are estimated to increase approximately 100 fold, ranging from a 0.5% 5-year risk for normal aging changes to a 50% risk for the highest intermediate AMD risk group. The proposed basic clinical classification scale seems to be of value in predicting the risk of late AMD. Incorporating consistent nomenclature into the practice patterns of all eye care providers may improve communication and patient care. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

S Gilchrist; A Gates; E Elzinga

The abandoned Phillips sulfide mine in the critical Highlands watershed in New York has been shown to produce strongly acidic mine drainage (AMD) with anomalous metal contaminants in first-order streams that exceeded local water standards by up to several orders of magnitude (Gilchrist et al., 2009). The metal-sulfide-rich tailings also produce contaminated soils with pH < 4, organic matter < 2.5% and trace metals sequestered in soil oxides. A geochemical transect to test worst-case soil contamination showed that Cr, Co and Ni correlated positively with Mn, (r = 0.72, r = 0.89, r = 0.80, respectively), suggesting Mn-oxide sequestration andmore » that Cu and Pb correlated with Fe (r = 0.76, r = 0.83, respectively), suggesting sequestration in goethite. Ubiquitous, yellow coating on the mine wastes, including jarosite and goethite, is a carrier of the metals. Geochemical and {mu}-SXRF analyses determined Cu to be the major soil contaminant, {mu}-SXRF also demonstrated that the heterogeneous nature of the soil chemistry at the micro-meter scale is self-similar to those in the bulk soil samples. Generally metals decreased, with some fluctuations, rapidly downslope through suspension of fines and dissolution in AMD leaving the area of substantial contamination << 0.5 km from the source.« less

Micro-Organ Device

NASA Technical Reports Server (NTRS)

Sun, Wei (Inventor); Chang, Robert C. (Inventor); Starly, Binil (Inventor); Holtorf, Heidi L. (Inventor); Leslie, Julia (Inventor); Culbertson, Christopher (Inventor); Gonda, Steve R. (Inventor)

2013-01-01

A method for fabricating a micro-organ device comprises providing a microscale support having one or more microfluidic channels and one or more micro-chambers for housing a micro-organ and printing a micro-organ on the microscale support using a cell suspension in a syringe controlled by a computer-aided tissue engineering system, wherein the cell suspension comprises cells suspended in a solution containing a material that functions as a three-dimensional scaffold. The printing is performed with the computer-aided tissue engineering system according to a particular pattern. The micro-organ device comprises at least one micro-chamber each housing a micro-organ; and at least one microfluidic channel connected to the micro-chamber, wherein the micro-organ comprises cells arranged in a configuration that includes microscale spacing between portions of the cells to facilitate diffusion exchange between the cells and a medium supplied from the at least one microfluidic channel.

Micro-organ device

NASA Technical Reports Server (NTRS)

von Gustedt-Gonda, legal representative, Iris (Inventor); Holtorf, Heidi L. (Inventor); Gonda, Steve R. (Inventor); Leslie, Julia (Inventor); Chang, Robert C. (Inventor); Sun, Wei (Inventor); Starly, Binil (Inventor); Culbertson, Christopher (Inventor)

2013-01-01

A method for fabricating a micro-organ device comprises providing a microscale support having one or more microfluidic channels and one or more micro-chambers for housing a micro-organ and printing a micro-organ on the microscale support using a cell suspension in a syringe controlled by a computer-aided tissue engineering system, wherein the cell suspension comprises cells suspended in a solution containing a material that functions as a three-dimensional scaffold. The printing is performed with the computer-aided tissue engineering system according to a particular pattern. The micro-organ device comprises at least one micro-chamber each housing a micro-organ; and at least one microfluidic channel connected to the micro-chamber, wherein the micro-organ comprises cells arranged in a configuration that includes microscale spacing between portions of the cells to facilitate diffusion exchange between the cells and a medium supplied from the at least one microfluidic channel.

Micro-supercapacitors from carbide derived carbon (CDC) films on silicon chips

NASA Astrophysics Data System (ADS)

Huang, Peihua; Heon, Min; Pech, David; Brunet, Magali; Taberna, Pierre-Louis; Gogotsi, Yury; Lofland, Samuel; Hettinger, Jeffrey D.; Simon, Patrice

2013-03-01

Interdigitated on-chip micro-supercapacitors based on Carbide Derived Carbon (CDC) films were fabricated and tested. A titanium carbide (TiC) film was patterned and treated with chlorine to obtain a TiC derived carbon (TiC-CDC) film, followed by the deposition of two types of current collectors (Ti/Au and Al) using standard micro-fabrication processes. CDC based micro-supercapacitors were electrochemically characterized by cyclic voltammetry and impedance spectroscopy using a 1 M tetraethylammonium tetrafluoroborate, NEt4BF4, in propylene carbonate (PC) electrolyte. A capacitance of 0.78 mF for the device and 1.5 mF cm-2 as the specific capacitance for the footprint of the device was measured for a 2 V potential range at 100 mV s-1. A specific energy of 3.0 mJ cm-2 and a specific power of 84 mW cm-2 were calculated for the devices. These devices provide a pathway for fabricating pure carbon-based micro-supercapacitors by micro-fabrication, and can be used for powering micro-electromechanical systems (MEMS) and electronic devices.

Detection of viability of micro-algae cells by optofluidic hologram pattern.

PubMed

Wang, Junsheng; Yu, Xiaomei; Wang, Yanjuan; Pan, Xinxiang; Li, Dongqing

2018-03-01

A rapid detection of micro-algae activity is critical for analysis of ship ballast water. A new method for detecting micro-algae activity based on lens-free optofluidic holographic imaging is presented in this paper. A compact lens-free optofluidic holographic imaging device was developed. This device is mainly composed of a light source, a small through-hole, a light propagation module, a microfluidic chip, and an image acquisition and processing module. The excited light from the light source passes through a small hole to reach the surface of the micro-algae cells in the microfluidic chip, and a holographic image is formed by the diffraction light of surface of micro-algae cells. The relation between the characteristics in the hologram pattern and the activity of micro-algae cells was investigated by using this device. The characteristics of the hologram pattern were extracted to represent the activity of micro-algae cells. To demonstrate the accuracy of the presented method and device, four species of micro-algae cells were employed as the test samples and the comparison experiments between the alive and dead cells of four species of micro-algae were conducted. The results show that the developed method and device can determine live/dead microalgae cells accurately.

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

PubMed

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

2017-12-01

Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Meta-analysis of prevalence data. A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Prevalence of early and late AMD, BCVA, and number of AMD cases. Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%-5.0%) in those aged 55-59 years to 17.6% (95% CI 13.6%-21.5%) in those aged ≥85 years; for late AMD these figures were 0.1% (95% CI 0.04%-0.3%) and 9.8% (95% CI 6.3%-13.3%), respectively. We observed a decreasing prevalence of late AMD after 2006, which became most prominent after age 70. Prevalences were similar for gender across all age groups except for late AMD in the oldest age category, and a trend was found showing a higher prevalence of CNV in Northern Europe. After 2006, fewer eyes and fewer ≥80-year-old subjects with CNV were visually impaired (P = 0.016). Projections of AMD showed an almost doubling of affected persons despite a decreasing prevalence. By 2040, the number of individuals in Europe with early AMD will range between 14.9 and 21.5 million, and for late AMD between 3.9 and 4.8 million. We observed a decreasing prevalence of AMD and an improvement in visual acuity in CNV occuring over the past 2 decades in Europe. Healthier lifestyles and implementation of anti-vascular endothelial growth factor treatment are the most likely explanations. Nevertheless, the numbers of affected subjects will increase considerably in the next 2 decades. AMD continues to remain a significant public health problem among Europeans. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Age-related macular degeneration: economic burden and value-based medicine analysis.

PubMed

Brown, Melissa M; Brown, Gary C; Stein, Joshua D; Roth, Zachary; Campanella, Joseph; Beauchamp, George R

2005-06-01

It can be estimated that 17,100 new cases of neovascular (wet) AMD and 180,000 new cases of geographic-atrophy (dry) AMD occur in Canada annually. In addition to having a devastating effect on patients' lives, the condition causes significant adverse consequences for the economy. The deleterious effect of AMD on quality of life is markedly underestimated by ophthalmologists who treat patients with AMD, by non-ophthalmic physicians and by the public. In fact, patients with different degrees of severity of AMD have a perceived impairment of their quality of life that is 96% to 750% greater than the impairment estimated by treating ophthalmologists. Mild AMD causes a 17% decrease in the quality of life of the average patient, a decrease similar to that encountered with symptomatic human immunodeficiency virus infection or moderate cardiac angina. Moderate AMD produces a 40% decrease in quality of life, a decrease similar to that associated with permanent renal dialysis or severe cardiac angina. Very severe AMD causes a 63% decrement in quality of life, a decrease similar to that encountered with advanced prostatic cancer with uncontrollable pain or a severe stroke that leaves a person bedridden, incontinent and requiring constant nursing care. The adverse economic consequences of AMD include an annual $2.6 billion negative impact on Canada's gross domestic product. The return on investment is high for both current AMD therapies and research into new treatment modalities.

Prevalence of Undiagnosed Age-Related Macular Degeneration in Primary Eye Care.

PubMed

Neely, David C; Bray, Kevin J; Huisingh, Carrie E; Clark, Mark E; McGwin, Gerald; Owsley, Cynthia

2017-06-01

Age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment in older adults in the United States, yet little is known about whether AMD is appropriately diagnosed in primary eye care. To examine the prevalence of eyes with AMD in patients seen in primary eye care clinics who purportedly have normal macular health per their medical record and the association of AMD with patient and physician characteristics. In this cross-sectional study of primary eye care practices in Birmingham, Alabama, 644 persons 60 years or older with normal macular health per medical record based on their most recent dilated comprehensive eye examination by a primary eye care ophthalmologist or optometrist were enrolled from May 1, 2009, through December 31, 2011. Data analysis was performed from May 1, 2016, through December 20, 2016. Presence of AMD as defined by the Clinical Age-Related Maculopathy Staging system based on color fundus photography and a masked grader. Types of AMD-associated lesions were noted. Patient health and physician characteristics were collected. The sample consisted of 1288 eyes from 644 participants (231 [35.9%] male and 413 [64.1%] female; mean [SD] age, 69.4 [6.1] years; 611 white [94.9%]) seen by 31 primary eye care ophthalmologists or optometrists. A total of 968 eyes (75.2%) had no AMD, in agreement with their medical record; 320 (24.8%) had AMD despite no diagnosis of AMD in the medical record. Among eyes with undiagnosed AMD, 32 (10.0%) had hyperpigmentation, 43 (13.4%) had hypopigmentation, 249 (77.8%) had small drusen, 250 (78.1%) had intermediate drusen, and 96 (30.0%) had large drusen. Undiagnosed AMD was associated with older patient age (odds ratio [OR], 1.06; 95% CI, 1.04-1.09; P < .001), male sex (age-adjusted OR, 1.39; 95% CI, 1.02-1.91; P = .04), and less than a high school education (age-adjusted OR, 2.40; 95% CI, 1.03-5.62; P = .04). Prevalence of undiagnosed AMD was not different for ophthalmologists and optometrists (age adjusted OR, 0.99; 95% CI, 0.71-1.36; P = .94). Approximately 25.0% of eyes deemed to be normal based on dilated eye examination by primary eye care physicians had macular characteristics that indicated AMD revealed by fundus photography and trained raters. A total of 30.0% of eyes with undiagnosed AMD had AMD with large drusen that would have been treatable with nutritional supplements had it been diagnosed. Improved AMD detection strategies may be needed in primary eye care as more effective treatment strategies for early AMD become available in the coming years.

Development and Evaluation of Micro-Electrocorticography Arrays for Neural Interfacing Applications

NASA Astrophysics Data System (ADS)

Schendel, Amelia Ann

Neural interfaces have great promise for both electrophysiological research and therapeutic applications. Whether for the study of neural circuitry or for neural prosthetic or other therapeutic applications, micro-electrocorticography (micro-ECoG) arrays have proven extremely useful as neural interfacing devices. These devices strike a balance between invasiveness and signal resolution, an important step towards eventual human application. The objective of this research was to make design improvements to micro-ECoG devices to enhance both biocompatibility and device functionality. To best evaluate the effectiveness of these improvements, a cranial window imaging method for in vivo monitoring of the longitudinal tissue response post device implant was developed. Employment of this method provided valuable insight into the way tissue grows around micro-ECoG arrays after epidural implantation, spurring a study of the effects of substrate geometry on the meningeal tissue response. The results of the substrate footprint comparison suggest that a more open substrate geometry provides an easy path for the tissue to grow around to the top side of the device, whereas a solid device substrate encourages the tissue to thicken beneath the device, between the electrode sites and the brain. The formation of thick scar tissue between the recording electrode sites and the neural tissue is disadvantageous for long-term recorded signal quality, and thus future micro-ECoG device designs should incorporate open-architecture substrates for enhanced longitudinal in vivo function. In addition to investigating improvements for long-term device reliability, it was also desired to enhance the functionality of micro-ECoG devices for neural electrophysiology research applications. To achieve this goal, a completely transparent graphene-based device was fabricated for use with the cranial window imaging method and optogenetic techniques. The use of graphene as the conductive material provided the transparency necessary to image tissues directly below the micro-ECoG electrode sites, and to transmit light through the electrode sites to underlying neural tissue, for optical stimulation of neural cells. The flexibility and broad-spectrum transparency of graphene make it an ideal choice for thin-film, flexible electronic devices.

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

PubMed

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.

Window-assisted nanosphere lithography for vacuum micro-nano-electronics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Nannan; Institute of Electronic Engineering, Chinese Academy of Engineering Physics, Mianyang, 621900; Pang, Shucai

2015-04-15

Development of vacuum micro-nano-electronics is quite important for combining the advantages of vacuum tubes and solid-state devices but limited by the prevailing fabricating techniques which are expensive, time consuming and low-throughput. In this work, window-assisted nanosphere lithography (NSL) technique was proposed and enabled the low-cost and high-efficiency fabrication of nanostructures for vacuum micro-nano-electronic devices, thus allowing potential applications in many areas. As a demonstration, we fabricated high-density field emitter arrays which can be used as cold cathodes in vacuum micro-nano-electronic devices by using the window-assisted NSL technique. The details of the fabricating process have been investigated. This work provided amore » new and feasible idea for fabricating nanostructure arrays for vacuum micro-nano-electronic devices, which would spawn the development of vacuum micro-nano-electronics.« less

Identification of pathogenic genes and upstream regulators in age-related macular degeneration.

PubMed

Zhao, Bin; Wang, Mengya; Xu, Jing; Li, Min; Yu, Yuhui

2017-06-26

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in older individuals. Our study aims to identify the key genes and upstream regulators in AMD. To screen pathogenic genes of AMD, an integrated analysis was performed by using the microarray datasets in AMD derived from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were further discovered by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We constructed the AMD-specific transcriptional regulatory network to find the crucial transcriptional factors (TFs) which target the DEGs in AMD. Quantitative real time polymerase chain reaction (qRT-PCR) was performed to verify the DEGs and TFs obtained by integrated analysis. From two GEO datasets obtained, we identified 1280 DEGs (730 up-regulated and 550 down-regulated genes) between AMD and normal control (NC). After KEGG analysis, steroid biosynthesis is a significantly enriched pathway for DEGs. The expression of 8 genes (TNC, GRP, TRAF6, ADAMTS5, GPX3, FAP, DHCR7 and FDFT1) was detected. Except for TNC and GPX3, the other 6 genes in qRT-PCR played the same pattern with that in our integrated analysis. The dysregulation of these eight genes may involve with the process of AMD. Two crucial transcription factors (c-rel and myogenin) were concluded to play a role in AMD. Especially, myogenin was associated with AMD by regulating TNC, GRP and FAP. Our finding can contribute to developing new potential biomarkers, revealing the underlying pathogenesis, and further raising new therapeutic targets for AMD.

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

PubMed Central

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

2018-01-01

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 photography and interview with comprehensive questionnaires were conducted at each visit of three studies. AMD was assessed following the modified Wisconsin AMD grading protocol. Progression to bilateral any (early and late) or late AMD was assessed among participants with unilateral involvement only. Factors associated with the progression were assessed using logistic regression models while simultaneously adjusting for other significant risk factors. Results In any 5-year duration, 19–28% of unilateral any AMD cases became bilateral and 27–68% of unilateral late AMD became bilateral. Factors associated with the progression to bilateral involvement of any AMD were age (per year increase, adjusted OR 1.07), carrying risk alleles of the complement factor H and age-related maculopathy susceptibility 2 genes (compared with none, OR 1.76 for 1 risk allele and OR 3.34 for 2+ risk alleles), smoking (compared with non-smokers, OR 1.64 for past and OR 1.67 for current smokers), and the presence of large drusen area or retinal pigmentary abnormalities in the first eye. Conclusion One in four to one in five unilateral any AMD cases, and up to one in two unilateral late AMD cases, progressed to bilateral in 5 years. Known AMD risk factors, including smoking, are significantly associated with the progression to bilateral involvement. PMID:28108569

Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration.

PubMed

Kaarniranta, Kai; Tokarz, Paulina; Koskela, Ali; Paterno, Jussi; Blasiak, Janusz

2017-04-01

Age-related macular degeneration (AMD) is an eye disease underlined by the degradation of retinal pigment epithelium (RPE) cells, photoreceptors, and choriocapillares, but the exact mechanism of cell death in AMD is not completely clear. This mechanism is important for prevention of and therapeutic intervention in AMD, which is a hardly curable disease. Present reports suggest that both apoptosis and pyroptosis (cell death dependent on caspase-1) as well as necroptosis (regulated necrosis dependent on the proteins RIPK3 and MLKL, caspase-independent) can be involved in the AMD-related death of RPE cells. Autophagy, a cellular clearing system, plays an important role in AMD pathogenesis, and this role is closely associated with the activation of the NLRP3 inflammasome, a central event for advanced AMD. Autophagy can play a role in apoptosis, pyroptosis, and necroptosis, but its contribution to AMD-specific cell death is not completely clear. Autophagy can be involved in the regulation of proteins important for cellular antioxidative defense, including Nrf2, which can interact with p62/SQSTM, a protein essential for autophagy. As oxidative stress is implicated in AMD pathogenesis, autophagy can contribute to this disease by deregulation of cellular defense against the stress. However, these and other interactions do not explain the mechanisms of RPE cell death in AMD. In this review, we present basic mechanisms of autophagy and its involvement in AMD pathogenesis and try to show a regulatory role of autophagy in RPE cell death. This can result in considering the genes and proteins of autophagy as molecular targets in AMD prevention and therapy.

21 CFR 862.2170 - Micro chemistry analyzer for clinical use.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Micro chemistry analyzer for clinical use. 862... SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2170 Micro chemistry analyzer for clinical use. (a) Identification. A micro chemistry...

21 CFR 862.2170 - Micro chemistry analyzer for clinical use.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Micro chemistry analyzer for clinical use. 862... SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2170 Micro chemistry analyzer for clinical use. (a) Identification. A micro chemistry...

21 CFR 862.2170 - Micro chemistry analyzer for clinical use.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Micro chemistry analyzer for clinical use. 862... SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2170 Micro chemistry analyzer for clinical use. (a) Identification. A micro chemistry...

21 CFR 862.2170 - Micro chemistry analyzer for clinical use.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Micro chemistry analyzer for clinical use. 862... SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2170 Micro chemistry analyzer for clinical use. (a) Identification. A micro chemistry...

21 CFR 862.2170 - Micro chemistry analyzer for clinical use.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Micro chemistry analyzer for clinical use. 862... SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory Instruments § 862.2170 Micro chemistry analyzer for clinical use. (a) Identification. A micro chemistry...

Alteration of travel patterns with vision loss from glaucoma and macular degeneration.

PubMed

Curriero, Frank C; Pinchoff, Jessie; van Landingham, Suzanne W; Ferrucci, Luigi; Friedman, David S; Ramulu, Pradeep Y

2013-11-01

The distance patients can travel outside the home influences how much of the world they can sample and to what extent they can live independently. Recent technological advances have allowed travel outside the home to be directly measured in patients' real-world routines. To determine whether decreased visual acuity (VA) from age-related macular degeneration (AMD) and visual field (VF) loss from glaucoma are associated with restricted travel patterns in older adults. Cross-sectional study. Patients were recruited from an eye clinic, while travel patterns were recorded during their real-world routines using a cellular tracking device. Sixty-one control subjects with normal vision, 84 subjects with glaucoma with bilateral VF loss, and 65 subjects with AMD with bilateral or severe unilateral loss of VA had their location tracked every 15 minutes between 7 am and 11 pm for 7 days using a tracking device. Average daily excursion size (defined as maximum distance away from home) and average daily excursion span (defined as maximum span of travel) were defined for each individual. The effects of vision loss on travel patterns were evaluated after controlling for individual and geographic factors. In multivariable models comparing subjects with AMD and control subjects, average excursion size and span decreased by approximately one-quarter mile for each line of better-eye VA loss (P ≤ .03 for both). Similar but not statistically significant associations were observed between average daily excursion size and span for severity of better-eye VF loss in subjects with glaucoma and control subjects. Being married or living with someone and younger age were associated with more distant travel, while less-distant travel was noted for older individuals, African Americans, and those living in more densely populated regions. Age-related macular degeneration-related loss of VA, but not glaucoma-related loss of VF, is associated with restriction of travel to more nearby locations. This constriction of life space may impact quality of life and restrict access to services.

Colloidal precipitates related to Acid Mine Drainage: bacterial diversity and micro fungi-heavy metal interactions

NASA Astrophysics Data System (ADS)

Lucchetti, G.; Carbone, C.; Consani, S.; Zotti, M.; Di Piazza, S.; Pozzolini, M.; Giovine, M.

2015-12-01

In Acid Mine Drainage (AMD) settings colloidal precipitates control the mobility of Potential Toxic Elements (PTEs). Mineral-contaminant relationships (i.e. adsorption, ion-exchange, desorption) are rarely pure abiotic processes. Microbes, mainly bacteria and microfungi, can catalyze several reactions modifying the element speciation, as well as the bioavailability of inorganic pollutants. Soil, sediments, and waters heavily polluted with PTEs through AMD processes are a potential reservoir of extremophile bacteria and fungi exploitable for biotechnological purposes. Two different AMD related colloids, an ochraceous precipitate (deposited in weakly acidic conditions, composed by nanocrystalline goethite) and a greenish-blue precipitate (deposited at near-neutral pH, composed by allophane + woodwardite) were sampled. The aims of this work were to a) characterize the mycobiota present in these colloidal minerals by evaluating the presence of alive fungal propagules and extracting bacteria DNA; b) verify the fungal strains tolerance, and bioaccumulation capability on greenish-blue and ZnSO4 enriched media; c) evaluate potential impact of bacteria in the system geochemistry. The preliminary results show an interesting and selected mycobiota able to survive under unfavourable environmental conditions. A significant number of fungal strains were isolated in pure culture. Among them, species belonging to Penicillium and Trichoderma genera were tested on both greenish-blue and ZnSO4 enriched media. The results show a significant tolerance and bioaccumulation capability to some PTEs. The same colloidal precipitates were processed to extract bacteria DNA by using a specific procedure developed for sediments. The results give a good yield of nucleic acids and a positive PCR amplification of 16S rDNA accomplished the first step for future metagenomic analyses.

The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment

PubMed Central

Wang, Y; Wang, V M; Chan, C-C

2011-01-01

Although age-related macular degeneration (AMD) is not a classic inflammatory disease like uveitis, inflammation has been found to have an important role in disease pathogenesis and progression. Innate immunity and autoimmune components, such as complement factors, chemokines, cytokines, macrophages, and ocular microglia, are believed to be heavily involved in AMD development. Targeting these specific inflammatory molecules has recently been explored in an attempt to better understand and treat AMD. Although antivascular endothelial growth factor therapy is the first line of defence against neovascular AMD, anti-inflammatory agents such as corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressive agents (eg, methotrexate and rapamycin), and biologics (eg, infliximab, daclizumab, and complement inhibitors) may provide an adjunct or alternative mechanism to suppress the inflammatory processes driving AMD progression. Further investigation is required to evaluate the long-term safety and efficacy of these drugs for both neovascular and non-neovascular AMD. PMID:21183941

Pseudo 1-D Micro/Nanofluidic Device for Exact Electrokinetic Responses.

PubMed

Kim, Junsuk; Kim, Ho-Young; Lee, Hyomin; Kim, Sung Jae

2016-06-28

Conventionally, a 1-D micro/nanofluidic device, whose nanochannel bridged two microchannels, was widely chosen in the fundamental electrokinetic studies; however, the configuration had intrinsic limitations of the time-consuming and labor intensive tasks of filling and flushing the microchannel due to the high fluidic resistance of the nanochannel bridge. In this work, a pseudo 1-D micro/nanofluidic device incorporating air valves at each microchannel was proposed for mitigating these limitations. High Laplace pressure formed at liquid/air interface inside the microchannels played as a virtual valve only when the electrokinetic operations were conducted. The identical electrokinetic behaviors of the propagation of ion concentration polarization layer and current-voltage responses were obtained in comparison with the conventional 1-D micro/nanofluidic device by both experiments and numerical simulations. Therefore, the suggested pseudo 1-D micro/nanofluidic device owned not only experimental conveniences but also exact electrokinetic responses.

Micro-Scale Regenerative Heat Exchanger

NASA Technical Reports Server (NTRS)

Moran, Matthew E.; Stelter, Stephan; Stelter, Manfred

2004-01-01

A micro-scale regenerative heat exchanger has been designed, optimized and fabricated for use in a micro-Stirling device. Novel design and fabrication techniques enabled the minimization of axial heat conduction losses and pressure drop, while maximizing thermal regenerative performance. The fabricated prototype is comprised of ten separate assembled layers of alternating metal-dielectric composite. Each layer is offset to minimize conduction losses and maximize heat transfer by boundary layer disruption. A grating pattern of 100 micron square non-contiguous flow passages were formed with a nominal 20 micron wall thickness, and an overall assembled ten-layer thickness of 900 microns. Application of the micro heat exchanger is envisioned in the areas of micro-refrigerators/coolers, micropower devices, and micro-fluidic devices.

Cellular models and therapies for age-related macular degeneration

PubMed Central

Forest, David L.; Johnson, Lincoln V.; Clegg, Dennis O.

2015-01-01

ABSTRACT 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. PMID:26035859

The role of omega-3 and micronutrients in age-related macular degeneration.

PubMed

Querques, Giuseppe; Souied, Eric H

2014-01-01

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the United States, Europe, and other developed countries. Although the pathogenesis of AMD remains unclear, current evidence suggests a multifactorial aetiology. Nutrition may play an important role in the development and progression of AMD. There have been several epidemiological studies suggesting that omega-3 fatty acids could have a protective role in AMD, but a beneficial effect remains to be demonstrated in randomized controlled trials. There also exists a substantial body of evidence suggesting that protection against AMD may be provided by specific micronutrients (vitamins and minerals and antioxidants). The identification of risk factors for the development and progression of AMD is of particular importance for understanding the origins of the disorder and for establishing strategies for its prevention. We examine the relationship between dietary omega-3 intake and the incidence and progression of AMD, as well as the role of omega-3 supplementation in the prevention of the disorder, and also explore the role of other micronutrients in AMD. Copyright © 2014 Elsevier Inc. All rights reserved.

C-Reactive Protein as a Therapeutic Target in Age-Related Macular Degeneration.

PubMed

Molins, Blanca; Romero-Vázquez, Sara; Fuentes-Prior, Pablo; Adan, Alfredo; Dick, Andrew D

2018-01-01

Age-related macular degeneration (AMD), a retinal degenerative disease, is the leading cause of central vision loss among the elderly population in developed countries and an increasing global burden. The major risk is aging, compounded by other environmental factors and association with genetic variants for risk of progression. Although the etiology of AMD is not yet clearly understood, several pathogenic pathways have been proposed, including dysfunction of the retinal pigment epithelium, inflammation, and oxidative stress. The identification of AMD susceptibility genes encoding complement factors and the presence of complement and other inflammatory mediators in drusen, the hallmark deposits of AMD, support the concept that local inflammation and immune-mediated processes play a key role in AMD pathogenesis that may be accelerated through systemic immune activation. In this regard, increased levels of circulating C-reactive protein (CRP) have been associated with higher risk of AMD. Besides being a risk marker for AMD, CRP may also play a role in the progression of the disease as it has been identified in drusen, and we have recently found that its monomeric form (mCRP) induces blood retinal barrier disruption in vitro . In this review, we will address recent evidence that links CRP and AMD pathogenesis, which may open new therapeutic opportunities to prevent the progression of AMD.

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

NASA Astrophysics Data System (ADS)

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.

Lack of association of CFD polymorphisms with advanced age-related macular degeneration.

PubMed

Zeng, Jiexi; Chen, Yuhong; Tong, Zongzhong; Zhou, Xinrong; Zhao, Chao; Wang, Kevin; Hughes, Guy; Kasuga, Daniel; Bedell, Matthew; Lee, Clara; Ferreyra, Henry; Kozak, Igor; Haw, Weldon; Guan, Jean; Shaw, Robert; Stevenson, William; Weishaar, Paul D; Nelson, Mark H; Tang, Luosheng; Zhang, Kang

2010-11-03

Age-related macular degeneration (AMD) is the most common cause of irreversible central vision loss worldwide. Research has linked AMD susceptibility with dysregulation of the complement cascade. Typically, complement factor H (CFH), complement factor B (CFB), complement component 2 (C2), and complement component 3 (C3) are associated with AMD. In this paper, we investigated the association between complement factor D (CFD), another factor of the complement system, and advanced AMD in a Caucasian population. Six single nucleotide polymorphisms (SNPs), rs1683564, rs35186399, rs1683563, rs3826945, rs34337649, and rs1651896, across the region covering CFD, were chosen for this study. One hundred and seventy-eight patients with advanced AMD and 161 age-matched normal controls were genotyped. Potential positive signals were further tested in another independent 445 advanced AMD patients and 190 controls. χ2 tests were performed to compare the allele frequencies between case and control groups. None of the six SNPs of CFD was found to be significantly associated with advanced AMD in our study. Our findings suggest that CFD may not play a major role in the genetic susceptibility to AMD because no association was found between the six SNPs analyzed in the CFD region and advanced AMD.

Do nutritional supplements have a role in age macular degeneration prevention?

PubMed

Pinazo-Durán, Maria D; Gómez-Ulla, Francisco; Arias, Luis; Araiz, Javier; Casaroli-Marano, Ricardo; Gallego-Pinazo, Roberto; García-Medina, Jose J; López-Gálvez, Maria Isabel; Manzanas, Lucía; Salas, Anna; Zapata, Miguel; Diaz-Llopis, Manuel; García-Layana, Alfredo

2014-01-01

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

Bmp6 Regulates Retinal Iron Homeostasis and Has Altered Expression in Age-Related Macular Degeneration

PubMed Central

Hadziahmetovic, Majda; Song, Ying; Wolkow, Natalie; Iacovelli, Jared; Kautz, Leon; Roth, Marie-Paule; Dunaief, Joshua L.

2011-01-01

Iron-induced oxidative stress causes hereditary macular degeneration in patients with aceruloplasminemia. Similarly, retinal iron accumulation in age-related macular degeneration (AMD) may exacerbate the disease. The cause of retinal iron accumulation in AMD is poorly understood. Given that bone morphogenetic protein 6 (Bmp6) is a major regulator of systemic iron, we examined the role of Bmp6 in retinal iron regulation and in AMD pathogenesis. Bmp6 was detected in the retinal pigment epithelium (RPE), a major site of pathology in AMD. In cultured RPE cells, Bmp6 was down-regulated by oxidative stress and up-regulated by iron. Intraocular Bmp6 protein injection in mice up-regulated retinal hepcidin, an iron regulatory hormone, and altered retinal labile iron levels. Bmp6−/− mice had age-dependent retinal iron accumulation and degeneration. Postmortem RPE from patients with early AMD exhibited decreased Bmp6 levels. Because oxidative stress is associated with AMD pathogenesis and down-regulates Bmp6 in cultured RPE cells, the diminished Bmp6 levels observed in RPE cells in early AMD may contribute to iron build-up in AMD. This may in turn propagate a vicious cycle of oxidative stress and iron accumulation, exacerbating AMD and other diseases with hereditary or acquired iron excess. PMID:21703414

Education, socio-economic status and age-related macular degeneration in Asians: the Singapore Malay Eye Study.

PubMed

Cackett, P; Tay, W T; Aung, T; Wang, J J; Shankar, A; Saw, S M; Mitchell, P; Wong, T Y

2008-10-01

Low socio-economic status is increasingly being identified as a risk marker for chronic diseases, but few studies have investigated the link between socio-economic factors and age-related macular degeneration (AMD). The present study aimed to assess the association between socio-economic status and the prevalence of AMD. A population-based cross-sectional study of 3280 (78.7% response rate) Malay adults aged 40-80 years residing in 15 south-western districts of Singapore. AMD was graded from retinal photographs at a central reading centre using the modified Wisconsin AMD scale. Early and late AMD signs were graded from retinal photographs following the Wisconsin grading system. Socio-economic status including education, housing type and income were determined from a detailed interview. Of the participants, 3265 had photographs of sufficient quality for grading of AMD. Early AMD was present in 168 (5.1%) and late AMD in 21 (0.6%). After adjusting for age, gender, smoking, hypertension, diabetes and body mass index, participants with lower educational levels were significantly more likely to have early AMD (multivariate OR 2.2, 95% CI 1.2 to 4.0). This association was stronger in persons who had never smoked (multivariate OR 3.6, 95% confidence CI 1.4 to 9.4). However, no association with housing type or income was seen. Low educational level is associated with a higher prevalence of early AMD signs in our Asian population, independent of age, cardiovascular risk factors and cigarette smoking.

Healthy Lifestyles Related to Subsequent Prevalence of Age-Related Macular Degeneration

PubMed Central

Mares, JA; Voland, R.; Sondel, SA; Millen, A.E.; LaRowe, T; Moeller, SM; Klein, M.L.; Blodi, B.A; Chappell, R.; Tinker, L.; Ritenbaugh, C; Gehrs, K; Sarto, G; Johnson, E.J; Snodderly, M; Wallace, RB

2010-01-01

Purpose The relationships between lifestyle behaviors of diet, smoking and physical activity and the subsequent prevalence of age-related macular degeneration (AMD) were investigated. Methods The population included 1,313 participants (55 to 74 years) in the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study (WHIOS). Scores on a modified 2005 Healthy Eating Index (mHEI) were assigned using responses to a food frequency questionnaire administered at WHIOS baseline (1994-1998). Physical activity and lifetime smoking history were queried. An average of six years later, stereoscopic fundus photographs were taken to assess presence and severity of AMD; present in 202 women, 94% of whom had early AMD, the primary outcome. Results In multivariate models, women whose diets scored in the highest compared with the lowest quintile on the mHEI had a 46% lower odds for early AMD. Women in the highest vs. lowest quintile for physical activity (MET- Hrs/Wk) had 54% lower odds for early AMD. Although smoking, alone was not independently associated with AMD, having a combination of three healthy lifestyles (healthy diet, physical activity and not smoking) was associated with a 71% lower odds for AMD compared with having high risk scores (P=0.0004). Conclusions Modifying lifestyles might reduce risk for early AMD as much as 3-fold, lowering the risk for advanced AMD in a person's lifetime and the social and economic costs of AMD to society. PMID:21149749

Prevalence of age-related macular degeneration in rural southern China: the Yangxi Eye Study.

PubMed

Jin, Guangming; Ding, Xiaohu; Xiao, Wei; Xu, Xiao; Wang, Lanhua; Han, Xiaotong; Xiao, Ou; Liu, Ran; Wang, Wei; Yan, William; An, Lei; Zhao, Jialiang; He, Mingguang

2018-05-01

To describe the prevalence of age-related macular degeneration (AMD) among older adults in rural southern mainland China. Eligible persons aged 50 years or over were identified by geographically defined cluster sampling from Yangxi County, Guangdong Province, China. Participants underwent a standardised interview and comprehensive eye examinations from August to November in 2014. Digital retinal photographs were graded for AMD lesions using the Clinical Classification of Age-Related Macular Degeneration developed by the Beckman Initiative for Macular Research Classification Committee. Age-standardised prevalence of AMD and AMD lesions was calculated using the 2010 world population data and compared with those of other populations. Of 5825 subjects who participated (90.7% response rate), 4881 (83.8%) had fundus photographs gradable for AMD. Early, intermediate and late AMD were present in 2003 (41.0%), 879 (18.0%) and 42 (0.86%) participants. The age-standardised prevalence of early, intermediate and late AMD was 40.4% (95% CI 39.6% to 41.2%), 17.6% (95% CI 17.0% to 18.2%) and 0.79% (95% CI 0.65% to 0.95%), respectively. Total AMD was more prevalent in men than in women (62.8% vs 57.1%). AMD is an important public health concern for rural southern China, and the prevalence of AMD was higher in men than in women. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Retinal vascular caliber, iris color, and age-related macular degeneration in the Irish Nun Eye Study.

PubMed

McGowan, Amy; Silvestri, Giuliana; Moore, Evelyn; Silvestri, Vittorio; Patterson, Christopher C; Maxwell, Alexander P; McKay, Gareth J

2014-12-18

To evaluate the relationship between retinal vascular caliber (RVC), iris color, and age-related macular degeneration (AMD) in elderly Irish nuns. Data from 1233 participants in the cross-sectional observational Irish Nun Eye Study were assessed from digital photographs with a standardized protocol using computer-assisted software. Macular images were graded according to the modified Wisconsin Age-related Maculopathy Grading System. Regression models were used to assess associations, adjusting for age, mean arterial blood pressure, body mass index, refraction, and fellow RVC. In total, 1122 (91%) participants had gradable retinal images of sufficient quality for vessel assessment (mean age: 76.3 years [range, 56-100 years]). In an unadjusted analysis, we found some support for a previous finding that individuals with blue iris color had narrower retinal venules compared to those with brown iris color (P < 0.05), but this was no longer significant after adjustment. Age-related macular degeneration status was categorized as no AMD, any AMD, and late AMD only. Individuals with any AMD (early or late AMD) had significantly narrower arterioles and venules compared to those with no AMD in an unadjusted analysis, but this was no longer significant after adjustment. A nonsignificant reduced risk of any AMD or late AMD only was observed in association with brown compared to blue iris color, in both unadjusted and adjusted analyses. Retinal vascular caliber was not significantly associated with iris color or early/late AMD after adjustment for confounders. A lower but nonsignificant AMD risk was observed in those with brown compared to blue iris color. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

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.

PubMed

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 < 0.05; PCV, 0.534 ± 0.618, P < 0.05) and at 5 years (AMD, 0.873 ± 0.718, P < 0.05; PCV, 0.635 ± 0.668, P < 0.05) than at baseline. In eyes with tAMD, absence of blocked fluorescence was associated with 5-year maintenance of the baseline BCVA. Regarding PCV, the presence of polypoidal lesions and cystoid 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.

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

PubMed

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.

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

PubMed

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.

Compacted Sewage Sludge as a Barrier for Tailings: The Heavy Metal Speciation and Total Organic Carbon Content in the Compacted Sludge Specimen

PubMed Central

Zhang, Huyuan; Zhang, Qing; Yang, Bo; Wang, Jinfang

2014-01-01

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. PMID:24979755

Preferential Hyperacuity Perimeter (PreView PHP) for detecting choroidal neovascularization study.

PubMed

Alster, Yair; Bressler, Neil M; Bressler, Susan B; Brimacombe, Judith A; Crompton, R Michael; Duh, Yi-Jing; Gabel, Veit-Peter; Heier, Jeffrey S; Ip, Michael S; Loewenstein, Anat; Packo, Kirk H; Stur, Michael; Toaff, Techiya

2005-10-01

To assess the ability of the Preferential Hyperacuity Perimeter (PreView PHP; Carl Zeiss Meditec, Dublin, CA) to detect recent-onset choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and to differentiate it from an intermediate stage of AMD. Prospective, comparative, concurrent, nonrandomized, multicenter study. Eligible participants' study eyes had a corrected visual acuity of 20/160 or better and either untreated CNV from AMD diagnosed within the last 60 days or an intermediate stage of AMD. After obtaining consent, visual acuity with habitual correction, masked PHP testing, stereoscopic color fundus photography, and fluorescein angiography were performed. Photographs and angiograms were evaluated by graders masked to diagnosis and PHP results. The reading center's diagnosis determined if the patient was categorized as having intermediate AMD or neovascular AMD. A successful study outcome was defined a priori as a sensitivity of at least 80% and a specificity of at least 80%. Of 185 patients who gave consent to be enrolled, 11 (6%) had PHP results judged to be unreliable. An additional 52 were not included because they did not meet all eligibility criteria. Of the remaining 122 patients, 57 had an intermediate stage of AMD and 65 had neovascular AMD. The sensitivity to detect newly diagnosed CNV using PHP testing was 82% (95% confidence interval [CI], 70%-90%). The specificity to differentiate newly diagnosed CNV from the intermediate stage of AMD using PHP testing was 88% (95% CI, 76%-95%). Preferential Hyperacuity Perimeter testing can detect recent-onset CNV resulting from AMD and can differentiate it from an intermediate stage of AMD with high sensitivity and specificity. These data suggest that monitoring with PHP should detect most cases of CNV of recent onset with few false-positive results at a stage when treatment usually would be beneficial. Thus, this monitoring should be considered in the management of the intermediate stage of AMD.

C-Reactive Protein and the Incidence of Macular Degeneration – Pooled Analysis of 5 Cohorts

PubMed Central

Mitta, Vinod P.; Christen, William G.; Glynn, Robert J.; Semba, Richard D.; Ridker, Paul M.; Rimm, Eric B.; Hankinson, Susan E.; Schaumberg, Debra A.

2013-01-01

Objectives To investigate the relationship between high-sensitivity C-reactive protein (hsCRP) and future risk of age-related macular degeneration (AMD) in US men and women. Methods We measured hsCRP in baseline blood samples from participants in five ongoing cohort studies. Patients were initially free of AMD. We prospectively identified 647 incident cases of AMD and selected age- and sex-matched controls for each AMD case (2 controls for each case with dry AMD, or 3 controls for each case of neovascular AMD). We used conditional logistic regression models to examine the relationship between hsCRP and AMD, and pooled findings using meta-analytic techniques. Results After adjusting for cigarette smoking status, participants with high (> 3 mg/L) compared with low (< 1 mg/L) hsCRP levels, had cohort-specific odds ratios (OR) for incident AMD ranging from 0.94 (95% CI 0.58-1.51) in the Physicians’ Health Study to 2.59 (95% CI 0.58-11.67) in the Women’s Antioxidant and Folic Acid Cardiovascular Study. After testing for heterogeneity between studies (Q=5.61, p=0.23), we pooled findings across cohorts, and observed a significantly increased risk of incident AMD for high versus low hsCRP levels (OR=1.49, 95% CI 1.06-2.08). Risk of neovascular AMD was also increased among those with high hsCRP levels (OR=1.84, 95% CI 1.14-2.98). Conclusion Overall these pooled findings from 5 prospective cohorts add further evidence that elevated levels of hsCRP predict greater future risk of AMD. This information might shed light on underlying mechanisms, and could be of clinical utility in the identification of persons at high risk of AMD who may benefit from increased adherence to lifestyle recommendations, eye examination schedules, and therapeutic protocols. PMID:23392454

The effect of non-neovascular age-related macular degeneration on face recognition performance.

PubMed

Taylor, Deanna J; Smith, Nicholas D; Binns, Alison M; Crabb, David P

2018-04-01

There is a well-established research base surrounding face recognition in patients with age-related macular degeneration (AMD). However, much of this existing research does not differentiate between results obtained for 'wet' AMD and 'dry' AMD. Here, we test the hypothesis that face recognition performance is worse in patients with dry AMD compared with visually healthy peers. Patients (>60 years of age, logMAR binocular visual acuity 0.7 or better) with dry AMD of varying severity and visually healthy age-related peers (controls) completed a modified version of the Cambridge Face Memory Test (CFMT). Percentage of correctly identified faces was used as an outcome measure for performance for each participant. A 90% normative reference limit was generated from the distribution of CFMT scores recorded in the visually healthy controls. Scores for AMD participants were then specifically compared to this limit, and comparisons between average scores in the AMD severity groups were investigated. Thirty patients (median [interquartile range] age of 76 [70, 79] years) and 34 controls (median age of 70 [64, 75] years) were examined. Four, seventeen and nine patients were classified as having early, intermediate and late AMD (geographic atrophy) respectively. Five (17%) patients recorded a face recognition performance worse than the 90% limit (Fisher's exact test, p = 0.46) set by controls; four of these had geographic atrophy. Patients with geographic atrophy identified fewer faces on average (±SD) (61% ± 22%) than those with early and intermediate AMD (75 ± 11%) and controls (74% ± 11%). People with dry AMD may not suffer from problems with face recognition until the disease is in its later stages; those with late AMD (geographic atrophy) are likely to have difficulty recognising faces. The results from this study should influence the management and expectations of patients with dry AMD in both community practice and hospital clinics.

Fabrication of a co-culture micro-bioreactor device for efficient hepatic differentiation of human induced pluripotent stem cells (hiPSCs).

PubMed

Kehtari, Mousa; Zeynali, Bahman; Soleimani, Masoud; Kabiri, Mahboubeh; Seyedjafari, Ehsan

2018-04-27

Primary hepatocytes, as the gold standard cell type for in vitro models, lose their characteristic morphology and functions after few days. There is an urgent need to develop physiologically relevant models that recapitulate liver microenvironment to obtain mature hepatocyte from stem cells. We designed and fabricated a micro-bioreactor device mimicking the physiological shear stress and cell-cell interaction in liver sinusoid microenvironment. Induced pluripotent stem cells (iPSCs) were co-cultured with human umbilical vein endothelial cells (HUVECs) in the micro-bioreactor device with continuous perfusion of hepatic differentiation medium (100 μL/h). Simulation results showed that flow field inside our perfusion device was uniform and shear stress was adjusted to physiological condition (<2 dyne/cm 2 ). IPSCs-derived hepatocytes (iPSCs-Heps) that were cultured in micro-bioreactor device showed a higher level of hepatic markers compared to those in static condition. Flow cytometry and immunocytochemistry analysis revealed iPSCs cultured in the device sequentially acquired characteristics of definitive endodermal cells (SOX17 positive), hepatoblasts (AFP positive) and mature hepatocyte (ALB positive). Moreover, the albumin and urea secretion were significantly higher in micro-bioreactor device than those cultured in culture dishes during experiment. Thus, based on our results, we propose our micro-bioreactor as a beneficial device to generate mature hepatocytes for drug screening and basic research.

Fate of Acrylamide in Soil and Groundwater Systems: Microbial Degradation

NASA Astrophysics Data System (ADS)

Labahn, S.; Moser, D.; Arrowood, T.; Young, M.; Robleto, E.

2007-12-01

Acrylamide monomer (AMD), a suspected human neurotoxin and carcinogen, is present as a contaminant (up to 0.05%) in commercial preparations of polyacrylamide (PAM). PAM is currently being evaluated for wide-spread use as a temporary water-delivery canal sealant across the western United States. To better constrain potential risks associated with PAM applications, we examined the capacity of natural canal microorganisms to degrade AMD in laboratory and field experiments. Dilution cultivation and enrichment approaches were employed to determine the abundance of culturable microorganisms in several canal habitats which can utilize AMD as a sole nitrogen source (typically 104-106/mL) and a collection of isolates was developed. AMD-degrading microorganisms in our collection fell within a limited diversity of genera including Arthrobacter, Xanthomonas, and Pseudomonas; with the latter demonstrating highest capacity for degrading AMD under laboratory conditions. One strain of Pseudomonas fluorescens, isolated from Klamath Irrigation District (Klamath Falls, OR) canal sediment, was chosen for further study in part because this species is well-studied and ubiquitous. The potential for microbial AMD degradation was tested under laboratory conditions using this strain in repacked short (15 cm) column tests with two relevant soil types (sand and loam). Subsequently, the capacity of mixed natural microbial populations to degrade AMD was examined using soil cores collected from the Highline Canal (Rocky Ford, CO), and canal water/sediment slurries with spiked (5 ppm AMD) in situ bottle tests. Degradation of the monomer in the repacked column experiments was evaluated using a step input of 5 ppm AMD and the canal columns were tested with a range of AMD concentrations (1-5 ppm) followed by quantification with an HPLC. The repacked soil columns inoculated with P. fluorescens demonstrated 80-100% AMD degradation within 12 hours. Natural microbial communities in fresh canal sediment columns produced varying levels of AMD degradation, ranging from 40-50% after 36 hours. The in situ bottle test resulted in 50% degradation after 72 hours. Experimental AMD degradation rates and transport parameters, such as sorption and retardation, were combined to model AMD transport in canal and ground water systems (Arrowood et al. 2007). Initial calculations demonstrate the importance of the microbial role in removal of the monomer and infer possible implications informing the development of safe and effective PAM application protocols.

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

PubMed

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 effect with genotype on AMD risk. The C statistic for the full model with all variables was 0.831 for progression to advanced AMD. Factors reflective of nature and nurture are independently related to prevalence and incidence of advanced AMD, with excellent predictive power.

Association of Anticholinergic Drug Use With Risk for Late Age-Related Macular Degeneration.

PubMed

Aldebert, Gauthier; Faillie, Jean-Luc; Hillaire-Buys, Dominique; Mura, Thibault; Carrière, Isabelle; Delcourt, Cécile; Creuzot-Garcher, Catherine; Villain, Max; Daien, Vincent

2018-05-24

Amyloid-β is a major component of retinal drusen, the primary lesions of age-related macular degeneration (AMD), and autopsy and animal models suggested that anticholinergic drug (ACD) use increased brain amyloid-β deposition. To investigate the association between exposure to ACDs and late AMD (features of neovascular AMD or geographic atrophy of the retinal pigment epithelium in at least 1 eye). A multicenter case-control study in 4 French ophthalmologic centers comprising 200 cases with late AMD and 200 controls enrolled from July 2016 to June 2017. Exposure to at least 3 months of ACDs started before AMD diagnosis was recorded during a specific interview. A dose-effect association with cumulative exposure duration and Anticholinergic Burden Score was explored. The association between ACD exposure and AMD was assessed by multivariate logistic regression analysis adjusted for age, sex, smoking status, family history of AMD, alcohol consumption, and use of anticoagulant and anti-inflammatory drugs. Odds ratios (ORs) and 95% confidence intervals were estimated. Association between exposure to ACDs and late AMD. Among case participants, the mean (SD) age was 74.8 (9.2) years, 129 (64.5%) were women, 192 (96%) were white, 65 (32.5%) had geographic atrophy, 135 (67.5%) had neovascular AMD, 116 (58%) had unilateral AMD, and 84 (42%) had bilateral AMD. Among control participants, the mean (SD) age was 75.5 (7.2) years, with 116 (58%) women and 187 (93.5%) white participants. Twenty-six cases (13%) and 10 controls (5%) were exposed to ACDs throughout life for at least 3 months before AMD onset. Risk of AMD was increased with ever exposure to ACDs (adjusted OR [aOR], 2.84; 95% CI, 1.33-6.06; P = .007), high Anticholinergic Burden Score (≥3) (aOR, 6.42; 95% CI, 1.38-29.92; P = .02), and longest cumulative exposure to ACD (≥15 years) (aOR, 5.88; 95% CI, 1.22-28.31; P = .03). Risk of late AMD may be increased with at least 3 months' use of ACDs. A dose-effect association was suggested by a greater association with prolonged use and high Anticholinergic Burden Score. Further studies, in particular those with longitudinal design, are needed to confirm this association.

Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration.

PubMed

Meyers, Kristin J; Liu, Zhe; Millen, Amy E; Iyengar, Sudha K; Blodi, Barbara A; Johnson, Elizabeth; Snodderly, D Max; Klein, Michael L; Gehrs, Karen M; Tinker, Lesley; Sarto, Gloria E; Robinson, Jennifer; Wallace, Robert B; Mares, Julie A

2015-11-01

Unhealthy lifestyles have been associated with increased odds for age-related macular degeneration (AMD). Whether this association is modified by genetic risk for AMD is unknown and was investigated. Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later. Women 50 to 79 years of age in the Carotenoids in Age-Related Eye Disease Study with exposure and AMD data (n=1663). Healthy lifestyle scores (0-6 points) were assigned based on Healthy Eating Index scores, physical activity (metabolic equivalent of task hours/week), and smoking pack years assessed in 1994 and 1998. Genetic risk was based on Y402H in complement factor H (CFH) and A69S in age-related maculopathy susceptibility locus 2 (ARMS2). Additive and multiplicative interactions in odds ratios were assessed using the synergy index and a multiplicative interaction term, respectively. AMD presence and severity were assessed from grading of stereoscopic fundus photographs taken in 2001-2004. AMD was present in 337 women, 91% of whom had early AMD. The odds of AMD were 3.3 times greater (95% confidence interval [CI], 1.8-6.1) in women with both low healthy lifestyle score (0-2) and high-risk CFH genotype (CC), relative to those who had low genetic risk (TT) and high healthy lifestyle scores (4-6). There were no significant additive (synergy index [SI], 1.08; 95% CI, 0.70-1.67) or multiplicative (Pinteraction=0.94) interactions in the full sample. However, when limiting the sample to women with stable diets before AMD assessment (n=728) the odds for AMD associated with low healthy lifestyle scores and high-risk CFH genotype were strengthened (odds ratio, 4.6; 95% CI, 1.8-11.6) and the synergy index was significant (SI, 1.34; 95% CI, 1.05-1.70). Adjusting for dietary lutein and zeaxanthin attenuated, and therefore partially explained, the joint association. There were no significant additive or multiplicative interactions for ARMS2 and lifestyle score. Having unhealthy lifestyles and 2 CFH risk alleles increased AMD risk (primarily in the early stages), in an or additive or greater (synergistic) manner. However, unhealthy lifestyles increased AMD risk regardless of AMD risk genotype. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Pulse-driven micro gas sensor fitted with clustered Pd/SnO2 nanoparticles.

PubMed

Suematsu, Koichi; Shin, Yuka; Ma, Nan; Oyama, Tokiharu; Sasaki, Miyuki; Yuasa, Masayoshi; Kida, Tetsuya; Shimanoe, Kengo

2015-08-18

Real-time monitoring of specific gas concentrations with a compact and portable gas sensing device is required to sense potential health risk and danger from toxic gases. For such purposes, we developed an ultrasmall gas sensor device, where a micro sensing film was deposited on a micro heater integrated with electrodes fabricated by the microelectromechanical system (MEMS) technology. The developed device was operated in a pulse-heating mode to significantly reduce the heater power consumption and make the device battery-driven and portable. Using clustered Pd/SnO2 nanoparticles, we succeeded in introducing mesopores ranging from 10 to 30 nm in the micro gas sensing film (area: ϕ 150 μm) to detect large volatile organic compounds (VOCs). The micro sensor showed quick, stable, and high sensor responses to toluene at ppm (parts per million) concentrations at 300 °C even by operating the micro heater in a pulse-heating mode where switch-on and -off cycles were repeated at one-second intervals. The high performance of the micro sensor should result from the creation of efficient diffusion paths decorated with Pd sensitizers by using the clustered Pd/SnO2 nanoparticles. Hence we demonstrate that our pulse-driven micro sensor using nanostructured oxide materials holds promise as a battery-operable, portable gas sensing device.

A Revised Hemodynamic Theory of Age-Related Macular Degeneration

PubMed Central

Gelfand, Bradley D.; Ambati, Jayakrishna

2016-01-01

Age-related macular degeneration (AMD) afflicts one out of every 40 individuals worldwide, causing irreversible central blindness in millions. The transformation of various tissue layers within the macula in the retina has led to competing conceptual models of the molecular pathways, cell types, and tissues responsible for the onset and progression of AMD. A model that has persisted for over 6 decades is the hemodynamic, or vascular theory of AMD progression, which states that vascular dysfunction of the choroid underlies AMD pathogenesis. Here, we re-evaluate this hypothesis in light of recent advances on molecular, anatomic, and hemodynamic changes underlying choroidal dysfunction in AMD. We propose an updated, detailed model of hemodynamic dysfunction as a mechanism of AMD development and progression. PMID:27423265

Microbial communities, processes and functions in acid mine drainage ecosystems.

PubMed

Chen, Lin-xing; Huang, Li-nan; Méndez-García, Celia; Kuang, Jia-liang; Hua, Zheng-shuang; Liu, Jun; Shu, Wen-sheng

2016-04-01

Acid mine drainage (AMD) is generated from the oxidative dissolution of metal sulfides when water and oxygen are available largely due to human mining activities. This process can be accelerated by indigenous microorganisms. In the last several decades, culture-dependent researches have uncovered and validated the roles of AMD microorganisms in metal sulfides oxidation and acid generation processes, and culture-independent studies have largely revealed the diversity and metabolic potentials and activities of AMD communities, leading towards a full understanding of the microbial diversity, functions and interactions in AMD ecosystems. This review describes the diversity of microorganisms and their functions in AMD ecosystems, and discusses their biotechnological applications in biomining and AMD bioremediation according to their capabilities. Copyright © 2016 Elsevier Ltd. All rights reserved.

The performance of residential micro-cogeneration coupled with thermal and electrical storage

NASA Astrophysics Data System (ADS)

Kopf, John

Over 80% of residential secondary energy consumption in Canada and Ontario is used for space and water heating. The peak electricity demands resulting from residential energy consumption increase the reliance on fossil-fuel generation stations. Distributed energy resources can help to decrease the reliance on central generation stations. Presently, distributed energy resources such as solar photovoltaic, wind and bio-mass generation are subsidized in Ontario. Micro-cogeneration is an emerging technology that can be implemented as a distributed energy resource within residential or commercial buildings. Micro-cogeneration has the potential to reduce a building's energy consumption by simultaneously generating thermal and electrical power on-site. The coupling of a micro-cogeneration device with electrical storage can improve the system's ability to reduce peak electricity demands. The performance potential of micro-cogeneration devices has yet to be fully realized. This research addresses the performance of a residential micro-cogeneration device and it's ability to meet peak occupant electrical loads when coupled with electrical storage. An integrated building energy model was developed of a residential micro-cogeneration system: the house, the micro-cogeneration device, all balance of plant and space heating components, a thermal storage device, an electrical storage device, as well as the occupant electrical and hot water demands. This model simulated the performance of a micro-cogeneration device coupled to an electrical storage system within a Canadian household. A customized controller was created in ESP-r to examine the impact of various system control strategies. The economic performance of the system was assessed from the perspective of a local energy distribution company and an end-user under hypothetical electricity export purchase price scenarios. It was found that with certain control strategies the micro-cogeneration system was able to improve the economic performance for both the end user and local distribution company.

Potential public health impact of Age-Related Eye Disease Study results: AREDS report no. 11.

PubMed

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.

A thermographic study on eyes affected by Age-related Macular Degeneration: Comparison among various forms of the pathology and analysis of risk factors

NASA Astrophysics Data System (ADS)

Matteoli, Sara; Finocchio, Lucia; Biagini, Ilaria; Giacomelli, Giovanni; Sodi, Andrea; Corvi, Andrea; Virgili, Gianni; Rizzo, Stanislao

2016-05-01

The aims of this study are to investigate (1) the ocular thermographic profiles in eyes affected by Age related Macular Degeneration (AMD) and age-matched controls to detect possible hemodynamic abnormalities that could be involved in the pathogenesis of the disease, (2) whether any risk factors associated with the disease could affect the development of a form of AMD rather than another. Thirty-four eyes with Age-Related Maculopathy (ARM), 41 eyes with dry AMD, 60 eyes affected by wet AMD, and 74 eyes with fibrotic AMD were included in the study. The control group consisted of 48 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, systemic diseases and a body temperature higher than 37.5 °C. A total of 210 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The Ocular Surface Temperature (OST) of five ocular areas was calculated by means of an image processing technique from the infrared images. Two-sample t-test, one-way ANOVA test and multivariate analysis were used for statistical analyses. ANOVA analyses showed no significant differences among AMD groups (P-value > 0.05), however, OST in AMD patients was significantly lower than in controls (P-value < 0.0001). Smokers showed higher possibility (P-value = 0.012) of developing wet AMD instead of dry AMD. Infrared thermography may be a helpful, non-invasive and not time-consuming method to be used in the management of patients with this common degenerative maculopathy.

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

PubMed Central

Mach, Steven; Garas, Shady; Kim, Ivana K; Vavvas, Demetrios G; Miller, Joan W; Husain, Deeba; Miller, John B

2017-01-01

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 for the exploration of peripheral retinal pathology associated with AMD. PMID:29184386

Symptoms of anxiety and mood disturbance alter cardiac and peripheral autonomic control in patients with metabolic syndrome.

PubMed

Toschi-Dias, Edgar; Trombetta, Ivani C; da Silva, Valdo José Dias; Maki-Nunes, Cristiane; Alves, Maria Janieire N N; Angelo, Luciana F; Cepeda, Felipe X; Martinez, Daniel G; Negrão, Carlos Eduardo; Rondon, Maria Urbana P B

2013-03-01

Previous investigations show that metabolic syndrome (MetSyn) causes sympathetic hyperactivation. Symptoms of anxiety and mood disturbance (AMd) provoke sympatho-vagal imbalance. We hypothesized that AMd would alter even further the autonomic function in patients with MetSyn. Twenty-six never-treated patients with MetSyn (ATP-III) were allocated to two groups, according to the levels of anxiety and mood disturbance: (1) with AMd (MetSyn + AMd, n = 15), and (2) without AMd (MetSyn, n = 11). Ten healthy control subjects were also studied (C, n = 10). AMd was determined using quantitative questionnaires. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure (oscillometric beat-to-beat basis), and heart rate (ECG) were measured during a baseline 10-min period. Spectral analysis of RR interval and systolic arterial pressure were analyzed, and the power of low (LF) and high (HF) frequency bands were determined. Sympatho-vagal balance was obtained by LF/HF ratio. Spontaneous baroreflex sensitivity (BRS) was evaluated by calculation of α-index. MSNA was greater in patients with MetSyn + AMd compared with MetSyn and C. Patients with MetSyn + AMd showed higher LF and lower HF power compared with MetSyn and C. In addition, LF/HF balance was higher in MetSyn + AMd than in MetSyn and C groups. BRS was decreased in MetSyn + AMd compared with MetSyn and C groups. Anxiety and mood disturbance alter autonomic function in patients with MetSyn. This autonomic dysfunction may contribute to the increased cardiovascular risk observed in patients with mood alterations.

Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families that manifest both Stargardt disease and age-related macular degeneration.

PubMed

Shroyer, N F; Lewis, R A; Yatsenko, A N; Wensel, T G; Lupski, J R

2001-11-01

Mutations in ABCR (ABCA4) have been reported to cause a spectrum of autosomal recessively inherited retinopathies, including Stargardt disease (STGD), cone-rod dystrophy and retinitis pigmentosa. Individuals heterozygous for ABCR mutations may be predisposed to develop the multifactorial disorder age-related macular degeneration (AMD). We hypothesized that some carriers of STGD alleles have an increased risk to develop AMD. We tested this hypothesis in a cohort of families that manifest both STGD and AMD. With a direct-sequencing mutation detection strategy, we found that AMD-affected relatives of STGD patients are more likely to be carriers of pathogenic STGD alleles than predicted based on chance alone. We further investigated the role of AMD-associated ABCR mutations by testing for expression and ATP-binding defects in an in vitro biochemical assay. We found that mutations associated with AMD have a range of assayable defects ranging from no detectable defect to apparent null alleles. Of the 21 missense ABCR mutations reported in patients with AMD, 16 (76%) show abnormalities in protein expression, ATP-binding or ATPase activity. We infer that carrier relatives of STGD patients are predisposed to develop AMD.

Crystal structure and superconductivity in atomic hydrogen: Deformation between I41/amd and Fddd

NASA Astrophysics Data System (ADS)

Ishikawa, T.; Nagara, H.; Oda, T.; Suzuki, N.; Shimizu, K.

2017-10-01

We investigated crystal structures of solid metallic hydrogen using the potential energy surface trekking for structure search. We applied this technique to a tetragonal I41/amd structure at pressures of 500 and 600 GPa and obtained the transformation into multiple orthorhombic Fddd structures, which are formed by distortions in the ab plane of I41/amd. The potential barriers are easily surmounted by few trekking steps, which indicates that in solid metallic hydrogen crystal structure is softened with respect to the distortion and is easily fluctuated among the I41/amd and Fddd structures. Calculated superconducting critical temperatures show 269 K for I41/amd and 263 K for Fddd at 500 GPa. The structures are softened and the electron-phonon coupling are enhanced with pressurization to 600 GPa. As the results, the superconducting critical temperature is increased to 281 K for I41/amd, whereas it is decreased to 252 K for Fddd owing to its larger phonon softening than that of I41/amd.

Ranibizumab for the treatment of neovascular AMD.

PubMed

Kaiser, P K; Do, D V

2007-03-01

Age-related macular degeneration (AMD) is the leading cause of adult blindness among individuals aged 50 and older in the Western world, with the neovascular form of AMD responsible for the most severe and rapid visual loss. Although monotherapy with currently available treatments can slow the rate of loss of vision in eyes with neovascular AMD, they do not significantly improve vision. Vascular endothelial growth factor-A (VEGF-A) plays a critical role in the pathogenesis of neovascular AMD, and ranibizumab is a promising new treatment that targets all VEGF-A isoforms and their biologically active degradation products. Clinical trials have reported that ranibizumab treatment resulted in greater proportions of patients achieving a < 15 letter loss of visual acuity and improved vision at 12 and 24 months than control groups. The incidence of serious ocular and systemic adverse events was low in all ranibizumab trials to date. Currently, ranibizumab is the only treatment for neovascular AMD to demonstrate significant improvement in vision for many patients and represents a major advance in treating neovascular AMD.

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

PubMed

Downie, Laura Elizabeth; Keller, Peter Richard

2014-08-01

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

Novel technique for fabrication of multi-layered microcoils in microelectromechanical systems (MEMS) applications

NASA Astrophysics Data System (ADS)

Chang, Hung-Pin; Qian, Jiangyuan; Bachman, Mark; Congdon, Philip; Li, Guann-pyng

2002-07-01

A novel planarization technique, compressive molding planarization (CMP) is developed for implementation of a multi-layered micro coil device. Applying CMP and other micromachining techniques, a multi-layered micro coil device has been designed and fabricated, and its use in the magnetic micro actuators for hard disk drive applications has been demonstrated, showing that it can produce milli-Newton of magnetic force suitable for driving a micro actuator. The novel CMP technique can be equally applicable in other MEMS devices fabrication to ease the process integration for the complicated structure.

Micro Computer Tomography for medical device and pharmaceutical packaging analysis.

PubMed

Hindelang, Florine; Zurbach, Raphael; Roggo, Yves

2015-04-10

Biomedical device and medicine product manufacturing are long processes facing global competition. As technology evolves with time, the level of quality, safety and reliability increases simultaneously. Micro Computer Tomography (Micro CT) is a tool allowing a deep investigation of products: it can contribute to quality improvement. This article presents the numerous applications of Micro CT for medical device and pharmaceutical packaging analysis. The samples investigated confirmed CT suitability for verification of integrity, measurements and defect detections in a non-destructive manner. Copyright © 2015 Elsevier B.V. All rights reserved.

A design multifunctional plasmonic optical device by micro ring system

NASA Astrophysics Data System (ADS)

Pornsuwancharoen, N.; Youplao, P.; Amiri, I. S.; Ali, J.; Yupapin, P.

2018-03-01

A multi-function electronic device based on the plasmonic circuit is designed and simulated by using the micro-ring system. From which a nonlinear micro-ring resonator is employed and the selected electronic devices such as rectifier, amplifier, regulator and filter are investigated. A system consists of a nonlinear micro-ring resonator, which is known as a modified add-drop filter and made of an InGaAsP/InP material. The stacked waveguide of an InGaAsP/InP - graphene -gold/silver is formed as a part of the device, the required output signals are formed by the specific control of input signals via the input and add ports. The material and device aspects are reviewed. The simulation results are obtained using the Opti-wave and MATLAB software programs, all device parameters are based on the fabrication technology capability.

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

NASA Astrophysics Data System (ADS)

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 %.

Brueckner-AMD Study of Light Nuclei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kato, Kiyoshi; Yamamoto, Yuhei; Togashi, Tomoaki

2011-06-28

We applied the Brueckner theory to the Antisymmetrized Molecular Dynamics (AMD) and examined the reliability of the AMD calculations based on realistic nuclear interactions. In this method, the Bethe-Goldstone equation in the Brueckner theory is solved for every nucleon pair described by wave packets of AMD, and the G-matrix is calculated with single-particle orbits in AMD self-consistently. We apply this framework to not only {alpha}-nuclei but also N{ne}Z nuclei with A{approx}10. It is confirmed that these results present the description of reasonable cluster structures and energy-level schemes comparable with the experimental ones in light nuclei.

Natural history of drusenoid pigment epithelial detachment in age-related macular degeneration: Age-Related Eye Disease Study Report No. 28.

PubMed

Cukras, Catherine; Agrón, Elvira; Klein, Michael L; Ferris, Frederick L; Chew, Emily Y; Gensler, Gary; Wong, Wai T

2010-03-01

To describe the natural history of eyes with drusenoid pigment epithelial detachments (DPEDs) associated with age-related macular degeneration (AMD). Multicenter, clinic-based, prospective cohort study. Among 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), 255 were identified as having DPED in at least 1 eye and having 5 or more years of follow-up after the initial detection of the DPED. Baseline and annual fundus photographs were evaluated for the evolution of the fundus features and the development of advanced AMD in the forms of central geographic atrophy (CGA) or neovascular (NV) AMD. Kaplan-Meier analyses of progression to advanced AMD and of moderate vision loss (> or =15 letters compared with baseline) were performed. Rate of progression to advanced AMD and change in visual acuity from baseline (in terms of mean letters lost and proportion losing > or =15 letters). A total of 311 eyes (from 255 participants) with DPED were followed for a median follow-up time of 8 years subsequent to the initial detection of a DPED. Of the 282 eyes that did not have advanced AMD at baseline, advanced AMD developed within 5 years in 119 eyes (42%) (19% progressing to CGA and 23% progressing to NV-AMD). In the remaining eyes that did not develop advanced AMD (n=163), progressive fundus changes, typified by the development of calcified drusen and pigmentary changes, were detected. Visual decline was prominent among study eyes, with approximately 40% of all eyes decreasing in visual acuity by > or =15 letters at 5 years follow-up. Mean visual acuity decreased from 76 letters ( approximately 20/30) at baseline to 61 letters ( approximately 20/60) at 5 years. Five-year decreases in mean visual acuity averaged 26 letters for eyes progressing to advanced AMD and 8 letters for non-progressing eyes. The natural history of eyes containing DPED is characterized by a high rate of progression to both CGA and NV-AMD. Among eyes not progressing to advanced AMD, progressive development of pigmentary changes and calcified drusen were observed. Decline of visual acuity is a common outcome, with or without progression to advanced forms of AMD. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Retinal Spectral Domain Optical Coherence Tomography in Early Atrophic Age-Related Macular Degeneration (AMD) and a New Metric for Objective Evaluation of the Efficacy of Ocular Nutrition

PubMed Central

Richer, Stuart; Cho, Jane; Stiles, William; Levin, Marc; Wrobel, James S.; Sinai, Michael; Thomas, Carla

2012-01-01

Purpose: A challenge in ocular preventive medicine is identification of patients with early pathological retinal damage that might benefit from nutritional intervention. The purpose of this study is to evaluate retinal thinning (RT) in early atrophic age-related macular degeneration (AMD) against visual function data from the Zeaxanthin and Visual Function (ZVF) randomized double masked placebo controlled clinical trial (FDA IND #78973). Methods: Retrospective, observational case series of medical center veterans with minimal visible AMD retinopathy (AREDS Report #18 simplified grading 1.4/4.0 bilateral retinopathy). Foveal and extra-foveal four quadrant SDOCT RT measurements were evaluated in n = 54 clinical and ZVF AMD patients. RT by age was determined and compared to the OptoVue SD OCT normative database. RT by quadrant in a subset of n = 29 ZVF patients was correlated with contrast sensitivity and parafoveal blue cone increment thresholds. Results: Foveal RT in AMD patients and non-AMD patients was preserved with age. Extrafoveal regions, however, showed significant slope differences between AMD patients and non-AMD patients, with the superior and nasal quadrants most vulnerable to retinal thinning (sup quad: −5.5 μm/decade thinning vs. Non-AMD: −1.1 μm/decade, P < 0.02; nasal quad: −5.0 μm/decade thinning vs. Non-AMD: −1.0 μm/decade, P < 0.04). Two measures of extrafoveal visual deterioration were correlated: A significant inverse correlation between % RT and contrast sensitivity (r = −0.33, P = 0.01, 2 Tailed Paired T) and an elevated extrafoveal increment blue cone threshold (r = +0.34, P = 0.01, 2 Tailed T). Additional SD OCT RT data for the non-AMD oldest age group (ages 82–91) is needed to fully substantiate the model. Conclusion: A simple new SD OCT clinical metric called “% extra-foveal RT” correlates well with functional visual loss in early AMD patients having minimal visible retinopathy. This metric can be used to follow the effect of repleting ocular nutrients, such as zinc, antioxidants, carotenoids, n-3 essential fats , resveratrol and vitamin D. PMID:23363992

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

PubMed

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 majority of previous studies. Statins have been demonstrated to reduce the risk of cardiovascular disease, but our data do not provide evidence of a beneficial effect on slowing AMD progression. Published by Elsevier Inc.

HUMAN HtrA1 IN THE ARCHIVED EYES WITH AGE-RELATED MACULAR DEGENERATION

PubMed Central

Chan, Chi-Chao; Shen, Defen; Zhou, Min; Ross, Robert J.; Ding, Xiaoyan; Zhang, Kang; Green, W. Richard; Tuo, Jingsheng

2007-01-01

Purpose HtrA1 belongs to the high temperature requirement factor A family of serine proteases, which are involved in protein quality control and cell fate. A single-nucleotide polymorphism (SNP), rs11200638, in the promoter of HtrA1 at chromosome 10q26 is reported as a likely causal variant for age-related macular degeneration (AMD). The SNP is located in the regulatory region and increases production of HtrA1 protein. This study investigates HtrA1 expression and SNP genotypes in archived ocular slides with AMD. Methods Macular, nonretinal, and peripheral retinal cells were microdissected from archived slides from 57 eyes with AMD and 16 age-matched, non-AMD controls. HtrA1 rs11200638 SNP genotyping was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis. HtrA1 transcripts were measured using real-time reverse transcriptase–PCR. HtrA1 protein expression was evaluated using avidin-biotin complex immunohistochemistry. Results HtrA1 (G/A) SNP was successfully genotyped in 52 AMD cases and 13 non-AMD subjects. The frequencies of the risk allele (A) were 55 of 104 (52.9%) and 8 of 26 (30.8%) in AMD and control groups, respectively. HtrA1 mRNA was detected in normal peripheral and macular retinas, higher in the periphery than maculae. HtrA1 mRNA was much higher in the macula and a lot lower in the periphery of the AMD eyes as compared to control eyes. HtrA1 protein was expressed in normal retinal vascular endothelia and retinal pigment epithelia. Intense immunoreaction against HtrA1 was found in AMD lesions, slightly more in wet than dry AMD lesions. Conclusion This study successfully analyzes HtrA1 SNP and transcript expression in microdissected cells from archived paraffin fixed slides. Up-regulation of HtrA1 is detected in the macular lesions of AMD eyes. The data further suggest that rs11200638 in HtrA1 promoter is associated with AMD development. PMID:18427598

A prospective study of common variants in the RAR-related orphan receptor alpha (RORalpha) gene and risk of neovascular age-related macular degeneration

PubMed Central

Schaumberg, Debra A.; Chasman, Daniel; Morrison, Margaux A.; Adams, Scott M.; Guo, Qun; Hunter, David J.; Hankinson, Susan E.; DeAngelis, Margaret M.

2010-01-01

Objectives The RAR-related orphan receptor alpha (RORalpha) gene is implicated as a candidate for age-related macular degeneration (AMD) through a previous microarray expression study, linkage data, biological plausibility, and two clinic-based cross sectional studies. We aimed to determine if common variants in RORalpha predict future risk of neovascular AMD. Methods We measured genotypes for 18 variants in intron 1 of the RORalpha gene among 164 cases who developed neovascular AMD and 485 age- and sex-matched controls in a prospective nested case-control study within the Nurses’ Health Study and the Health Professionals Follow-up Study. We determined the incidence rate ratios (IRR) and 95% confidence intervals (CI) for neovascular AMD for each variant, and examined interactions with other AMD-associated variants and modifiable risk factors. Results We identified a single SNP (rs12900948) that was significantly associated with increased incidence of neovascular AMD. Participants with one and two copies of the “G” allele were 1.73 (CI= 1.32–2.27) and 2.99 (CI=1.74–5.14) times more likely to develop neovascular AMD. Individuals homozygous for both the “G” allele of rs12900948 and ARMS2 A69S had a 40.8-fold increased risk of neovascular AMD (CI=10.1–164; P for interaction=0.017). Cigarette smokers who carried two copies of the “G” allele had a 9.89-fold risk of neovascular AMD, but the interaction was not significant (P=0.08). We identified a significant AMD-associated haplotype block containing SNPs rs730754, rs8034864, and rs12900948, with P-values for ACA=1.16 × 10−9, ACG=5.85 × 10−12, and GAA=0.0001 when compared to all other haplotypes. Conclusion Common variants and haplotypes within the RORalpha gene appear to act synergistically with the ARMS2 A69S polymorphism to increase risk of neovascular AMD. These data add further evidence of a high level of complexity linking genetic and modifiable risk factors to AMD development and should help efforts at risk prediction. PMID:21060049

On-chip micro-power: three-dimensional structures for micro-batteries and micro-supercapacitors

NASA Astrophysics Data System (ADS)

Beidaghi, Majid; Wang, Chunlei

2010-04-01

With the miniaturization of portable electronic devices, there is a demand for micro-power source which can be integrated on the semiconductor chips. Various micro-batteries have been developed in recent years to generate or store the energy that is needed by microsystems. Micro-supercapacitors are also developed recently to couple with microbatteries and energy harvesting microsystems and provide the peak power. Increasing the capacity per footprint area of micro-batteries and micro-supercapacitors is a great challenge. One promising route is the manufacturing of three dimensional (3D) structures for these micro-devices. In this paper, the recent advances in fabrication of 3D structure for micro-batteries and micro-supercapacitors are briefly reviewed.

[An implantable micro-device using wireless power transmission for measuring aortic aneurysm sac pressure].

PubMed

Guo, Xudong; Ge, Bin; Wang, Wenxing

2013-08-01

In order to detect endoleaks after endovascular aneurysm repair (EVAR), we developed an implantable micro-device based on wireless power transmission to measure aortic aneurysm sac pressure. The implantable micro-device is composed of a miniature wireless pressure sensor, an energy transmitting coil, a data recorder and a data processing platform. Power transmission without interconnecting wires is performed by a transmitting coil and a receiving coil. The coupling efficiency of wireless power transmission depends on the coupling coefficient between the transmitting coil and the receiving coil. With theoretical analysis and experimental study, we optimized the geometry of the receiving coil to increase the coupling coefficient. In order to keep efficiency balance and satisfy the maximizing conditions, we designed a closed loop power transmission circuit, including a receiving voltage feedback module based on wireless communication. The closed loop improved the stability and reliability of transmission energy. The prototype of the micro-device has been developed and the experiment has been performed. The experiments showed that the micro-device was feasible and valid. For normal operation, the distance between the transmitting coil and the receiving coil is smaller than 8cm. Besides, the distance between the micro-device and the data recorder is within 50cm.

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

NASA Astrophysics Data System (ADS)

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.

Scalable fabrication of high-power graphene micro-supercapacitors for flexible and on-chip energy storage

NASA Astrophysics Data System (ADS)

El-Kady, Maher F.; Kaner, Richard B.

2013-02-01

The rapid development of miniaturized electronic devices has increased the demand for compact on-chip energy storage. Microscale supercapacitors have great potential to complement or replace batteries and electrolytic capacitors in a variety of applications. However, conventional micro-fabrication techniques have proven to be cumbersome in building cost-effective micro-devices, thus limiting their widespread application. Here we demonstrate a scalable fabrication of graphene micro-supercapacitors over large areas by direct laser writing on graphite oxide films using a standard LightScribe DVD burner. More than 100 micro-supercapacitors can be produced on a single disc in 30 min or less. The devices are built on flexible substrates for flexible electronics and on-chip uses that can be integrated with MEMS or CMOS in a single chip. Remarkably, miniaturizing the devices to the microscale results in enhanced charge-storage capacity and rate capability. These micro-supercapacitors demonstrate a power density of ~200 W cm-3, which is among the highest values achieved for any supercapacitor.

A comparison of risk factors for age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese patients.

PubMed

Chen, Xiao-Li; Hu, Qin-Rui; Bai, Yu-Jing; Deng, Yu; Wang, Hai-Wei; Liu, Shan; Wang, Yin-Lin; Yue, Yan-Kun

2018-06-01

Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) are important vision-threatening diseases worldwide. For effective treatment, the risk factors for the diseases merit investigation. This study aimed to compare the risk factors for nAMD vs. PCV in Chinese patients. A total of 946 participants were recruited in this case-control study, including 281 patients with nAMD, 306 patients with PCV, and 359 controls. All participants underwent comprehensive ophthalmic examinations. Information on risk factors were collected by questionnaire. Multivariate logistic regression analyses were performed to investigate the difference in risk factors between nAMD and PCV. In a subgroup of subjects, serum lipid data were obtained and analyzed. Risk factors for nAMD included older age (OR 1.03, P = 0.001), male gender (OR 1.55, P = 0.020), asthma (OR 2.50, P = 0.028), smoking (OR 1.92, P = 0.001), and family history (OR 6.82, P = 0.001), while smoking (OR 1.67, P = 0.013) was the only risk factor for PCV. Compared to patients with PCV, patients with nAMD were more likely to be older and suffer from hyperlipidemia, coronary artery disease, rheumatism, and tumor. Interestingly, higher levels of high-density lipoprotein were positively associated with PCV in the subgroup analysis (OR 7.74, P = 0.011). Besides, results were quite different between the combination of patients with nAMD and PCV and patients with nAMD or PCV alone. The risk factors for nAMD and PCV is varying with the exception of smoking. Our findings suggest that different strategies might be applied in the clinical management and scientific research on nAMD and PCV.

Tear film proteome in age-related macular degeneration.

PubMed

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.

Perceptual Speech Assessment After Anterior Maxillary Distraction in Patients With Cleft Maxillary Hypoplasia.

PubMed

Richardson, Sunil; Seelan, Nikkie S; Selvaraj, Dhivakar; Khandeparker, Rakshit V; Gnanamony, Sangeetha

2016-06-01

To assess speech outcomes after anterior maxillary distraction (AMD) in patients with cleft-related maxillary hypoplasia. Fifty-eight patients at least 10 years old with cleft-related maxillary hypoplasia were included in this study irrespective of gender, type of cleft lip and palate, and amount of required advancement. AMD was carried out in all patients using a tooth-borne palatal distractor by a single oral and maxillofacial surgeon. Perceptual speech assessment was performed by 2 speech language pathologists preoperatively, before placement of the distractor device, and 6 months postoperatively using the scoring system of Perkins et al (Plast Reconstr Surg 116:72, 2005); the system evaluates velopharyngeal insufficiency (VPI), resonance, nasal air emission, articulation errors, and intelligibility. The data obtained were tabulated and subjected to statistical analysis using Wilcoxon signed rank test. A P value less than .05 was considered significant. Eight patients were lost to follow-up. At 6-month follow-up, improvements of 62% (n = 31), 64% (n = 32), 50% (n = 25), 68% (n = 34), and 70% (n = 35) in VPI, resonance, nasal air emission, articulation, and intelligibility, respectively, were observed, with worsening of all parameters in 1 patient (2%). The results for all tested parameters were highly significant (P ≤ .001). AMD offers a substantial improvement in speech for all 5 parameters of perceptual speech assessment. Copyright © 2016 The American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

A thermally self-sustained micro-power plant with integrated micro-solid oxide fuel cells, micro-reformer and functional micro-fluidic carrier

NASA Astrophysics Data System (ADS)

Scherrer, Barbara; Evans, Anna; Santis-Alvarez, Alejandro J.; Jiang, Bo; Martynczuk, Julia; Galinski, Henning; Nabavi, Majid; Prestat, Michel; Tölke, René; Bieberle-Hütter, Anja; Poulikakos, Dimos; Muralt, Paul; Niedermann, Philippe; Dommann, Alex; Maeder, Thomas; Heeb, Peter; Straessle, Valentin; Muller, Claude; Gauckler, Ludwig J.

2014-07-01

Low temperature micro-solid oxide fuel cell (micro-SOFC) systems are an attractive alternative power source for small-size portable electronic devices due to their high energy efficiency and density. Here, we report on a thermally self-sustainable reformer-micro-SOFC assembly. The device consists of a micro-reformer bonded to a silicon chip containing 30 micro-SOFC membranes and a functional glass carrier with gas channels and screen-printed heaters for start-up. Thermal independence of the device from the externally powered heater is achieved by exothermic reforming reactions above 470 °C. The reforming reaction and the fuel gas flow rate of the n-butane/air gas mixture controls the operation temperature and gas composition on the micro-SOFC membrane. In the temperature range between 505 °C and 570 °C, the gas composition after the micro-reformer consists of 12 vol.% to 28 vol.% H2. An open-circuit voltage of 1.0 V and maximum power density of 47 mW cm-2 at 565 °C is achieved with the on-chip produced hydrogen at the micro-SOFC membranes.

Recovery of Rare Earth Elements and Yttrium from Passive-Remediation Systems of Acid Mine Drainage.

PubMed

Ayora, Carlos; Macías, Francisco; Torres, Ester; Lozano, Alba; Carrero, Sergio; Nieto, José-Miguel; Pérez-López, Rafael; Fernández-Martínez, Alejandro; Castillo-Michel, Hiram

2016-08-02

Rare earth elements and yttrium (REY) are raw materials of increasing importance for modern technologies, and finding new sources has become a pressing need. Acid mine drainage (AMD) is commonly considered an environmental pollution issue. However, REY concentrations in AMD can be several orders of magnitude higher than in naturally occurring water bodies. With respect to shale standards, the REY distribution pattern in AMD is enriched in intermediate and valuable REY, such as Tb and Dy. The objective of the present work is to study the behavior of REY in AMD passive-remediation systems. Traditional AMD passive remediation systems are based on the reaction of AMD with calcite-based permeable substrates followed by decantation ponds. Experiments with two columns simulating AMD treatment demonstrate that schwertmannite does not accumulate REY, which, instead, are retained in the basaluminite residue. The same observation is made in two field-scale treatments from the Iberian Pyrite Belt (IPB, southwest Spain). On the basis of the amplitude of this process and on the extent of the IPB, our findings suggest that the proposed AMD remediation process can represent a modest but suitable REY source. In this sense, the IPB could function as a giant heap-leaching process of regional scale in which rain and oxygen act as natural driving forces with no energy investment. In addition to having environmental benefits of its treatment, AMD is expected to last for hundreds of years, and therefore, the total reserves are practically unlimited.

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

PubMed

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

2017-07-01

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

Association of glutathione S-transferase pi isoform single-nucleotide polymorphisms with exudative age-related macular degeneration in a Chinese population.

PubMed

Gu, Hong; Sun, Erdan; Cui, Lei; Yang, Xiufen; Lim, Apiradee; Xu, Jun; Snellingen, Torkel; Liu, Xipu; Wang, Ningli; Liu, Ningpu

2012-10-01

To investigate the association between single-nucleotide polymorphisms in the pi isoform of glutathione S-transferase (GSTP1) gene and the risk of exudative age-related macular degeneration (AMD) in a Chinese case-control cohort. A total of 131 Chinese patients with exudative AMD and 138 control individuals were recruited. Genomic DNA was extracted from venous blood leukocytes. Two common nonsynonymous single-nucleotide polymorphisms in GSTP1 (rs1695 and rs1138272) were genotyped by polymerase chain reaction followed by allele-specific restriction enzyme digestion and direct sequencing. Significant association with exudative AMD was detected for single-nucleotide polymorphism, rs1695 (P = 0.019). The risk G allele frequencies were 21.8% in AMD patients and 12.7% in control subjects (P = 0.007). Compared with the wild-type AA genotype, odds ratio for the risk of AMD was 1.91 (95% confidence interval, 1.09-3.35) for the heterozygous AG genotype and 2.52 (95% confidence interval, 0.6-10.61) for the homozygous GG genotype. In contrast, rs1138272 was not associated with exudative AMD (P = 1.00). The risk G allele frequencies of rs1138272 were 0.4% in AMD patients and 0.4% in control subjects (P = 1.00). Our data suggest that the GSTP1 variant rs1695 moderately increases the risk of exudative AMD. The variant rs1138272 was rare and was not associated with exudative AMD in this Chinese cohort.

HEALTH CONDITIONS LINKED TO AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH DARK ADAPTATION.

PubMed

Laíns, Inês; Miller, John B; Mukai, Ryo; Mach, Steven; Vavvas, Demetrios; Kim, Ivana K; Miller, Joan W; Husain, Deeba

2018-06-01

To determine the association between dark adaption (DA) and different health conditions linked with age-related macular degeneration (AMD). Cross-sectional study, including patients with AMD and a control group. Age-related macular degeneration was graded according to the Age-Related Eye Disease Study (AREDS) classification. We obtained data on medical history, medications, and lifestyle. Dark adaption was assessed with the extended protocol (20 minutes) of AdaptDx (MacuLogix). For analyses, the right eye or the eye with more advanced AMD was selected. Multivariate linear and logistic regressions were performed, accounting for age and AMD stage. Seventy-eight subjects (75.6% AMD; 24.4% controls) were included. Multivariate assessments revealed that body mass index (BMI; β = 0.30, P = 0.045), taking AREDS vitamins (β = 5.51, P < 0.001), and family history of AMD (β = 2.68, P = 0.039) were significantly associated with worse rod intercept times. Abnormal DA (rod intercept time ≥ 6.5 minutes) was significantly associated with family history of AMD (β = 1.84, P = 0.006), taking AREDS supplements (β = 1.67, P = 0.021) and alcohol intake (β = 0.07, P = 0.017). Besides age and AMD stage, a higher body mass index, higher alcohol intake, and a family history of AMD seem to impair DA. In this cohort, the use of AREDS vitamins was also statistically linked with impaired DA, most likely because of an increased severity of disease in subjects taking them.

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

PubMed

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 < 0.001). Poor baseline visual acuity was associated with cystoid 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.

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

PubMed

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.

Review of nutrient actions on age-related macular degeneration.

PubMed

Zampatti, Stefania; Ricci, Federico; Cusumano, Andrea; Marsella, Luigi Tonino; Novelli, Giuseppe; Giardina, Emiliano

2014-02-01

The actions of nutrients and related compounds on age-related macular degeneration (AMD) are explained in this review. The findings from 80 studies published since 2003 on the association between diet and supplements in AMD were reviewed. Antioxidants and other nutrients with an effect on AMD susceptibility include carotenoids (lutein and zeaxanthin, β-carotene), vitamins (vitamin A, E, C, D, B), mineral supplements (zinc, copper, selenium), dietary fatty acids [monounsaturated fatty acids, polyunsaturated fatty acids (PUFA both omega-3 PUFA and omega-6 PUFA), saturated fatty acids and cholesterol], and dietary carbohydrates. The literature revealed that many of these antioxidants and nutrients exert a protective role by functioning synergistically. Specifically, the use of dietary supplements with targeted actions can provide minimal benefits on the onset or progression of AMD; however, this does not appear to be particularly beneficial in healthy people. Furthermore, some supplements or nutrients have demonstrated discordant effects on AMD in some studies. Since intake of dietary supplements, as well as exposure to damaging environmental factors, is largely dependent on population habits (including dietary practices) and geographical localization, an overall healthy diet appears to be the best strategy in reducing the risk of developing AMD. As of now, the precise mechanism of action of certain nutrients in AMD prevention remains unclear. Thus, future studies are required to examine the effects that nutrients have on AMD and to determine which factors are most strongly correlated with reducing the risk of AMD or preventing its progression. Copyright © 2014 Elsevier Inc. All rights reserved.

Microfabricated instruments and methods to treat recurrent corneal erosions

DOEpatents

Britton, Jr., Charles L.; D'urso, Brian R.; Chaum, Edward; Simpson, John T.; Baba, Justin S.; Ericson, M. Nance; Warmack, Robert J.

2015-06-02

In one embodiment, the present invention provides a device and method for treating recurrent corneal erosion. In one embodiment, the method includes the steps of contacting an epithelium layer of a cornea with an array of glass micro-rods including a plurality of sharp features having a length that penetrates a Bowman's layer of the eye, wherein the plurality of sharp features of the array of glass micro-rods produces a plurality of punctures in the Bowman's layer of the eye that are of micro-scale or less. In another embodiment, the present invention provides a method and device for drug delivery. In one embodiment, the device includes an array of glass micro-rods, wherein at least one glass micro-rod of the array of glass micro-rods includes a sharp feature opposite a base of the array of glass micro-rods, wherein the sharp feature includes a treated surface for delivering a chemical compound to the eye.

Microfabricated instruments and methods to treat recurrent corneal erosion

DOEpatents

Britton, Charles L; D& #x27; Urso, Brian R; Chaum, Edward; Simpson, John T; Baba, Justin S; Ericson, M. Nance; Warmack, Robert J

2013-11-26

In one embodiment, the present invention provides a device and method for treating recurrent corneal erosion. In one embodiment, the method includes the steps of contacting an epithelium layer of a cornea with an array of glass micro-rods including a plurality of sharp features having a length that penetrates a Bowman's layer of the eye, wherein the plurality of sharp features of the array of glass micro-rods produces a plurality of punctures in the Bowman's layer of the eye that are of micro-scale or less. In another embodiment, the present invention provides a method and device for drug delivery. In one embodiment, the device includes an array of glass micro-rods, wherein at least one glass micro-rod of the array of glass micro-rods includes a sharp feature opposite a base of the array of glass micro-rods, wherein the sharp feature includes a treated surface for delivering a chemical compound to the eye.

Modified cataract surgery with telescopic magnification for patients with age-related macular degeneration.

PubMed

Iizuka, Megumi; Gorfinkel, John; Mandelcorn, Mark; Lam, Wai-Ching; Devenyi, Robert; Markowitz, Samuel N

2007-12-01

The most desirable effect following cataract surgery in the presence of age-related macular degeneration (AMD) is to obtain an improvement in distance resolution acuity, and the only optical solution to this is the use of telescopic magnification. The purpose of the study was to develop and verify the clinical utility of inducing low-grade telescopic magnification (<33%) at the time of cataract surgery by the choice of an appropriate intraocular lens power and spectacle glasses in patients with AMD and cataract. The design was a prospective, nonrandomized, interventional case series involving 6 patients aged 74-86 (mean 80; SD 4) years with AMD and cataract. Participants were males and females, equal in number, who had visual acuity of less than 20/400 in the weaker eye. Standard cataract surgery was performed in the weaker eye. The power of the intraocular lens was derived from the reduced Gullstrand model of the eye in such a way that at the intraocular lens plane a minus lens was created, which, together with a plus lens in matching glasses, formed a Galilean telescopic system with magnification of up to 33%. Outcome measures were visual acuity, contrast sensitivity, and activities of daily living (ADL) scores. The mean power of the implanted intraocular lenses was 6.31 (SD 2.42) diopters and, according to the theoretical derivations, achieved magnification between 20% and 30% (mean 26%; SD 4.92%). Visual acuity improved for the group from a mean of 20/525 (logMAR 1.48; SD 0.13) to a mean of 20/290 (logMAR 1.20; SD 0.21). Contrast sensitivity improved significantly (p < 0.001) only in the lower spatial frequencies. Postoperatively, ADL scores improved significantly in all patients except one. At the end of the follow-up period, 3 patients reported that they would like to proceed with similar surgery for the other eye. An optimal surgical telescopic device based on low-grade telescopic magnification may improve functional vision for usage in all tasks in AMD patients. All patients from this study were satisfied following surgery and viewed study outcomes as positive and beneficial, and some patients responded with enthusiasm. Surgeons are encouraged to use this modified technique of cataract surgery in low-vision patients with AMD and cataract.

Complement pathway biomarkers and age-related macular degeneration

PubMed Central

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

Visual, Musculoskeletal, and Balance Complaints in AMD: A Follow-Up Study

PubMed Central

Richter, Hans Olof

2016-01-01

Purpose. To investigate whether patients with age-related macular degeneration (AMD) run a potentially higher risk of developing visual, musculoskeletal, and balance complaints than age-matched controls with normal vision. Methods. Visual assessments, self-rated visual function, self-rated visual, musculoskeletal, and balance complaints, and perceived general health were obtained in 37 AMD patients and 18 controls, at baseline and after an average of 3.8 years later. Results. At follow-up both groups reported decreased visual acuity (VA) and visual function, but only AMD patients reported significantly increased visual, musculoskeletal, and balance complaints. Decreased VA, need for larger font size when reading, need for larger magnification, and decreased self-rated visual function were identified as risk markers for increased complaints in AMD patients. These complaints were also identified as risk markers for decreased health. For controls, decreased VA and self-reported visual function were associated with increased visual and balance complaints. Conclusions. Visual deterioration was a risk marker for increased visual, musculoskeletal, balance, and health complaints in AMD patients. Specifically, magnifying visual aids, such as CCTV, were a risk marker for increased complaints in AMD patients. This calls for early and coordinated actions to treat and prevent visual, musculoskeletal, balance, and health complaints in AMD patients. PMID:27830084

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

PubMed

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.

Population-based incidence of exudative age-related macular degeneration and ranibizumab treatment load.

PubMed

Geirsdottir, Asbjorg; Jonsson, Oskar; Thorisdottir, Sigridur; Helgadottir, Gudleif; Jonasson, Fridbert; Stefansson, Einar; Sigurdsson, Haraldur

2012-03-01

The use of intravitreal vascular endothelial growth factor antibodies for exudative age-related macular degeneration (AMD) has stressed ophthalmology services and drug budgets throughout the world. The authors study the population-based incidence of exudative AMD in Iceland and the use of intravitreal ranibizumab in a defined population. This is a prospective study of 439 consecutive patients aged 60 years and older with exudative AMD starting intravitreal ranibizumab for exudative AMD in Iceland from March 2007 to December 2009. All patients initially received three consecutive ranibizumab injections, with regular follow-up visits and re-treatment as needed. In total, 517 eyes from 439 patients received treatment for exudative AMD (mean age 79 years). The annual incidence of exudative AMD in the population 60 years and older is 0.29%. The incidence increased with advancing age, double for patients 85 years and older compared with those 75-79 years. Approximately 2400 ranibizumab injections per 100,000 persons aged 60 years and older were given each year for exudative AMD. These data allow an estimation of the incidence of exudative AMD in a Caucasian population and the treatment load with ranibizumab, which may help plan anti-vascular endothelial growth factor treatment programmes and estimate costs.

Plasma Homocysteine and Asymmetrical Dimethyl-l-Arginine (ADMA) and Whole Blood DNA Methylation in Early and Neovascular Age-Related Macular Degeneration: A Pilot Study.

PubMed

Pinna, Antonio; Zinellu, Angelo; Tendas, Donatella; Blasetti, Francesco; Carru, Ciriaco; Castiglia, Paolo

2016-01-01

To compare the plasma levels of homocysteine and asymmetrical dimethyl-l-arginine (ADMA) and the degree of whole blood DNA methylation in patients with early and neovascular age-related macular degeneration (AMD) and in controls without maculopathy of any sort. This observational case-control pilot study included 39 early AMD patients, 27 neovascular AMD patients and 132 sex- and age-matched controls without maculopathy. Plasma homocysteine and ADMA concentrations and the degree of whole blood DNA methylation were measured. Quantitative variables were compared by Student's t-test or Mann-Whitney test. Logistic regression models were used to investigate the significance of the association between early or wet AMD and some variables. There were no significant differences in mean plasma homocysteine and ADMA concentrations and in the degree of whole blood DNA methylation between patients with early or neovascular AMD and their controls. Similarly, logistic regression analysis disclosed that plasma homocysteine and ADMA levels were not associated with an increased risk for early or neovascular AMD. We failed to demonstrate an association between early or neovascular AMD and increased plasma homocysteine and/or ADMA. Results also suggest that the degree of whole blood DNA methylation is not a marker of AMD.

Early and intermediate age-related macular degeneration: update and clinical review.

PubMed

García-Layana, Alfredo; Cabrera-López, Francisco; García-Arumí, José; Arias-Barquet, Lluís; Ruiz-Moreno, José M

2017-01-01

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries. With the aging of population, AMD will become globally an increasingly important and prevalent disease worldwide. It is a complex disease whose etiology is associated with both genetic and environmental risk factors. An extensive decline in the quality of life and progressive need of daily living assistance resulting from AMD among those most severely affected highlights the essential role of preventive strategies, particularly advising patients to quit smoking. In addition, maintaining a healthy diet, controlling other risk factors (such as hypertension, obesity, and atherosclerosis), and the use of nutritional supplements (antioxidants) are recommendable. Genetic testing may be especially important in patients with a family history of AMD. Recently, unifying criteria for the clinical classification of AMD, defining no apparent aging changes; normal aging changes; and early, intermediate, and late AMD stages, are of value in predicting AMD risk of progression and in establishing recommendations for the diagnosis, therapeutic approach, and follow-up of patients. The present review is focused on early and intermediate AMD and presents a description of the clinical characteristics and ophthalmological findings for these stages, together with algorithms for the diagnosis and management of patients, which are easily applicable in daily clinical practice.

Early and intermediate age-related macular degeneration: update and clinical review

PubMed Central

García-Layana, Alfredo; Cabrera-López, Francisco; García-Arumí, José; Arias-Barquet, Lluís; Ruiz-Moreno, José M

2017-01-01

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries. With the aging of population, AMD will become globally an increasingly important and prevalent disease worldwide. It is a complex disease whose etiology is associated with both genetic and environmental risk factors. An extensive decline in the quality of life and progressive need of daily living assistance resulting from AMD among those most severely affected highlights the essential role of preventive strategies, particularly advising patients to quit smoking. In addition, maintaining a healthy diet, controlling other risk factors (such as hypertension, obesity, and atherosclerosis), and the use of nutritional supplements (antioxidants) are recommendable. Genetic testing may be especially important in patients with a family history of AMD. Recently, unifying criteria for the clinical classification of AMD, defining no apparent aging changes; normal aging changes; and early, intermediate, and late AMD stages, are of value in predicting AMD risk of progression and in establishing recommendations for the diagnosis, therapeutic approach, and follow-up of patients. The present review is focused on early and intermediate AMD and presents a description of the clinical characteristics and ophthalmological findings for these stages, together with algorithms for the diagnosis and management of patients, which are easily applicable in daily clinical practice. PMID:29042759

OpenACC acceleration of an unstructured CFD solver based on a reconstructed discontinuous Galerkin method for compressible flows

DOE PAGES

Xia, Yidong; Lou, Jialin; Luo, Hong; ...

2015-02-09

Here, an OpenACC directive-based graphics processing unit (GPU) parallel scheme is presented for solving the compressible Navier–Stokes equations on 3D hybrid unstructured grids with a third-order reconstructed discontinuous Galerkin method. The developed scheme requires the minimum code intrusion and algorithm alteration for upgrading a legacy solver with the GPU computing capability at very little extra effort in programming, which leads to a unified and portable code development strategy. A face coloring algorithm is adopted to eliminate the memory contention because of the threading of internal and boundary face integrals. A number of flow problems are presented to verify the implementationmore » of the developed scheme. Timing measurements were obtained by running the resulting GPU code on one Nvidia Tesla K20c GPU card (Nvidia Corporation, Santa Clara, CA, USA) and compared with those obtained by running the equivalent Message Passing Interface (MPI) parallel CPU code on a compute node (consisting of two AMD Opteron 6128 eight-core CPUs (Advanced Micro Devices, Inc., Sunnyvale, CA, USA)). Speedup factors of up to 24× and 1.6× for the GPU code were achieved with respect to one and 16 CPU cores, respectively. The numerical results indicate that this OpenACC-based parallel scheme is an effective and extensible approach to port unstructured high-order CFD solvers to GPU computing.« less

Micro-Devices Using Resistance Change Materials (MODERN Materials)

DTIC Science & Technology

2014-03-07

subcontractors/co-PIs on this program Taskl; subtaskl Design of micro-devices based on resistance change materials Taskl; subtask2 Fabrication and process...currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE ( DD -MM-YYYY) 07/03/2014 2. REPORT TYPE Final...Technical Report 3. DATES COVERED (From Jan 2013-May 2014 To) 4. TITLE AND SUBTITLE Micro Devices based on Resistance Change Materials 5a

A micro alkaline direct ethanol fuel cell with platinum-free catalysts

NASA Astrophysics Data System (ADS)

Verjulio, R. W.; Alcaide, F.; Álvarez, G.; Sabaté, N.; Torres-Herrero, N.; Esquivel, J. P.; Santander, J.

2013-11-01

This paper presents the fabrication and characterization of a micro alkaline direct ethanol fuel cell. The device has been conceived as a feasibility demonstrator, using microtechnologies for the fabrication of the current collectors and traditional techniques for the membrane electrode assembly production. The fuel cell works in passive mode, as expected for the simplicity required for micro power systems. Non-noble catalysts have been used in order to implement the main advantage of alkaline systems, showing the feasibility of such a device as a potential very-low-cost power device at mini- and micro scales.

Animal models of age related macular degeneration

PubMed Central

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

2013-01-01

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

Dry Age-Related Macular Degeneration Pharmacology

PubMed Central

Wright, Charles B.

2017-01-01

Age-related macular degeneration (AMD), the most common form of irreversible blindness in the industrially developed world, can present years before a patient begins to lose vision. For most of these patients, AMD never progresses past its early stages to the advanced forms that are principally responsible for the vast majority of vision loss. Advanced AMD can manifest as either an advanced avascular form known as geographic atrophy (GA) marked by regional retinal pigment epithelium (RPE) cell death or as an advanced form known as neovascular AMD marked by the intrusion of fragile new blood vessels into the normally avascular retina. Physicians have several therapeutic interventions available to combat neovascular AMD, but GA has no approved effective therapies as of yet. In this chapter, we will discuss the current strategies for limiting dry AMD in patients. We will also discuss previous attempts at pharmacological intervention that were tested in a clinical setting and consider reasons why these putative therapeutics did not perform successfully in large-scale trials. Despite the number of unsuccessful past trials, new pharmacological interventions may succeed. These future therapies may aid millions of AMD patients worldwide. PMID:27900609

Source and fate of inorganic soil contamination around the abandoned Phillips sulfide mine, hudson Highlands, New York

USGS Publications Warehouse

Gilchrist, S.; Gates, A.; Elzinga, E.; Gorring, M.; Szabo, Z.

2011-01-01

The abandoned Phillips sulfide mine in the critical Highlands watershed in New York has been shown to produce strongly acidic mine drainage (AMD) with anomalous metal contaminants in first-order streams that exceeded local water standards by up to several orders of magnitude (Gilchrist et al., 2009). The metal-sulfide-rich tailings also produce contaminated soils with pH < 4, organic matter < 2.5% and trace metals sequestered in soil oxides. A geochemical transect to test worst-case soil contamination showed that Cr, Co and Ni correlated positively with Mn, (r = 0.72, r= 0.89, r = 0.80, respectively), suggesting Mn-oxide sequestration and that Cu and Pb correlated with Fe (r = 0.76, r = 0.83, respectively), suggesting sequestration in goethite. Ubiquitous, yellow coating on the mine wastes, including jarosite and goethite, is a carrier of the metals. Geochemical and μ-SXRF analyses determined Cu to be the major soil contaminant. μ-SXRF also demonstrated that the heterogeneous nature of the soil chemistry at the micro-meter scale is self-similar to those in the bulk soil samples. Generally metals decreased, with some fluctuations, rapidly downslope through suspension of fines and dissolution in AMD leaving the area of substantial contamination << 0.5 km from the source.

Acute mental disorders and short and long term morbidity in patients with third degree flame burn: A population-based outcome study of 96,451 patients from the Nationwide Inpatient Sample (NIS) database (2001-2011).

PubMed

Mahendraraj, Krishnaraj; Durgan, Diane M; Chamberlain, Ronald S

2016-12-01

Although burn patients with preexisting mood disorders have been shown to have diminished clinical recovery, acute mental disorders (AMD) are often unrecognized despite a link with post-traumatic stress disorder and social maladjustment later on. This study assessed the clinical profile of a large cohort of burn patients who developed AMD compared to those with chronic mental illness (CMI) and those without mental health problems to assess the impact of AMI on burn outcomes. Admission data on 96,451 patients with third degree flame burns was abstracted from the Nationwide Inpatient Sample (NIS) Database from 2001 to 2011. AMD was defined as adjustment disorder (ICD-10 codes F43.2-F43.29) and acute stress disorder (F43.0), while CMI was defined as major depressive disorder (F33.0-F33.9) and bipolar disorder (F31.0-F31.9). Data was compared across three subgroups: AMD, CMI, and patients without any mood disorders. Categorical variables were compared using the Chi-square test, and continuous variables were compared using Student t-test and analysis of variance (ANOVA). Multivariate analysis using the "backward Wald" method was performed to calculate odds ratios (OR) and determine independent factors which increased the risk of developing AMD after burn. 979 (1%) burn patients were diagnosed with AMD, compared to 5971 (6.2%) with CMI and 89,501 (92.8%) without mood disorders at the time of the burn. Patients with AMD were significantly younger, predominantly male and Caucasian. Patients with AMD had a higher frequency of multiple third-degree burn sites. AMD patients had a significantly longer length of hospitalization and shorter actuarial survival. More AMD patients lacked social or family support, suffered from alcoholism or illicit drug abuse, and had a history of psychological trauma or self-inflicted injuries compared to other groups. After burn, 4.9% of AMD patients developed burn wound infections, 5.0% had nutritional deficiencies, 1.7% had skin graft failure, 0.7% had acute psychosis, and 3.7% had suicidal ideation, p<0.05. Multivariate analysis identified age 10-39 (OR 4.6), alcoholism (OR 1.4), drug abuse (OR 1.9), psychoses (OR 1.4), and total body surface are (TBSA) 10-39% third degree burns (OR 1.8) as independently associated with developing AMD, p<0.005. The development of AMD in burn patients is associated with poor clinical outcomes including longer hospitalization, decreased survival, and increased complication rates. Premorbid psychopathology, substance abuse and age were associated with a higher incidence AMD after burn than was the severity of the burn wound itself. Routine screening for psychological symptoms of AMD should be performed in all burn patients to avoid increased rates of short and long-term morbidity and mortality. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Biotechnology

NASA Image and Video Library

2000-12-15

NASA is looking to biological techniques that are millions of years old to help it develop new materials and nanotechnology for the 21st century. Sponsored by NASA, Jerzy Bernholc, a principal investigator in the microgravity materials science program and a physics professor at North Carolina State University, Bernholc works with very large-scale computations to model carbon molecules as they assemble themselves to form nanotubes. The strongest confirmed material known, nanotubes are much stronger than graphite, a more common material made of carbon, and weigh six times less than steel. Nanotubes have potential uses such as strain gauges, advanced electronic devices, amd batteries. The strength, light weight, and conductive qualities of nanotubes, shown in light blue in this computed electron distribution, make them excellent components of nanoscale devices. One way to conduct electricity to such devices is through contact with aluminum, shown in dark blue.

Complement activation and choriocapillaris loss in early AMD: Implications for pathophysiology and therapy

PubMed Central

Whitmore, S.Scott; Sohn, Elliott H.; Chirco, Kathleen R.; Drack, Arlene V.; Stone, Edwin M.; Tucker, Budd A.; Mullins, Robert F.

2015-01-01

Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies. PMID:25486088

Complement activation and choriocapillaris loss in early AMD: implications for pathophysiology and therapy.

PubMed

Whitmore, S Scott; Sohn, Elliott H; Chirco, Kathleen R; Drack, Arlene V; Stone, Edwin M; Tucker, Budd A; Mullins, Robert F

2015-03-01

Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies. Copyright © 2014 Elsevier Ltd. All rights reserved.

miRNAs as potential therapeutic targets for age-related macular degeneration.

PubMed

Wang, Shusheng; Koster, Kyle M; He, Yuguang; Zhou, Qinbo

2012-03-01

Since their recent discovery, miRNAs have been shown to play critical roles in a variety of pathophysiological processes. Such processes include pathological angiogenesis, the oxidative stress response, immune response and inflammation, all of which have been shown to have important and interdependent roles in the pathogenesis and progression of age-related macular degeneration (AMD). Here we present a brief review of the pathological processes involved in AMD and review miRNAs and other noncoding RNAs involved in regulating these processes. Specifically, we discuss several candidate miRNAs that show promise as AMD therapeutic targets due to their direct involvement in choroidal neovascularization or retinal pigment epithelium atrophy. We discuss potential miRNA-based therapeutics and delivery methods for AMD and provide future directions for the field of miRNA research with respect to AMD. We believe the future of miRNAs in AMD therapy is promising.

Age-related macular degeneration: current treatments

PubMed Central

Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D

2009-01-01

Purpose: Although important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options. Design: Interpretative essay. Methods: Literature review and interpretation. Results: Current treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intravitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system. Conclusion: By better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity. PMID:19668560

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

PubMed

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.

Micro Ring Grating Spectrometer with Adjustable Aperture

NASA Technical Reports Server (NTRS)

Park, Yeonjoon (Inventor); King, Glen C. (Inventor); Elliott, James R. (Inventor); Choi, Sang H. (Inventor)

2012-01-01

A spectrometer includes a micro-ring grating device having coaxially-aligned ring gratings for diffracting incident light onto a target focal point, a detection device for detecting light intensity, one or more actuators, and an adjustable aperture device defining a circular aperture. The aperture circumscribes a target focal point, and directs a light to the detection device. The aperture device is selectively adjustable using the actuators to select a portion of a frequency band for transmission to the detection device. A method of detecting intensity of a selected band of incident light includes directing incident light onto coaxially-aligned ring gratings of a micro-ring grating device, and diffracting the selected band onto a target focal point using the ring gratings. The method includes using an actuator to adjust an aperture device and pass a selected portion of the frequency band to a detection device for measuring the intensity of the selected portion.

HIgh-Q Optical Micro-cavity Resonators as High Sensitive Bio-chemical and Ultrasonic Sensors

NASA Astrophysics Data System (ADS)

Ling, Tao

Optical micro-cavity resonators have quickly emerged in the past few years as a new sensing platform in a wide range of applications, such as bio-chemical molecular detection, environmental monitoring, acoustic and electromagnetic waves detection. In this thesis, we will mainly focus on developing high sensitivity silica micro-tube resonator bio-chemical sensors and high sensitivity polymer micro-ring resonator acoustic sensors. In high sensitivity silica micro-tube resonator bio-chemical sensors part: We first demonstrated a prism coupled silica micro-tube bio-chemical sensing platform to overcome the reliability problem in a fiber coupled thin wall silica micro-tube sensing platform. In refractive index sensing experiment, a unique resonance mode with sensitivity around 600nm/refractive index unit (RIU) has been observed. Surface sensing experiments also have been performed in this platform to detect lipid monolayer, lipid bilayer, electrostatic self assemble layer-by-layer as well as the interaction between the lipid bilayer and proteins. Then a theoretical study on various sensing properties on the silica micro-tube based sensing platform has been realized. Furthermore, we have proposed a coupled cavity system to further enhance the device's sensitivity above 1000nm/RIU. In high sensitivity polymer micro-ring resonator acoustic sensors part: We first presented a simplified fabrication process and realized a polymer microring with a Q factor around 6000. The fabricated device has been used to detect acoustic wave with noise equivalent pressure (NEP) around 230Pa over 1-75MHz frequency rang, which is comparable to state-of-art piezoelectric transducer and the device's frequency response also have been characterized to be up to 90MHz. A new fabrication process combined with resist reflow and thermal oxidation process has been used to improve the Q factor up to 10 5 and the device's NEP has been tested to be around 88Pa over 1-75MHz range. Further improving the device's Q factor has been realized by shifting the device's working wavelength to near-visible wavelength and further reducing the device's sidewall roughness. A record new high Q-˜x105 has been measured and the device's NEP as low as 21Pa has been measured. Furthermore, a smaller size polymer microring device has been developed and fabricated to realize larger angle beam forming applications.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Erin W.; Schaumberg, Debra A.; Center for Translational Medicine, Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT

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 2005–2008more » 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-related macular degeneration (AMD) in U.S. adults. • Cadmium in both blood and urine was borderline significantly associated with the risk of AMD. • Blood lead was not associated with the risk of AMD. • The association between urine cadmium and AMD was stronger in whites than in blacks.« less

Incidence of Age-Related Macular Degeneration in a Multi-Ethnic United States Population: The Multi-Ethnic Study of Atherosclerosis.

PubMed

Fisher, Diana E; Klein, Barbara E K; Wong, Tien Y; Rotter, Jerome I; Li, Xiaohui; Shrager, Sandi; Burke, Gregory L; Klein, Ronald; Cotch, Mary Frances

2016-06-01

To describe the incidence of age-related macular degeneration (AMD) and associated risk factors in 4 racial/ethnic groups (white, black, Hispanic, and Chinese) residing in the United States. Prospective cohort study. A total of 3811 participants, aged 46 to 86 years, from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, with retinal data collected twice, on average, 8 years apart. Fundus images, taken using a digital camera through dark-adapted pupils using a standard protocol and the same equipment at both study visits, were graded centrally for early and late AMD on the basis of drusen size, type and area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Demographic, clinical, and laboratory measures were included in multivariable regression models to determine their impact on the variation in AMD incidence among racial/ethnic groups. Incident early and late AMD. The overall 8-year age- and sex-standardized incidence of early and late AMD were 4.1% and 2.3%, respectively, with incidence of early and late AMD highest in whites (5.3% and 4.1%, respectively), intermediate in Chinese (4.5% and 2.2%, respectively) and Hispanics (3.3% and 0.8%, respectively), and lowest in blacks (1.6% and 0.4%, respectively). By adjusting for age and sex, blacks had a 70% lower risk of developing early AMD than whites, and this decreased only slightly to a 67% lower risk after multivariable adjustment. By adjusting for age, sex, and race/ethnicity, hyperopia was associated with early AMD (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.20), as was astigmatism (OR, 1.47; 95% CI, 1.00-2.16), but not myopia (P = 0.29). Age, race/ethnicity, current smoking, hyperopia, and AMD-susceptibility genotypes Complement Factor H (CFH) RS1061170 and Age Related Maculopathy Susceptibility 2 (ARMS2) RS3793917 were independently associated with incident early AMD in multivariable models for the combined sample. However, the only statistically significant factor consistently associated with incident early AMD across the 4 racial/ethnic groups was increasing age. Risk factors for late AMD were not assessed because of its low incidence, particularly across racial/ethnic groups. Variation in the incidence of early AMD exists among racial/ethnic groups in the United States and is not explained by the clinical, genetic, and environmental factors included in this study. Published by Elsevier Inc.

Peripheral blood mononuclear cells from neovascular age-related macular degeneration patients produce higher levels of chemokines CCL2 (MCP-1) and CXCL8 (IL-8).

PubMed

Lechner, Judith; Chen, Mei; Hogg, Ruth E; Toth, Levente; Silvestri, Giuliana; Chakravarthy, Usha; Xu, Heping

2017-02-23

Infiltrating immune cells including monocytes/macrophages have been implicated in the pathogenesis of neovascular age-related macular degeneration (nAMD). The aim of this study was to investigate the cytokine and chemokine expression and secretion profile of peripheral blood mononuclear cells (PBMCs) from nAMD patients and the relationship between the cytokine/chemokine expression profile and clinical phenotype of nAMD, including macular fibrosis, macular atrophy or the responsiveness to anti-VEGF therapy. One hundred sixty-one nAMD patients and 43 controls were enrolled in this study. nAMD patients were divided into subgroups based on the presence/absence of (1) macular atrophy, (2) macular fibrosis and (3) responsiveness to anti-VEGF therapy; 25-30 ml of peripheral blood were obtained from all participants and 5 ml were used for serum collection, and the remaining were used for PBMC isolation using density gradient centrifugation. Intracellular cytokine expressions by PBMCs following phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulation were examined using flow cytometry. Cytokine productions in lipopolysaccharides (LPS)-or 1% oxygen -treated PBMC were measured using cytometric bead array (CBA) assay. In addition, cytokine and chemokine levels in the serum were also measured by CBA assay. PBMCs from nAMD patients secreted higher levels of IL-8, CCL2 and VEGF, especially following LPS and 1% oxygen stimulation, than those from controls. 60~80% of IL-8 producing cells were CD11b + CD3 - monocytes. The percentage of CD11b + CD3 - IL-8 + was significantly increased in nAMD patients compared to controls. PBMCs from nAMD patients without macular fibrosis produced the highest levels of IL-8 and CCL2, whilst PBMCs from nAMD patients with macular atrophy produced highest levels of VEGF. In addition, PBMCs from patients who partially responded to anti-VEGF produced higher levels of IL-8 compared to the cells from complete responders. Interestingly, serum level of CCL2 was not increased in nAMD patients although there was a trend of increased IL-8 in nAMD patients. PBMCs, in particular monocytes, may contribute to CNV development in nAMD through secreting elevated levels of IL-8, CCL2 and VEGF after they are recruited to the macula. Apart from VEGF, IL-8 and CCL2 may be additional targets for nAMD management.

Oxidative stress, innate immunity, and age-related macular degeneration

PubMed Central

Shaw, Peter X.; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

2016-01-01

Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have previously hypothesized that the tight homeostatic control of inflammation via the innate immune system is likely critical for avoidance of disease progression. However, the presence of a multitude of potential triggers of inflammation results in a sensitive balance in which perturbations thereof would subsequently alter the inflammatory state of the retina, leading to a state of chronic inflammation and pathologic progression. In this review, we will highlight the background literature surrounding the known genetic and environmental contributors to AMD risk, as well as a discussion of the potential mechanistic interplay of these factors that lead to disease pathogenesis with particular emphasis on the delicate control of inflammatory homeostasis and the centrality of the innate immune system in this process. PMID:27239555

[Macular choroidal blood flow in concurrent age-related macular degeneration and primary open-angle glaucoma].

PubMed

Panova, I E; Ermak, E M; Shaimova, T A; Shaimova, V A

2016-01-01

Ocular circulation disorders are an important factor in the development of primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD). To date, however, there have been no studies on choroidal blood flow peculiarities in case of concurrent AMD and POAG. to determine distinctive features of choroidal blood flow characteristic of concurrent AMD and POAG and to assess their role in disease pathogenesis. Macular choroidal blood flow, including blood supply, was assessed in 54 patients (102 eyes) by means of Doppler ultrasound. Three groups were formed: group 1 - 38 eyes with both AMD and POAG; group 2 - 41 eyes with AMD and no signs of optic nerve pathology; and group 3 - 23 eyes with POAG and no signs of AMD. Groups 1 and 2 were subdivided into two subgroups each: А - atrophic AMD and B - macular drusen. The mean patient age was 78.7±8.4 years. The following parameters of choroidal blood flow were of interest: peak systolic velocity (Vps), end diastolic velocity (Ved), time-averaged maximum velocity (Vtamax), and resistance index (RI). Groups 1, 3, and 2A had an evident choroidal hypoperfusion in the macular area (decreased Vtamax) with uncompensated perfusion deficit, despite autoregulation efforts (decreased Vps, Ved, decreased or normal RI). Group 2B demonstrated a significantly higher rate of choroidal hyperperfusion (increased Vps, Ved, Vtamax, and RI). Concurrent AMD and POAG are notable for choroidal hypoperfusion in the macular area that leads to inadequate trophism of the neurosensory retina and can aggravate the course of AMD contributing to progression of its atrophic form.

Age-related macular degeneration: the importance of family history as a risk factor.

PubMed

Shahid, Humma; Khan, Jane C; Cipriani, Valentina; Sepp, Tiina; Matharu, Baljinder K; Bunce, Catey; Harding, Simon P; Clayton, David G; Moore, Anthony T; Yates, John R W

2012-03-01

Family history is considered a risk factor for age-related macular degeneration (AMD). With the advent of effective therapy for the disease, the importance of family history merits further investigation. This study quantifies the risk associated with family history, first, by a case-control study of reported family history and, second, by examining the siblings of AMD cases. The authors recruited cases with advanced AMD, spouses and siblings. All subjects were carefully phenotyped. Clinical findings in the siblings were compared with spouses. Information about family history was collected. The ORs for reported family history of AMD were calculated. Analyses were adjusted for age, smoking and genotype. 495 AMD cases, 259 spouses and 171 siblings were recruited. The OR for AMD was 27.8 (CI 3.8 to 203.0; p=0.001) with a reported family history of an affected parent and 12.0 (CI 3.7 to 38.6; p<0.0001) with a history of an affected sibling. ORs adjusted for age and smoking were higher. Examination of siblings confirmed their increased risk with 23% affected by AMD and an OR of 10.8 (4.5 to 25.8; p<0.0001). Adjusting for age increased the OR to 16.1 (6.2 to 41.8). The risk of AMD is greatly increased by having an affected first-degree relative. Those at risk need to be made aware of this and AMD patients should advise siblings and children to seek prompt ophthalmological advice if they develop visual symptoms of distortion or reduced vision.

Complement Factor D in Age-Related Macular Degeneration

PubMed Central

Stanton, Chloe M.; Yates, John R.W.; den Hollander, Anneke I.; Seddon, Johanna M.; Swaroop, Anand; Stambolian, Dwight; Fauser, Sascha; Hoyng, Carel; Yu, Yi; Atsuhiro, Kanda; Branham, Kari; Othman, Mohammad; Chen, Wei; Kortvely, Elod; Chalmers, Kevin; Hayward, Caroline; Moore, Anthony T.; Dhillon, Baljean; Ueffing, Marius

2011-01-01

Purpose. To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations. Methods. Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by binary logistic regression. CFD gene copy number was analyzed by gene copy number assay. Plasma CFD was measured by an enzyme-linked immunosorbent assay. Results. Genetic association was found between CFD gene SNP rs3826945 and AMD (odds ratio 1.44; P = 0.028) in a small discovery case-control series (462 cases and 325 controls) and replicated in a combined cohorts meta-analysis of 4765 cases and 2693 controls, with an odds ratio of 1.11 (P = 0.032), with the association almost confined to females. Copy number variation in the CFD gene was identified in 13 out of 640 samples examined but there was no difference in frequency between AMD cases (1.3%) and controls (2.7%). Plasma CFD concentration was measured in 751 AMD cases and 474 controls and found to be elevated in AMD cases (P = 0.00025). The odds ratio for those in the highest versus lowest quartile for plasma CFD was 1.81. The difference in plasma CFD was again almost confined to females. Conclusions. CFD regulates activation of the alternative complement pathway, which is implicated in AMD pathogenesis. The authors found evidence for genetic association between a CFD gene SNP and AMD and a significant increase in plasma CFD concentration in AMD cases compared with controls, consistent with a role for CFD in AMD pathogenesis. PMID:22003108

Dactinomycin and Vincristine Toxicity in the Treatment of Childhood Cancer: A Retrospective Study from the Children’s Oncology Group

PubMed Central

Langholz, Bryan; Skolnik, Jeffrey M.; Barrett, Jeffrey S.; Renbarger, Jamie; Seibel, Nita L.; Zajicek, Anne; Arndt, Carola A.S.

2011-01-01

Background Dactinomycin (AMD) and vincristine (VCR) have been used for the treatment of childhood cancer over the past 40 years but evidence-based dosing guidance is lacking. Methods Patient AMD and VCR dose and drug-related adverse event (AE) information from four rhabdomyosarcoma (RMS) and two Wilms tumor (WT) studies were assembled. Statistical modeling was used to account for differences in AE data collection across studies, develop rate models for grade 3/4 CTCAE v3 hepatic- (AMD) and neuro- (AMD) toxicity, assess variation in toxicity rates over age and other factors, and predict toxicity risk under current dosing guidelines. Results For the same dose/body size, AMD toxicity rates were higher in patients <1 year than older patients and VCR toxicity rates increased with age. The statistical model provided estimates for AMD and VCR toxicity risk under current dosing schedules and indicated that patients of smaller body size were at lower risk of VCR toxicity than larger patients of the same age. The rate of AMD toxicity was highest early in treatment and was lower in patients who tolerated initial AMD without toxicity. Conclusion The observed decrease in AMD toxicity rate with cumulative dose may indicate sensitivity in a subgroup of patients while the observed increase in VCR toxicity risk with age may indicate changing sensitivity to VCR. Current dosing practices result in a fairly uniform toxicity profile within age group. However, PK/PD studies should be done to provide further provide further information on best dosing guidelines. PMID:21671362

The association of aspirin use with age-related macular degeneration.

PubMed

Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Rochtchina, Elena; Wang, Jie Jin

2013-02-25

To determine whether regular aspirin use is associated with a higher risk for developing age-related macular degeneration (AMD) by using analyzed data from a 15-year prospective cohort. A prospective analysis was conducted of data from an Australian population-based cohort with 4 examinations during a 15-year period (1992-1994 to 2007-2009). Participants completed a detailed questionnaire at baseline assessing aspirin use, cardiovascular disease status, and AMD risk factors. Age-related macular degeneration was graded side-by-side from retinal photographs taken at each study visit to assess the incidence of neovascular (wet) AMD and geographic atrophy (dry AMD) according to the international AMD classification. Of 2389 baseline participants with follow-up data available, 257 individuals (10.8%) were regular aspirin users and 63 of the 2389 developed neovascular AMD. Persons who were regular aspirin users were more likely to have incident neovascular AMD: the 15-year cumulative incidence was 9.3% in users and 3.7% in nonusers. After adjustment for age, sex, smoking, history of cardiovascular disease, systolic blood pressure, and body mass index, persons who were regular aspirin users had a higher risk of developing neovascular AMD (odds ratio [OR], 2.46; 95% CI, 1.25-4.83). The association showed a dose-response effect (multivariate-adjusted P = .01 for trend). Aspirin use was not associated with the incidence of geographic atrophy (multivariate-adjusted OR, 0.99; 95% CI, 0.59-1.65). Regular aspirin use is associated with increased risk of incident neovascular AMD, independent of a history of cardiovascular disease and smoking.

Fabrication of microfluidic architectures for optimal flow rate and concentration measurement for lab on chip application

NASA Astrophysics Data System (ADS)

Adam, Tijjani; Hashim, U.

2017-03-01

Optimum flow in micro channel for sensing purpose is challenging. In this study, The optimizations of the fluid sample flows are made through the design and characterization of the novel microfluidics' architectures to achieve the optimal flow rate in the micro channels. The biocompatibility of the Polydimetylsiloxane (Sylgard 184 silicon elastomer) polymer used to fabricate the device offers avenue for the device to be implemented as the universal fluidic delivery system for bio-molecules sensing in various bio-medical applications. The study uses the following methodological approaches, designing a novel microfluidics' architectures by integrating the devices on a single 4 inches silicon substrate, fabricating the designed microfluidic devices using low-cost solution soft lithography technique, characterizing and validating the flow throughput of urine samples in the micro channels by generating pressure gradients through the devices' inlets. The characterization on the urine samples flow in the micro channels have witnessed the constant flow throughout the devices.

Whole-Exome Sequencing in Age-Related Macular Degeneration Identifies Rare Variants in COL8A1, a Component of Bruch's Membrane.

PubMed

Corominas, Jordi; Colijn, Johanna M; Geerlings, Maartje J; Pauper, Marc; Bakker, Bjorn; Amin, Najaf; Lores Motta, Laura; Kersten, Eveline; Garanto, Alejandro; Verlouw, Joost A M; van Rooij, Jeroen G J; Kraaij, Robert; de Jong, Paulus T V M; Hofman, Albert; Vingerling, Johannes R; Schick, Tina; Fauser, Sascha; de Jong, Eiko K; van Duijn, Cornelia M; Hoyng, Carel B; Klaver, Caroline C W; den Hollander, Anneke I

2018-04-26

Genome-wide association studies and targeted sequencing studies of candidate genes have identified common and rare variants that are associated with age-related macular degeneration (AMD). Whole-exome sequencing (WES) studies allow a more comprehensive analysis of rare coding variants across all genes of the genome and will contribute to a better understanding of the underlying disease mechanisms. To date, the number of WES studies in AMD case-control cohorts remains scarce and sample sizes are limited. To scrutinize the role of rare protein-altering variants in AMD cause, we performed the largest WES study in AMD to date in a large European cohort consisting of 1125 AMD patients and 1361 control participants. Genome-wide case-control association study of WES data. One thousand one hundred twenty-five AMD patients and 1361 control participants. A single variant association test of WES data was performed to detect variants that are associated individually with AMD. The cumulative effect of multiple rare variants with 1 gene was analyzed using a gene-based CMC burden test. Immunohistochemistry was performed to determine the localization of the Col8a1 protein in mouse eyes. Genetic variants associated with AMD. We detected significantly more rare protein-altering variants in the COL8A1 gene in patients (22/2250 alleles [1.0%]) than in control participants (11/2722 alleles [0.4%]; P = 7.07×10 -5 ). The association of rare variants in the COL8A1 gene is independent of the common intergenic variant (rs140647181) near the COL8A1 gene previously associated with AMD. We demonstrated that the Col8a1 protein localizes at Bruch's membrane. This study supported a role for protein-altering variants in the COL8A1 gene in AMD pathogenesis. We demonstrated the presence of Col8a1 in Bruch's membrane, further supporting the role of COL8A1 variants in AMD pathogenesis. Protein-altering variants in COL8A1 may alter the integrity of Bruch's membrane, contributing to the accumulation of drusen and the development of AMD. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The calibration of a model for simulating the thermal and electrical performance of a 2.8 kW AC solid-oxide fuel cell micro-cogeneration device

NASA Astrophysics Data System (ADS)

Beausoleil-Morrison, Ian; Lombardi, Kathleen

The concurrent production of heat and electricity within residential buildings using solid-oxide fuel cell (SOFC) micro-cogeneration devices has the potential to reduce primary energy consumption, greenhouse gas emissions, and air pollutants. A realistic assessment of this emerging technology requires the accurate simulation of the thermal and electrical production of SOFC micro-cogeneration devices concurrent with the simulation of the building, its occupants, and coupled plant components. The calibration of such a model using empirical data gathered from experiments conducted with a 2.8 kW AC SOFC micro-cogeneration device is demonstrated. The experimental configuration, types of instrumentation employed, and the operating scenarios examined are treated. The propagation of measurement uncertainty into the derived quantities that are necessary for model calibration are demonstrated by focusing upon the SOFC micro-cogeneration system's gas-to-water heat exchanger. The calibration coefficients necessary to accurately simulate the thermal and electrical performance of this prototype device are presented and the types of analyses enabled to study the potential of the technology are demonstrated.

Immunology of age-related macular degeneration

PubMed Central

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

2014-01-01

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

Immunology of age-related macular degeneration.

PubMed

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

2013-06-01

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

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

PubMed

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.

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

PubMed

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.

A review of the evidence for dietary interventions in preventing or slowing the progression of age-related macular degeneration.

PubMed

Evans, Jennifer R; Lawrenson, John G

2014-07-01

To summarise the results of recent Cochrane systematic reviews that have investigated whether nutritional supplements prevent or slow the progression of age-related macular degeneration (AMD). There is no good evidence from randomised controlled trials that the general population should be taking antioxidant vitamin supplements to reduce their risk of developing AMD later on in life. By contrast, there is moderate quality evidence that people with AMD may experience a delay in progression by taking specific antioxidant vitamin and mineral supplements. This finding is drawn from one large randomised controlled trial conducted in the USA in a relatively well-nourished population. Although observational studies have shown that the consumption of dietary omega 3 long chain polyunsaturated fatty acids may reduce the risk of progression to advanced AMD, two recently published randomised controlled trials failed to show any benefit of omega 3 supplements on AMD progression. There is no high quality experimental evidence that nutritional supplementation is beneficial for the primary prevention of AMD. However, people with AMD may benefit from supplementation with antioxidant vitamins. There is currently no evidence to support increasing levels of omega 3 long chain polyunsaturated fatty acids in the diet for the explicit purpose of preventing or slowing the progression of AMD. © 2014 The Authors Ophthalmic & Physiological Optics © 2014 The College of Optometrists.

Altered gene expression in dry age-related macular degeneration suggests early loss of choroidal endothelial cells.

PubMed

Whitmore, S Scott; Braun, Terry A; Skeie, Jessica M; Haas, Christine M; Sohn, Elliott H; Stone, Edwin M; Scheetz, Todd E; Mullins, Robert F

2013-01-01

Age-related macular degeneration (AMD) is a major cause of blindness in developed countries. The molecular pathogenesis of early events in AMD is poorly understood. We investigated differential gene expression in samples of human retinal pigment epithelium (RPE) and choroid from early AMD and control maculas with exon-based arrays. Gene expression levels in nine human donor eyes with early AMD and nine control human donor eyes were assessed using Affymetrix Human Exon ST 1.0 arrays. Two controls did not pass quality control and were removed. Differentially expressed genes were annotated using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and gene set enrichment analysis (GSEA) was performed on RPE-specific and endothelium-associated gene sets. The complement factor H (CFH) genotype was also assessed, and differential expression was analyzed regarding high AMD risk (YH/HH) and low AMD risk (YY) genotypes. Seventy-five genes were identified as differentially expressed (raw p value <0.01; ≥50% fold change, mean log2 expression level in AMD or control ≥ median of all average gene expression values); however, no genes were significant (adj. p value <0.01) after correction for multiple hypothesis testing. Of 52 genes with decreased expression in AMD (fold change <0.5; raw p value <0.01), 18 genes were identified by DAVID analysis as associated with vision or neurologic processes. The GSEA of the RPE-associated and endothelium-associated genes revealed a significant decrease in genes typically expressed by endothelial cells in the early AMD group compared to controls, consistent with previous histologic and proteomic studies. Analysis of the CFH genotype indicated decreased expression of ADAMTS9 in eyes with high-risk genotypes (fold change = -2.61; raw p value=0.0008). GSEA results suggest that RPE transcripts are preserved or elevated in early AMD, concomitant with loss of endothelial cell marker expression. These results are consistent with the notion that choroidal endothelial cell dropout or dedifferentiation occurs early in the pathogenesis of AMD.

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

PubMed

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

2017-08-01

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

Risk factors for age-related macular degeneration: findings from the Andhra Pradesh eye disease study in South India.

PubMed

Krishnaiah, Sannapaneni; Das, Taraprasad; Nirmalan, Praveen K; Nutheti, Rishita; Shamanna, Bindiganavale R; Rao, Gullapalli N; Thomas, Ravi

2005-12-01

To assess prevalence, potential risk factors, and population attributable risk percentage (PAR%) for age-related macular degeneration (AMD) in the Indian state of Andhra Pradesh. A population-based study, using a stratified, random, cluster, systematic sampling strategy, was conducted in the state of Andhra Pradesh in India from 1996 to 2000. Participants from 94 clusters in one urban and three rural areas representative of the population of Andhra Pradesh underwent a detailed interview and a detailed dilated ocular evaluation by trained professionals. In this report, the authors present the prevalence estimates of AMD and examine the association of AMD with potential risk factors in persons aged 40 to 102 years (n = 3723). AMD was defined according to the international classification and grading system. Standard bivariate and multivariate analyses were performed to identify the potential risk factors for AMD. PAR% was calculated by Levin's formula. AMD was present in 71 subjects--an age-gender-area-adjusted prevalence of 1.82% (95% confidence interval [CI], 1.39%-2.25%). Risk factors that were significant in bivariate analyses were considered for multivariate logistic regression analysis. Multivariate analysis showed that the adjusted prevalence of AMD was significantly higher in those 60 years of age or older (odds ratio [OR], 3.55; 95% CI, 1.61-7.82) and history of prior cigar smoking (OR, 3.29; 95%CI, 1.42-7.57). Presence of cortical cataract and prior cataract surgery were significantly associated with increased prevalence of AMD (adjusted OR, 2.87; 95% CI, 1.57-5.26 and 3.79; 95% CI, 2.1-6.78), respectively. The prevalence of AMD was significantly lower in light alcohol drinkers (adjusted OR, 0.38; 95% CI, 0.19-0.76) compared with nondrinkers. The PAR% for hypertension and heavy cigar smoking was 10% and 14%, respectively, in this population. The prevalence of AMD in this south Indian population is similar to those reported in other developed countries. Abstinence from smoking may reduce the risk of AMD in this population.

Prevalence and the risk factors for visual impairment in age-related macular degeneration.

PubMed

Srinivasan, S; Swaminathan, G; Kulothungan, V; Raman, R; Sharma, T

2017-06-01

PurposeTo characterize the type, and the causes of visual impairment (VI) in various stages of early and late age-related macular degeneration (AMD) and the factors associated with visual impairment in subjects with AMDMethods6617 subjects ≥60 years were enumerated; 5495 (83.04%) participated in eye examination. Of which, 4791 subjects had gradable fundus images. AMD was graded per International ARM Epidemiological Study Group. Subjects underwent detailed ophthalmic exam. VI was defined per the WHO classification. Mild VI was defined as VA less than 6/12 to 6/18, moderate VI-VA less than 6/18 but up to 6/60, severe VI-VA less than 6/60 but up to 3/60 and legal blindness-VA worse than 3/60. Factors associated with VI in AMD was analyzed with univariate and logistic regression analysis.ResultsNine hundred and eighty-eight subjects were identified as having AMD (893 with early AMD and 95 with late AMD); 85% of the subjects (95% CI: 82.7-87.1) had no VI, 13.1% had mild VI (95% CI: 11.1-15.3), 0.8% had severe VI (95% CI: 0.4-1.6), 1.1% had legal blindness (95% CI: 0.6-1.9). Prevalence of any VI was 13.7% in early AMD and 27.4% in late AMD, P=0.0004; age group 65-70 years (OR=1.89, 95% CI: 1.16-3.08, P=0.011), and those ≥75 years (OR=3.67, 95% CI: 1.95-6.91, P=0.0001) had greater odds of VI compared with age group 60-64 years. Male gender was a protective factor for VI (OR=0.57, CI: 0.36-0.90, P=0.016). Cataract (31.8%) and refractive error (28.4%) accounted for a majority of the VI.ConclusionsCataract and refractive error account for a significant proportion of VI in the south Indian population with AMD. Early AMD is the third leading cause of VI. Greater age and female gender are associated with VI in subjects with AMD.

Death by a Thousand Cuts: Micro-Air Vehicles (MAV) in the Service of Air Force Missions

DTIC Science & Technology

2001-04-01

25 Microjets ...based designs need to overcome high operating temperature limitations.67 Microjets A promising, but technically difficult, propulsion and/or power...source is the microjet , a micro-electromechanical system based device about the size of a dime. These devices are based on micro-turbines that are

Multi-layer micro/nanofluid devices with bio-nanovalves

DOEpatents

Li, Hao; Ocola, Leonidas E.; Auciello, Orlando H.; Firestone, Millicent A.

2013-01-01

A user-friendly multi-layer micro/nanofluidic flow device and micro/nano fabrication process are provided for numerous uses. The multi-layer micro/nanofluidic flow device can comprise: a substrate, such as indium tin oxide coated glass (ITO glass); a conductive layer of ferroelectric material, preferably comprising a PZT layer of lead zirconate titanate (PZT) positioned on the substrate; electrodes connected to the conductive layer; a nanofluidics layer positioned on the conductive layer and defining nanochannels; a microfluidics layer positioned upon the nanofluidics layer and defining microchannels; and biomolecular nanovalves providing bio-nanovalves which are moveable from a closed position to an open position to control fluid flow at a nanoscale.

Automated detection of exudative age-related macular degeneration in spectral domain optical coherence tomography using deep learning.

PubMed

Treder, Maximilian; Lauermann, Jost Lennart; Eter, Nicole

2018-02-01

Our purpose was to use deep learning for the automated detection of age-related macular degeneration (AMD) in spectral domain optical coherence tomography (SD-OCT). A total of 1112 cross-section SD-OCT images of patients with exudative AMD and a healthy control group were used for this study. In the first step, an open-source multi-layer deep convolutional neural network (DCNN), which was pretrained with 1.2 million images from ImageNet, was trained and validated with 1012 cross-section SD-OCT scans (AMD: 701; healthy: 311). During this procedure training accuracy, validation accuracy and cross-entropy were computed. The open-source deep learning framework TensorFlow™ (Google Inc., Mountain View, CA, USA) was used to accelerate the deep learning process. In the last step, a created DCNN classifier, using the information of the above mentioned deep learning process, was tested in detecting 100 untrained cross-section SD-OCT images (AMD: 50; healthy: 50). Therefore, an AMD testing score was computed: 0.98 or higher was presumed for AMD. After an iteration of 500 training steps, the training accuracy and validation accuracies were 100%, and the cross-entropy was 0.005. The average AMD scores were 0.997 ± 0.003 in the AMD testing group and 0.9203 ± 0.085 in the healthy comparison group. The difference between the two groups was highly significant (p < 0.001). With a deep learning-based approach using TensorFlow™, it is possible to detect AMD in SD-OCT with high sensitivity and specificity. With more image data, an expansion of this classifier for other macular diseases or further details in AMD is possible, suggesting an application for this model as a support in clinical decisions. Another possible future application would involve the individual prediction of the progress and success of therapy for different diseases by automatically detecting hidden image information.

Antimicrobial Resistance in Escherichia coli Recovered from Feedlot Cattle and Associations with Antimicrobial Use

PubMed Central

Benedict, Katharine M.; Gow, Sheryl P.; McAllister, Tim A.; Booker, Calvin W.; Hannon, Sherry J.; Checkley, Sylvia L.; Noyes, Noelle R.; Morley, Paul S.

2015-01-01

The objectives of this study were to estimate the prevalence of antimicrobial resistance (AMR) and to investigate the associations between exposures to antimicrobial drugs (AMDs) and AMR in fecal non-type specific Escherichia coli (NTSEC) recovered from a large population of feedlot cattle. Two-stage random sampling was used to select individually identified cattle for enrollment, which were sampled at arrival and then a second time later in the feeding period. Advanced regression techniques were used to estimate resistance prevalences, and to investigate associations between AMD exposures in enrolled cattle and penmates and AMR identified in NTSEC recovered from the second sample set. Resistance was most commonly detected to tetracycline, streptomycin, and sulfisoxazole, and was rarely identified for critically important AMDs. All cattle were exposed to AMDs in feed, and 45% were treated parenterally. While resistance prevalence generally increased during the feeding period, most AMD exposures were not significantly associated with AMR outcomes. Exposures of enrolled cattle to tetracycline were associated with increased resistance to tetracycline and trimethoprim sulfa, while beta-lactam exposures were associated with decreased likelihood of detecting streptomycin resistance. Pen-level AMD exposure measures were not associated with resistance outcomes. These findings suggest that tetracycline treatment of feedlot cattle can be associated with modest increases in risk for recovery of resistant NTSEC, but the numerous treatments with an advanced macrolide (tulathromycin) were not associated with detectable increases in resistance in NTSEC. All cattle were exposed to in-feed treatments of tetracycline and this could limit the ability to identify the full impact of these exposures, but these exposures varied for enrolled cattle varied, providing an opportunity to evaluate a dose response. While AMD exposures were not associated with detectably increased risks for resistance to critically important AMDs, rare resistance outcomes and infrequent exposure to other important AMDs (e.g., cephalosporins) limited our ability to rigorously investigate questions regarding factors that can influence resistance to these important AMDs. PMID:26633649

Cardiovascular Disease, its Risk Factors and Treatment, and Age-related Macular Degeneration: Women’s Health Initiative Sight Exam Ancillary Study

PubMed Central

Klein, Ronald; Deng, Yingzi; Klein, Barbara E. K.; Hyman, Leslie; Seddon, Johanna; Frank, Robert N.; Wallace, Robert B.; Hendrix, Susan L.; Kuppermann, Baruch D.; Langer, Robert D.; Kuller, Lewis; Brunner, Robert; Johnson, Karen C.; Thomas, Asha M.; Haan, Mary

2010-01-01

Purpose To examine the association of cardiovascular disease (CVD), CVD risk factors, and CVD treatment with age-related macular degeneration (AMD). Design Observational analysis of a randomized clinical trial. Methods Setting The Women’s Health Initiative Sight Examination (WHISE), an ancillary study to the Women’s Health Initiative’s (WHI) clinical trial of hormone replacement therapy. Study Population 4,288 women aged 63 years and older. Observation Procedures Information on CVD and its risk factors were obtained from a standardized questionnaire and examination. Main Outcome Measure AMD as determined by standardized grading of fundus photographs. Results Prevalence of any AMD was 21.4% (n=919). Of those with AMD, 5.8% (n=53) had signs of exudative AMD (n=39) or pure geographic atrophy (n=14), limiting the power to examine associations. Significant associations between late AMD and CVD risk factors were (odds ratio [OR], 95% confidence interval [CI]) older age (1.19, 1.13, 1.27, p < 0.0001), more pack years smoked (1.02 per pack-year smoked, 1.003, 1.03, p = 0.01), systolic blood pressure (0.84 per 10 mmHg, 0.71, 0.995, p = 0.04), report of taking calcium channel blockers (CCB) (2.49, 1.21, 5.12, p = 0.04), self-reported history of diabetes (2.00, 1.01, 3.96, p = 0.05), and greater body mass index (1.05 per 1 kg/m2, 1.001, 1.10, p = 0.05). History of myocardial infarction, stroke, use of statins, or white blood cell were not associated with AMD. Conclusions Results suggest that smoking, use of CCBs, diabetes, and obesity are risk factors for late AMD in women. However, the association of late AMD with systolic blood pressure and the effects of other CVD risk factors on early AMD need to be further explored. PMID:17317391

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

PubMed

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

2016-12-02

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. Systematic review. 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). 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%. 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. 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/.

Folic Acid, Vitamin B6, and Vitamin B12 in Combination and Age-related Macular Degeneration in a Randomized Trial of Women

PubMed Central

Christen, William G.; Glynn, Robert J.; Chew, Emily Y.; Albert, Christine M.; Manson, JoAnn E.

2008-01-01

Context Observational epidemiologic studies indicate a direct association between homocysteine concentration in the blood and risk of age-related macular degeneration (AMD), but randomized trial data to examine the effect of homocysteine-lowering in AMD are lacking. Objective To examine incidence of AMD in a trial of folic acid/vitamin B6/vitamin B12. Design Randomized, double-masked, placebo-controlled trial. Participants 5,442 female health professionals aged 40 years or older with preexisting cardiovascular disease (CVD) or 3 or more CVD risk factors. A total of 5,205 of these women did not have a diagnosis of AMD at baseline and were included in this analysis. Intervention Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), vitamin B6 (50 mg/d), and vitamin B12 (1 mg/d), or placebo. Main Outcome Measures Total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually-significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition. Results After an average of 7.3 years of treatment and follow-up, there were 55 cases of AMD in the folic acid/B6/B12 group and 82 in the placebo group (relative risk [RR], 0.66; 95% confidence interval [CI], 0.47–0.93; p=0.02). For visually-significant AMD, there were 26 cases in the folic acid/B6/B12 group and 44 in the placebo group (RR, 0.59; 95% CI, 0.36–0.95; p=0.03). Conclusions These randomized trial data from a large cohort of women at high risk of CVD indicate that daily supplementation with folic acid/B6/B12 may reduce the risk of AMD. PMID:19237716

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

PubMed Central

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:27913556

Fish Consumption and Age-Related Macular Degeneration Incidence: A Meta-Analysis and Systematic Review of Prospective Cohort Studies.

PubMed

Zhu, Wei; Wu, Yan; Meng, Yi-Fang; Xing, Qian; Tao, Jian-Jun; Lu, Jiong

2016-11-22

The association between fish consumption and risk of age-related macular degeneration (AMD) is still unclear. The aim of the current meta-analysis and systematic review was to quantitatively evaluate findings from observational studies on fish consumption and the risk of AMD. Relevant studies were identified by searching electronic databases (Medline and EMBASE) and reviewing the reference lists of relevant articles up to August, 2016. Prospective cohort studies that reported relative risks (RRs) and 95% confidence intervals (CIs) for the link between fish consumption and risk of AMD were included. A total of 4202 cases with 128,988 individuals from eight cohort studies were identified in the current meta-analysis. The meta-analyzed RR was 0.76 (95% CI, 0.65-0.90) when any AMD was considered. Subgroup analyses by AMD stages showed that fish consumption would reduce the risk of both early (RR, 0.83; 95% CI, 0.72-0.96) and late (RR; 0.76; 95% CI, 0.60-0.97) AMD. When stratified by the follow-up duration, fish consumption was a protective factor of AMD in both over 10 years ( n = 5; RR, 0.81; 95% CI, 0.67-0.97) and less than 10 years ( n = 3; RR, 0.70; 95% CI, 0.51 to 0.97) follow-up duration. Stratified analyses by fish type demonstrated that dark meat fish (RR, 0.68, 95% CI, 0.46-0.99), especially tuna fish (RR, 0.58; 95% CI, 95% CI, 0.47-0.71) intake was associated with reduced AMD risk. Evidence of a linear association between dose of fish consumption and risk of AMD was demonstrated. The results of this meta-analysis demonstrated that fish consumption can reduce AMD risk. Advanced, well-designed, randomized clinical trials are required in order to validate the conclusions in this study.

Stem cell therapies for age-related macular degeneration: the past, present, and future.

PubMed

Dang, Yalong; Zhang, Chun; Zhu, Yu

2015-01-01

In the developed world, age-related macular degeneration (AMD) is one of the major causes of irreversible blindness in the elderly. Although management of neovascular AMD (wet AMD) has dramatically progressed, there is still no effective treatment for nonneovascular AMD (dry AMD), which is characterized by retinal pigment epithelial (RPE) cell death (or dysfunction) and microenvironmental disruption in the retina. Therefore, RPE replacement and microenvironmental regulation represent viable treatments for dry AMD. Recent advances in cell biology have demonstrated that RPE cells can be easily generated from several cell types (pluripotent stem cells, multipotent stem cells, or even somatic cells) by spontaneous differentiation, coculturing, defined factors or cell reprogramming, respectively. Additionally, in vivo studies also showed that the restoration of visual function could be obtained by transplanting functional RPE cells into the subretinal space of recipient. More importantly, clinical trials approved by the US government have shown promising prospects in RPE transplantation. However, key issues such as implantation techniques, immune rejection, and xeno-free techniques are still needed to be further investigated. This review will summarize recent advances in cell transplantation for dry AMD. The obstacles and prospects in this field will also be discussed.

Recent Developments for Remediating Acidic Mine Waters Using Sulfidogenic Bacteria

PubMed Central

Bitencourt, José A. P.; Sahoo, Prafulla K.; Alves, Joner Oliveira; Siqueira, José O.

2017-01-01

Acidic mine drainage (AMD) is regarded as a pollutant and considered as potential source of valuable metals. With diminishing metal resources and ever-increasing demand on industry, recovering AMD metals is a sustainable initiative, despite facing major challenges. AMD refers to effluents draining from abandoned mines and mine wastes usually highly acidic that contain a variety of dissolved metals (Fe, Mn, Cu, Ni, and Zn) in much greater concentration than what is found in natural water bodies. There are numerous remediation treatments including chemical (lime treatment) or biological methods (aerobic wetlands and compost bioreactors) used for metal precipitation and removal from AMD. However, controlled biomineralization and selective recovering of metals using sulfidogenic bacteria are advantageous, reducing costs and environmental risks of sludge disposal. The increased understanding of the microbiology of acid-tolerant sulfidogenic bacteria will lead to the development of novel approaches to AMD treatment. We present and discuss several important recent approaches using low sulfidogenic bioreactors to both remediate and selectively recover metal sulfides from AMD. This work also highlights the efficiency and drawbacks of these types of treatments for metal recovery and points to future research for enhancing the use of novel acidophilic and acid-tolerant sulfidogenic microorganisms in AMD treatment. PMID:29119111

Age-related macular degeneration

PubMed Central

Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H

2011-01-01

Clinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. Implementation: strategy of administration, safety of intravitreal injection PMID:21654887

Nano-stepper-driven optical shutter for applications in free-space micro-optics

NASA Astrophysics Data System (ADS)

Zawadzka, Justyna; Li, Lijie; Unamuno, Anartz; Uttamchandani, Deepak G.

2002-09-01

In this paper we report a simple design of a micro-optical shutter/attenuator. The standard MUMPS process was used to fabricate the device. A vertically erected, gold-coated, 200x300 mm side length micro-mirror was precisely placed between the end faces of two closely spaced optical fibers. The position of the micro-mirror with respect to the optical fiber end face was controlled by a nano-stepping motor array. Optical and mechanical tests were performed on the device. A 1.55 mm laser beam was sent along the optical fiber. When the micro-mirror was removed from the front of the fiber, the coupling efficiency between two fibers was -10 dBm. Once the micro-mirror was placed in the optical path the coupling efficiency dropped to -51.5 dBm. The best attenuation was obtained when the micro-mirror blocked the whole cross-section of the laser beam diameter. It is evident that the device can operate as a high precision fiber optic attenuator or shutter.

Visualization of Dietary Patterns and Their Associations With Age-Related Macular Degeneration.

PubMed

Chiu, Chung-Jung; Chang, Min-Lee; Li, Tricia; Gensler, Gary; Taylor, Allen

2017-03-01

We aimed to visualize the relationship of predominant dietary patterns and their associations with AMD. A total of 8103 eyes from 4088 participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into three groups: control (n = 2739), early AMD (n = 4599), and advanced AMD (n = 765). Using principle component analysis, two major dietary patterns and eight minor dietary patterns were characterized. Applying logistic regression in our analysis, we related dietary patterns to the prevalence of AMD. Qualitative comparative analysis by operating Boolean algebra and drawing Venn diagrams was used to visualize our findings. In general, the eight minor patterns were subsets or extensions of either one of the two major dietary patterns (Oriental and Western patterns) and consisted of fewer characteristic foods than the two major dietary patterns. Unlike the two major patterns, which were more strongly associated with both early and advanced AMD, none of the eight minors were associated with early AMD and only four minor patterns, including the Steak pattern (odds ratio comparing the highest to lowest quintile of the pattern score = 1.73 [95% confidence interval: 1.24 to 2.41; Ptrend = 0.02]), the Breakfast pattern (0.60 [0.44 to 0.82]; Ptrend = 0.004]), the Caribbean pattern (0.64 [0.47 to 0.89; Ptrend = 0.009]), and the Peanut pattern (0.64 [0.46 to 0.89; Ptrend = 0.03]), were significantly associated with advanced AMD. Our data also suggested several potential beneficial (peanuts, pizza, coffee, and tea) and harmful (salad dressing) foods for AMD. Our data indicate that a diet of various healthy foods may be optimal for reducing AMD risk. The effects of some specific foods in the context of overall diet warrant further study.

Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis

PubMed Central

2010-01-01

Background Age-related macular degeneration (AMD) is the leading cause of blindness in Western countries. Numerous risk factors have been reported but the evidence and strength of association is variable. We aimed to identify those risk factors with strong levels of evidence which could be easily assessed by physicians or ophthalmologists to implement preventive interventions or address current behaviours. Methods A systematic review identified 18 prospective and cross-sectional studies and 6 case control studies involving 113,780 persons with 17,236 cases of late AMD that included an estimate of the association between late AMD and at least one of 16 pre-selected risk factors. Fixed-effects meta-analyses were conducted for each factor to combine odds ratio (OR) and/or relative risk (RR) outcomes across studies by study design. Overall raw point estimates of each risk factor and associated 95% confidence intervals (CI) were calculated. Results Increasing age, current cigarette smoking, previous cataract surgery, and a family history of AMD showed strong and consistent associations with late AMD. Risk factors with moderate and consistent associations were higher body mass index, history of cardiovascular disease, hypertension, and higher plasma fibrinogen. Risk factors with weaker and inconsistent associations were gender, ethnicity, diabetes, iris colour, history of cerebrovascular disease, and serum total and HDL cholesterol and triglyceride levels. Conclusions Smoking, previous cataract surgery and a family history of AMD are consistent risk factors for AMD. Cardiovascular risk factors are also associated with AMD. Knowledge of these risk factors that may be easily assessed by physicians and general ophthalmologists may assist in identification and appropriate referral of persons at risk of AMD. PMID:21144031

Investigating the modulation of genetic effects on late AMD by age and sex: Lessons learned and two additional loci

PubMed Central

Grassmann, Felix; Gorski, Mathias; Loss, Julika; Heid, Iris M.

2018-01-01

Late-stage age-related macular degeneration (AMD) is the leading cause of visual impairment in the elderly with a complex etiology. The most important non-modifiable risk factors for onset and progression of late AMD are age and genetic risk factors, however, little is known about the interplay between genetics and age or sex. Here, we conducted a large-scale age- and sex-stratified genome-wide association study (GWAS) using 1000 Genomes imputed genome-wide and ExomeChip data (>12 million variants). The data were established by the International Age-related Macular Degeneration Genomics Consortium (IAMDGC) from 16,144 late AMD cases and 17,832 controls. Our systematic search for interaction effects yielded significantly stronger effects among younger individuals at two known AMD loci (near CFH and ARMS2/HTRA1). Accounting for age and gene-age interaction using a joint test identified two additional AMD loci compared to the previous main effect scan. One of these two is a novel AMD GWAS locus, near the retinal clusterin-like protein (CLUL1) gene, and the other, near the retinaldehyde binding protein 1 (RLBP1), was recently identified in a joint analysis of nuclear and mitochondrial variants. Despite considerable power in our data, neither sex-dependent effects nor effects with opposite directions between younger and older individuals were observed. This is the first genome-wide interaction study to incorporate age, sex and their interaction with genetic effects for late AMD. Results diminish the potential for a role of sex in the etiology of late AMD yet highlight the importance and existence of age-dependent genetic effects. PMID:29529059

AMISH EYE STUDY: Baseline Spectral Domain Optical Coherence Tomography Characteristics of Age-Related Macular Degeneration.

PubMed

Nittala, Muneeswar G; Song, Yeunjoo E; Sardell, Rebecca; Adams, Larry D; Pan, Samuel; Velaga, Swetha B; Horst, Violet; Dana, Debra; Caywood, Laura; Laux, Renee; Fuzzell, Denise; Fuzzell, Sarada; Scott, William K; Cooke Bailey, Jessica N; Igo, Robert P; Haines, Jonathan; Pericak-Vance, Margaret A; Sadda, SriniVas R; Stambolian, Dwight

2018-05-09

To describe spectral domain optical coherence tomography (SD-OCT) findings in an Amish cohort to assess SD-OCT markers for early age-related macular degeneration (AMD). The authors performed a family-based prospective cohort study of 1,146 elderly Amish subjects (age range 50-99 years) (2,292 eyes) who had a family history of at least 1 individual with AMD. All subjects underwent complete ophthalmic examinations, SD-OCT using both Cirrus and Spectralis (20 × 20° scan area) instruments, fundus autofluorescence, infrared imaging, and color fundus photography. Spectral domain optical coherence tomography characteristics were analyzed in subjects with AMD (with and without subretinal drusenoid deposits [SDDs]) and normal healthy cohorts. Participants' mean age was 65.2 years (SD ± 11). Color fundus photographic findings in 596 (53%) subjects (1,009 eyes) were consistent with AMD; the remaining 478 (43%) subjects showed no signs of AMD. The choroid was significantly thinner on OCT (242 ± 76 µm, P < 0.001) in those with AMD compared with those without (263 ± 63 µm). Subretinal drusenoid deposits were found in 143 eyes (7%); 11 of the 143 eyes (8%) had no other manifestations of AMD. Drusen volume (P < 0.001) and area of geographic atrophy (P < 0.001) were significantly greater, and choroid was significantly (P < 0.001) thinner in subjects with SDDs versus those without SDDs. The authors describe spectral domain optical coherence tomography characteristics in an elderly Amish population with and without AMD, including the frequency of SDD. Although relatively uncommon in this population, the authors confirmed that SDDs can be found in the absence of other features of AMD and that eyes with SDDs have thinner choroids.

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

PubMed

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.

Refractive Error and the Risk of Age-Related Macular Degeneration in the South Korean Population.

PubMed

Lin, Shuai-Chun; Singh, Kuldev; Chao, Daniel L; Lin, Shan C

2016-01-01

We investigated the association between refractive error and the prevalence of age-related macular degeneration (AMD) in a population-based study. This was a cross-sectional study. Right eyes were included from 14,067 participants aged 40 years and older with gradable fundus photographs and refraction data from the fourth and the fifth Korea National Health and Nutrition Examination Survey 2008 to 2011. Early and late AMD was graded based on the International Age-Related Maculopathy Epidemiological Study Group grading system. Autorefraction data were collected to calculate spherical equivalent refraction in diopters (D) and classified into 4 groups: hyperopia (≥1.0 D), emmetropia (-0.99 to 0.99 D), mild myopia (-1.0 to -2.99 D), and moderate to high myopia (≤-3.0 D). After adjustment for potential confounders, each diopter increase in spherical equivalent was associated with a 16% [odds ratio (OR), 1.16; 95% confidence interval (CI), 1.08-1.25] and 18% (OR, 1.18; 95% CI, 1.10-1.27) increased risk of any (early + late) and early AMD, respectively. Mild and moderate to high myopia were associated with lower odds of any and early AMD compared with hyperopia (any AMD: OR, 0.62; 95% CI, 0.4-0.95 for mild myopia; OR, 0.41; 95% CI, 0.21-0.81 for moderate to high myopia; early AMD: OR, 0.63; 95% CI, 0.4-0.99 for mild myopia; OR, 0.36; 95% CI, 0.16-0.77 for moderate to high myopia group). There was no association between refractive status and the likelihood of late AMD (P = 0.91). Myopia is associated with lower odds of any and early AMD, but not with late AMD in the South Korean population.

Lifestyle modification, nutritional and vitamins supplements for age-related macular degeneration.

PubMed

Sin, Helena P Y; Liu, David T L; Lam, Dennis S C

2013-02-01

To provide a systematic review of the published studies pertaining to the lifestyle modification, dietary, nutritional and vitamins supplements for preventing occurrence or halting deterioration of age-related macular degeneration (AMD). The literature searches from 1990 to December 2010 with following keywords, 'age related macular degeneration', 'nutrition', 'antioxidant', 'diet' and 'vitamins supplements' using search engines Pubmed, Google Scholar, Medline and the Cochrane Library. Meta-analyses, population-based cohort studies and case-controlled trials were reviewed, whereas small cases series, case reports, commentaries, abstracts in proceedings or personal observations were excluded. Smoking and obesity are identified risk factors for AMD. High dietary intakes of omega-3 fatty acids, and macular xanthophylls lutein and zeaxanthin have been associated with a lower risk of prevalence and incidence in AMD. Vitamin B and extracts from wolfberry, Gingko biloba and berry anthocyanins were also subjects of intense research interests, but there has been no concluding scientific evidence yet. The Age-Related Eye Disease study (AREDS) is the only large-scale randomized controlled clinical trial to show beneficial effect of AREDS formulation of vitamins C, E, beta-carotene and zinc with copper in reducing the risk progression to advanced AMD in patients with intermediate AMD or with advanced AMD in one eye. Quit smoking is an important advice to patients to prevent or slow the progress of AMD. There is no recommendation for routine nutritional or vitamins supplementation for primary prevention. However, patients with documented intermediate risk of AMD or advanced AMD in one eye are recommended to take AREDS-type vitamin supplements. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

Assessment of characteristics and remedial alternatives for abandoned mine drainage : case study at Staple Bend Tunnel unit of Allegheny Portage Railroad National Historic Site, Cambria County, Pennsylvania, 2004

USGS Publications Warehouse

Cravotta, Charles A.

2005-01-01

This report describes field, laboratory, and computational methods that could be used to assess remedial strategies for abandoned mine drainage (AMD). During April-June, 2004, the assessment process was applied to AMD from bituminous coal deposits at a test site in the Staple Bend Tunnel Unit of Allegheny Portage Railroad National Historic Site (ALPO-SBTU) in Cambria County, Pennsylvania. The purpose of this study was (1) to characterize the AMD quantity and quality within the ALPO-SBTU test site; (2) to evaluate the efficacy of limestone or steel slag for neutralization of the AMD on the basis of reaction-rate measurements; and (3) to identify possible alternatives for passive or active treatment of the AMD. The data from this case study ultimately will be used by the National Park Service (NPS) to develop a site remediation plan. The approach used in this study could be applicable at other sites subject to drainage from abandoned coal or metal mines.During April 2004, AMD from 9 sources (sites1, 1Fe, Fe, 2, 3, 3B, 5, 6, and 7) at the ALPO-SBTU test site had a combined flow rate of 1,420 gallons per minute (gal/min) and flow-weighted averages for pH of 3.3, net acidity of 55 milligrams per liter (mg/L) as CaCO3, and concentrations of dissolved sulfate, aluminum, iron, and manganese of 694 mg/L, 4.4 mg/L, 0.74 mg/L, and 1.2 mg/L, respectively. These pH, net acidity, sulfate, and aluminum values exceed effluent criteria for active mines in Pennsylvania.During April-June 2004, limestone and steel slag that were locally available were tested in the laboratory for their composition, approximate surface area, and potential to neutralize samples of the AMD. Although the substrates had a similar particle-size distribution and identical calcium content (43 percent as calcium oxide), the limestone was composed of crystalline carbonates and the slag was composed of silicate glass and minerals. After a minimum of 8 hours contact between the AMD and limestone or steel slag in closed containers (cubitainers), near-neutral effluent was produced. With prolonged contact between the AMD and limestone or steel slag, the concentrations of iron, aluminum, and most dissolved trace elements in effluent from the cubitainers declined while pH was maintained greater than 6.0 and less than 9.0. The cubitainer testing demonstrated (1) lower alkalinity production but higher pH of AMD treated with steel slag compared to limestone, and (2) predictable relations between the effluent quality, detention time, and corresponding flow rate and bulk volume for a bed of crushed limestone or steel slag in an AMD passive-treatment system.The process for evaluating AMD remedial strategies at the ALPO-SBTU test site involved the computation and ranking of the metal loadings during April 2004 for each of the AMD sources and a comparison of the data on AMD flow and chemistry (alkalinity, acidity, dissolved oxygen, ferric iron, aluminum) with published criteria for selection of passive-treatment technology. Although neutralization of the AMD by reaction with limestone was demonstrated with cubitainer tests, an anoxic limestone drain (ALD) was indicated as inappropriate for any AMD source at the test site because all had excessive concentrations of dissolved oxygen and (or) aluminum. One passive-treatment scenario that was identified for the individual or combined AMD sources involved an open limestone channel (OLC) to collect the AMD source(s), a vertical flow compost wetland (VFCW) to add alkalinity, and an aerobic wetland to facilitate iron and manganese oxidation and retention of precipitated solids. Innovative passive-system designs that direct flow upward through submerged layers of limestone and/or steel slag and that incorporate siphons for automatic flushing of solids to a pond also may warrant consideration. Alternatively, an active-treatment system with a hydraulic-powered lime doser could be employed instead of the VFCW or upflow system. Now, given these data on AMD flow and chemistry and identified remedial technologies, a resource manager can use a publicly available computer program such as "AMDTreat" to evaluate the potential sizes and costs of various remedial alternatives.

Optimization of Sparse Matrix-Vector Multiplication on Emerging Multicore Platforms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Samuel; Oliker, Leonid; Vuduc, Richard

2008-10-16

We are witnessing a dramatic change in computer architecture due to the multicore paradigm shift, as every electronic device from cell phones to supercomputers confronts parallelism of unprecedented scale. To fully unleash the potential of these systems, the HPC community must develop multicore specific-optimization methodologies for important scientific computations. In this work, we examine sparse matrix-vector multiply (SpMV) - one of the most heavily used kernels in scientific computing - across a broad spectrum of multicore designs. Our experimental platform includes the homogeneous AMD quad-core, AMD dual-core, and Intel quad-core designs, the heterogeneous STI Cell, as well as one ofmore » the first scientific studies of the highly multithreaded Sun Victoria Falls (a Niagara2 SMP). We present several optimization strategies especially effective for the multicore environment, and demonstrate significant performance improvements compared to existing state-of-the-art serial and parallel SpMV implementations. Additionally, we present key insights into the architectural trade-offs of leading multicore design strategies, in the context of demanding memory-bound numerical algorithms.« less

Protect Your Eyes: Age-Related Macular Degeneration (AMD) Facts and Prevention Tips

MedlinePlus

PROTECT YOUR EYES Age-Related Macular Degeneration ( AMD ) FACTS & PREVENTION TIPS A LEADING CAUSE OF VISION LOSS IN THE U.S . AMD is a ... Black 2% Other 89% White As the population ages, the number of cases is expected to increase ...

Distribution pattern of anthropogenic marine debris along the gastrointestinal tract of green turtles (Chelonia mydas) as implications for rehabilitation.

PubMed

Colferai, André S; Silva-Filho, Rodolfo Pinho; Martins, Aryse Moreira; Bugoni, Leandro

2017-06-15

Pollution from anthropogenic marine debris (AMD) is currently the most widely distributed and lasting anthropic impact in the marine environment, affecting hundreds of species, including all sea turtles. In this study, the patterns of AMD distribution along the gastrointestinal tract (GT) and their relationship with obstructions and faecalomas in 62 green turtles (Chelonia mydas) that died during rehabilitation in southern Brazil were determined. The GT was split in seven sections, corresponding to the natural organs and intestinal areas morphologically and physiologically distinct. Mean mass (4.24g) and area (146.74cm 2 ) of AMD in the stomach were higher than in other sections. The anterior portion of the rectum had the highest number of obstructions, followed by the stomach. AMD was associated with the obstructions, with positive correlation between faecalomas and AMD masses. Organs and subdivisions showed marked differences in susceptibility to obstructions caused by AMD, which deserves attention in clinical interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nutrition, Genes, and Age-Related Macular Degeneration: What Have We Learned from the Trials?

PubMed

Chew, Emily Y

2017-01-01

The Age-Related Eye Disease Study (AREDS) and AREDS2 provided evidence for treating persons with age-related macular degeneration (AMD) with antioxidant vitamins and minerals to reduce the risk of development of late AMD. The AREDS2 data suggest that the beta-carotene in the original AREDS supplements be replaced by lutein and zeaxanthin, providing a safer drug for those who are smokers or former smokers. Even though consuming fish reduced the risk of AMD in observational studies, the AREDS2 results showed that omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid/eicosapentaenoic acid) had no beneficial effect on AMD. Despite the major progress in the discovery of gene variants associated with AMD, the use of genetic testing to predict disease has not been clinically useful. The use of genetic testing prior to AMD therapies such as administering AREDS supplements is not recommended by the American Academy of Ophthalmology and other organizations. © 2017 S. Karger AG, Basel.

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

USGS Publications Warehouse

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.

Association of neovascular age-related macular degeneration with month and season of birth in Italy

PubMed Central

Longo, Antonio; Casuccio, Alessandra; Pani, Luca; Avitabile, Teresio; Cillino, Salvatore; Uva, Maurizio G.; Bonfiglio, Vincenza; Russo, Andrea; Parisi, Guglielmo; Cennamo, Gilda; Furino, Claudio; Parravano, Mariacristina; Xoxi, Entela; Reibaldi, Michele

2017-01-01

In order to investigate the influence of season and month of birth on the risk of neovascular age-related macular degeneration (n-AMD) in Italy, we evaluated the month birth and sex of all patients, recorded in the anti-vascular endothelial growth factor (VEGF) monitoring registry of the Italian Medicines Agency, born between 1925–1944, who received intravitreal anti-VEGF injections for n-AMD between January 1, 2013 and July 29, 2015. The numbers of all births in Italy in the same years, extracted from the Italian National Institute of Statistics, were used to calculate the expected number of n-AMD cases. Overall, 45,845 patients (19,207 men, 26,638 women) received intravitreal anti-VEGF for n-AMD; in the same years, 20,140,426 people (10,334,262 male, 9,806,164 female) were born in Italy. Comparing the observed number of n-AMD cases with the expected number of n- AMD cases in each season, we found that the season-specific risk for n-AMD was 2.5% higher for those born in summer (OR=1.03, Bonferroni-corrected P=0.008) and 3% lower for those born in winter (OR=0.96, Bonferroni-corrected P=0.0004). When considering the month of birth, the risk of n-AMD was 5.9% lower for people born in January (OR=0.93, Bonferroni-corrected P=0.0012). The factors causing such differences should be determined. PMID:27997361

Association between dietary fats and age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women’s Health Initiative123

PubMed Central

Parekh, Niyati; Voland, Rickie P.; Moeller, Suzen M.; Blodi, Barbara A.; Ritenbaugh, Cheryl; Chappell, Richard J.; Wallace, Robert B.; Mares, Julie A.

2011-01-01

Objective Evaluating relationships of amount and type of dietary fat to intermediate AMD. Design Women, ages 50–79, from the Women’s Health Initiative-Observational Study, with high and low lutein intakes, were recruited into the Carotenoids in Age-Related Eye Disease Study (CAREDS). Fat intake in 1994–1998 was estimated using food frequency questionnaires. AMD was assessed in 2001–2004 from stereoscopic fundus photographs. Results Intakes of omega-6 and omega-3 polyunsaturated fats (ω-6 and ω-3 PUFA), which were highly correlated (r=0.8), were associated with higher prevalence of intermediate AMD. Significant age-interactions were noted for associations with total fat, monounsaturated and saturated fat (p= 0.01–0.02). In women <75 years (n=1,325), diets high in total fat (% energy) were associated with increased prevalence of AMD (OR (95% CI) for quintile five vs. one = 1.73 (1.02–2.7; p-trend=0.10); the association was reversed in older women. Monounsaturated fat (MUFA) intakes in quintiles three through five vs. one were associated with lower prevalence of AMD in the whole population. Conclusions Overall associations of dietary fat to AMD differed by type of fat and, often, by age in this cohort. These findings contribute insights about sources of inconsistencies of fat to AMD in epidemiological studies. PMID:19901214

Microalgae-bacteria biofilms: a sustainable synergistic approach in remediation of acid mine drainage.

PubMed

Abinandan, Sudharsanam; Subashchandrabose, Suresh R; Venkateswarlu, Kadiyala; Megharaj, Mallavarapu

2018-02-01

Microalgae and bacteria offer a huge potential in delving interest to study and explore various mechanisms under extreme environments. Acid mine drainage (AMD) is one such environment which is extremely acidic containing copious amounts of heavy metals and poses a major threat to the ecosystem. Despite its extreme conditions, AMD is the habitat for several microbes and their activities. The use of various chemicals in prevention of AMD formation and conventional treatment in a larger scale is not feasible under different geological conditions. It implies that microbe-mediated approach is a viable and sustainable alternative technology for AMD remediation. Microalgae in biofilms play a pivotal role in such bioremediation as they maintain mutualism with heterotrophic bacteria. Synergistic approach of using microalgae-bacteria biofilms provides supportive metabolites from algal biomass for growth of bacteria and mediates remediation of AMD. However, by virtue of their physiology and capabilities of metal removal, non-acidophilic microalgae can be acclimated for use in AMD remediation. A combination of selective acidophilic and non-acidophilic microalgae together with bacteria, all in the form of biofilms, may be very effective for bioremediation of metal-contaminated waters. The present review critically examines the nature of mutualistic interactions established between microalgae and bacteria in biofilms and their role in removal of metals from AMDs, and consequent biomass production for the yield of biofuel. Integration of microalgal-bacterial consortia in fuel cells would be an attractive emerging approach of microbial biotechnology for AMD remediation.

PGC-1α repression and high fat diet induce age-related macular degeneration-like phenotypes in mice.

PubMed

Zhang, Meng; Chu, Yi; Mowery, Joseph; Konkel, Brandon; Galli, Susana; Theos, Alexander C; Golestaneh, Nady

2018-06-20

Age-related macular degeneration (AMD) is the major cause of blindness in the elderly in developed countries and its prevalence is increasing with the aging population. AMD initially affects the retinal pigment epithelium (RPE) and gradually leads to secondary photoreceptor degeneration. Recent studies have associated mitochondrial damage with AMD, and we have observed mitochondrial and autophagic dysfunction and repressed peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α in native RPE from AMD donor eyes and their respective induced pluripotent stem cell-derived RPE (AMD RPE-iPSC-RPE). To further investigate the effect of PGC-1α repression we have established a mouse model by feeding PGC-1α + /- mice with high fat diet (HFD) and investigated the RPE and retinal health. Here we show that when mice expressing lower levels of Pgc-1α are exposed to HFD, they present AMD-like abnormalities in RPE and retinal morphology and function. These abnormalities include basal laminar deposits, thickening of Bruch's membrane (BM) with drusen marker-containing deposits, RPE and photoreceptor degeneration, decreased mitochondrial activity, increased ROS levels, decreased autophagy dynamics/ flux, and increased inflammatory response in the RPE/retina. Our study show that the PGC-1α is important in outer retina biology and that PGC-1α + /- mouse fed with HFD is a promising model to study AMD and opens doors for novel treatment strategies in AMD. © 2018. Published by The Company of Biologists Ltd.

The role of apolipoprotein E (rs7412 and rs429358) in age-related macular degeneration.

PubMed

Liutkeviciene, Rasa; Vilkeviciute, Alvita; Smalinskiene, Alina; Tamosiunas, Abdonas; Petkeviciene, Janina; Zaliuniene, Dalia; Lesauskaite, Vaiva

2018-05-31

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in the developed countries. The main pathological change in AMD is the formation of drusen containing 40% of lipids, dominated by esterified cholesterol (EC) and phosphatidylcholine (PC), and protein. Haplotype ε4 of apolipoprotein E (ApoE) acts as a ligand for the low-density lipoprotein receptor and is involved in the maintenance and repair of neuronal cell membranes. This study aimed to evaluate the association of AMD with ApoE gene polymorphism variants (rs7412 and rs429358). A total of 2133 subjects were enrolled in our research. The study group comprised patients with early AMD (n = 413) and exudative AMD (n = 307), and the control group enrolled randomly selected persons (n = 1413). The genotyping of ApoE (rs7412 and rs429358) was performed using the real-time polymerase chain reaction (PCR) method. Statistical analysis revealed that ApoE 4/2 genotype was less frequently observed in in older patients with exudative AMD compared to older healthy controls (0.4% vs. 4.0%, p = 0.003). Our data demonstrated that ApoE 4/2 genotype was less frequently observed in old patients (65 years and more) with exudative AMD compared to old healthy controls. It leads to hypothesis on the protective effect of ApoE 4/2 to develop AMD in the elderly.

Retinal instrument

DOEpatents

Britton, Charles L; D& #x27; Urso, Brian R; Chaum, Edward; Simpson, John T; Baba, Justin S; Ericson, M. Nance; Warmack, Robert J

2013-04-23

In one embodiment, the present invention provides a method of removing scar tissue from an eye that includes inserting a device including an array of micro-rods into an eye, wherein at least one glass micro-rod of the array of glass micro-rods includes a sharp feature; contacting a scar tissue with the array of micro-rods; and removing the array of micro-rods and the scar tissue from the eye. In another embodiment, the present invention provides a medical device for engaging a tissue including and an array of glass micro-rods, wherein at least one glass micro-rod of the array of glass micro-rods includes a sharp feature opposite a base of the array of glass micro-rods that is connected to the cannula, wherein the sharp feature of the at least one micro-rod is angled from a plane that is normal to a face of the base of the array of glass micro-rods.

Printed Biopolymer-Based Electro-Optic Device Components

DTIC Science & Technology

2013-07-01

devices and fabricated e-beam lithography-based master molds. Printed micro and nanostructures using a newly developed spin-on nanoprinting (SNAP...polymeric materials. Among the natural biopolymers , deoxyribonucleic acid (DNA) is an attractive material which can be used to make electronic and...photonic devices [2, 3]. If patterned on the micro and nanoscale using a soft lithography technique, high quality biodegradable optical devices can be

Resonant optical transducers for in-situ gas detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bond, Tiziana C.; Cole, Garrett; Goddard, Lynford

Configurations for in-situ gas detection are provided, and include miniaturized photonic devices, low-optical-loss, guided-wave structures and state-selective adsorption coatings. High quality factor semiconductor resonators have been demonstrated in different configurations, such as micro-disks, micro-rings, micro-toroids, and photonic crystals with the properties of very narrow NIR transmission bands and sensitivity up to 10.sup.-9 (change in complex refractive index). The devices are therefore highly sensitive to changes in optical properties to the device parameters and can be tunable to the absorption of the chemical species of interest. Appropriate coatings applied to the device enhance state-specific molecular detection.

Resonant optical transducers for in-situ gas detection

DOEpatents

Bond, Tiziana C; Cole, Garrett; Goddard, Lynford

2016-06-28

Configurations for in-situ gas detection are provided, and include miniaturized photonic devices, low-optical-loss, guided-wave structures and state-selective adsorption coatings. High quality factor semiconductor resonators have been demonstrated in different configurations, such as micro-disks, micro-rings, micro-toroids, and photonic crystals with the properties of very narrow NIR transmission bands and sensitivity up to 10.sup.-9 (change in complex refractive index). The devices are therefore highly sensitive to changes in optical properties to the device parameters and can be tunable to the absorption of the chemical species of interest. Appropriate coatings applied to the device enhance state-specific molecular detection.

Multivariate Analysis To Quantify Species in the Presence of Direct Interferents: Micro-Raman Analysis of HNO 3 in Microfluidic Devices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lines, Amanda M.; Nelson, Gilbert L.; Casella, Amanda J.

Microfluidic devices are a growing field with significant potential for application to small scale processing of solutions. Much like large scale processing, fast, reliable, and cost effective means of monitoring the streams during processing are needed. Here we apply a novel Micro-Raman probe to the on-line monitoring of streams within a microfluidic device. For either macro or micro scale process monitoring via spectroscopic response, there is the danger of interfering or confounded bands obfuscating results. By utilizing chemometric analysis, a form of multivariate analysis, species can be accurately quantified in solution despite the presence of overlapping or confounded spectroscopic bands.more » This is demonstrated on solutions of HNO 3 and NaNO 3 within micro-flow and microfluidic devices.« less

The 'Displacing Foods of Modern Commerce' Are the Primary and Proximate Cause of Age-Related Macular Degeneration: A Unifying Singular Hypothesis.

PubMed

Knobbe, Chris A; Stojanoska, Marija

2017-11-01

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss and blindness in developed nations. AMD is anticipated to affect 196 million people worldwide, by 2020. However, the etiology of this disease remains unknown. Aging, genetic, and environmental influences have generally been implicated as major etiologic factors. We sought to examine the hypothesis that consumption of the 'displacing foods of modern commerce,' which equate to processed, nutrient-deficient and potentially toxic foods, may be the primary and proximate cause of AMD. To evaluate this hypothesis, we ran correlative AMD prevalence data against well-known proxy markers of processed food consumption, namely, sugar and vegetable oils, in 25 nations. In twenty-one nations, published studies provided AMD prevalence data and in four Pacific Island nations, practicing ophthalmologists in the regions completed retrospective chart analyses to estimate AMD prevalence in their respective regions. To estimate AMD prevalence historically, an extensive review of published papers and ophthalmic literature was completed. This review indicates that, between the years 1851 and 1930, AMD was a medical rarity worldwide, which then rose modestly in prevalence in the 1930s in the U.S. and U.K, finally elevating to epidemic proportions by 1975 in the U.S. Numerous developed nations have followed suit in recent decades. Simultaneously, between approximately 1880 and 2009, processed, nutrient-deficient foods gradually supplanted and displaced whole, unprocessed, nutrient-dense foods in developed nations, such that by 2009, 63 percent of the American diet was made up of nutrient-deficient foods in the form of refined white flour, added sugars, vegetable oils, and artificially created trans fats. The correlative data in 25 nations shows that increasing sugar and polyunsaturated vegetable oil consumption is invariably associated with new onset or rising prevalence of AMD, generally within about 30-40years of the beginning of increasing consumption of these proxy marker processed food components. The correlative data also demonstrates that, when consumption of sugar is moderate, but "harmful vegetable oil" consumption remains extremely low or absent, the prevalence of AMD remains rare. This study supports the hypothesis that the 'displacing foods of modern commerce,' which equate to processed, nutrient-deficient, and potentially toxic foods, are the primary and proximate cause of AMD. This study also supports the conclusion that macular degeneration is entirely preventable, through ancestral dietary strategy and avoidance of processed foods. Finally, this research has implications for patients with existing early and intermediate stages of AMD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta-analysis.

PubMed

Rudnicka, Alicja R; Jarrar, Zakariya; Wormald, Richard; Cook, Derek G; Fletcher, Astrid; Owen, Christopher G

2012-03-01

To obtain prevalence estimates of age-related macular degeneration (AMD; late, geographic atrophy, neovascular) by age and gender amongst populations of European ancestry taking into account study design and time trends. Systematic review of population-based studies published by September 2010 with quantitative estimates of geographic atrophy (GA), neovascular (NV), and late AMD prevalence. Studies were identified by a literature search of MEDLINE (from 1950), EMBASE (from 1980), and Web of Science (from 1980) databases. Data from 25 published studies (57 173 subjects: 455 with GA, 464 with NVAMD, and 1571 with late AMD). Bayesian meta-regression of the log odds of AMD with age, gender, and year of study allowing for differences in study design characteristics, to estimate prevalences of AMD (late, GA, NVAMD) along with 95% credible intervals (CrI). Log odds and prevalence of AMD. There was considerable heterogeneity in prevalence rates between studies; for late AMD, 20% of the variability in prevalence rates was explained by differences in age and 50% by study characteristics. The prevalence of AMD increased exponentially with age (odds ratio [OR], 4.2 per decade; 95% CrI, 3.8-4.6), which did not differ by gender. There was some evidence to suggest higher risk of NVAMD in women compared with men (OR, 1.2; 95% CrI, 1.0-1.5). Compared with studies using fundus imaging and international classification systems, studies using fundus imaging with alternative classifications were more likely (OR, 2.7; 95% CrI, 1.1-2.8), and studies using alternative classifications without fundus imaging most likely to diagnose late AMD (OR, 2.9; 95% CrI, 1.3-7.8). There was no good evidence of trends in AMD prevalence over time. Estimated prevalence of late AMD is 1.4% (95% CrI, 1.0%-2.0%) at 70 years of age, rising to 5.6% (95% CrI, 3.9%-7.7%) at age 80 and 20% (95% CrI, 14%-27%) at age 90. Studies using recognized classifications systems with fundus photography reported the lowest prevalences of AMD taking account of age and gender, and were stable over time, with a potentially higher risk of NVAMD for women. These prevalence estimates can be used to guide health service provision in populations of European ancestry. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Wafer-scale micro-optics fabrication

NASA Astrophysics Data System (ADS)

Voelkel, Reinhard

2012-07-01

Micro-optics is an indispensable key enabling technology for many products and applications today. Probably the most prestigious examples are the diffractive light shaping elements used in high-end DUV lithography steppers. Highly-efficient refractive and diffractive micro-optical elements are used for precise beam and pupil shaping. Micro-optics had a major impact on the reduction of aberrations and diffraction effects in projection lithography, allowing a resolution enhancement from 250 nm to 45 nm within the past decade. Micro-optics also plays a decisive role in medical devices (endoscopes, ophthalmology), in all laser-based devices and fiber communication networks, bringing high-speed internet to our homes. Even our modern smart phones contain a variety of micro-optical elements. For example, LED flash light shaping elements, the secondary camera, ambient light and proximity sensors. Wherever light is involved, micro-optics offers the chance to further miniaturize a device, to improve its performance, or to reduce manufacturing and packaging costs. Wafer-scale micro-optics fabrication is based on technology established by the semiconductor industry. Thousands of components are fabricated in parallel on a wafer. This review paper recapitulates major steps and inventions in wafer-scale micro-optics technology. The state-of-the-art of fabrication, testing and packaging technology is summarized.

Comparative study between a spectral domain and a high-speed single-beam swept source OCTA system for identifying choroidal neovascularization in AMD

NASA Astrophysics Data System (ADS)

Told, R.; Ginner, L.; Hecht, A.; Sacu, S.; Leitgeb, R.; Pollreisz, A.; Schmidt-Erfurth, U.

2016-12-01

This comparative study between a SD- and SS-OCTA system for visualizing neovascular patterns in AMD, also assessed the influence of cataract on OCTA imaging. 25 eyes with active CNV (AMD) were documented by FA, ICGA and SD-OCT. Two OCTA devices were used: A custom built SS-OCTA (1050 nm, 400,000 A-scans/s, 5 × 5 mm, no image segmentation); AngioVue (OptoVue, CA, USA) SD-OCTA (840 nm, 70.000 A-scans/s, 3 × 3 mm, SSADA technology). Two retina experts graded CNV types and vascular patterns. Cataract influence on OCTA image quality was reported for the superficial retinal plexus (6 eyes). The SS-OCTA prototype showed more CNV lesions compared to the SD-OCTA system (p = 0.01). Overall sensitivity of SD- and SS-OCTA systems to detect CNV lesions was.32 and.68, respectively. The SS-OCTA system was able to detect discrete lesion characteristics better than the SD-OCTA. No significant difference was found in the ability to identify CNV in treatment-naïve eyes. There was no significant influence of cataract. The SS-OCTA prototype detected CNV-associated vascular patterns more reliably than the SD-OCTA system. This is attributed to the SS-OCTA system’s longer center wavelength and higher A-scan rate yielding higher definition and contrast of small neovascular structures. The SS-OCTA system used showed no advantage regarding cataract influence.

Direct laser writing for micro-optical devices using a negative photoresist.

PubMed

Tsutsumi, Naoto; Hirota, Junichi; Kinashi, Kenji; Sakai, Wataru

2017-12-11

Direct laser writing (DLW) via two-photon absorption (TPA) has attracted much attention as a new microfabrication technique because it can be applied to fabricate complex, three-dimensional (3D) microstructures. In this study, 3D microstructures and micro-optical devices of micro-lens array on the micrometer scale are fabricated using the negative photoresist SU-8 through TPA with a femtosecond laser pulse under a microscope. The effects of the irradiation conditions on linewidths, such as laser power, writing speed, and writing cycles (a number of times a line is overwritten), are investigated before the fabrication of the 3D microstructures. Various microstructures such as woodpiles, hemisphere and microstructures, 3D micro-lens and micro-lens array for micro-optical devices are fabricated. The shape of the micro-lens is evaluated using the shape analysis mode of a laser microscope to calculate the working distance of the fabricated micro-lenses. The calculated working distance corresponds well to the experimentally measured value. The focusing performance of the fabricated micro-lens is confirmed by the TPA fluorescence of an isopropyl thioxanthone (ITX) ethanol solution excited by a Ti:sapphire femtosecond laser at 800 nm. Micro-lens array (assembled 9 micro-lenses) are fabricated. Nine independent woodpile structures are simultaneously manufactured by DLW via TPA to confirm the multi-focusing ability using the fabricated micro-lens array.

Involvement of a gut-retina axis in protection against dietary glycemia induced age-related macular degeneration

USDA-ARS?s Scientific Manuscript database

Age-related macular degeneration (AMD) is the major cause of blindness in developed nations. AMD is characterized by retinal pigmented epithelial cell (RPE) dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate important contributions of dietary patterns on risk for AMD, but th...

Introduction to the issue regarding research regarding age related macular degeneration

USDA-ARS?s Scientific Manuscript database

Blindness is the second greatest fear among the elderly. Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly in most industrialized nations. AMD first compromises central high acuity vision. Subsequently, all vision may be lost. AMD is a progressive retinal d...

Age-Related Macular Degeneration: Advances in Management and Diagnosis

PubMed Central

Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.

2015-01-01

Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

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

PubMed

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.

Estrogen signalling in the pathogenesis of age-related macular degeneration.

PubMed

Kaarniranta, Kai; Machalińska, Anna; Veréb, Zoltán; Salminen, Antero; Petrovski, Goran; Kauppinen, Anu

2015-02-01

Age-related macular degeneration (AMD) is a multifactorial eye disease that is associated with aging, family history, smoking, obesity, cataract surgery, arteriosclerosis, hypertension, hypercholesterolemia and unhealthy diet. Gender has commonly been classified as a weak or inconsistent risk factor for AMD. This disease is characterized by degeneration of retinal pigment epithelial (RPE) cells, Bruch's membrane, and choriocapillaris, which secondarily lead to damage and death of photoreceptor cells and central visual loss. Pathogenesis of AMD involves constant oxidative stress, chronic inflammation, and increased accumulation of lipofuscin and drusen. Estrogen has both anti-oxidative and anti-inflammatory capacity and it regulates signaling pathways that are involved in the pathogenesis of AMD. In this review, we discuss potential cellular signaling targets of estrogen in retinal cells and AMD pathology.

Haneş and Valea Vinului (Romania) closed mines Acid Mine Drainages (AMDs)--actual condition and passive treatment remediation proposal.

PubMed

Măicăneanu, Andrada; Bedelean, Horea; Ardelean, Marius; Burcă, Silvia; Stanca, Maria

2013-10-01

Acid Mine Drainages (AMDs) from Haneş and Valea Vinului (Romania) closed mines were considered for characterization and treatment using a local zeolitic volcanic tuff, ZVT, (Măcicaş, Cluj County, Romania). Water samples were collected from two locations, before and after discharging point in case of Haneş mine, and on three horizons in case of Valea Vinului mine. Physico-chemical (pH, total solid, heavy metal ions concentration) analyses showed that the environment is strongly affected by these AMD discharges even if the mines were closed years ago. Iron, manganese and zinc were the main pollutants identified in Haneş mine AMD, while zinc is the one mainly present in case of Valea Vinului AMD. A batch technique (no stirring) in which the ZVT was put in contact with the AMD sample was proposed as a passive remediation technique. ZVT successfully remove heavy metal ion from AMD. According to heavy metal ion concentrations, removal efficiencies are reaching 100%, varying as follows, Fe(2+)>Zn(2+)>Mn(2+). When the ZVT was compared with two cationic resins (strong, SAR and weak acid, WAR) the following series was depicted, SAR>ZVT>WAR. Copyright © 2013 Elsevier Ltd. All rights reserved.

Application of AMDS mortar as a treatment agent for arsenic in subsurface environment

NASA Astrophysics Data System (ADS)

Choi, J.; Lee, H.; Choi, U. K.; Yang, I. J.

2014-12-01

Among the treatment technologies available for As in soil and groundwater, adsorption or precipitation using acid mine drainage (AMD) sludge has become a promised technique because of high efficiency, inexpensiveness and simple to handling. The adsorbents were prepared by addition of Cement, Joomoonjin sand, fly ash, and Ca(OH)2 to air dry AMD sludge. In this work, the adsorption of As (III) and As (V) on AMDS mortar has been studied as a function of kinetic, pH, and initial arsenic concentration. Results of batch study showed that 75-90% of both As (III) and As (V) were removed at pH 7. Arsenic adsorption capacities were the highest at neutral pH condition and the adsorption equilibrium time reached in 7 days using AMDS mortar. Additionally, the adsorption kinetic process is expressed well by pseudo-second-order model. The adsorption capacities of AMDS mortar for As(III) and As(V) were found 19.04 and 30.75 mg g-1, respectively. The results of As (III) adsorption isotherms were fitted well to the Freundlich model. Moreover, As (V) adsorption isotherms were fitted well to the Langmuir model rather than Freundlich model. Based on experimental results in this study, we could conclude that AMDS mortar can be effectively used for arsenic removal agent from subsurface environment.

Minor improvement for intertidal seaweeds and invertebrates after acid mine drainage diversion at Britannia Beach, Pacific Canada.

PubMed

Zis, Thalia; Ronningen, Vera; Scrosati, Ricardo

2004-06-01

In December 2001, acid mine drainage (AMD) from an abandoned copper mine at Britannia Beach (British Columbia, Canada) was diverted to flow from Britannia Creek into an outfall at 30 m depth in Howe Sound. Britannia Beach was studied in early 2003 to determine whether AMD diversion resulted in improved conditions for intertidal organisms. Species number and abundance have increased at the intertidal zone since AMD diversion, although they were still lower than at an unpolluted control site nearby (Furry Creek). Survivorship and growth rates of transplanted Mytilus trossulus (mussel) have increased since AMD diversion, although they were still significantly lower than at the control site. Transplanted Fucus gardneri (seaweed) performed better than before the AMD diversion; at Britannia Beach the chlorophyll a concentration in tissues was not significantly different from that at the control site, although the concentration of chlorophyll c in tissues and the chlorophyll c to a ratio was lower than at the control site six weeks after transplantation. Britannia Beach is still subject to leaching of metals from surrounding soils, low levels of AMD coming down the creek, and AMD discharge from the deep outfall. Although there has been an improvement, the intertidal environment at Britannia Beach still seems unable to support normal growth and survival of organisms.

Diversity of the Sediment Microbial Community in the Aha Watershed (Southwest China) in Response to Acid Mine Drainage Pollution Gradients

PubMed Central

Sun, Weimin; Sun, Min; Dong, Yiran; Ning, Zengping; Xiao, Enzong; Tang, Song; Li, Jiwei

2015-01-01

Located in southwest China, the Aha watershed is continually contaminated by acid mine drainage (AMD) produced from upstream abandoned coal mines. The watershed is fed by creeks with elevated concentrations of aqueous Fe (total Fe > 1 g/liter) and SO42− (>6 g/liter). AMD contamination gradually decreases throughout downstream rivers and reservoirs, creating an AMD pollution gradient which has led to a suite of biogeochemical processes along the watershed. In this study, sediment samples were collected along the AMD pollution sites for geochemical and microbial community analyses. High-throughput sequencing found various bacteria associated with microbial Fe and S cycling within the watershed and AMD-impacted creek. A large proportion of Fe- and S-metabolizing bacteria were detected in this watershed. The dominant Fe- and S-metabolizing bacteria were identified as microorganisms belonging to the genera Metallibacterium, Aciditerrimonas, Halomonas, Shewanella, Ferrovum, Alicyclobacillus, and Syntrophobacter. Among them, Halomonas, Aciditerrimonas, Metallibacterium, and Shewanella have previously only rarely been detected in AMD-contaminated environments. In addition, the microbial community structures changed along the watershed with different magnitudes of AMD pollution. Moreover, the canonical correspondence analysis suggested that temperature, pH, total Fe, sulfate, and redox potentials (Eh) were significant factors that structured the microbial community compositions along the Aha watershed. PMID:25979900

Recent developments in age-related macular degeneration: a review.

PubMed

Al-Zamil, Waseem M; Yassin, Sanaa A

2017-01-01

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

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

PubMed Central

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 progression to late AMD in the AREDS2 participants, and these findings are consistent with the findings in the majority of previous studies. Statins have been demonstrated to reduce the risks of cardiovascular disease, but our data do not provide evidence of a beneficial effect on slowing AMD progression. PMID:26435335

The Association of Serum Iron-Binding Proteins and the Antioxidant Parameter Levels in Age-Related Macular Degeneration.

PubMed

Čolak, Emina; Žorić, Lepša; Radosavljević, Aleksandra; Ignjatović, Svetlana

2018-05-01

Age-related macular degeneration (AMD) is the leading cause of the irreversible central visual loss among the elderly in the developed countries. Iron is considered a potent generator of the oxidative damage whose levels increase with age, potentially exacerbating the age-related diseases. The aim of this study was to assess the serum values of iron, and iron-binding proteins (transferrin, ferritin, and haptoglobin) in patients with AMD along with the parameters of the antioxidant defense: superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase, and total antioxidant status (TAS), in order to analyze the possible impact of iron and iron-binding proteins to the development of oxidative stress in AMD patients, and the association of the selected parameters with the AMD. In addition, the aim was to examine the gender differences and calculate the cutoff points of tested parameters that could be associated with AMD. A cross-sectional study included 55 AMD patients aged 71.7 ± 7.36 years and 65 aged-matched control subjects aged 70.25 ± 6.46 years. Significantly lower ferritin (P = 0.025), SOD (P = 0.026), GPx (P = 0.019), and TAS (P < 0.004) values were found in patients with AMD compared to the controls (P < 0.05). Significant association of GPx < 27 U/gHb (odds ratio [OR]: 1.13; 95% confidence interval [CI] 0.78-2.10; P = 0.049), TAS < 1.25 mmol/L (OR: 5.77; 95% CI 0.98-367.0; P < 0.000), ferritin < 84.8 pg/mL (OR: 2.52; 95% CI 1.37-4.62; P = 0.002), and haptoglobin<1.51 g/L (OR: 1.94; 95% CI 1.05-3.56; P = 0.031) was found with the AMD. According to receiver operating characteristic curve analysis, ferritin concentration <84.8 pg/L, GPx < 27 U/gHb, and TAS < 1.25 mmol/L have sufficient predictive ability for AMD. Significantly reduced capacity of the antioxidant defense system and iron-binding storage proteins (ferritin) found in AMD could have an important role in the development of increase oxidative stress in AMD patients.

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

PubMed

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 < .001). Predicted plasma 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 < .001). We did not identify any associations of carotenoids, either as predicted plasma score or calculated intake, with intermediate AMD. Higher intake of bioavailable lutein/zeaxanthin is associated with a long-term reduced risk of advanced AMD. Given that some other carotenoids are also associated with a lower risk, a public health strategy aimed at increasing dietary consumption of a wide variety of fruits and vegetables rich in carotenoids may reduce the incidence of advanced AMD.

Integration of micro-/nano-/quantum-scale photonic devices: scientific and technological considerations

NASA Astrophysics Data System (ADS)

Lee, El-Hang; Lee, Seung-Gol; O, Beom Hoan; Park, Se Geun

2004-08-01

Scientific and technological issues and considerations regarding the integration of miniaturized microphotonic devices, circuits and systems in micron, submicron, and quantum scale, are presented. First, we examine the issues regarding the miniaturization of photonic devices including the size effect, proximity effect, energy confinement effect, microcavity effect, optical and quantum interference effect, high field effect, nonlinear effect, noise effect, quantum optical effect, and chaotic effect. Secondly, we examine the issues regarding the interconnection including the optical alignment, minimizing the interconnection losses, and maintaining optical modes. Thirdly, we address the issues regarding the two-dimensional or three-dimensional integration either in a hybrid format or in a monolithic format between active devices and passive devices of varying functions. We find that the concept of optical printed circuit board (O-PCB) that we propose is highly attractive as a platform for micro/nano/quantum-scale photonic integration. We examine the technological issues to be addressed in the process of fabrication, characterization, and packaging for actual implementation of the miniaturization, interconnection and integration. Devices that we have used for our study include: mode conversion schemes, micro-ring and micro-racetrack resonator devices, multimode interference devices, lasers, vertical cavity surface emitting microlasers, and their arrays. Future prospects are also discussed.

Collection, Measurement and Treatment of Microorganism Using Dielectrophoretic Micro Devices

NASA Astrophysics Data System (ADS)

Uchida, Satoshi

Constant monitoring of manufacturing processes has been essential in food industry because of global expansion of microbial infection. Micro-scale dielectrophoretic method is an attractive technique for direct operation and quantitative detection of bioparticles. The electrical system is capable of rapid and simple treatments corresponding to severe legal control for food safety. In this paper, newly developed techniques are reviewed for bacterial concentration, detection and sterilization using dielectrophoresis in a micro reactor. The perspective to an integrated micro device of those components is also discussed.

A Novel Tool for the Assessment Oxidative Stress in Age-Related Macular Degeneration: Thiol/Disulfide Homeostasis Revisited.

PubMed

Arıkan Yorgun, Mücella; Toklu, Yasin; Altınkaynak, Hasan; Tanrıverdi, Burak; Ergin, Merve; Biçer, Cemile

2016-12-01

To investigate thiol/disulfide status using a novel automated assay in patients with age-related macular degeneration (AMD) compared to age-matched healthy controls. A total of 64 AMD patients [51 (79%) non-exudative, 13 (21%) exudative AMD] and 21 age-matched healthy control subjects were enrolled in this study. Plasma total thiol, native thiol, disulfide levels were measured and native thiol/disulfide ratio (TDR) was calculated using a novel spectrophotometric assay. Patients with AMD had significantly lower levels of total thiol (434.8 ± 7.0 μmol/L vs. 472.2 ± 7.9 μmol/L, p < 0.001), native thiol (393.6 ± 6.5 μmol/L vs. 437.5 ± 7.1 μmol/L, p = 0.004) compared to healthy controls. However, plasma disulfide levels were higher in AMD patients (20.6 ± 0.9 μmol/L vs. 17.3 ± 1.3 μmol/L, p = 0.113) compared to healthy controls. The TDR was not statistically different between the early AMD group and healthy controls (24.2 ± 2.3 vs. 29.5 ± 3.1, p = 0.345). However, intermediate and advanced stage AMD groups had significantly lower levels of TDR compared to healthy controls (21.6 ± 2.6 vs. 29.5 ± 3.1, p = 0.023 and 20.3 ± 1.2 vs. 29.5 ± 3.1, p = 0.005, respectively). Native TDR was significantly lower in patients with exudative and non-exudative AMD (19.9 ± 2.3 vs. 29.5 ± 3.1, p = 0.024 and 21.8 ± 1.14 vs. 29.47 ± 3.1 respectively, p = 0.011). A greater extent of thiol consumption occurred in AMD patients compared to age-matched healthy controls. However, despite the similar levels of total thiol levels between several grades of AMD, the plasma native TDR value was decreased in accordance with the severity of the disease, which reflected the disease grade better.

Impact of Legacy Surface Mining on Water Quality in the Lake Harris Watershed, Tuscaloosa County, Alabama.

NASA Astrophysics Data System (ADS)

Donahoe, R. J.; Hawkins, P. D.

2017-12-01

The Lake Harris watershed was the site of legacy surface mining of coal conducted from approximately 1969 to 1976. The mine site was abandoned and finally reclaimed in 1986. Water quality in the stream draining the mined area is still severely impacted by acid mine drainage (AMD), despite the reclamation effort. Lake Harris is used as a source of industrial water, but shows no negative water quality effects from the legacy mining activities despite receiving drainage from the AMD-impacted stream. Water samples were collected monthly between October 2016 and September 2017 from a first-order stream impacted by acid mine drainage (AMD), a nearby first-order control stream, and Lake Harris. Stream water chemistry was observed to vary both spatially and seasonally, as monitored at five sample stations in each stream over the study period. Comparison of the two streams shows the expected elevated concentrations of AMD-indicator solutes (sulfate and iron), as well as significant increases in conductivity and acidity for the stream draining the reclaimed mine site. In addition, dramatic (1-2 orders of magnitude) increases in major element (Al, Ca, Mg, K), minor element (Mn, Sr) and trace element (Co, Ni) concentrations are also observed for the AMD-impacted stream compared to the control stream. The AMD-impacted stream also shows elevated (2-4 times) levels of other stream water solutes (Cl, Na, Si, Zn), compared to the control stream. As the result of continuing AMD input, the stream draining the reclaimed mine site is essentially sterile, in contrast to the lake and control stream, which support robust aquatic ecosystems. A quantitative model, constrained by isotopic data (δD and δ18O), will be presented that seeks to explain the observed temporal differences in water quality for the AMD-impacted stream as a function of variable meteoric water, groundwater, and AMD inputs. Similar models may be developed for other AMD-impacted streams to better understand and predict temporal variations in water quality parameters and their effect on aquatic ecosystems.

Vitamin D Deficiency in Community-Dwelling Elderly Is Not Associated with Age-Related Macular Degeneration.

PubMed

Cougnard-Grégoire, Audrey; Merle, Bénédicte M J; Korobelnik, Jean-Francois; Rougier, Marie-Bénédicte; Delyfer, Marie-Noëlle; Féart, Catherine; Le Goff, Mélanie; Dartigues, Jean-François; Barberger-Gateau, Pascale; Delcourt, Cécile

2015-08-01

Elderly persons are at elevated risk of vitamin D deficiency, which is involved in various health problems. However, its relation with age-related macular degeneration (AMD) is debated. We investigated factors associated with plasma 25-hydroxyvitamin D [25(OH)D] deficiency and the associations between plasma 25(OH)D concentrations and AMD in elderly subjects. Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes (ALIENOR) is a population-based study on eye diseases performed in elderly residents of Bordeaux, France. Plasma 25(OH)D concentrations were assessed from blood samples and categorized as <25 nmol/L (deficiency), 25-49 nmol/L (insufficiency), or ≥50 nmol/L (sufficiency). AMD was classified as: no AMD, early AMD, and late AMD. Associations between baseline characteristics and plasma 25(OH)D status were examined with multinomial logistic regression analysis. Associations between AMD and plasma 25(OH)D status were estimated using generalized estimating equation logistic regressions. Six hundred ninety-seven subjects with complete data were included. The prevalence of plasma 25(OH)D deficiency and insufficiency were 27.3% and 55.9%, respectively. In multivariate analysis, 25(OH)D deficiency was significantly associated with older age (P = 0.0007), females (P = 0.0007), absence of physical activity (P = 0.01), absence of vitamin D supplementation (P < 0.0001), higher plasma total cholesterol (P = 0.007), use of fibrates (P < 0.0001), lower alcohol consumption (P = 0.02), and season of blood sampling (P < 0.0001). After adjustment for these covariates and dietary omega-3 polyunsaturated fatty acid intake, smoking, and body mass index, no significant associations were found between early AMD and 25(OH)D insufficiency or deficiency (OR: 0.71, P = 0.12; OR: 0.73, P = 0.23, respectively) or with late AMD (OR: 1.04, P = 0.93; OR: 0.74, P = 0.59, respectively). These findings underline the very high prevalence of plasma 25(OH)D deficiency in this elderly population but do not support a specific role for vitamin D in AMD. © 2015 American Society for Nutrition.

Updates on the Epidemiology of Age-Related Macular Degeneration.

PubMed

Jonas, Jost B; Cheung, Chui Ming Gemmy; Panda-Jonas, Songhomitra

2017-01-01

This meta-analysis reports on current estimates of the prevalence of age-related macular degeneration (AMD) based on a review of recent meta-analyses and literature research. Within an age of 45-85 years, global prevalences of any AMD, early AMD, and late AMD were 8.7% [95% credible interval (CrI), 4.3‒17.4], 8.0% (95% CrI, 4.0‒15.5), and 0.4% (95% CrI, 0.2-0.8). Early AMD was more common in individuals of European ancestry (11.2%) than in Asians (6.8%), whereas prevalence of late AMD did not differ significantly. AMD of any type was less common in individuals of African ancestry. The number of individuals with AMD was estimated to be 196 million (95% CrI, 140‒261) in 2020 and 288 million (95% CrI, 205‒399) in 2040. The worldwide number of persons blind (presenting visual acuity < 3/60) or with moderate to severe vision impairment (MSVI; presenting visual acuity < 6/18 to 3/60 inclusive) due to macular disease in 2010 was 2.1 million [95% uncertainty interval (UI), 1.9‒2.7] individuals out of 32.4 million individuals blind and 6.0 million (95% UI, 5.2‒8.1) persons out of 191 million people with MSVI. Age-standardized prevalence of macular diseases as cause of blindness in adults aged 50+ years worldwide decreased from 0.2% (95% UI, 0.2‒0.2) in 1990 to 0.1% (95% UI, 0.1‒0.2) in 2010; as cause for MSVI, it remained mostly unchanged (1990: 0.4%; 95% UI, 0.3‒0.5; 2010: 0.4%; 95% UI, 0.4‒0.6), with no significant sex difference. In 2015, AMD was the fourth most common cause of blindness globally (in approximately 5.8% of blind individuals) and third most common cause for MSVI (3.9%). These data show the globally increasing importance of AMD. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

Veterinary Medicine Needs New Green Antimicrobial Drugs

PubMed Central

Toutain, Pierre-Louis; Ferran, Aude A.; Bousquet-Melou, Alain; Pelligand, Ludovic; Lees, Peter

2016-01-01

Given that: (1) the worldwide consumption of antimicrobial drugs (AMDs) used in food-producing animals will increase over the coming decades; (2) the prudent use of AMDs will not suffice to stem the rise in human antimicrobial resistance (AMR) of animal origin; (3) alternatives to AMD use are not available or not implementable, there is an urgent need to develop novel AMDs for food-producing animals. This is not for animal health reasons, but to break the link between human and animal resistomes. In this review we establish the feasibility of developing for veterinary medicine new AMDs, termed “green antibiotics,” having minimal ecological impact on the animal commensal and environmental microbiomes. We first explain why animal and human commensal microbiota comprise a “turnstile” exchange, between the human and animal resistomes. We then outline the ideal physico-chemical, pharmacokinetic, and pharmacodynamic properties of a veterinary green antibiotic and conclude that they can be developed through a rational screening of currently used AMD classes. The ideal drug will be hydrophilic, of relatively low potency, slow clearance and small volume of distribution. It should be eliminated principally by the kidney as inactive metabolite(s). For oral administration, bioavailability can be enhanced by developing lipophilic pro-drugs. For parenteral administration, slow-release formulations of existing eco-friendly AMDs with a short elimination half-life can be developed. These new eco-friendly veterinary AMDs can be developed from currently used drug classes to provide alternative agents to those currently used in veterinary medicine and mitigate animal contributions to the human AMR problem. PMID:27536285

Burden of Wet Age-Related Macular Degeneration and Its Economic Implications in Singapore in the Year 2030.

PubMed

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

2016-08-01

To estimate the prevalence of wet age-related macular degeneration (AMD) in Singapore in the year 2030. This projection will help in planning appropriate care provision and build health services capacity to cater to the increasing healthcare demand in 2030. The number of AMD patients aged 40-79 years from all Singaporeans was estimated using prevalence rates from a local study and using the United Nations population projections for Singapore to 2030. Age-specific mortality was accounted for. Additionally, two main scenarios were presented: (1) Projected number of wet AMD cases if patients were not taking preventive antioxidant vitamins; (2) projected number of wet AMD cases if patients were taking preventive antioxidant vitamins. Based on these scenarios, the economic burden was calculated. The number of quality-adjusted life years (QALYs) gained as a result of improvement in visual acuity (VA) due to anti-vascular endothelial growth factor (VEGF) treatment was also calculated. An estimated growth of 42% in the number of wet AMD cases is expected by 2030. The estimated economic burden of wet AMD in 2030 for scenarios 1 and 2 is Singapore $203.1 million and $162.9 million, respectively. The QALYs gained as a result of improved VA from wet AMD treatment ranged from 10,114.4 to 14,058.8 over a 5-year period for the 2030 cohort. The burden of wet AMD is set to increase over the next 15 years. Appropriate measures to build healthcare capacity and plan for this expected surge in patients should be a priority in Singapore.

Diagnostic Sensitivity and Specificity of Dark Adaptometry for Detection of Age-Related Macular Degeneration

PubMed Central

Jackson, Gregory R.; Scott, Ingrid U.; Kim, Ivana K.; Quillen, David A.; Iannaccone, Alessandro; Edwards, John G.

2014-01-01

Purpose. Difficulty with night vision is a common complaint of patients with age-related macular degeneration (AMD). Consistent with this complaint, dark adaptation (DA) is substantially impaired in these patients. Because of the severity of the deficit, measurement of DA has been suggested as a means for the diagnosis of AMD. Previous methods for measurement of DA were time intensive (>30 minutes), which made them unsuitable for clinical use. This study evaluated a rapid DA test (≤6.5 minutes) for the detection of AMD. Methods. Dark adaptation was measured by using the AdaptDx dark adaptometer in two groups: subjects with normal retinal health and subjects with AMD. Subjects were assigned to their group by clinical examination and grading of fundus photographs. Subjects were classified as having DA consistent with normal retinal health (rod intercept ≤ 6.5 minutes) or having dark adaptation consistent with AMD (rod intercept > 6.5 minutes). Results. The eligible sample for analysis included 21 normal adults and 127 AMD patients. The rapid test was found to have a diagnostic sensitivity of 90.6% (P < 0.001) and specificity of 90.5% (P < 0.027). Thus, abnormal DA was detected in 115 of 127 AMD patients, and normal DA was found in 19 of 21 normal adults. Conclusions. The high diagnostic sensitivity and specificity compared favorably to long-duration research methods for the measurement of DA, and slit lamp biomicroscopy performed by a retina specialist. These results suggest that a rapid DA test is useful for the detection of AMD. PMID:24550363

Exposure to Atomic Bomb Radiation and Age-Related Macular Degeneration in Later Life: The Hiroshima-Nagasaki Atomic Bomb Survivor Study.

PubMed

Itakura, Katsumasa; Takahashi, Ikuno; Nakashima, Eiji; Yanagi, Masahide; Kawasaki, Ryo; Neriishi, Kazuo; Wang, Jie Jin; Wong, Tien Yin; Hida, Ayumi; Ohishi, Waka; Kiuchi, Yoshiaki

2015-08-01

To investigate the association between radiation exposure from the atomic bombings and the prevalence of age-related macular degeneration (AMD) among older residents of Hiroshima and Nagasaki. The Adult Health Study is a cohort study of atomic bomb survivors living in Hiroshima and Nagasaki, comprising 2153 participants who underwent examinations with retinal fundus photographs in 2006-2008. The radiation dose to the eye for the analysis was estimated with the revised dosimetry system (DS02). The retinal photographs were graded according to the Wisconsin Age-Related Maculopathy Grading System modified for nonstereoscopic retinal images. Early and late AMD were defined according to the type of lesion detected in the worse eye of the participants. Person-specific data were analyzed by using a logistic regression model to assess the association between radiation dose and AMD. Among the 1824 subjects with gradable retinal images (84.7% of the overall participants), the estimated eye dose was widely distributed, with a mean of 0.45 Gy and standard deviation of 0.74 Gy. The prevalence of early and late AMD was 10.5% and 0.3%, respectively. There were no significant associations between radiation dose and AMD, with each 1-Gy increase in exposure, adjusted odds ratio was 0.93 (95% confidence interval [CI], 0.75-1.15) for early AMD and 0.79 (95% CI, 0.21-2.94) for late AMD. No significant associations were found between atomic bomb irradiation early in life and the prevalence of early or late AMD later in life among Japanese atomic bomb survivors.

Allyl methyl disulfide inhibits IL-8 and IP-10 secretion in intestinal epithelial cells via the NF-кB signaling pathway.

PubMed

Zhang, Yongchun; Wang, Ying; Zhang, Fang; Wang, Kaiming; Liu, Guangpu; Yang, Min; Luan, Yuxia; Zhao, Zhongxi; Zhang, Jianqiang; Cao, Xinke; Zhang, Daizhou

2015-07-01

Garlic and its active constituents have shown versatile medicinal activities in the prevention and treatment of various disorders. Allyl methyl disulfide (AMDS) was identified as one of the major bioactive components in an effective inhalation fork remedy using fresh garlic paste in our previous study. In this work, we investigated the immunological properties of AMDS to elucidate the underlying mechanisms of the fork inhalation treatment using fresh garlic. The inhibition effect of AMDS on TNF-α-induced IL-8 and IP-10 production in intestinal epithelial cell lines HT-29 and Caco-2 was first evaluated. Pretreatment of the cells with AMDS attenuated IL-8 and IP-10 secretion induced by TNF-α in a dose-dependent manner in the non-cytotoxic concentration range of 20 to 150 μM. Mechanistic studies revealed that AMDS suppressed the accumulation of IL-8 mRNA and inhibited IкBα degradation and NF-кB p65 translocation into the nucleus at both the transcriptional and translational levels, suggesting that the attenuation effort of AMDS on cytokine IL-8 secretion might at least be partially related to the NF-κB signaling pathway. These results suggest that AMDS may be a promising phytochemical agent in the treatment of immunological disorders, such as ulcerative colitis, Crohn's disease, intestinal inflammatory diseases and others. In addition, the mechanistic study data indicated that immune modulation could be one of the therapeutic mechanisms of the effective fork treatment containing AMDS as one of the major components. Copyright © 2015 Elsevier B.V. All rights reserved.

Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration1234

PubMed Central

Koo, Euna; Neuringer, Martha; SanGiovanni, John Paul

2014-01-01

Plant-based macular xanthophylls (MXs; lutein and zeaxanthin) and the lutein metabolite meso-zeaxanthin are the major constituents of macular pigment, a compound concentrated in retinal areas that are responsible for fine-feature visual sensation. There is an unmet need to examine the genetics of factors influencing regulatory mechanisms and metabolic fates of these 3 MXs because they are linked to processes implicated in the pathogenesis of age-related macular degeneration (AMD). In this work we provide an overview of evidence supporting a molecular basis for AMD-MX associations as they may relate to DNA sequence variation in AMD- and lipoprotein-related genes. We recognize a number of emerging research opportunities, barriers, knowledge gaps, and tools offering promise for meaningful investigation and inference in the field. Overviews on AMD- and high-density lipoprotein (HDL)–related genes encoding receptors, transporters, and enzymes affecting or affected by MXs are followed with information on localization of products from these genes to retinal cell types manifesting AMD-related pathophysiology. Evidence on the relation of each gene or gene product with retinal MX response to nutrient intake is discussed. This information is followed by a review of results from mechanistic studies testing gene-disease relations. We then present findings on relations of AMD with DNA sequence variants in MX-associated genes. Our conclusion is that AMD-associated DNA variants that influence the actions and metabolic fates of HDL system constituents should be examined further for concomitant influence on MX absorption, retinal tissue responses to MX intake, and the capacity to modify MX-associated factors and processes implicated in AMD pathogenesis. PMID:24829491

Age-related macular degeneration.

PubMed

Cheung, Lily K; Eaton, Angie

2013-08-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease. © 2013 Pharmacotherapy Publications, Inc.

Past physical activity and age-related macular degeneration: the Melbourne Collaborative Cohort Study.

PubMed

McGuinness, Myra B; Karahalios, Amalia; Simpson, Julie A; Guymer, Robyn H; Robman, Luba D; Hodge, Allison M; Cerin, Ester; Giles, Graham G; Finger, Robert P

2016-10-01

To assess the association between past physical activity and early, intermediate and late age-related macular degeneration (AMD) in a community-based cohort study in Melbourne, Australia. Diet and lifestyle information was recorded at baseline (1990-1994) and total recreational activity was derived from walking, vigorous and non-vigorous exercise. At follow-up (2003-2007), digital macular photographs were graded for early, intermediate and late AMD. Data were analysed using multinomial logistic regression controlling for age, sex, smoking, region of descent, diet and alcohol. Effect modification by sex was investigated. Out of 20 816 participants, early, intermediate and late AMD were detected at follow-up in 4244 (21%), 2661 (13%) and 122 (0.6%) participants, respectively. No association was detected between past total recreational physical activity and early, intermediate or late AMD. Frequent (≥3 times/week) and less frequent (1-2 times/week) vigorous exercise were associated with lower odds of intermediate and late AMD in univariable models. After controlling for confounders, there was evidence of effect modification by sex and frequent vigorous exercise was associated with a 22% decrease in the odds of intermediate AMD (95% CI 4% to 36%) in women, but no association was found for men. Past frequent vigorous exercise may be inversely related to the presence of intermediate AMD in women. Further studies are needed to confirm whether physical activity and exercise have a protective effect for AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Investigation of Diffusion Characteristics through Microfluidic Channels for Passive Drug Delivery Applications

PubMed Central

Ghuman, Alyssa P.; Collins, Stephanie B.; Handa, Hitesh

2016-01-01

Microfluidics has many drug delivery applications due to the ability to easily create complex device designs with feature sizes reaching down to the 10s of microns. In this work, three different microchannel designs for an implantable device are investigated for treatment of ocular diseases such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy. Devices were fabricated using polydimethylsiloxane (PDMS) and soft lithography techniques, where surface chemistry of the channels was altered using 2-[methoxy(polyethyleneoxy)propyl]trimethoxysilane (PEG-silane). An estimated delivery rate for a number of common drugs was approximated for each device through the ratio of the diffusion coefficients for the dye and the respective drug. The delivery rate of the model drugs was maintained at a physiological condition and the effects of channel design and surface chemistry on the delivery rate of the model drugs were recorded over a two-week period. Results showed that the surface chemistry of the device had no significant effect on the delivery rate of the model drugs. All designs were successful in delivering a constant daily dose for each model drug. PMID:27313895

Ethnic Differences in the Association Between Age-Related Macular Degeneration and Vision-Specific Functioning

PubMed Central

Fenwick, Eva K.; Man, Ryan E. K.; Cheung, Chui Ming Gemmy; Sabanayagam, Charumathi; Cheng, Ching-Yu; Neelam, Kumari; Chua, Jacqueline; Gan, Alfred T. L.; Mitchell, Paul; Wong, Tien Y.

2017-01-01

Importance Understanding the link between ethnicity and health is critical to making appropriate public policy decisions. Few population-level data are available about this connection, however, including the influence of ethnicity on the association between age-related macular degeneration (AMD) and vision-specific functioning (VSF). Objective To identify the influence of ethnicity on VSF among Chinese, Malay, and Indian patients with AMD. Design, Setting, and Participants This cross-sectional, population-based study relied on patients and their data from 3 population-based studies in 3 ethnic groups: Chinese, Malay and Indian. Of 10 033 Chinese, Malay, and Indian adults who participated in the study, 9962 (99.3%) who had gradable fundus images and Visual Function Index (VF-11) data available were included in the analyses for the present study. Uniocular presenting distance visual acuity was measured using the logMAR chart. Separate multiple linear regression models examined the association between AMD and VSF in the 3 ethnic groups, adjusting for age, sex, presenting visual acuity in the better-seeing eye, educational level, income, smoking status, hypertension, diabetes, cardiovascular disease, total cholesterol level, and other eye conditions. Data were collected between January 20, 2004, and December 19, 2011; data analysis was conducted between November 12, 2015, and December 28, 2016. Exposures Age-related macular degeneration according to fundus photographs graded using a modified Wisconsin Age-Related Maculopathy Grading System. Main Outcomes and Measures Rasch analysis was used to convert VF-11 questionnaire scores to estimated interval measures of VSF. Results Of the 9962 participants, the mean (SD) age was 58.8 (10.4) years; 4909 (49.3%) were male; 590 (5.9%) had early AMD (241 Chinese, 161 Malays, and 188 Indians) and 60 (0.6%) had late AMD (25 Chinese, 21 Malays, and 14 Indians). In the adjusted models, compared with no AMD, early AMD was associated with a small reduction in VSF (2.9%; β = −0.12; 95% CI, −0.23 to −0.00; P = .046) in the Chinese group but not in the Indian and Malay groups. Moreover, Chinese participants with late AMD had a clinically significant 19.1% loss of VSF (β = −0.78; 95% CI, −1.13 to −0.43, P < .001). In the Malay group, those with late AMD had a 13.5% drop in VSF (β = −0.49; 95% CI, −1.01 to 0.04; P = .07) compared with their counterparts without AMD. Similarly, late AMD was not associated with VSF in the Indian group. Conclusions and Relevance Early and late AMD negatively affected VSF in Chinese but not in Indian and Malay participants. This finding suggests that there is an independent ethnic influence in the association of the disease with VSF in multiethnic Asian populations, thus warranting ethnicity-based strategies to delay the onset or progression of AMD. PMID:28358956

Evaluation of stability and size distribution of sunflower oil-coated micro bubbles for localized drug delivery.

PubMed

Filho, Walter Duarte de Araujo; Schneider, Fábio Kurt; Morales, Rigoberto E M

2012-09-20

Micro bubbles were initially introduced as contrast agents for ultrasound examinations as they are able to modify the signal-to-noise ratio in imaging, thus improving the assessment of clinical information on human tissue. Recent developments have demonstrated the feasibility of using these bubbles as drug carriers in localized delivery. In micro fluidics devices for generation of micro bubbles, the bubbles are formed at interface of liquid gas through a strangulation process. A device that uses these features can produce micro bubbles with small size dispersion in a single step. A T-junction micro fluidic device constructed using 3D prototyping was made for the production of mono dispersed micro bubbles. These micro bubbles use sunflower oil as a lipid layer. Stability studies for micro bubbles with diameters different generated from a liquid phase of the same viscosity were conducted to evaluate whether micro bubbles can be used as drug carriers. The biocompatibility of coating layer, the ability to withstand environmental pressure variations combined with echogenicity, are key factors that they can safely play the role of drug transporters. The normal distribution curve with small dispersion of the diameter of bubbles validates the process of generating micro bubbles with low value of variation coefficient, i.e., 0.381 at 1.90%. The results also showed the feasibility of using sunflower oil as the lipid matrix with stable population of bubbles over 217 minutes for micro bubbles with an average diameter of 313.04 μm and 121 minutes for micro bubbles with an average diameter of 73.74 μm, considering bubbles with air as gaseous phase. The results indicate that the micro fluidic device designed can be used for producing micro bubbles with low variation coefficient using sunflower oil as a coating of micro bubbles. These carriers were stable for periods of time that are long enough for clinical applications even when regular air is used as the gas phase. Improved stability can be achieved when biocompatible gas with lower permeability is used.

Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

2012-01-01

Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

Can innate and autoimmune reactivity forecast early and advance stages of age-related macular degeneration?

PubMed

Adamus, Grazyna

2017-03-01

Age-related macular degeneration (AMD) is a major cause of central vision loss in persons over 55years of age in developed countries. AMD is a complex disease in which genetic, environmental and inflammatory factors influence its onset and progression. Elevation in serum anti-retinal autoantibodies, plasma and local activation of complement proteins of the alternative pathway, and increase in secretion of proinflammatory cytokines have been seen over the course of disease. Genetic studies of AMD patients confirmed that genetic variants affecting the alternative complement pathway have a major influence on AMD risk. Because the heterogeneity of this disease, there is no sufficient strategy to identify the disease onset and progression sole based eye examination, thus identification of reliable serological biomarkers for diagnosis, prognosis and response to treatment by sampling patient's blood is necessary. This review provides an outline of the current knowledge on possible serological (autoantibodies, complement factors, cytokines, chemokines) and related genetic biomarkers relevant to the pathology of AMD, and discusses their application for prediction of disease activity and prognosis in AMD. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2014-10-10

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

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

PubMed Central

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

2014-01-01

Metastatic prostate cancer (mPCa) relapses after a short period of androgen deprivation therapy and becomes the castration-resistant prostate cancer (CR PCa); to which the treatment is limited. Hence, it is imperative to identify novel therapeutic agents towards this patient population. In the present study, antiproliferative activities of novel imidazopyridines were compared. Among three derivatives, PHE, AMD and AMN, examined, AMD showed the highest inhibitory activity on LNCaP C-81 cell proliferation, following dose- and time-dependent manner. Additionally, AMD exhibited significant antiproliferative effect against a panel of PCa cells, but not normal prostate epithelial cells. Further, when compared to AMD, its derivative DME showed higher inhibitory activities on PCa cell proliferation, clonogenic potential and in vitro tumorigenicity. The inhibitory activity was apparently in part due to the induction of apoptosis. Mechanistic studies indicate that AMD and DME treatments inhibited both AR and PI3K/Akt signaling. The results suggest that better understanding of inhibitory mechanisms of AMD and DME could help design novel therapeutic agents for improving the treatment of CR PCa. PMID:25050738

Automatic Screening and Grading of Age-Related Macular Degeneration from Texture Analysis of Fundus Images

PubMed Central

Phan, Thanh Vân; Seoud, Lama; Chakor, Hadi; Cheriet, Farida

2016-01-01

Age-related macular degeneration (AMD) is a disease which causes visual deficiency and irreversible blindness to the elderly. In this paper, an automatic classification method for AMD is proposed to perform robust and reproducible assessments in a telemedicine context. First, a study was carried out to highlight the most relevant features for AMD characterization based on texture, color, and visual context in fundus images. A support vector machine and a random forest were used to classify images according to the different AMD stages following the AREDS protocol and to evaluate the features' relevance. Experiments were conducted on a database of 279 fundus images coming from a telemedicine platform. The results demonstrate that local binary patterns in multiresolution are the most relevant for AMD classification, regardless of the classifier used. Depending on the classification task, our method achieves promising performances with areas under the ROC curve between 0.739 and 0.874 for screening and between 0.469 and 0.685 for grading. Moreover, the proposed automatic AMD classification system is robust with respect to image quality. PMID:27190636

Advances in Age-related Macular Degeneration Understanding and Therapy

PubMed Central

Miller, Joan W; Bagheri, Saghar; Vavvas, Demetrios G

2017-01-01

While the development of anti-vascular endothelial growth factor (anti-VEGF) as a therapy for neovascular age-related macular degeneration (AMD) was a great success, the pathologic processes underlying dry AMD that eventually leads to photoreceptor dysfunction, death, and vision loss remain elusive to date, with a lack of effective therapies and increasing prevalence of the disease. There is an overwhelming need to improve the classification system of AMD, to increase our understanding of cell death mechanisms involved in both neovascular and non-neovascular AMD, and to develop better biomarkers and clinical endpoints to eventually be able to identify better therapeutic targets—especially early in the disease process. There is no doubt that it is a matter of time before progress will be made and better therapies will be developed for non-neovascular AMD. PMID:29142592

Hypomethylation of IL17RC Promoter Associates with Age-related Macular Degeneration

PubMed Central

Wei, Lai; Liu, Baoying; Tuo, Jingsheng; Shen, Defen; Chen, Ping; Li, Zhiyu; Liu, Xunxian; Ni, Jia; Dagur, Pradeep; Sen, H. Nida; Jawad, Shayma; Ling, Diamond; Park, Stanley; Chakrabarty, Sagarika; Meyerle, Catherine; Agron, Elvira; Ferris, Frederick L.; Chew, Emily Y.; McCoy, J. Philip; Blum, Emily; Francis, Peter J.; Klein, Michael L.; Guymer, Robyn H.; Baird, Paul N.; Chan, Chi-Chao; Nussenblatt, Robert B.

2012-01-01

SUMMARY Age related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population worldwide. While recent studies have demonstrated strong genetic associations of single nucleotide polymorphisms within a number of genes and AMD, other modes of regulation are also likely to play a role in its etiology. We identified a significantly decreased level of methylation on the IL17RC promoter in AMD patients. Further, we showed that hypomethylation of the IL17RC promoter in AMD patients led to an elevated expression of its protein and mRNA in peripheral blood as well as in the affected retina and choroid, suggesting that the DNA methylation pattern and expression of IL17RC may potentially serve as a biomarker for the diagnosis of AMD and likely plays a role in disease pathogenesis. PMID:23177625

Direct laser-patterned micro-supercapacitors from paintable MoS2 films.

PubMed

Cao, Liujun; Yang, Shubin; Gao, Wei; Liu, Zheng; Gong, Yongji; Ma, Lulu; Shi, Gang; Lei, Sidong; Zhang, Yunhuai; Zhang, Shengtao; Vajtai, Robert; Ajayan, Pulickel M

2013-09-09

Micrometer-sized electrochemical capacitors have recently attracted attention due to their possible applications in micro-electronic devices. Here, a new approach to large-scale fabrication of high-capacitance, two-dimensional MoS2 film-based micro-supercapacitors is demonstrated via simple and low-cost spray painting of MoS2 nanosheets on Si/SiO2 chip and subsequent laser patterning. The obtained micro-supercapacitors are well defined by ten interdigitated electrodes (five electrodes per polarity) with 4.5 mm length, 820 μm wide for each electrode, 200 μm spacing between two electrodes and the thickness of electrode is ∼0.45 μm. The optimum MoS2 -based micro-supercapacitor exhibits excellent electrochemical performance for energy storage with aqueous electrolytes, with a high area capacitance of 8 mF cm(-2) (volumetric capacitance of 178 F cm(-3) ) and excellent cyclic performance, superior to reported graphene-based micro-supercapacitors. This strategy could provide a good opportunity to develop various micro-/nanosized energy storage devices to satisfy the requirements of portable, flexible, and transparent micro-electronic devices. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Job Aid Manuals for Phase I-ANALYZE of the Instructional systems Development Model

DTIC Science & Technology

1980-05-01

with thuTb amd index Pinchinq nose shut finger. pre ents air leakage 7.2 Use hand to exert pressure on fore- head to maintain backward head tilt. 8...ALlMEE Prep tiol /o- Firi . (1) Turn the slot in the striker (at the nose of the frze) to Mine with the SQ index or the D index on the fuze body...12 Index and Description of Army Training Devices Good * Course materials: Correspondance course lessons and materials used in Good resident courses

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

PubMed

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.

Six-Year Incidence of Age-Related Macular Degeneration in Asian Malays: The Singapore Malay Eye Study.

PubMed

Cheung, Chui Ming Gemmy; Ong, Peng Guan; Neelam, Kumari; Tan, Pok Chien; Shi, Yuan; Mitchell, Paul; Wang, Jie Jin; Sabanayagam, Charumathi; Cheng, Ching-Yu; Wong, Tien Yin

2017-09-01

To determine the 6-year incidence of early and late age-related macular degeneration (AMD) in a Singaporean Malay population and to validate the Age-Related Eye Disease Study (AREDS) simplified severity scale in Asians. Prospective, population cohort study. The Singapore Malay Eye Study baseline participants (age, ≥40 years; 2006-2008) were followed up in 2011 through 2013, and 1901 of 3280 of eligible participants (72.1%) took part. Fundus photographs were graded using the Wisconsin AMD grading system. Incidence of early and late AMD. Gradable fundus photographs were available for 1809 participants who attended both baseline and 6-year follow-up examinations. The age-standardized incidences of early and late AMD were 5.89% (95% confidence interval [CI], 4.81-7.16) and 0.76% (95% CI, 0.42-1.29), respectively. The 5-year age-standardized incidence of early AMD (calculated based on the 6-year incidence) was lower in our population (5.58%; 95% CI, 4.43-7.01) compared with the Beaver Dam Eye Study population (8.19%). The incidence of late AMD in our population was similar to that of the Beaver Dam Eye Study population (0.98% [95% CI, 0.49-1.86] vs. 0.91%), the Blue Mountains Eye Study population (1.10% [95% CI, 0.52-9.56] vs. 1.10%), and the Hisayama Study population (1.09% [95% CI, 0.54-4.25] vs. 0.84%). The incidence of late AMD increased markedly with increasing baseline AREDS score (step 0, 0.23%; step 4, 9.09%). This study documented the incidence of early and late AMD in a Malay population. The AREDS simplified severity scale is useful in predicting the risk of late AMD development in Asians. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Comparison of macular pigment optical density in patients with dry and wet age-related macular degeneration.

PubMed

Ozyurt, Ayhan; Kocak, Nilufer; Akan, Pınar; Calan, Ozlem Gursoy; Ozturk, Taylan; Kaya, Mahmut; Karahan, Eyup; Kaynak, Suleyman

2017-06-01

The aim of the study was to evaluate the macular pigment optical density (MPOD) levels in patients with wet age-related macular degeneration (AMD), dry AMD, and also in healthy controls. This study was conducted at Department of Ophthalmology, and the study design was a prospective study. Forty-eight patients with wet AMD, 51 patients with dry AMD, and 50 controls were included in the study. All patients were naive to both previous lutein or zeaxanthin administration and any previous intravitreal injections. Fundus reflectance (VISUCAM 500, reflectance of a single 460 nm wavelength) was used to measure the MPOD levels. Three groups were compared regarding age, gender, serum lutein, and zeaxanthin concentrations as well as MPOD levels. Serum lutein and zeaxanthin levels were significantly higher in control group when compared with wet AMD (Group 1) and dry AMD (Group 2) (P = 0.001 and P< 0.001, respectively). Mean MPOD was found to be similar in all of the three study subgroups (P = 0.630). However, maximum MPOD was significantly higher in control group when compared with Group 1 and 2 (P = 0.003). There was no correlation between serum lutein or zeaxanthin concentrations and mean MPOD levels (P = 0.815, r = 0.014 and P = 0.461, r = 0.043, respectively), but there was a weak correlation between serum zeaxanthin concentration and maximum MPOD level (P = 0.042, r = 0.124). Maximum MPOD level was found to be correlated with the level of AMD (Group 1, 2, and 3; r = 0.184, P = 0.041). Maximum MPOD level was found to be lower in patients with AMD when compared with control cases. Mean MPOD and maximum MPOD levels were similar in wet and dry AMD Groups. These results can be applied clinically keeping in mind that MPOD measurements with one wavelength reflectometry may not be completely reliable.

Smoking, Dietary Betaine, Methionine, and Vitamin D in Monozygotic Twins with Discordant Macular Degeneration: Epigenetic Implications

PubMed Central

Seddon, Johanna M.; Reynolds, Robyn; Shah, Heeral R.; Rosner, Bernard

2012-01-01

Objective We evaluated monozygotic twin pairs with discordant age-related macular degeneration (AMD) phenotypes to assess differences in behavioral and nutritional factors. Design Case series. Participants Caucasian male twin pairs from the United States Twin Study of Macular Degeneration. Methods Twin pairs were genotyped to confirm monozygosity. Ocular characteristics were evaluated based on fundus photographs using the Wisconsin Grading System and a 5-grade Clinical Age-Related Maculopathy Staging System. We selected twin pairs discordant in each of the following phenotypic categories: Stage of AMD (n = 28), drusen area (n = 60), drusen size (n = 40), and increased pigment area (n = 56). The Wilcoxon signed-rank test and linear regression were used to assess associations between behavioral and nutritional characteristics and each phenotype within discordant twin pairs. Main Outcome Measures Differences in smoking and dietary factors within twin pairs discordant for stage of AMD, drusen area, drusen size, and pigment area. Results Representative fundus photographs depict the discordant phenotypes. Pack-years of smoking were higher for the twin with the more advanced stage of AMD (P = 0.05). Higher dietary intake of vitamin D was present in the twins with less severe AMD (P = 0.01) and smaller drusen size (P = 0.05) compared with co-twins, adjusted for smoking and age. Dietary intakes of betaine and methionine were significantly higher in the twin with lower stage of AMD (P = 0.009) and smaller drusen area (P = 0.03), respectively. Conclusions The twin with the more advanced stage of AMD, larger drusen area, drusen size, and pigment area tended to be the heavier smoker. The twin with the earlier stage of AMD, smaller drusen size and area, and less pigment tended to have higher dietary vitamin D, betaine, or methionine intake. Results suggest that behavioral and nutritional factors associated with epigenetic mechanisms are involved in the etiology of AMD, in addition to genetic susceptibility. PMID:21620475

Clinical characteristics of reticular pseudodrusen in Korean patients.

PubMed

Lee, Mee Yon; Yoon, Jaemoon; Ham, Don-Il

2012-03-01

To clarify the clinical characteristics of reticular pseudodrusen in Korean patients. Retrospective, observational, consecutive case series. A total of 255 eyes of 130 patients diagnosed with reticular pseudodrusen were evaluated. Reticular pseudodrusen were diagnosed by characteristic fundus findings using ophthalmoscopy, color fundus photography with blue-channel examination, near-infrared photography, red-free photography, autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and spectral-domain optical coherence tomography. Age-related macular degeneration (AMD) was determined by the International Classification and Grading System. The mean age was 72.6 ± 9.0 years (range, 43 to 92 years). Most reticular pseudodrusen patients had bilateral disease (97.7%), with a female preponderance (86.2%). All 3 patients who showed unilateral reticular pseudodrusen had neovascular AMD in the eye with no reticular pseudodrusen. AMD was found in 183 eyes (71.8 %), among which early AMD was found in 115 eyes (45.1%), geographic atrophy was found in 41 eyes (16.1%), and neovascular AMD was found in 27 eyes (10.6%). The mean age of patients with AMD and with no AMD was 73.7 ± 9.2 years (range, 58 to 92 years) and 69.9 ± 11.7 years (range, 43 to 90 years), respectively, and there was a statistical difference between these 2 groups (P < .05). Classic choroidal neovascularization was found in 13 eyes (48.1%), and occult choroidal neovascularization was found in 14 eyes (51.9%) in the neovascular AMD group. Reticular pseudodrusen occurs in Koreans, and clinical manifestations of reticular pseudodrusen in Koreans did not differ significantly from those described in white persons. However, our study demonstrated a higher rate of bilaterality compared with those previously reported, and geographic atrophy was found to be associated more commonly with reticular pseudodrusen than with neovascular AMD. Ethnical differences may be associated with these findings, and further studies are required. Copyright © 2012 Elsevier Inc. All rights reserved.

Increase in peripheral blood mononuclear cell Toll-like receptor 2/3 expression and reactivity to their ligands in a cohort of patients with wet age-related macular degeneration

PubMed Central

Zhu, Yi; Liang, Liang; Qian, Dan; Yu, Hongsong; Yang, Peizeng; Lei, Bo

2013-01-01

Purpose To investigate Toll-like receptor (TLR) expression and reactivity in patients with the wet form age-related macular degeneration (AMD). Methods Blood samples were collected from 25 patients with wet AMD and 25 age-matched healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated with Ficoll-Hypaque density gradient centrifugation. Expression of TLR1 to TLR10 mRNAs in PBMCs from 15 patients with wet AMD and 15 controls was assessed with real-time PCR. TLR2 and TLR3 protein levels in PBMCs from six patients with wet AMD and six controls were measured with flow cytometry. After PBMCs were stimulated with peptidoglycan (PGN) and poly(I:C), the specific ligands of TLR2 and TLR3, cytokines interleukin-6 (IL-6), IL-8, VEGF, and monocyte chemoattractant protein-1 (MCP-1) production in 11 patients with wet AMD and 11 controls were assessed. Results TLR2 and TLR3 mRNA and protein expression in the PBMCs of the patients with wet AMD was significantly higher than that in the controls. However, the difference in TLR1 and TLR4–10 mRNA expression between the two groups was not significant. The PBMCs of the patients with wet AMD produced more IL-6 and IL-8 proteins than the controls in response to PGN, a ligand for TLR2, and more IL-6 protein than the controls in response to poly(I:C), the ligand for TLR3. However, there was no significant difference in vascular endothelial growth factor and monocyte chemoattractant protein-1 production between the wet AMD group and the control group when the PBMCs were stimulated with PGN or poly(I:C). Conclusions Our data suggested that upregulation of TLR2 and TLR3 may be associated with the pathogenesis of wet AMD. PMID:23946637

Age-related macular degeneration—emerging pathogenetic and therapeutic concepts

PubMed Central

GEHRS, KAREN M.; ANDERSON, DON H.; JOHNSON, LINCOLN V.; HAGEMAN, GREGORY S.

2014-01-01

Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden. Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage ‘wet’ form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common ‘dry’ AMD, except for the use of antioxidants that delay progression in 20%–25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene—which encodes the major inhibitor of the complement alternative pathway—is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development of novel diagnostic and therapeutic approaches for this disease that will dramatically improve the quality of our prolonged lifespan. PMID:17101537

Age-related macular degeneration in Portugal: prevalence and risk factors in a coastal and an inland town. The Coimbra Eye Study - Report 2.

PubMed

Cachulo, Maria da Luz; Laíns, Inês; Lobo, Conceição; Figueira, João; Ribeiro, Luísa; Marques, João P; Costa, José; Vieira, António; Rodrigues, João; Alves, Dalila; Nunes, Sandrina; Costa, Miguel; Rodrigues, Victor; Cunha-Vaz, José; Delcourt, Cecile; Silva, Rufino

2016-09-01

To determine the age- and sex-specific prevalence of early and late age-related macular degeneration (AMD) in two Portuguese population-based samples and to identify its risk factors. A population of 6023 adults aged ≥55 years was recruited from two Portuguese primary healthcare units in the central region of Portugal - one from a coastal (n = 3000) and another from an inland town (n = 3023). Cross-sectional population-based study. Participants were enrolled in the two locations between August 2009 and October 2013. Responders underwent standardized interviews and ophthalmologic examination, including digital fundus imaging. All fundus photographs were graded according to an International Classification and Grading System. The main outcome measures consisted of age- and sex-adjusted prevalence of early and late AMD. Potential epidemiologic risk factors were also evaluated using logistic regression analysis. Of the 6023 subjects enrolled, 5996 had gradable fundus images and were included in the analysis. The crude prevalence of early and late AMD was 6.99 and 0.67%, respectively, for the coastal town and 15.39 and 1.29% for the inland town. Age- and sex-adjusted prevalence of any AMD for the Portuguese population was 12.48% (95% CI: 11.61-13.33) with late AMD accounting for 1.16% (95% CI: 0.85-1.46). Neovascular AMD (NV-AMD) and geographic atrophy (GA) accounted for 0.55% (95% CI: 0.36-0.75) and 0.61% (95% CI: 0.37-0.84) of individuals, respectively. After adjusting for possible confounding factors, prevalence of early and late AMD increased with increasing age (OR = 1.35; 95% CI: 1.23-1.49 for early and OR = 3.01; 95% CI: 2.22-4.08 for late AMD, per each decade of age increase, p < 0.001). After adjustment for age, sex, family history, smoking history, hypertension, diabetes and BMI, subjects from the inland town presented a significantly higher OR of early and late AMD than subjects from the coastal town (OR = 2.57, 95% CI: 2.12-3.12, p < 0.001 for early and OR = 2.06, 95% CI: 1.07-3.95, p = 0.029 for late AMD). The prevalence of early and late AMD in this Portuguese population was similar to other large-scale population-based cohorts. After controlling for confounders, age and study site of inclusion were significant independent predictors for both early and late forms of the disease. Further analysis will be needed to completely unravel the underlying reasons for this difference regarding geographic location. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Prevalence of age-related macular degeneration in a large European cohort: results from the population-based Gutenberg Health Study.

PubMed

Korb, Christina A; Kottler, Ulrike B; Wolfram, Christian; Hoehn, René; Schulz, Andreas; Zwiener, Isabella; Wild, Philipp S; Pfeiffer, Norbert; Mirshahi, Alireza

2014-09-01

The aim of this study was to describe the sex- and age-specific prevalence of age-related macular degeneration (AMD) and its correlation with urban or rural residence in a large and relatively young European cohort. We evaluated fundus photographs from participants in the Gutenberg Health Study (GHS), a population-based, prospective, observational, single-centre study in the Rhineland-Palatine region in midwestern Germany. The participants were 35-74 years of age at enrolment. The fundus images were classified as described in the Rotterdam Study and were graded independently by two experienced ophthalmologists (CK and UBK) based on the presence of hard and soft drusen, retinal pigmentary abnormalities, and signs of atrophic or neovascular age-related macular generation (AMD). Photographs from 4,340 participants were available for grading. Small, hard drusen (<63 μm, stages 0b and 0c) were present in 37.4% of participants (95% confidence interval [CI], stage 0b, 31.6% [30.3-33.7]; stage 0c, 5.8% [5.1-6.5]). Early AMD (soft drusen, pigmentary abnormalities, stages 1-3) was present in 3.8% of individuals in the youngest age group (35-44 years) (95% CI, stage 1a, 0.4% [0.3-0.5%]; stage 1b, 3.2% [2.9-3.5%]; stage 2a, 0.1% [0.1-0.2%]; stage 2b, 0% [0-0.0%]; stage 3, 0.1% [0.1-0.2%]), whereas late AMD (stages 4a and 4b) did not appear in the youngest age group. In all age groups, signs of early AMD were detected in 11.9% of individuals (stage 1a, 2.1% [1.7-2.6]; stage 1b, 8.0% [7.2-8.8]; stage 2a, 1.0% [0.7-1.3]; stage 2b, 0.5% [0.3-0.7]; stage 3, 0.3% [0.2-0.6]). Late AMD (geographic atrophy or neovascular AMD) was found in 0.2% of individuals (stage 4a, 0.1 % [0.0-0.2]; stage 4b, 0.1% [0.0-0.2]). AMD increased significantly with age (odds ratio [OR], 1.09; 95% CI, 1.08-1.10). Sex, iris colour, and residence (rural vs. urban) were not associated with different rates of AMD. In this study, the prevalence of AMD increased dramatically with age; however, although AMD is usually thought to occur after age 50, signs of early AMD were found in 3.8% of individuals in the youngest age group (younger than 45 years). This population-based sample is the first to provide substantial epidemiologic data from a large German cohort, including data on macular degeneration in younger age groups and incidence data after recall.

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

PubMed Central

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

Background 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). Methods 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. Results 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 – these animals also showed 70% reduction in retinal NV (P≤0.001). Conclusion Ligands and co-activators of the ω-3 LCPUFA sensing PPAR-RXR axis may influence retinal angiogenesis in NV AMD via the complement and VEGF signaling systems. We have linked the co-activator of a lipid-sensing transcription factor (PPARG co-activator 1 alpha, PPARGC1A) to age-related macular degeneration (AMD) and AMD-associated genes. PMID:23335958

Microengineering of magnetic bearings and actuators

NASA Astrophysics Data System (ADS)

Ghantasala, Muralihar K.; Qin, LiJiang; Sood, Dinesh K.; Zmood, Ronald B.

2000-06-01

Microengineering has evolved in the last decade as a subject of its own with the current research encompassing every possible area of devices from electromagnetic to optical and bio-micro electromechanical systems (MEMS). The primary advantage of the micro system technology is its small size, potential to produce high volume and low cost devices. However, the major impediments in the successful realization of many micro devices in practice are the reliability, packaging and integration with the existing microelectronics technology. Microengineering of actuators has recently grown tremendously due to its possible applicability to a wide range of devices of practical importance and the availability of a choice of materials. Selection of materials has been one of the important aspects of the design and fabrication of many micro system and actuators. This paper discusses the issues related to the selection of materials and subsequently their effect on the performance of the actuator. These will be discussed taking micro magnetic actuators and bearings, in particular, as examples. Fabrication and processing strategies and performance evaluation methods adopted will be described. Current status of the technology and projected futuristic applications in this area will be reviewed.

Micro-Scale Thermoacoustics

NASA Astrophysics Data System (ADS)

Offner, Avshalom; Ramon, Guy Z.

2016-11-01

Thermoacoustic phenomena - conversion of heat to acoustic oscillations - may be harnessed for construction of reliable, practically maintenance-free engines and heat pumps. Specifically, miniaturization of thermoacoustic devices holds great promise for cooling of micro-electronic components. However, as devices size is pushed down to micro-meter scale it is expected that non-negligible slip effects will exist at the solid-fluid interface. Accordingly, new theoretical models for thermoacoustic engines and heat pumps were derived, accounting for a slip boundary condition. These models are essential for the design process of micro-scale thermoacoustic devices that will operate under ultrasonic frequencies. Stability curves for engines - representing the onset of self-sustained oscillations - were calculated with both no-slip and slip boundary conditions, revealing improvement in the performance of engines with slip at the resonance frequency range applicable for micro-scale devices. Maximum achievable temperature differences curves for thermoacoustic heat pumps were calculated, revealing the negative effect of slip on the ability to pump heat up a temperature gradient. The authors acknowledge the support from the Nancy and Stephen Grand Technion Energy Program (GTEP).

Micro transport machine and methods for using same

DOEpatents

Stalford, Harold

2015-10-13

A micro transport machine may include a substrate and a movable device comprising a drive component responsive to a wireless power source. The movable device is operable to move between a plurality of disparate areas on the substrate.

Micro-tube mass production device for microbial culture.

PubMed

Fujimoto, K; Ogawa, M; Higashi, K; Miki, N

2016-08-01

This paper describes mass production system of micro-tubes for microbial culture in an open environment. Microbes are used in many fields, such as food, medicine, environmental and energy. We proposed a microbe culture system using hydrogel micro-tubes, which can protect the target microbes inside from competitive microbes outside of the tubes while allow oxygen and nutrition to diffuse through. The hydrogel micro-tubes can be produced by a microfluidic device, which can precisely control the flow and therefore, the tube geometry. For practical applications of the micro-tube-based microbial culture, one of the biggest challenges is the scale-up of the micro-tube-based culture system, or mass production of the tubes. We developed a fluidic system that can produce multiple micro-tubes in parallel. We characterized the mass-produced micro channels and verified the effectiveness of the system.

Laser deposition and direct-writing of thermoelectric misfit cobaltite thin films

NASA Astrophysics Data System (ADS)

Chen, Jikun; Palla-Papavlu, Alexandra; Li, Yulong; Chen, Lidong; Shi, Xun; Döbeli, Max; Stender, Dieter; Populoh, Sascha; Xie, Wenjie; Weidenkaff, Anke; Schneider, Christof W.; Wokaun, Alexander; Lippert, Thomas

2014-06-01

A two-step process combining pulsed laser deposition of calcium cobaltite thin films and a subsequent laser induced forward transfer as micro-pixel is demonstrated as a direct writing approach of micro-scale thin film structures for potential applications in thermoelectric micro-devices. To achieve the desired thermo-electric properties of the cobaltite thin film, the laser induced plasma properties have been characterized utilizing plasma mass spectrometry establishing a direct correlation to the corresponding film composition and structure. The introduction of a platinum sacrificial layer when growing the oxide thin film enables a damage-free laser transfer of calcium cobaltite thereby preserving the film composition and crystallinity as well as the shape integrity of the as-transferred pixels. The demonstrated direct writing approach simplifies the fabrication of micro-devices and provides a large degree of flexibility in designing and fabricating fully functional thermoelectric micro-devices.

Wafer-level micro-optics: trends in manufacturing, testing, packaging, and applications

NASA Astrophysics Data System (ADS)

Voelkel, Reinhard; Gong, Li; Rieck, Juergen; Zheng, Alan

2012-11-01

Micro-optics is an indispensable key enabling technology (KET) for many products and applications today. Probably the most prestigious examples are the diffractive light shaping elements used in high-end DUV lithography steppers. Highly efficient refractive and diffractive micro-optical elements are used for precise beam and pupil shaping. Micro-optics had a major impact on the reduction of aberrations and diffraction effects in projection lithography, allowing a resolution enhancement from 250 nm to 45 nm within the last decade. Micro-optics also plays a decisive role in medical devices (endoscopes, ophthalmology), in all laser-based devices and fiber communication networks (supercomputer, ROADM), bringing high-speed internet to our homes (FTTH). Even our modern smart phones contain a variety of micro-optical elements. For example, LED flashlight shaping elements, the secondary camera, and ambient light and proximity sensors. Wherever light is involved, micro-optics offers the chance to further miniaturize a device, to improve its performance, or to reduce manufacturing and packaging costs. Wafer-scale micro-optics fabrication is based on technology established by semiconductor industry. Thousands of components are fabricated in parallel on a wafer. We report on the state of the art in wafer-based manufacturing, testing, packaging and present examples and applications for micro-optical components and systems.

Evaluation of airborne thermal infrared imagery for locating mine drainage sites in the Lower Kettle Creek and Cooks Run Basins, Pennsylvania, USA

USGS Publications Warehouse

Sams, James I.; Veloski, Garret

2003-01-01

High-resolution airborne thermal infrared (TIR) imagery data were collected over 90.6 km2 (35 mi2) of remote and rugged terrain in the Kettle Creek and Cooks Run Basins, tributaries of the West Branch of the Susquehanna River in north-central Pennsylvania. The purpose of this investigation was to evaluate the effectiveness of TIR for identifying sources of acid mine drainage (AMD) associated with abandoned coal mines. Coal mining from the late 1800s resulted in many AMD sources from abandoned mines in the area. However, very little detailed mine information was available, particularly on the source locations of AMD sites. Potential AMD sources were extracted from airborne TIR data employing custom image processing algorithms and GIS data analysis. Based on field reconnaissance of 103 TIR anomalies, 53 sites (51%) were classified as AMD. The AMD sources had low pH (<4) and elevated concentrations of iron and aluminum. Of the 53 sites, approximately 26 sites could be correlated with sites previously documented as AMD. The other 27 mine discharges identified in the TIR data were previously undocumented. This paper presents a summary of the procedures used to process the TIR data and extract potential mine drainage sites, methods used for field reconnaissance and verification of TIR data, and a brief summary of water-quality data.

Reticular pseudodrusen in age-related macular degeneration.

PubMed

Hogg, Ruth Esther

2014-08-01

Historically, drusen, which are recognized as the hallmark of age-related macular degeneration (AMD), have been described in terms of size, margins, and texture, and several studies have emphasized the importance of large soft drusen particularly when combined with focal pigmentary irregularities in determining the risk of progression to neovascular AMD. However, recent developments in imaging over the past decade have revealed a further distinct phenotype strongly associated with the development of late AMD, namely, reticular pseudodrusen (RPD) or reticular drusen. Reticular pseudodrusen appear as yellowish interlacing networks in the fundus and, although visible on color photography, are better visualized using infrared imaging or spectral domain optical coherence tomography. Studies correlating spectral domain optical coherence tomography and confocal scanning laser ophthalmoscopy have shown that RPD are subretinal deposits located internal to the retinal pigment epithelium in contrast to traditional drusen, which are located external to the retinal pigment epithelium. As multiple longitudinal studies have revealed RPD are strong predictors for progression to both neovascular AMD and geographic atrophy, the interest in understanding the role that RPD play in the pathogenesis of AMD has grown. This review focuses on the current literature concerning RPD and considers what is currently known regarding their epidemiology, risk factors, appearance in both retinal imaging and histology, impact on visual function, relationship to other AMD lesions, and association with the development of late AMD.

Association between CFH Y402H Polymorphism and Age Related Macular Degeneration in North Indian Cohort

PubMed Central

Gupta, Amod; Prabhakar, Sudesh; Singh, Ramandeep; Sharma, Suresh Kumar; Chen, Wei

2013-01-01

The purpose of the study was to determine serum complement factor H (CFH) levels in patients of age related macular degeneration (AMD) and examine its association with CFH Y402H polymorphism. 115 AMD patients and 61 normal controls were recruited in this study. The single nucleotide polymorphism was assayed by real time PCR and serum CFH levels were measured by ELISA and standardized to total serum protein. Chi-square test was applied to polymorphism analysis while Mann Whitney U-statistic for CFH-levels. Mendelian randomization approach was used for determining causal relationship. The genotype frequency differed between the AMD patients (TT- 18.3%, TC-41.3% and CC-40.4%) and controls (TT-76.3%, TC-13.6%, and CC-10.1%) (p = 0001). The frequency of alleles was also significantly different when AMD (T-39% and C-61%) was compared to controls (T-83% and C-17%) (p = 0.0001). Level of serum CFH was significantly lower in AMD patients as compared to normal controls (p = 0.001). Our data showed that the CFH Y402H polymorphism is a risk factor for AMD in the North Indian population. Mendelian randomization approach revealed that CFH Y402H polymorphism affects AMD risk through the modification of CFH serum levels. PMID:23922956

Stable sulfur and oxygen isotopes as geochemical tracers of sulfate in karst waters

NASA Astrophysics Data System (ADS)

Sun, Jing; Kobayashi, Tatsuaki; Strosnider, William H. J.; Wu, Pan

2017-08-01

Karst water resources, which are extremely sensitive to mining activities, are critical for the support of human societies and ecological systems in many regions worldwide. In order to determine the sources and fate of dissolved sulfate in low-pH karst waters, hydrochemical variations of karst waters with and without acid mine drainage (AMD) impacts were investigated along with stable isotope dynamics. As expected, hydrochemical characteristics and isotopic compositions of the AMD and AMD-downstream water (ADW) were dramatically different from that of the non-AMD-impacted water (NAW). The sources of sulfur isotopes in sulfate were predominantly pyrite oxidation for the AMD and ADW, and atmospheric deposition for the NAW. Based on the general isotope-balance model, the relative proportions of sulfate oxygen derived from water and air were calculated. The mean proportion of sulfate oxygen derived from water in ADW was roughly double that of AMD. This suggests that the sulfate associated with AMD is predominantly influenced by aerobic pyrite oxidation, while that of ADW is likely affected by the dissolution of pyrite under anaerobic conditions in reservoir sediment. This observation was coincident with the noted variations of hydrochemical characteristics and was supported by principal component analysis. These results provide a better understanding of how stable isotopes of sulfate and water can be used to track mining contamination in karst aquifers, which could benefit remediation planning for these distinctive systems.

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

PubMed

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

2009-04-01

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

Smoking, antioxidant supplementation and dietary intakes among older adults with age-related macular degeneration over 10 years.

PubMed

Gopinath, Bamini; Flood, Victoria M; Kifley, Annette; Liew, Gerald; Mitchell, Paul

2015-01-01

We aimed to compare the micronutrient usage and other lifestyle behaviors over 10 years among those with and without age-related macular degeneration (AMD). 1612 participants aged 49+ years at baseline were re-examined over 10 years, west of Sydney, Australia. AMD was assessed from retinal photographs. Dietary data were collected using a semi-quantitative food frequency questionnaire. Smoking status was self-reported. 56 participants had any AMD at baseline, of these 25% quit smoking at 5 years and were still not smoking at 10-year follow-up. Among participants who had below the recommended intake of vitamins A, C or E supplements at baseline, those who did compared to those who did not develop late AMD over 10 years were more likely to report vitamins A (total), C or E supplement intake above the recommended intake at 10-year follow-up: multivariable-adjusted OR 4.21 (95% CI 1.65-10.73); OR 6.52 (95% CI 2.76-15.41); and OR 5.71 (95% CI 2.42-13.51), respectively. Participants with compared to without AMD did not appreciably increase fish, fruit and vegetable consumption and overall diet quality. Adherence to smoking and dietary recommendations was poor among older adults with AMD. However, uptake of antioxidant supplements increased significantly among those with late AMD.

Diversity of the Sediment Microbial Community in the Aha Watershed (Southwest China) in Response to Acid Mine Drainage Pollution Gradients.

PubMed

Sun, Weimin; Xiao, Tangfu; Sun, Min; Dong, Yiran; Ning, Zengping; Xiao, Enzong; Tang, Song; Li, Jiwei

2015-08-01

Located in southwest China, the Aha watershed is continually contaminated by acid mine drainage (AMD) produced from upstream abandoned coal mines. The watershed is fed by creeks with elevated concentrations of aqueous Fe (total Fe > 1 g/liter) and SO4 (2-) (>6 g/liter). AMD contamination gradually decreases throughout downstream rivers and reservoirs, creating an AMD pollution gradient which has led to a suite of biogeochemical processes along the watershed. In this study, sediment samples were collected along the AMD pollution sites for geochemical and microbial community analyses. High-throughput sequencing found various bacteria associated with microbial Fe and S cycling within the watershed and AMD-impacted creek. A large proportion of Fe- and S-metabolizing bacteria were detected in this watershed. The dominant Fe- and S-metabolizing bacteria were identified as microorganisms belonging to the genera Metallibacterium, Aciditerrimonas, Halomonas, Shewanella, Ferrovum, Alicyclobacillus, and Syntrophobacter. Among them, Halomonas, Aciditerrimonas, Metallibacterium, and Shewanella have previously only rarely been detected in AMD-contaminated environments. In addition, the microbial community structures changed along the watershed with different magnitudes of AMD pollution. Moreover, the canonical correspondence analysis suggested that temperature, pH, total Fe, sulfate, and redox potentials (Eh) were significant factors that structured the microbial community compositions along the Aha watershed. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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

PubMed

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

2013-12-01

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

The association between statin use and risk of age-related macular degeneration

PubMed Central

Ma, Le; Wang, Yafeng; Du, Junhui; Wang, Mingxu; Zhang, Rui; Fu, Yihao

2015-01-01

The aim of the present study was to evaluate the association between statin use and the risk of age-related macular degeneration (AMD). A systematic search of the PubMed, EMBASE and ISI web of science databases was used to identify eligible published literatures without language restrictions up to April 2015. Summary relative ratios (RRs) and 95% CIs were estimated using a fixed-effect or random-effects model. A total of 14 studies met the inclusion criteria and were included in this meta-analysis. No significant association was observed between statin use and the risk of any AMD (RR, 0.95; 95% CI, 0.74–1.15); and stratified analysis showed that statins had a significantly different effects on early and late stages of AMD. For early AMD, statin use significantly reduced the risk approximately 17% (RR, 0.83; 95% CI, 0.66–0.99). At the late stage, we observed a significant protective association of statin use with exudative AMD (RR, 0.90; 95% CI, 0.80–0.99), in contrast with the absent association between statins and geographic atrophy (RR, 1.16; 95% CI, 0.77–1.56). These results demonstrated that statin use was protective for early and exudative AMD. Additional large prospective cohort studies and RCTs are required to determine the potential effect of statins on AMD prevention. PMID:26658620

Effects of Age-Related Macular Degeneration on Postural Sway

PubMed Central

Chatard, Hortense; Tepenier, Laure; Jankowski, Olivier; Aussems, Antoine; Allieta, Alain; Beydoun, Talal; Salah, Sawsen; Bucci, Maria P.

2017-01-01

Purpose: To compare the impact of unilateral vs. bilateral age-related macular degeneration (AMD) on postural sway, and the influence of different visual conditions. The hypothesis of our study was that the impact of AMD will be different between unilateral and bilateral AMD subjects compared to age-matched healthy elderly. Methods: Postural stability was measured with a platform (TechnoConcept®) in 10 elderly unilateral AMD subjects (mean age: 71.1 ± 4.6 years), 10 elderly bilateral AMD subjects (mean age: 70.8 ± 6.1 years), and 10 healthy age-matched control subjects (mean age: 69.8 ± 6.3 years). Four visual conditions were tested: both eyes viewing condition (BEV), dominant eye viewing (DEV), non-dominant eye viewing (NDEV), and eyes closed (EC). We analyzed the surface area, the length, the mean speed, the anteroposterior (AP), and mediolateral (ML) displacement of the center of pressure (CoP). Results: Bilateral AMD subjects had a surface area (p < 0.05) and AP displacement of the CoP (p < 0.01) higher than healthy elderly. Unilateral AMD subjects had more AP displacement of the CoP (p < 0.05) than healthy elderly. Conclusions: We suggest that ADM subjects could have poor postural adaptive mechanisms leading to increase their postural instability. Further studies will aim to improve knowledge on such issue and to develop reeducation techniques in these patients. PMID:28408876

T-cell differentiation and CD56+ levels in polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

PubMed

Subhi, Yousif; Nielsen, Marie Krogh; Molbech, Christopher Rue; Oishi, Akio; Singh, Amardeep; Nissen, Mogens Holst; Sørensen, Torben Lykke

2017-11-20

Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) are prevalent age-related diseases characterized by exudative changes in the macula. Although they share anatomical and clinical similarities, they are also distinctly characterized by their own features, e.g. vascular abnormalities in PCV and drusen-mediated progression in neovascular AMD. PCV remains etiologically uncharacterized, and ongoing discussion is whether PCV and neovascular AMD share the same etiology or constitute two substantially different diseases. In this study, we investigated T-cell differentiation and aging profile in human patients with PCV, patients with neovascular AMD, and age-matched healthy control individuals. Fresh venous blood was prepared for flow cytometry to investigate CD4 + and CD8 + T-cell differentiation (naïve, central memory, effector memory, effector memory CD45ra + ), loss of differentiation markers CD27 and CD28, and expression of aging marker CD56. Patients with PCV were similar to the healthy controls in all aspects. In patients with neovascular AMD we found significantly accelerated T-cell differentiation (more CD28 - CD27 - cells) and aging (more CD56 + cells) in the CD8 + T-cell compartment. These findings suggest that PCV and neovascular AMD are etiologically different in terms of T cell immunity, and that neovascular AMD is associated with T-cell immunosenescence.

QR-on-a-chip: a computer-recognizable micro-pattern engraved microfluidic device for high-throughput image acquisition.

PubMed

Yun, Kyungwon; Lee, Hyunjae; Bang, Hyunwoo; Jeon, Noo Li

2016-02-21

This study proposes a novel way to achieve high-throughput image acquisition based on a computer-recognizable micro-pattern implemented on a microfluidic device. We integrated the QR code, a two-dimensional barcode system, onto the microfluidic device to simplify imaging of multiple ROIs (regions of interest). A standard QR code pattern was modified to arrays of cylindrical structures of polydimethylsiloxane (PDMS). Utilizing the recognition of the micro-pattern, the proposed system enables: (1) device identification, which allows referencing additional information of the device, such as device imaging sequences or the ROIs and (2) composing a coordinate system for an arbitrarily located microfluidic device with respect to the stage. Based on these functionalities, the proposed method performs one-step high-throughput imaging for data acquisition in microfluidic devices without further manual exploration and locating of the desired ROIs. In our experience, the proposed method significantly reduced the time for the preparation of an acquisition. We expect that the method will innovatively improve the prototype device data acquisition and analysis.

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

Treesearch

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...

Spatial Variations In The Fate And Transport Of Metals In A Mining-Influenced Stream, North Fork Clear Creek, Colorado

EPA Science Inventory

North Fork Clear Creek (NFCC) receives acid-mine drainage (AMD) from multiple abandoned mines in the Clear Creek Watershed. Point sources of AMD originate In the Black Hawk/Central City region of the stream. Water chemistry also is influenced by several non-point sources of AMD,...

Methods and systems for positioning micro elements

DOEpatents

Stalford, Harold L

2015-04-28

A micro device may comprise a substrate, a first micro structure coupled to the substrate, a second micro structure coupled to the substrate, and port configured to receive an input. The first micro structure is configured to move into engagement with the second micro structure in response to the input.

Reconfigurable and responsive droplet-based compound micro-lenses.

PubMed

Nagelberg, Sara; Zarzar, Lauren D; Nicolas, Natalie; Subramanian, Kaushikaram; Kalow, Julia A; Sresht, Vishnu; Blankschtein, Daniel; Barbastathis, George; Kreysing, Moritz; Swager, Timothy M; Kolle, Mathias

2017-03-07

Micro-scale optical components play a crucial role in imaging and display technology, biosensing, beam shaping, optical switching, wavefront-analysis, and device miniaturization. Herein, we demonstrate liquid compound micro-lenses with dynamically tunable focal lengths. We employ bi-phase emulsion droplets fabricated from immiscible hydrocarbon and fluorocarbon liquids to form responsive micro-lenses that can be reconfigured to focus or scatter light, form real or virtual images, and display variable focal lengths. Experimental demonstrations of dynamic refractive control are complemented by theoretical analysis and wave-optical modelling. Additionally, we provide evidence of the micro-lenses' functionality for two potential applications-integral micro-scale imaging devices and light field display technology-thereby demonstrating both the fundamental characteristics and the promising opportunities for fluid-based dynamic refractive micro-scale compound lenses.

Reconfigurable and responsive droplet-based compound micro-lenses

PubMed Central

Nagelberg, Sara; Zarzar, Lauren D.; Nicolas, Natalie; Subramanian, Kaushikaram; Kalow, Julia A.; Sresht, Vishnu; Blankschtein, Daniel; Barbastathis, George; Kreysing, Moritz; Swager, Timothy M.; Kolle, Mathias

2017-01-01

Micro-scale optical components play a crucial role in imaging and display technology, biosensing, beam shaping, optical switching, wavefront-analysis, and device miniaturization. Herein, we demonstrate liquid compound micro-lenses with dynamically tunable focal lengths. We employ bi-phase emulsion droplets fabricated from immiscible hydrocarbon and fluorocarbon liquids to form responsive micro-lenses that can be reconfigured to focus or scatter light, form real or virtual images, and display variable focal lengths. Experimental demonstrations of dynamic refractive control are complemented by theoretical analysis and wave-optical modelling. Additionally, we provide evidence of the micro-lenses' functionality for two potential applications—integral micro-scale imaging devices and light field display technology—thereby demonstrating both the fundamental characteristics and the promising opportunities for fluid-based dynamic refractive micro-scale compound lenses. PMID:28266505

The national and subnational prevalence and burden of age–related macular degeneration in China

PubMed Central

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

2017-01-01

Background 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. Methods 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. Results 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 9.44 million (95% CI = 7.74–11.15) to 20.91 million (95% CI = 17.16–24.68), and those with late AMD rose from 2.58 million (95% CI = 1.56–4.30) to 5.74 million (95% CI = 3.46–9.59). In late AMD, the number of people living with GA ranged from 0.87 million (95% CI = 0.40–1.83) in 1990 to 1.93 million (95% CI = 0.89–4.08) in 2015, and NVAMD from 1.71 million (95% CI = 1.16–2.47) to 3.81 million (95% CI = 2.57–5.51). The projected number of people with any AMD in 2020 is 31.23 million (95% CI = 24.18–40.14), increasing to 55.19 million (95% CI = 43.04–70.30) in 2050. Between different regions, the South Central owed the most AMD cases (5.50 million in 2000 and 7.52 million in 2010), whereas the North–West China the least (0.66 million in 2000 and 0.95 million in 2010). Conclusions The estimates in this study suggest a substantial burden of AMD in China, with the ageing process in Chinese society, this burden will be increasing in the foreseen future. Primary and secondary prevention and treatment and effective government response are urgently needed. Improved epidemiological studies are also required to better develop eye–care strategies and health services. PMID:29302323

Retinal Ultrastructure of Murine Models of Dry Age-related Macular Degeneration (AMD)

PubMed Central

Ramkumar, Hema L.; Zhang, Jun; Chan, Chi-Chao

2010-01-01

Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. The pathology of dry AMD consists of degeneration of photoreceptors and the RPE, lipofuscin (A2E) accumulation, and drusen formation. Mice have been widely used for generating models that simulate human AMD features for investigating the pathogenesis, treatment and prevention of the disease. Although the mouse has no macula, focal atrophy of photorecptors and RPE, lipofuscin accumulation, and increased A2E can develop in aged mouse eyes. However, drusen are rarely seen in mice because of their simpler Bruch’s membrane and different process of lipofuscin extrusion compared with humans. Thus, analyzing basal deposits at the ultrastructural level and understanding the ultrastructural pathologic differences between various mouse AMD models are critical to comprehending the significance of research findings and response to possible therapeutic options for dry AMD. Based on the multifactorial pathogenesis of AMD, murine dry AMD models can be classified into three groups. First, genetically engineered mice that target genes related to juvenile macular dystrophies are the most common models, and they include abcr−/− (Stargardt disease), transgenic ELOVL4 (Stargardt-3 dominant inheritary disease), Efemp1R345W/R345W (Doyne honeycomb retinal dystrophy), and Timp3S156C/S156C (Sorsby fundus dystrophy) mice. Other murine models target genes relevant to AMD, including inflammatory genes such as Cfh−/−, Ccl2−/−, Ccr2−/−, Cx3cr1−/−, and Ccl2−/−/cx3cr1−/−, oxidative stress associated genes such as Sod1−/− and Sod2 knockdown, metabolic pathway genes such as neprilysin −/− (amyloid β), transgenic mcd/mcd (cathepsin D), Cp−/−/Heph−/Y (ferroxidase ceruloplasmin/hepaestin, iron metabolism), and transgenic ApoE4 on high fat and high cholesterol diet (lipid metabolism). Second, mice have also been immunologically manipulated by immunization with carboxyethylpyrrole (CEP), an oxidative fragment of DHA found in drusen, and found to present with dry AMD features. Third, natural mouse strains such as arrd2/arrd2 (Mdm gene mutation) and the senescence accelerated mice (SAM) spontaneously develop features of dry AMD like photoreceptor atrophy and thickening of Bruch’s membrane. All the aforementioned models develop retinal lesions with various features that simulate dry AMD lesions: focal photoreceptor degeneration, abnormal RPE with increased lipofuscin, basal infolding, decreased melanosomes and degeneration. However, Bruch’s membrane changes are less common. Most mice develop retinal lesions at an older age (6–24 months, depending on the models), while the Ccl2−/−/cx3cr1−/− mice develop lesions by 4–6 weeks. Although murine models present various degrees of retinal and/or RPE degeneration, classical drusen is extremely rare. Using electron microscopy, small drusenoid deposits are found between RPE and Bruch’s membrane in a few models including Efemp1 R345W/R345W, Ccl2−/−/cx3cr1−/−, neprilysin −/−, transgenic mcd/mcd, and ApoE4 transgenic mice on a high fat diet. High A2E levels are measured in the retinas of abcr−/−, transgenic ELOVL4, and Ccl2−/−/cx3cr1−/− mice. In summary, murine models provide useful tools for studying AMD pathogenesis and evaluating novel therapies for this disease. This review compares the major dry AMD murine models and discusses retinal pathology at the ultrastructural level. PMID:20206286

Extracting information of fixational eye movements through pupil tracking

NASA Astrophysics Data System (ADS)

Xiao, JiangWei; Qiu, Jian; Luo, Kaiqin; Peng, Li; Han, Peng

2018-01-01

Human eyes are never completely static even when they are fixing a stationary point. These irregular, small movements, which consist of micro-tremors, micro-saccades and drifts, can prevent the fading of the images that enter our eyes. The importance of researching the fixational eye movements has been experimentally demonstrated recently. However, the characteristics of fixational eye movements and their roles in visual process have not been explained clearly, because these signals can hardly be completely extracted by now. In this paper, we developed a new eye movement detection device with a high-speed camera. This device includes a beam splitter mirror, an infrared light source and a high-speed digital video camera with a frame rate of 200Hz. To avoid the influence of head shaking, we made the device wearable by fixing the camera on a safety helmet. Using this device, the experiments of pupil tracking were conducted. By localizing the pupil center and spectrum analysis, the envelope frequency spectrum of micro-saccades, micro-tremors and drifts are shown obviously. The experimental results show that the device is feasible and effective, so that the device can be applied in further characteristic analysis.

Inflammation, Complement Factor H, and Age-Related Macular Degeneration: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Klein, Ronald; Knudtson, Michael D.; Klein, Barbara E. K.; Wong, Tien Y.; Cotch, Mary Frances; Liu, Kiang; Cheng, Ching Y.; Burke, Gregory L.; Saad, Mohammed F.; Jacobs, David R.; Sharrett, A. Richey

2010-01-01

Objective To describe the relationship of systemic inflammatory disease, complement factor H (CFH) Y402H (1277T→C) genotype status and age-related macular degeneration (AMD) prevalence in a multiethnic population of whites, blacks, Hispanics, and Chinese. Design Population-based, cross-sectional study. Participants We included 5887 persons aged 45 to 84 years with gradable AMD. Methods Digital fundus photographs were used to measure AMD. Two years earlier, biomarkers of inflammation were measured and history of inflammatory disease and use of antiinflammatory agents obtained. Main Outcome Measure Prevalence of AMD. Results While controlling for age, gender, race/ethnicity, and study site, there were no associations between systemic inflammatory factors and AMD severity. Higher levels of high-sensitivity C-reactive protein (odds ratio [OR] per standard deviation [SD] increase in natural log [ln] units, 2.34; 95% confidence interval [CI], 1.33–4.13) and interleukin-6 (OR per SD in ln, 2.06; 95% CI, 1.21–3.49) were associated with geographic atrophy but not other AMD end points. History of periodontal disease (OR, 1.68; 95% CI, 1.14–2.47) was related to increased retinal pigment. A history of arthritis was associated with soft distinct drusen (OR, 1.24; 95% CI, 1.06–1.46). A history of oral steroid use was related to large drusen (OR, 2.13; 95% CI, 1.14–3.97) and soft distinct drusen (OR, 1.76; 95% CI, 1.00–3.10) and history of cyclooxygenase 2 inhibitor use were associated with large drusen (OR, 1.50; 95% CI, 1.10–2.04), soft indistinct drusen (OR, 1.84; 95% CI, 1.09–3.10), and large drusen area (OR, 1.66; 95% CI, 1.02–2.71). Whites, blacks, and Hispanics with CFH Y402H CC variant genotype had the highest frequency of early AMD compared with those with wild TT genotype. The frequency of CFH did explain some of the difference in AMD prevalence between Chinese and Hispanics compared with whites, but did not explain the difference in prevalence between whites and blacks. Conclusions This study confirmed associations of the Y402H CFH gene variant with AMD in nonwhite populations, but neither explained the lack of association between inflammatory factors and AMD in the cohort nor the basis for the observed differences in AMD prevalence across ethnic groups. PMID:18538409

Identification of vinculin as a potential plasma marker for age-related macular degeneration.

PubMed

Kim, Hye-Jung; Woo, Se Joon; Suh, Eui Jin; Ahn, Jeeyun; Park, Ji Hyun; Hong, Hye Kyoung; Lee, Ji Eun; Ahn, Seong Joon; Hwang, Duck Jin; Kim, Ki Woong; Park, Kyu Hyung; Lee, Cheolju

2014-10-08

To identify plasma protein biomarkers for age-related macular degeneration (AMD) using a large-scale quantitative proteomic discovery procedure. Plasma proteomes from 20 exudative AMD patients and 20 healthy control patients were comparatively profiled by four-dimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS). Proteins existing at statistically different levels were validated by enzyme-linked immunosorbent assay (ELISA) and Western blotting in 233 case-controlled samples. Newly discovered plasma biomarkers were further confirmed using in vivo and in vitro experiments. Out of 320 proteins identified, vinculin, protein S100A9, triosephosphate isomerase, protein S100A8, protein Z-dependent protease inhibitor, C-X-C motif chemokine 7, and tenascin X showed significantly differential expression in AMD patient plasma compared to control plasma. Among these, the area under the curve (AUC) for vinculin was 0.871 for discriminating between exudative AMD and controls (n = 201) and 0.879 for discriminating between AMD and controls (n = 233). A proteogenomic combination model using vinculin and two known risk genotypes in ARMS2 and CFH genes additionally provided excellent discrimination of AMD from controls (AUC = 0.916). The plasma level of vinculin was not associated with any confounding clinical variables, such as age, smoking, and other comorbidities. Additionally, vinculin was strongly expressed in retinal pigment epithelial cells of human eyes, and its expression was elevated when exposed to oxidative stress in vitro. Vinculin was identified as a potential plasma biomarker for AMD. The early detection of AMD using novel plasma biomarkers with genetic modeling may enable timely treatment and vision preservation in the elderly. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

ASSOCIATION BETWEEN THE VITREOMACULAR INTERFACE AND OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS IN WET AGE-RELATED MACULAR DEGENERATION.

PubMed

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

2017-09-01

To study the effect of the vitreomacular interface on various wet age-related macular degeneration (AMD) characteristics including the size and type of choroidal neovascularization (CNV), choroidal thickness, and activity of the CNV. This was a retrospective observational cross-sectional study. The study included 43 patients (51 eyes) with treatment-naive age-related macular degeneration. Twenty-six patients with wet AMD in one eye and dry AMD in the other eye were included in a paired-eye analysis. Patients underwent optical coherence tomography examination using Heidelberg Spectralis (spectral domain optical coherence tomography) at presentation to determine the type of CNV and the vitreomacular status. In addition, various parameters were measured including the choroidal thickness and horizontal width and vertical height measurements of the CNV. There was no correlation between the height, width, activity or type of the CNV, and the presence or absence of vitreomacular adhesion. The mean choroidal thickness (using enhanced depth imaging) in cases with vitreomacular adhesion was 272.57 μm compared with 197.32 μm in cases with no vitreomacular adhesion, a statistically significant difference (P = 0.003). In the paired-eye study (21 patients), there was no significant difference between the eyes with wet AMD and dry AMD with regard to vitreomacular status or the choroidal thickness. In a subgroup analysis, patients with Type 1 CNV had a significantly higher percentage of vitreomacular adhesion compared with the other eye with dry AMD (P = 0.034). In conclusion, the vitreomacular interface does seem to be associated with an increased choroidal thickness in cases of wet AMD. Furthermore, the association between the vitreomacular interface and wet AMD is more significant for Type 1 CNV.

Complement factor H polymorphisms in Japanese population with age-related macular degeneration.

PubMed

Okamoto, Haru; Umeda, Shinsuke; Obazawa, Minoru; Minami, Masayoshi; Noda, Toru; Mizota, Atsushi; Honda, Miki; Tanaka, Minoru; Koyama, Risa; Takagi, Ikue; Sakamoto, Yoshihiro; Saito, Yoshihiro; Miyake, Yozo; Iwata, Takeshi

2006-03-06

To study the frequency of five haplotypes previously reported in the complement factor H (CFH) gene for Japanese patients with age-related macular degeneration (AMD). Genomic DNA was isolated from peripheral blood samples taken from 96 Japanese AMD patients and 89 age-matched controls. All patients were diagnosed as having exudative (wet-type) AMD. The amplified polymerase chain reaction (PCR) products of CFH exons 2, 9, and 13, and intron 6 were analyzed by temperature gradient capillary electrophoresis (TGCE) and by direct sequencing. The haplotypes were identified, and their frequencies were calculated and compared with reported results. Five haplotypes were identified in the Japanese population including four already reported in the American population. The frequencies of these haplotypes were significantly different between Japanese and American in both control and case groups. The haplotype containing Y402H, which was previously reported to be associated with AMD, was only 4% in the control and case population, with a p value of 0.802. However, two other haplotypes were found as risk factors, which gave an increased likelihood of AMD of 1.9 and 2.5 fold (95% CI 1.12-3.69 and 1.42-6.38). One protective haplotype that decreased the likelihood of AMD by 1.6 fold (95% CI 0.26-0.67) was identified. The frequencies for five haplotypes previously identified were analyzed in a Japanese population with AMD. Four previously found haplotypes were identified and one additional haplotype was found. The frequencies of each haplotype were significantly different from that in found Americans affected with AMD. Two of the haplotypes were identified as risk factors and one was considered protective.

A follow-up survey on the knowledge of age-related macular degeneration and its risk factors among Singapore residents after 5 years of nation-wide awareness campaigns.

PubMed

Sanjay, Srinivasan; Chin, You Chuen; Teo, Hui Ting; Ong, Shu Xuan; Toh, Serene Hui Fang; Khong, Ming Hui; Yeo, Anna C H; Au Eong, Kah-Guan

2014-08-01

To re-evaluate the awareness of age-related macular degeneration (AMD) and knowledge of its risk factors among Singapore residents after 5 years of awareness campaigns. Cross-sectional, questionnaire-based telephone survey (modified from the AMD Alliance International Global Report), conducted in Singapore in 2011. Participants were randomly selected using the Global Yellow Pages Singapore residential listings 2009/2010. Awareness of AMD and its risk factors was assessed among participants. Of 1773 Singapore residents contacted over the telephone, 559 participated (31.5% response rate). The mean age of participants was 43.1 years (range 21-85 years). A total of 157 participants (28.1%) were familiar with AMD. Among these, the number who correctly identified the risk factors were: smoking, n = 132 (84.1%); ageing, n = 123 (78.3%); lack of vitamins/nutrients, n = 121 (77.1%); genetics, n = 101 (64.3%); unprotected light exposure, n = 100 (63.7%) and; sex, n = 62 (39.5%). Participants aged >50 years (prevalence rate ratio, PRR 2.23, confidence interval, CI, 1.31-3.81) or who had undergone an eye test within the previous year (PRR 2.61, 95% CI 1.79-3.82) were more familiar with AMD, while females (PRR 0.68, 95% CI 0.47-0.98) were less familiar. Self-reported awareness of AMD among Singapore residents increased four-fold from 7.3% in 2006 to 28.1% in 2011 following 5 years of awareness campaigns. Participants who were >50 years or had undergone an eye test within the previous year were more aware of AMD while female participants were less aware of AMD.

Determinants for Sensitivity of Human Immunodeficiency Virus Coreceptor CXCR4 to the Bicyclam AMD3100

PubMed Central

Labrosse, Béatrice; Brelot, Anne; Heveker, Nikolaus; Sol, Nathalie; Schols, Dominique; De Clercq, Erik; Alizon, Marc

1998-01-01

The bicyclam AMD3100 is a potent and selective inhibitor of the replication of human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2). It was recently demonstrated that the compound inhibited HIV entry through CXCR4 but not through CCR5. Selectivity of AMD3100 for CXCR4 was further indicated by its lack of effect on HIV-1 and HIV-2 infection mediated by the CCR5, CCR3, Bonzo, BOB, and US28, coreceptors. AMD3100 completely blocked HIV-1 infection mediated by a mutant CXCR4 bearing a deletion of most of the amino-terminal extracellular domain. In contrast, relative resistance to AMD3100 was conferred by different single amino acid substitutions in the second extracellular loop (ECL2) or in the adjacent membrane-spanning domain, TM4. Only substitutions of a neutral residue for aspartic acid and of a nonaromatic residue for phenylalanine (Phe) were associated with drug resistance. This suggests a direct interaction of AMD3100 with these amino acids rather than indirect effects of their mutation on the CXCR4 structure. The interaction of aspartic acids of ECL2 and TM4 with AMD3100 is consistent with the positive charge of bicyclams, which might block HIV-1 entry by preventing electrostatic interactions between CXCR4 and the HIV-1 envelope protein gp120. Other features of AMD3100 must account for its high antiviral activity, in particular the presence of an aromatic linker between the cyclam units. This aromatic group might engage in hydrophobic interactions with the Phe-X-Phe motifs of ECL2 or TM4. These results confirm the importance of ECL2 for the HIV coreceptor activity of CXCR4. PMID:9658078

Associations of candidate genes to age-related macular degeneration among racial/ethnic groups in the multi-ethnic study of atherosclerosis.

PubMed

Klein, Ronald; Li, Xiaohui; Kuo, Jane Z; Klein, Barbara E K; Cotch, Mary Frances; Wong, Tien Y; Taylor, Kent D; Rotter, Jerome I

2013-11-01

To describe the relationships of selected candidate genes to the prevalence of early age-related macular degeneration (AMD) in a cohort of whites, blacks, Hispanics, and Chinese Americans. Cross-sectional study. setting: Multicenter study. study population: A total of 2456 persons aged 45-84 years with genotype information and fundus photographs. procedures: Twelve of 2862 single nucleotide polymorphisms (SNPs) from 11 of 233 candidate genes for cardiovascular disease were selected for analysis based on screening with marginal unadjusted P value <.001 within 1 or more racial/ethnic groups. Logistic regression models tested for association in case-control samples. main outcome measure: Prevalence of early AMD. Early AMD was present in 4.0% of the cohort and varied from 2.4% in blacks to 6.0% in whites. The odds ratio increased from 2.3 for 1 to 10.0 for 4 risk alleles in a joint effect analysis of Age-Related Maculopathy Susceptibility 2 rs10490924 and Complement Factor H Y402H (P for trend = 4.2×10(-7)). Frequencies of each SNP varied among the racial/ethnic groups. Adjusting for age and other factors, few statistically significant associations of the 12 SNPs with AMD were consistent across all groups. In a multivariate model, most candidate genes did not attenuate the comparatively higher odds of AMD in whites. The higher frequency of risk alleles for several SNPs in Chinese Americans may partially explain their AMD frequency's approaching that of whites. The relationships of 11 candidate genes to early AMD varied among 4 racial/ethnic groups, and partially explained the observed variations in early AMD prevalence among them. Copyright © 2013 Elsevier Inc. All rights reserved.

Sunlight exposure, pigmentation, and incident age-related macular degeneration.

PubMed

Klein, Barbara E K; Howard, Kerri P; Iyengar, Sudha K; Sivakumaran, Theru A; Meyers, Kristin J; Cruickshanks, Karen J; Klein, Ronald

2014-08-14

Examine potential effects of sunlight exposure, hair color, eye color, and selected gene single-nucleotide polymorphisms (SNPs) on incidence of AMD. Subjects participated in up to five examinations over a 20-year period. Eye color, self-reported hair color as a teenager, and sunlight exposure were ascertained at the baseline examination. Presence and severity of AMD and its lesions were determined via fundus photographs. Genetic data were available on a subset of participants. The SNPs CFH Y402H rs1061170 and ARMS2 A69S rs10490924 were used to analyze genetic risk of AMD; OCA2 rs4778241 and HERC2 rs12913832 represented genetic determinants of eye color. Incidence of early AMD was higher in blond/red-haired persons compared with brown/black-haired persons (hazard ratio [HR] 1.25, P = 0.02) and in persons with high sun exposure in their thirties (HR 1.41, P = 0.02). However, neither was significant after adjustment for multiple comparisons. Eye (HR 1.36, P = 0.006) and hair color (HR 1.42, P = 0.003) were associated with incidence of any retinal pigmentary abnormalities (RPAs). Both remained significant after adjustment for multiple comparisons. Neither presence of alleles for light-colored eyes nor those associated with high risk of late AMD altered the association of eye or hair color with early AMD. None of the characteristics studied were significantly associated with late AMD. Modest associations of eye color, hair color, and HERC2 genotype with any RPAs were found. Genes for AMD did not affect these associations. Eye color phenotype was more strongly associated with outcomes than HERC2 or OCA2 genotype. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

The Antarctic Master Directory -- the Electronic Card Catalog of Antarctic Data

NASA Astrophysics Data System (ADS)

Scharfen, G.; Bauer, R.

2003-12-01

The Antarctic Master Directory (AMD) is a Web-based, searchable record of thousands of Antarctic data descriptions. These data descriptions contain information about what data were collected, where they were collected, when they were collected, who the scientists are, who the point of contact is, how to get the data, and information about the format of the data and what documentation and bibliographic information exists. With this basic descriptive information about content and access for thousands of Antarctic scientific data sets, the AMD is a resource for scientists to advertise the data they have collected and to search for data they need. The AMD has been created by more than twenty nations which conduct research in the Antarctic under the auspices of the Antarctic Treaty. It is a part of the International Directory Network/Global Change Master Directory (IDN/GCMD). Using the AMD is easy. Users can search on subject matter key words, data types, geographic place-names, temporal or spatial ranges, or conduct free-text searches. To search the AMD go to: http://gcmd.nasa.gov/Data/portals/amd/. Contributing your own data descriptions for Antarctic data that you have collected is also easy. Scientists can start by submitting a short data description first (as a placeholder in the AMD, and to satisfy National Science Foundation (NSF) reporting requirements), and then add to, modify or update their record whenever it is appropriate. An easy to use on-line tool and a simple tutorial are available at: http://nsidc.org/usadcc. With NSF Office of Polar Programs (OPP) funding, the National Snow and Ice Data Center (NSIDC) operates the U.S. Antarctic Data Coordination Center (USADCC), partly to assist scientists in using and contributing to the AMD. The USADCC website is at http://nsidc.org/usadcc.

Risk of macular degeneration affected by polymorphisms in Matrix metalloproteinase-2: A case-control study in Chinese Han population.

PubMed

Cheng, Jie; Hao, Xiaolin; Zhang, Zhongchen

2017-11-01

The purpose of this study was to investigate the correlation of single nucleotide polymorphisms (SNPs) in Matrix metalloproteinase -2 (MMP-2) gene and the risk of age-related macular degeneration (AMD) in Chinese Han population.A total of 126 AMD patients and 141 healthy controls participated in this study. Genotypes of MMP-2 gene polymorphisms were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). χtest was used to detect the differences of genotypes and alleles frequencies between case and control groups. Relative risk of AMD was evaluated by odds ratios (ORs) with 95% confidence intervals (CIs).Distribution of variant allele carriers (computed tomography + TT genotypes) of MMP-2 gene rs243865 SNP was significantly different between case and control groups, and might act as protective factors for the onset of AMD (P = .044, OR = 0.583, 95% CI = 0.344-0.987). Nevertheless, the T allele might reduce the AMD risk (P = .030, OR = 0.611, 95% CI = 0.390-0.956). However, no significant association existed between rs243865 and AMD risk in the subgroup analysis based on age. GA + AA genotypes of rs243866 SNP may associate with a decreased risk of AMD in the age≤65 years subgroup (P = .028, OR = 0.399, 95% CI = 0.174-0.915).MMP-2 gene rs243865 and rs243866 SNPs associated with the risk of AMD. Further studies should be performed to confirm the results. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Lipids, lipid genes, and incident age-related macular degeneration: the three continent age-related macular degeneration consortium.

PubMed

Klein, Ronald; Myers, Chelsea E; Buitendijk, Gabriëlle H S; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T V M; Sivakumaran, Theru A; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K; Lee, Kristine E; Stricker, Bruno H; Vingerling, Johannes R; Mitchell, Paul; Klein, Barbara E K; Klaver, Caroline C W; Wang, Jie Jin

2014-09-01

To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Meta-analysis. setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES), and Rotterdam Study (RS). observation procedures: Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. main outcome measures: Incidence of AMD. The average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the 3 studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis. In a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD. Copyright © 2014 Elsevier Inc. All rights reserved.

PDT: special cases in front of legal regulations

NASA Astrophysics Data System (ADS)

Fischer, E.; Wegner, A.; Pfeiler, T.; Mertz, M.

2002-10-01

Introduction: The classic indication for photodynamic therapy (PDT) in ophthalmology is currently represented by classic subfoveal choroidal neovascularisation (CNV) due to age-related macular degeneration (AMD). PDT is a method, which almost selectively causes endothelial damage in neovascular lesions, followed by vascular occlusion and involution of the CNV. The mechanistic aspect suggests that non AMD-related choroidal neovascularisations might also benefit from PDT. PDT in AMD: Within the German health system, PDT indications follow the criteria based on the inclusion criteria of the TAP studies. For instance the CNV should be predominantly classic and located under the center of the foveal avascular zone. In the diagnosis and follow-up of exudative AMD, visual acuity measurements and fluorescein angiography are the established parameters. Retinal thickness analyzer (RTA) measurements might give further information. Before PDT, they show a significant retinal thickening due to intra- and subretinal exudation. Following PDT, early RTA follow-ups show a clear decrease in retinal thickening accompanies by increasing or stable acuity. PDT in CNV of other origins than AMD: New studies support a new spectrum of indications for PDT, hopefully leading to general cost reimbursement for patients. PDT should be viewed as a general method for vascular occlusion and does not represent a causal therapy for progressive exudative AMD. We present patients with CNV due to pathologic myopia, angioid streaks and POHS. Conclusion: The selective vascular occlusion caused by PDT, besides CNV associated with AMD and pathologic myopia, may also allow the treatment of choroidal neovascularisations based on other entities. Careful individual evaluation of those cases is recommended. Despite this wide array of possible indications, cost reimbursement has been limited to classic subfoveal CNV in AMD, although single case reimbursements in choroidal neovascular lesions due to pathologic myopia have been observed.

Orthostatic hypertension as a risk factor for age-related macular degeneration: Evidence from the Irish longitudinal study on ageing.

PubMed

Bhuachalla, Bláithín Ní; McGarrigle, Christine A; O'Leary, Neil; Akuffo, Kwadwo Owusu; Peto, Tunde; Beatty, Stephen; Kenny, Rose Anne

2018-06-01

Age related macular degeneration (AMD) is a leading cause of irreversible visual loss in developed countries. It is associated with vascular risk factors including hypertension. Dysregulated blood pressure (BP) behaviour including orthostatic hypertension (OHTN), hypotension (OH) and BP variability (BPV) are associated with end-organ damage, particularly in the brain. We investigated if abnormal orthostatic BP (OBP) was a risk factor for AMD, for which a vascular aetiology is implicated. A nationally representative, cross-sectional study was carried out 2009/2010 in The Irish Longitudinal Study on Ageing (TILDA). Beat-to-beat BP data, measured by digital photoplethysmography during active stand, was used to characterise OBP behaviour in the 30-110 s after standing. OH, OHTN, BPV and normal stabilisation recovery phenotypes were defined. AMD was identified following masked grading of 45° monoscopic colour retinal photographs, which were centred on the macula and taken with a NIDEK AFC-210 non-mydriatic auto-fundus camera. The relationship between OBP recovery phenotypes and AMD in 3750 adults aged ≥50 years was investigated using multivariate logistic regression models, adjusted for traditional AMD risk factors. From 30 to 110 s post active stand, systolic and diastolic OHTN was associated with increased odds of AMD after adjustment for demographics, health behaviours including smoking, family history of AMD, self-report (SR) diabetes, SR cataracts, objective hypertension and prescribed antihypertensives. No evidence of heterogeneity of OHTN effect was found between those who were hypertensive to those who were normotensive. This study provides evidence that OHTN may be an independent cardiovascular risk factor for AMD. Copyright © 2018 Elsevier Inc. All rights reserved.

Rare genetic variants in Tunisian Jewish patients suffering from age-related macular degeneration.

PubMed

Pras, Eran; Kristal, Dana; Shoshany, Nadav; Volodarsky, Dina; Vulih, Inna; Celniker, Gershon; Isakov, Ofer; Shomron, Noam; Pras, Elon

2015-07-01

To explore the molecular basis of familial, early onset, age-related macular degeneration (AMD) with diverse phenotypes, using whole exome sequencing (WES). We performed WES on four patients (two sibs from two families) manifesting early-onset AMD and searched for disease-causing genetic variants in previously identified macular degeneration related genes. Validation studies of the variants included bioinformatics tools, segregation analysis of mutations within the families and mutation screening in an AMD cohort of patients. The index patients were in their 50s when diagnosed and displayed a wide variety of clinical AMD presentations: from limited drusen in the posterior pole to multiple basal-laminar drusen extending peripherally. Severe visual impairment due to extensive geographic atrophy and/or choroidal-neovascularisation was common by the age of 75 years. Approximately, 400 000 genomic variants for each DNA sample were included in the downstream bioinformatics analysis, which ended in the discovery of two novel variants; in one family a single bp deletion was identified in the Hemicentin (HMCN1) gene (c.4162delC), whereas in the other, a missense variant (p.V412M) in the Complement Factor-I (CFI) gene was found. Screening for these variants in a cohort of patients with AMD identified another family with the CFI variant. This report uses WES to uncover rare genetic variants in AMD. A null-variant in HMCN1 has been identified in one AMD family, and a missense variant in CFI was discovered in two other families. These variants confirm the genetic complexity and significance of rare genetic variants in the pathogenesis of AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Pesticide Use and Age-Related Macular Degeneration in the Agricultural Health Study

PubMed Central

Montgomery, Martha P.; Postel, Eric; Umbach, David M.; Richards, Marie; Watson, Mary; Blair, Aaron; Chen, Honglei; Sandler, Dale P.; Schmidt, Silke

2017-01-01

Background: Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries. Few studies have investigated its relationship to environmental neurotoxicants. In previous cross-sectional studies, we found an association between pesticide use and self-reported retinal degeneration. Objective: We evaluated the association of pesticide use with physician-confirmed incident AMD. Methods: The Agricultural Health Study (AHS) is a prospective cohort of pesticide applicators and their spouses enrolled from 1993–1997 in Iowa and North Carolina. Cohort members reported lifetime use of 50 specific pesticides at enrollment. Self-reports of incident AMD during follow-up through 2007 were confirmed by reports from participants’ physicians and by independent evaluation of retinal photographs provided by the physicians. Confirmed cases (n=161) were compared with AHS cohort members without AMD (n=39,108). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by logistic regression with adjustment for age, gender, and smoking. Results: AMD was associated with ever use of organochlorine [OR=2.7 (95% CI: 1.8, 4.0)] and organophosphate [OR=2.0 (95% CI: 1.3, 3.0)] insecticides and phenoxyacetate herbicides [OR=1.9 (95% CI: 1.2, 2.8)]. Specific pesticides consistently associated with AMD included chlordane, dichlorodiphenyltrichloroethane (DDT), malathion, and captan; others with notable but slightly less consistent associations were heptachlor, diazinon, phorate, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and 2,4-dichlorophenoxyacetic acid (2,4-D). Results were similar for men and women. Some specific pesticides were associated with both early- and late-stage AMD, but others were associated with only one stage. Conclusions: Exposures to specific pesticides may be modifiable risk factors for AMD. https://doi.org/10.1289/EHP793 PMID:28886597

The Relationship of Major American Dietary Patterns to Age-related Macular Degeneration

PubMed Central

Chiu, Chung-Jung; Chang, Min-Lee; Zhang, Fang Fang; Li, Tricia; Gensler, Gary; Schleicher, Molly; Taylor, Allen

2014-01-01

PURPOSE We hypothesized that major American dietary patterns are associated with age-related macular degeneration (AMD) risk. DESIGN Cross-sectional study METHODS 8,103 eyes from 4,088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into control (n=2,739), early AMD (n=4,599), and advanced AMD (n=765) by AREDS AMD Classification System. Food consumption data were collected by a 90-item food frequency questionnaire. RESULTS Two major dietary patterns were identified by factor (principle component) analysis based on 37 food groups and named Oriental and Western patterns. The Oriental pattern was characterized by higher intake of vegetables, legumes, fruit, whole grains, tomatoes, and seafood. The Western pattern was characterized by higher intake of red meat, processed meat, high-fat dairy products, French fries, refined grains, and eggs. We ranked our participants according to how closely their diets line up with the two patterns by calculating the two factor scores for each participant. For early AMD, multivariate-adjusted odds ratio (OR) from generalized estimating equation logistic analysis comparing the highest to lowest quintile of the Oriental pattern score was ORE5O=0.74 (95% confidence interval (CI): 0.59–0.91; Ptrend=0.01), and the OR comparing the highest to lowest quintile of the Western pattern score was ORE5W=1.56 (1.18–2.06; Ptrend=0.01). For advanced AMD, the ORA5O was 0.38 (0.27–0.54; Ptrend<0.0001), and the ORA5W was 3.70 (2.31–5.92; Ptrend<0.0001). CONCLUSIONS Our data indicate that overall diet is significantly associated with the odds of AMD and that dietary management as an AMD prevention strategy warrants further study. PMID:24792100

The relationship of major American dietary patterns to age-related macular degeneration.

PubMed

Chiu, Chung-Jung; Chang, Min-Lee; Zhang, Fang Fang; Li, Tricia; Gensler, Gary; Schleicher, Molly; Taylor, Allen

2014-07-01

We hypothesized that major American dietary patterns are associated with risk for age-related macular degeneration (AMD). Cross-sectional study. We classified 8103 eyes in 4088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS). They were classified into control (n = 2739), early AMD (n = 4599), and advanced AMD (n = 765) by the AREDS AMD Classification System. Food consumption data were collected by using a 90-item food frequency questionnaire. Two major dietary patterns were identified by factor (principal component) analysis based on 37 food groups and named Oriental and Western patterns. The Oriental pattern was characterized by higher intake of vegetables, legumes, fruit, whole grains, tomatoes, and seafood. The Western pattern was characterized by higher intake of red meat, processed meat, high-fat dairy products, French fries, refined grains, and eggs. We ranked our participants according to how closely their diets line up with the 2 patterns by calculating the 2 factor scores for each participant. For early AMD, multivariate-adjusted odds ratio (OR) from generalized estimating equation logistic analysis comparing the highest to lowest quintile of the Oriental pattern score was ORE5O = 0.74 (95% confidence interval (CI): 0.59-0.91; Ptrend =0.01), and the OR comparing the highest to lowest quintile of the Western pattern score was ORE5W = 1.56 (1.18-2.06; Ptrend = 0.01). For advanced AMD, the ORA5O was 0.38 (0.27-0.54; Ptrend < 0.0001), and the ORA5W was 3.70 (2.31-5.92; Ptrend < 0.0001). Our data indicate that overall diet is significantly associated with the odds of AMD and that dietary management as an AMD prevention strategy warrants further study. Copyright © 2014 Elsevier Inc. All rights reserved.

Micro-patterned agarose gel devices for single-cell high-throughput microscopy of E. coli cells.

PubMed

Priest, David G; Tanaka, Nobuyuki; Tanaka, Yo; Taniguchi, Yuichi

2017-12-21

High-throughput microscopy of bacterial cells elucidated fundamental cellular processes including cellular heterogeneity and cell division homeostasis. Polydimethylsiloxane (PDMS)-based microfluidic devices provide advantages including precise positioning of cells and throughput, however device fabrication is time-consuming and requires specialised skills. Agarose pads are a popular alternative, however cells often clump together, which hinders single cell quantitation. Here, we imprint agarose pads with micro-patterned 'capsules', to trap individual cells and 'lines', to direct cellular growth outwards in a straight line. We implement this micro-patterning into multi-pad devices called CapsuleHotel and LineHotel for high-throughput imaging. CapsuleHotel provides ~65,000 capsule structures per mm 2 that isolate individual Escherichia coli cells. In contrast, LineHotel provides ~300 line structures per mm that direct growth of micro-colonies. With CapsuleHotel, a quantitative single cell dataset of ~10,000 cells across 24 samples can be acquired and analysed in under 1 hour. LineHotel allows tracking growth of > 10 micro-colonies across 24 samples simultaneously for up to 4 generations. These easy-to-use devices can be provided in kit format, and will accelerate discoveries in diverse fields ranging from microbiology to systems and synthetic biology.

Genetic studies of Age-related macular degeneration: lessons, challenges and opportunities for disease management

PubMed Central

Ratna Priya, Rinki; Chew, Emily Y.; Swaroop, Anand

2012-01-01

Age-related macular degeneration (AMD) is a common cause of visual impairment in individuals over 55 years of age worldwide. The varying clinical phenotypes of AMD result from contributions of genetic, epigenetic and non-genetic (environmental) factors. Genetic studies of AMD have come of age as a direct result of tremendous gains from human genome project, genomewide association studies and identification of numerous susceptibility loci. These findings have implicated immune response, high-density lipoprotein cholesterol metabolism, extracellular matrix, and angiogenesis signaling pathways in disease pathophysiology. Here, we address how the wealth of genetic findings in AMD is expected to impact the practice of medicine, providing opportunities for improved risk assessment, molecular diagnosis, preventive and therapeutic intervention. We propose that the potential of using genetic variants for monitoring treatment response (pharmacogenetics) may usher a new era of personalized medicine in the clinical management of AMD. PMID:23009893

Genetics of Age-Related Macular Degeneration: Current Concepts, Future Directions

PubMed Central

DeAngelis, Margaret M.; Silveira, Alexandra C.; Carr, Elizabeth A.; Kim, Ivana K.

2014-01-01

Age-related macular degeneration (AMD) is a progressive degenerative disease which leads to blindness, affecting the quality of life of millions of Americans. More than 1.75 million individuals in the United States are affected by the advanced form of AMD. The etiological pathway of AMD is not yet fully understood, but there is a clear genetic influence on disease risk. To date, the 1q32 (CFH) and 10q26 (PLEKHA1/ARMS2/HTRA1) loci are the most strongly associated with disease; however, the variation in these genomic regions alone is unable to predict disease development with high accuracy. Therefore, current genetic studies are aimed at identifying new genes associated with AMD and their modifiers, with the goal of discovering diagnostic or prognostic biomarkers. Moreover, these studies provide the foundation for further investigation into the pathophysiology of AMD by utilizing a systems-biology-based approach to elucidate underlying mechanistic pathways. PMID:21609220

Droplet Microfluidic Device Fabrication and Use for Isothermal Amplification and Detection of MicroRNA.

PubMed

Giuffrida, Maria Chiara; D'Agata, Roberta; Spoto, Giuseppe

2017-01-01

Droplet microfluidics combined with the isothermal circular strand displacement polymerization (ICSDP) represents a powerful new technique to detect both single-stranded DNA and microRNA sequences. The method here described helps in overcoming some drawbacks of the lately introduced droplet polymerase chain reaction (PCR) amplification when implemented in microfluidic devices. The method also allows the detection of nanoliter droplets of nucleic acids sequences solutions, with a particular attention to microRNA sequences that are detected at the picomolar level. The integration of the ICSDP amplification protocol in droplet microfluidic devices reduces the time of analysis and the amount of sample required. In addition, there is also the possibility to design parallel analyses to be integrated in portable devices.

Lighting Needs and Lighting Comfort During Reading with Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Fosse, Per; Valberg, Arne

2004-01-01

This study investigated the effects of changes in luminance on the oral reading speeds of 13 participants with age-related macular degeneration (AMD) and a control group of six age-matched persons with typical vision. For the AMD participants, self-reports of light preferences were also recorded. In the AMD group, reading rates depended on light…

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

PubMed Central

de Jong, Paulus T.V.M.

2016-01-01

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

[Quality of life in patients with age-related macular degeneration - medical and social problem].

PubMed

Muzyka-Woźniak, Maria; Misiuk-Hojło, Marta; Wesolowska, Alicja

2011-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness over the age of 50 in western countries. People with AMD are suffering from serious vision-related disability and their social life is compromised. The aim of our study was to assess quality of life (QoL) in patients with exudative AMD. The study group was 100 patients treated for AMD, the control group were 30 age and sex matched subjects without ophthalmic disorders. Patients were treated with anti-VEGF therapy, by means of National Eye Institute Visual Function Questionnaire (NEI VFQ-25). As well as visual function, the NEI-VFQ investigates social functioning, mental health and dependency. There was statistically significant difference in QoL overall score between study group and control group. Patients with AMD obtained 51.1 (+/- 20.5 ) overall score, control group reached 83.7 (+/- 11.7) overall score, p = 0.001. Detailed analysis of study group revealed low acceptance of the disease and strong dependency. QoL in patients with AMD assessed with NEI VFQ-25, is significantly impaired. Low quality of life and difficulties in performing daily activities point at the need of formal psychological and social care.

Accelerated molecular dynamics simulations of protein folding.

PubMed

Miao, Yinglong; Feixas, Ferran; Eun, Changsun; McCammon, J Andrew

2015-07-30

Folding of four fast-folding proteins, including chignolin, Trp-cage, villin headpiece and WW domain, was simulated via accelerated molecular dynamics (aMD). In comparison with hundred-of-microsecond timescale conventional molecular dynamics (cMD) simulations performed on the Anton supercomputer, aMD captured complete folding of the four proteins in significantly shorter simulation time. The folded protein conformations were found within 0.2-2.1 Å of the native NMR or X-ray crystal structures. Free energy profiles calculated through improved reweighting of the aMD simulations using cumulant expansion to the second-order are in good agreement with those obtained from cMD simulations. This allows us to identify distinct conformational states (e.g., unfolded and intermediate) other than the native structure and the protein folding energy barriers. Detailed analysis of protein secondary structures and local key residue interactions provided important insights into the protein folding pathways. Furthermore, the selections of force fields and aMD simulation parameters are discussed in detail. Our work shows usefulness and accuracy of aMD in studying protein folding, providing basic references in using aMD in future protein-folding studies. © 2015 Wiley Periodicals, Inc.

Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions

PubMed Central

2016-01-01

Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies suggest that DME, DR and AMD are inflammatory conditions characterized by a breakdown of the blood-retinal barrier, inflammatory processes and an increase in vascular permeability. Key factors that seem to have a dominant role in DME, DR and AMD are angiotensin II, prostaglandins and the vascular endothelial growth factor and a deficiency of anti-inflammatory bioactive lipids. The imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DME, DR and AMD. This implies that bioactive lipids that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DME, DR and AMD. PMID:27695506

Corneal thickness of eyes with unilateral age-related macular degeneration.

PubMed

Arikan, Sedat; Ersan, Ismail; Kara, Selcuk; Gencer, Baran; Korkmaz, Safak; Vural, Azer Sara

2015-01-01

To compare the central corneal thicknesses (CCT), peripheral corneal thicknesses, and corneal volumes (CV) of the 2 eyes of patients with unilateral age-related macular degeneration (AMD). Twenty patients who were diagnosed with unilateral AMD were included in this prospective study for the purpose of making comparison between the diseased and healthy eyes. Optical coherence tomography and fundus fluorescein angiography imaging were applied to all patients in order to confirm and reveal the presence of unilateral AMD. Then, the measurements of CCT, peripheral corneal thickness measured 4 mm distant from the center of the cornea (4 mm CT), and CV of each eye of these patients were obtained through the rotating Scheimpflug corneal topographer. Wilcoxon signed-rank test did not demonstrate a statistically significant difference between the 2 eyes of patients with unilateral AMD when we compared the CCT and CV of diseased and healthy eyes (p>0.05). However, 4 mm CT of the diseased eyes of these patients were statistically significantly thicker than the healthy eyes (p<0.05). The significant difference in terms of 4 mm CT between the diseased and healthy eyes of patients with unilateral AMD may demonstrate the possible effect of peripheral corneal thickness on the development of AMD.

A diffusion based long-range and steady chemical gradient generator on a microfluidic device for studying bacterial chemotaxis

NASA Astrophysics Data System (ADS)

Murugesan, Nithya; Singha, Siddhartha; Panda, Tapobrata; Das, Sarit K.

2016-03-01

Studies on chemotaxis in microfluidics device have become a major area of research to generate physiologically similar environment in vitro. In this work, a novel micro-fluidic device has been developed to study chemo-taxis of cells in near physiological condition which can create controllable, steady and long-range chemical gradients using various chemo-effectors in a micro-channel. Hydrogels like agarose, collagen, etc, can be used in the device to maintain exclusive diffusive flux of various chemical species into the micro-channel under study. Variations of concentrations and flow rates of Texas Red dextran in the device revealed that an increase in the concentration of the dye in the feed from 6 to 18 μg ml-1, causes a steeper chemical gradient in the device, whereas the flow rate of the dye has practically no effect on the chemical gradient in the device. This observation confirms that a diffusion controlled chemical gradient is generated in the micro-channel. Chemo-taxis of E. coli cells were studied under the steady gradient of a chemo-attractant and a chemo-repellent separately in the same chemical gradient generator. For sorbitol and NiSO4·6H2O, the bacterial cells exhibit a steady distribution in the micro channel after 1 h and 30 min, respectively. From the distribution of bacterial population chemo-tactic strength of the chemo-effectors was estimated for E. coli. In a long microfluidic channel, migration behavior of bacterial cells under diffusion controlled chemical gradient showed chemotaxis, random movement, aggregation, and concentration dependent reverse chemotaxis.

Modulation of Stromal Cell-Derived Factor-1/CXC Chemokine Receptor 4 Axis Enhances rhBMP-2-Induced Ectopic Bone Formation

PubMed Central

Wise, Joel K.; Sumner, Dale Rick

2012-01-01

Enhancement of in vivo mobilization and homing of endogenous mesenchymal stem cells (MSCs) to an injury site is an innovative strategy for improvement of bone tissue engineering and repair. The present study was designed to determine whether mobilization by AMD3100 and/or local homing by delivery of stromal cell-derived factor-1 (SDF-1) enhances recombinant human bone morphogenetic protein-2 (rhBMP-2) induced ectopic bone formation in an established rat model. Rats received an injection of either saline or AMD3100 treatment 1 h before harvesting of bone marrow for in vitro colony-forming unit-fibroblasts (CFU-F) culture or the in vivo subcutaneous implantation of absorbable collagen sponges (ACSs) loaded with saline, recombinant human bone morphogenetic protein-2 (rhBMP-2), SDF-1, or the combination of SDF-1 and rhBMP-2. AMD3100 treatment resulted in a significant decrease in CFU-F number, compared with saline, which confirmed that a single systemic AMD3100 treatment rapidly mobilized MSCs from the bone marrow. At 28 and 56 days, bone formation in the explanted ACS was assessed by microcomputed tomography (μCT) and histology. At 28 days, AMD3100 and/or SDF-1 had no statistically significant effect on bone volume (BV) or bone mineral content (BMC), but histology revealed more active bone formation with treatment of AMD3100, loading of SDF-1, or the combination of both AMD3100 and SDF-1, compared with saline-treated rhBMP-2 loaded ACS. At 56 days, the addition of AMD3100 treatment, loading of SDF-1, or the combination of both resulted in a statistically significant stimulatory effect on BV and BMC, compared with the saline-treated rhBMP-2 loaded ACS. Histology of the 56-day ACS were consistent with the μCT analysis, exhibiting more mature and mineralized bone formation with AMD3100 treatment, SDF-1 loading, or the combination of both, compared with the saline-treated rhBMP-2 loaded ACS. The present study is the first that provides evidence of the efficacy of AMD3100 and SDF-1 treatment to stimulate trafficking of MSCs to an ectopic implant site, in order to ultimately enhance rhBMP-2 induced long-term bone formation. PMID:22035136

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

PubMed

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-term, frequent intravitreal injections and the vital importance of personalized approaches to anti-VEGF treatment decision making and management for patients with nAMD. To address these challenges and reduce the number of yearly injections, studies have examined alternative dosing regimens, including extended fixed intervals, as needed, and treat-and-extend strategies in specific nAMD patient populations. New clinical evidence and insights into expert clinical practice discussed in this article can support managed care professionals in the key role they play in addressing challenges in nAMD treatment and management and optimizing patient outcomes through appropriate management of anti-VEGF treatment. PRIME Education is an independent medical education company and has been an accredited provider of continuing education for 23 years. There is no fee for this activity as it is sponsored by PRIME through an educational grant from Regeneron. All authors contributed to the writing and reviewing of the article. Wykoff reports consultancies/research grants from Alcon Laboratories, Genentech/Roche, Clearside, and Iconic Therapeutics; consultancies/honoraria, research grants, and speaker fees from Allergan and Regeneron; research grants from Allegro, Apellis, Aura, NEI, NIH, Novartis, OHR Pharmaceuticals, Ophthotech, pSivida, Roche, Santen, SciFluor, Tyrogenex; and consultancies for Alimera Sciences, Alnylam Pharmaceuticals, Bayer, DORC, ONL Therapeutics, Thrombogenics, and Valeant. Clark reports advisory board work, consultancies, research grants, and speaker fees from Genentech/Roche and Regeneron and consultancy for Bayer. Brill reports consultancies for Aries Pharma, Avella, BaroNova, Braeburn Pharmaceuticals, Cardinal Health, Endogastric Solutions, GeneNews, Halt Medical, Lumendi, Medtronic, Monteris Medical, Natera, Phosphorus, Rebiotix, Seno Medical, UCB, Vermillion, Echosens, and HAP Innovations. Brill is a shareholder in EndoChoice, GeneNews, SonarMD, and SynerZ and reports advisory board work with Nestle Health Sciences, Indivior Pharmaceuticals, Eli Lilly, Blue Earth Diagnostics, Bayer, and AstraZeneca. Nielson reports advisory board work/consultancy and research grants for Genentech/Roche; advisory board work and research grants from Regeneron; and research grants from Alcon and Ophthotech.

Degradable Networks Containing Silyl Ether Bonds

NASA Astrophysics Data System (ADS)

Bassampour, Zahra S.

Degradable networks possess applications in many fields such as medical implants, electrical devices, industrial coatings, adhesives, and aerospace. Silyl ether bonds are reactive functionalities capable of degrading under physiological condition without significantly affecting the pH of the surrounding environment. This dissertation focuses on preparative methods of degradable networks utilizing silyl ether functionalities. Epoxy polymers are broadly utilized in many different applications. Despite the broad utilization of epoxy polymer thermosets in long-term applications, these thermosets are not very popular candidates in short-term applications. This unpopularity is mostly due to the fact that epoxy networks are non-degradable systems, which results in their recycling being very costly and environmentally unfriendly. In the first and second part of this dissertation, the synthesis of various amine and thiol curing agents containing hydrolyzable silyl ether bonds is described. Using these curing agents, thermosetting epoxy polymers with degradable properties were prepared. The degradation behavior and thermal properties of the cured networks were studied. Age-related macular degeneration (AMD) is a leading cause of vision loss in the industrialized world. The high prevalence of AMD and the complications and shortcomings of available treatment options give rise to a great need for the development of novel types of biodegradable implants to provide sustainable drug release. The third part of this dissertation describes the utilization of hydrolyzable silyl ether bonds in the synthesis of novel implants capable of reserving and releasing a drug in a controlled manner in order to treat AMD. Base- catalyzed thiol-Michael reactions were exploited to prepare a series of biodegradable cross- linked networks. The networks were characterized by FTIR, TGA, and DMA. The effect of monomer structure on degradation, release behavior, and thermal properties was investigated.

Association of Serum Ferritin and Kidney Function with Age-Related Macular Degeneration in the General Population

PubMed Central

Oh, Il Hwan; Choi, Eun Young; Park, Joon-Sung; Lee, Chang Hwa

2016-01-01

Ferritin is considered to be a marker of the body’s iron stores and has a potential relationship with the systemic manifestations of inflammatory reactions. Data on the association between increased levels of serum ferritin and ocular problems are limited, particularly in relation to age-related macular degeneration (AMD). Serum ferritin levels, as a possible clinical parameter for predicting AMD, were analyzed in anthropometric, biochemical, and ophthalmologic data from a nation-wide, population-based, case-control study (KNHNES IV and V). All native Koreans aged ≥ 20 years and who had no medical illness were eligible to participate. Among them, 2.9% had AMD, and its prevalence was found to increase in the higher ferritin quintile groups (Ptrend < 0.0001). In multiple linear regression analysis, serum ferritin level was closely related to conventional risk factors for AMD. Comparison of early AMD with a control group showed that serum ferritin levels were closely associated with AMD (OR = 1.004, 95% CI = 1.002–1.006), and further adjustment for age, gender, serum iron, and kidney function did not reduce this association (OR = 1.003, 95% CI = 1.001–1.006). Furthermore, the relationship between ferritin quintile and early AMD was dose-dependent. Thus, an increased level of serum ferritin in a healthy person may be a useful indicator of neurodegenerative change in the macula. A large population-based prospective clinical study is needed to confirm these findings. PMID:27096155

Prevalence and risk factors for age-related macular degeneration in Indians: a comparative study in Singapore and India.

PubMed

Gemmy Cheung, Chui Ming; Li, Xiang; Cheng, Ching-Yu; Zheng, Yingfeng; Mitchell, Paul; Wang, Jie Jin; Jonas, Jost B; Nangia, Vinay; Wong, Tien Yin

2013-04-01

To compare the prevalence and risk factors for age-related macular degeneration (AMD) in 2 Indian populations, 1 living in urban Singapore and 1 in rural central India. Population-based, cross-sectional studies of Indians aged 40+ years. Our analysis included 3337 Singapore-residing participants and 3422 India-residing participants. All participants underwent comprehensive systemic and ocular examinations and retinal photography. AMD was graded from retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System. Systemic and ocular risk factors were assessed for association with AMD. Singapore-residing participants were older (mean age 57.8 years vs 53.8 years) and, after adjusting for age and sex, were more likely to have previous cataract surgery, higher body mass index, hypertension, diabetes, previous myocardial infarction, higher cholesterol, and lower creatinine levels, but less likely to be current smokers, than India-residing participants. The age-standardized prevalence of early and late AMD was 4.45% and 0.34%, respectively, in Singapore and 5.80% and 0.16%, respectively, in India. Shorter axial length was associated with early AMD in both Singapore and India, whereas previous cataract surgery, higher body mass index, hypertension, and lower cholesterol were associated with early AMD in Singapore but not in India. The prevalence of AMD was similar among Indian adults living in urban Singapore and rural India, despite differences in cardiovascular risk factor profile and demographics. Copyright © 2013 Elsevier Inc. All rights reserved.

GeoChip-Based Analysis of the Functional Gene Diversity and Metabolic Potential of Microbial Communities in Acid Mine Drainage▿ †

PubMed Central

Xie, Jianping; He, Zhili; Liu, Xinxing; Liu, Xueduan; Van Nostrand, Joy D.; Deng, Ye; Wu, Liyou; Zhou, Jizhong; Qiu, Guanzhou

2011-01-01

Acid mine drainage (AMD) is an extreme environment, usually with low pH and high concentrations of metals. Although the phylogenetic diversity of AMD microbial communities has been examined extensively, little is known about their functional gene diversity and metabolic potential. In this study, a comprehensive functional gene array (GeoChip 2.0) was used to analyze the functional diversity, composition, structure, and metabolic potential of AMD microbial communities from three copper mines in China. GeoChip data indicated that these microbial communities were functionally diverse as measured by the number of genes detected, gene overlapping, unique genes, and various diversity indices. Almost all key functional gene categories targeted by GeoChip 2.0 were detected in the AMD microbial communities, including carbon fixation, carbon degradation, methane generation, nitrogen fixation, nitrification, denitrification, ammonification, nitrogen reduction, sulfur metabolism, metal resistance, and organic contaminant degradation, which suggested that the functional gene diversity was higher than was previously thought. Mantel test results indicated that AMD microbial communities are shaped largely by surrounding environmental factors (e.g., S, Mg, and Cu). Functional genes (e.g., narG and norB) and several key functional processes (e.g., methane generation, ammonification, denitrification, sulfite reduction, and organic contaminant degradation) were significantly (P < 0.10) correlated with environmental variables. This study presents an overview of functional gene diversity and the structure of AMD microbial communities and also provides insights into our understanding of metabolic potential in AMD ecosystems. PMID:21097602

Identification of nitrogen-fixing genes and gene clusters from metagenomic library of acid mine drainage.

PubMed

Dai, Zhimin; Guo, Xue; Yin, Huaqun; Liang, Yili; Cong, Jing; Liu, Xueduan

2014-01-01

Biological nitrogen fixation is an essential function of acid mine drainage (AMD) microbial communities. However, most acidophiles in AMD environments are uncultured microorganisms and little is known about the diversity of nitrogen-fixing genes and structure of nif gene cluster in AMD microbial communities. In this study, we used metagenomic sequencing to isolate nif genes in the AMD microbial community from Dexing Copper Mine, China. Meanwhile, a metagenome microarray containing 7,776 large-insertion fosmids was constructed to screen novel nif gene clusters. Metagenomic analyses revealed that 742 sequences were identified as nif genes including structural subunit genes nifH, nifD, nifK and various additional genes. The AMD community is massively dominated by the genus Acidithiobacillus. However, the phylogenetic diversity of nitrogen-fixing microorganisms is much higher than previously thought in the AMD community. Furthermore, a 32.5-kb genomic sequence harboring nif, fix and associated genes was screened by metagenome microarray. Comparative genome analysis indicated that most nif genes in this cluster are most similar to those of Herbaspirillum seropedicae, but the organization of the nif gene cluster had significant differences from H. seropedicae. Sequence analysis and reverse transcription PCR also suggested that distinct transcription units of nif genes exist in this gene cluster. nifQ gene falls into the same transcription unit with fixABCX genes, which have not been reported in other diazotrophs before. All of these results indicated that more novel diazotrophs survive in the AMD community.

Plasma metabolomic study in Chinese patients with wet age-related macular degeneration.

PubMed

Luo, Dan; Deng, Tingting; Yuan, Wei; Deng, Hui; Jin, Ming

2017-09-06

Age-related macular degeneration (AMD) is a leading disease associated with blindness. It has a high incidence and complex pathogenesis. We aimed to study the metabolomic characteristics in Chinese patients with wet AMD by analyzing the morning plasma of 20 healthy controls and 20 wet AMD patients for metabolic differences. We used ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry for this analysis. The relationship of these differences with AMD pathophysiology was also assessed. Remaining data were normalized using Pareto scaling, and then valid data were handled using multivariate data analysis with MetaboAnalysis software, including unsupervised principal component analysis and supervised partial least squares-discriminate analysis. The purpose of the present work was to identify significant metabolites for the analyses. Hierarchical clustering was conducted to identify metabolites that differed between the two groups. Significant metabolites were then identified using the established database, and features were mapped on the Kyoto Encyclopedia of Genes and Genomes. A total of 5443 ion peaks were detected, all of them attributable to the same 10 metabolites. These included some amino acids, isomaltose, hydrocortisone, and biliverdin. The heights of these peaks differed significantly between the two groups. The biosynthesis of amino acids pathways also differed profoundly between patients with wet AMD and controls. These findings suggested that metabolic profiles and and pathways differed between wet AMD and controls and may provide promising new targets for AMD-directed therapeutics and diagnostics.

Identification of Nitrogen-Fixing Genes and Gene Clusters from Metagenomic Library of Acid Mine Drainage

PubMed Central

Yin, Huaqun; Liang, Yili; Cong, Jing; Liu, Xueduan

2014-01-01

Biological nitrogen fixation is an essential function of acid mine drainage (AMD) microbial communities. However, most acidophiles in AMD environments are uncultured microorganisms and little is known about the diversity of nitrogen-fixing genes and structure of nif gene cluster in AMD microbial communities. In this study, we used metagenomic sequencing to isolate nif genes in the AMD microbial community from Dexing Copper Mine, China. Meanwhile, a metagenome microarray containing 7,776 large-insertion fosmids was constructed to screen novel nif gene clusters. Metagenomic analyses revealed that 742 sequences were identified as nif genes including structural subunit genes nifH, nifD, nifK and various additional genes. The AMD community is massively dominated by the genus Acidithiobacillus. However, the phylogenetic diversity of nitrogen-fixing microorganisms is much higher than previously thought in the AMD community. Furthermore, a 32.5-kb genomic sequence harboring nif, fix and associated genes was screened by metagenome microarray. Comparative genome analysis indicated that most nif genes in this cluster are most similar to those of Herbaspirillum seropedicae, but the organization of the nif gene cluster had significant differences from H. seropedicae. Sequence analysis and reverse transcription PCR also suggested that distinct transcription units of nif genes exist in this gene cluster. nifQ gene falls into the same transcription unit with fixABCX genes, which have not been reported in other diazotrophs before. All of these results indicated that more novel diazotrophs survive in the AMD community. PMID:24498417

Effect of ambient light and age-related macular degeneration on precision walking.

PubMed

Alexander, M Scott; Lajoie, Kim; Neima, David R; Strath, Robert A; Robinovitch, Stephen N; Marigold, Daniel S

2014-08-01

To determine how age-related macular degeneration (AMD) and changes in ambient light affect the control of foot placement while walking. Ten older adults with AMD and 11 normal-sighted controls performed a precision walking task under normal (∼600 lx), dim (∼0.7 lx), and after a sudden reduction (∼600 to 0.7 lx) of light. The precision walking task involved subjects walking and stepping to the center of a series of irregularly spaced, low-contrast targets. Habitual visual acuity and contrast sensitivity and visual field function were also assessed. There were no differences between groups when performing the walking task in normal light (p > 0.05). In reduced lighting, older adults with AMD were less accurate and more variable when stepping across the targets compared to controls (p < 0.05). A sudden reduction of light proved the most challenging for this population. In the AMD group, contrast sensitivity and visual acuity were not significantly correlated with walking performance. Visual field thresholds in the AMD group were only associated with greater foot placement error and variability in the dim light walking condition (r = -0.69 to -0.87, p < 0.05). While walking performance is similar between groups in normal light, poor ambient lighting results in decreased foot placement accuracy in older adults with AMD. Improper foot placement while walking can lead to a fall and possible injury. Thus, to improve the mobility of those with AMD, strategies to enhance the environment in reduced lighting situations are necessary.

Age-related macular degeneration changes the processing of visual scenes in the brain.

PubMed

Ramanoël, Stephen; Chokron, Sylvie; Hera, Ruxandra; Kauffmann, Louise; Chiquet, Christophe; Krainik, Alexandre; Peyrin, Carole

2018-01-01

In age-related macular degeneration (AMD), the processing of fine details in a visual scene, based on a high spatial frequency processing, is impaired, while the processing of global shapes, based on a low spatial frequency processing, is relatively well preserved. The present fMRI study aimed to investigate the residual abilities and functional brain changes of spatial frequency processing in visual scenes in AMD patients. AMD patients and normally sighted elderly participants performed a categorization task using large black and white photographs of scenes (indoors vs. outdoors) filtered in low and high spatial frequencies, and nonfiltered. The study also explored the effect of luminance contrast on the processing of high spatial frequencies. The contrast across scenes was either unmodified or equalized using a root-mean-square contrast normalization in order to increase contrast in high-pass filtered scenes. Performance was lower for high-pass filtered scenes than for low-pass and nonfiltered scenes, for both AMD patients and controls. The deficit for processing high spatial frequencies was more pronounced in AMD patients than in controls and was associated with lower activity for patients than controls not only in the occipital areas dedicated to central and peripheral visual fields but also in a distant cerebral region specialized for scene perception, the parahippocampal place area. Increasing the contrast improved the processing of high spatial frequency content and spurred activation of the occipital cortex for AMD patients. These findings may lead to new perspectives for rehabilitation procedures for AMD patients.

Iris colour, ethnic origin and progression of age-related macular degeneration.

PubMed

Nicolas, Caroline M; Robman, Luba D; Tikellis, Gabriella; Dimitrov, Peter N; Dowrick, Adam; Guymer, Robyn H; McCarty, Catherine A

2003-12-01

To investigate the relationship between iris colour, ethnic origin and the progression of age-related macular degeneration (AMD). Participants were recruited from the population-based Melbourne Visual Impairment Project or the prospective, randomized, double-masked Vitamin E, Cataract and Age-Related Macular Degeneration study. From these two cohorts, 171 participants aged between 52 and 93 years who were identified as having early AMD features at their baseline examination (1992-1995) were followed for an average of 6.8 years (until 2001) to determine the progression rate of early AMD. The participants' iris colour was categorized as light, intermediate or dark. Ethnic origin was categorized as Anglo-Saxon or non-Anglo-Saxon, according to the participants' grandparents' country of birth. In total, 53 (31%) of the 171 participants showed signs of AMD progression. Participants with light iris colour had twofold the risk of AMD progression of those with dark or intermediate iris colours, although the age-adjusted and multivariate-adjusted associations were not significant (both P = 0.13). Age-adjusted and multivariate comparisons of Anglo-Saxon ethnic origin to non-Anglo-Saxon ethnic origin showed a noticeable but non-significant association with progression of AMD (P= 0.22 and P= 0.14, respectively). Individuals with light iris colour or of Anglo-Saxon ethnic origin had a strong tendency to greater progression of AMD. A larger sample is required to confirm these clinically important, but statistically non-significant, associations.

Effect of Soluble Inducible Costimulator Level and Its Polymorphisms on Age-Related Macular Degeneration

PubMed Central

Yu, Honghua; Zou, Xiulan; Peng, Lianghong; Wang, Yong; Zhang, Chu

2013-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. Evidence has shown that the human immune system may play critical roles in this disease. Inducible costimulator (ICOS) promotes T-cell activation, differentiation, and T:B-cell interactions. The aim of the study was to understand the effect of ICOS on the development of AMD from genetic polymorphism perspective and serum level perspective. Two ICOS polymorphisms, rs10183087A/C and rs10932037C/T, were tested in 223 AMD cases and 262 healthy controls. The serum level of soluble ICOS (sICOS) was compared among subjects with different genotypes, as well as between AMD patients and controls. Data showed that prevalence of rs10183087CC genotype was significantly increased in AMD than in controls (p=0.001). Function analysis revealed that subjects carrying rs10183087CC genotype had higher serum levels of sICOS than those with AA or AC genotypes (p<0.05). When we compared serum levels of sICOS between cases and controls, results showed that AMD patients had significantly increased sICOS levels than healthy donors (p<0.05). Also, wet type cases were observed to have higher sICOS levels than cases with dry type (p<0.05). These data suggested ICOS polymorphism could affect the susceptibility to AMD by elevating protein expression, and serum levels of sICOS may be closed correlated with the development and progression of this disease. PMID:24083358

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

PubMed Central

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

2017-01-01

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

Plasma levels of hypoxia-regulated factors in patients with age-related macular degeneration.

PubMed

Ioanna, Zygoula; Christian, Schori; Christian, Grimm; Daniel, Barthelmes

2018-02-01

Various hypoxia-related proteins are differentially expressed in the retina and secreted to the vitreous and/or aqueous humor of patients affected by dry or neovascular age-related macular degeneration (nAMD). To determine whether these conditions alter concentrations of cytokines also in the systemic circulation, we measured plasma levels of six hypoxia-related proteins. Plasma was prepared from EDTA blood that was collected from patients affected by dry AMD (n = 5), nAMD (n = 11), proliferative diabetic retinopathy (PDR; n = 9), and patients with an epiretinal membrane (ERM; n = 11). ERM samples served as negative controls, PDR samples as positive controls. Protein concentrations of vascular endothelial growth factor (VEGF), erythropoietin (EPO), angiopoietin-like 4 (ANGPTL4), placental growth factor (PlGF), tumor necrosis factor alpha (TNF-α), and pigment epithelium-derived factor (PEDF) were determined by enzyme-linked immunosorbent assay (ELISA). The concentration of PlGF was significantly increased in plasma of patients affected by nAMD. Although no statistically significant differences were found for EPO, ANGPTL4, PlGF, TNF-α, and PEDF, the mean concentration of VEGF was lowest in the nAMD group. Plasma concentrations of the six factors did not correlate with gender or age of patients. nAMD may increase plasma concentrations of PlGF, making it a candidate as a biomarker for the neovascular form of AMD. Other factors, however, were not differentially regulated, suggesting that their systemic concentrations are not generally increased in hypoxia-related retinal diseases.

Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

PubMed Central

Ardeljan, Daniel; Chan, Chi-Chao

2013-01-01

Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

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

PubMed

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

2017-01-01

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

Physical Activity and Age-related Macular Degeneration: A Systematic Literature Review and Meta-analysis.

PubMed

McGuinness, Myra B; Le, Jerome; Mitchell, Paul; Gopinath, Bamini; Cerin, Ester; Saksens, Nicole T M; Schick, Tina; Hoyng, Carel B; Guymer, Robyn H; Finger, Robert P

2017-08-01

To better understand the association, in a white population, of physical activity and age-related macular degeneration (AMD)-the main cause of irreversible severe vision loss in developed countries-given the suggestion that a healthy lifestyle may assist in delaying the onset and progression of AMD. Systematic review and meta-analysis. Medline, EMBASE, and Google Scholar were systematically searched for studies up to May 2015. Reference lists of published articles were hand searched and study authors were contacted to provide additional data. Those in the lowest category of activity in each study were compared with all other participants to assess the association between physical activity and both early and late AMD using random-effects meta-analysis. Nine studies (subject age range 30-97 years) were included in the meta-analysis. Physical activity was found to have a protective association with both early AMD (8 studies, n = 38 112, odds ratio (OR) 0.92, 95% confidence interval [CI] 0.86-0.98) and late AMD (7 studies, n = 28 854, OR 0.59, 95% CI 0.49-0.72). Physical activity is associated with lower odds of early and late AMD in white populations. These findings have important implications, reinforcing the public health message of staying active throughout life. However, further longitudinal studies are required to confirm and further characterize a protective effect of physical activity on the onset and/or progression of AMD. Copyright © 2017 Elsevier Inc. All rights reserved.

JNK inhibition reduces apoptosis and neovascularization in a murine model of age-related macular degeneration.

PubMed

Du, Hongjun; Sun, Xufang; Guma, Monica; Luo, Jing; Ouyang, Hong; Zhang, Xiaohui; Zeng, Jing; Quach, John; Nguyen, Duy H; Shaw, Peter X; Karin, Michael; Zhang, Kang

2013-02-05

Age-related macular degeneration (AMD) is the leading cause of registered blindness among the elderly and affects over 30 million people worldwide. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in pathogenesis of AMD. In advanced wet AMD, although, most of the severe vision loss is due to bleeding and exudation of choroidal neovascularization (CNV), and it is well known that vascular endothelial growth factor (VEGF) plays a pivotal role in the growth of the abnormal blood vessels. VEGF suppression therapy improves visual acuity in AMD patients. However, there are unresolved issues, including safety and cost. Here we show that mice lacking c-Jun N-terminal kinase 1 (JNK1) exhibit decreased inflammation, reduced CNV, lower levels of choroidal VEGF, and impaired choroidal macrophage recruitment in a murine model of wet AMD (laser-induced CNV). Interestingly, we also detected a substantial reduction in choroidal apoptosis of JNK1-deficient mice. Intravitreal injection of a pan-caspase inhibitor reduced neovascularization in the laser-induced CNV model, suggesting that apoptosis plays a role in laser-induced pathological angiogenesis. Intravitreal injection of a specific JNK inhibitor decreased choroidal VEGF expression and reduced pathological CNV. These results suggest that JNK1 plays a key role in linking oxidative stress, inflammation, macrophage recruitment apoptosis, and VEGF production in wet AMD and pharmacological JNK inhibition offers a unique and alternative avenue for prevention and treatment of AMD.

Biomimetic patterned surfaces for controllable friction in micro- and nanoscale devices

NASA Astrophysics Data System (ADS)

Singh, Arvind; Suh, Kahp-Yang

2013-12-01

Biomimetics is the study and simulation of biological systems for desired functional properties. It involves the transformation of underlying principles discovered in nature into man-made technologies. In this context, natural surfaces have significantly inspired and motivated new solutions for micro- and nano-scale devices (e.g., Micro/Nano-Electro-Mechanical Systems, MEMS/NEMS) towards controllable friction, during their operation. As a generic solution to reduce friction at small scale, various thin films/coatings have been employed in the last few decades. In recent years, inspiration from `Lotus Effect' has initiated a new research direction for controllable friction with biomimetic patterned surfaces. By exploiting the intrinsic hydrophobicity and ability to reduce contact area, such micro- or nano-patterned surfaces have demonstrated great strength and potential for applications in MEMS/NEMS devices. This review highlights recent advancements on the design, development and performance of these biomimetic patterned surfaces. Also, we present some hybrid approaches to tackle current challenges in biomimetic tribological applications for MEMS/NEMS devices.

Micro-optical elements produced using an photo-embossing technique in photopolymers

NASA Astrophysics Data System (ADS)

O'Neill, Feidhlim T.; Rowsome, Ita C.; Carr, Alun J.; Daniels, Stephen M.; Gleeson, Michael R.; Kelly, John V.; Close, Ciara; Lawrence, Justin R.; Sheridan, John T.

2005-09-01

Micro-optical devices are very important in current high-tech consumer items. The development of future products depends on both the evolution of fabrication techniques and on the development of new low cost mass production methods. Polymers offer ease of fabrication and low cost and are therefore excellent materials for the development of micro-optical devices. Polymer optical devices include passive optical elements, such as microlens arrays and waveguides, as well as active devices such as polymer based lasers. One of the most important areas of micro-optics is that of microlens design, manufacture and testing. The wide diversity of fabrication methods used for the production of these elements indicates their importance. One of these fabrication techniques is photo-embossing. The use of the photo-embossing technique and a photopolymer holographic recording material will be examined in this paper. A discussion of current attempts to model the fabrication process and a review of the experimental method will be given.

Plasmofluidics: Merging Light and Fluids at the Micro-/Nano-Scale

PubMed Central

Wang, Mingsong; Zhao, Chenglong; Miao, Xiaoyu; Zhao, Yanhui; Rufo, Joseph

2016-01-01

Plasmofluidics is the synergistic integration of plasmonics and micro/nano fluidics in devices and applications in order to enhance performance. There has been significant progress in the emerging field of plasmofluidics in recent years. By utilizing the capability of plasmonics to manipulate light at the nanoscale, combined with the unique optical properties of fluids, and precise manipulation via micro/nano fluidics, plasmofluidic technologies enable innovations in lab-on-a-chip systems, reconfigurable photonic devices, optical sensing, imaging, and spectroscopy. In this review article, we examine and categorize the most recent advances in plasmofluidics into plasmon-enhanced functionalities in microfluidics and microfluidics-enhanced plasmonic devices. The former focuses on plasmonic manipulations of fluids, bubbles, particles, biological cells, and molecules at the micro-/nano-scale. The latter includes technological advances that apply microfluidic principles to enable reconfigurable plasmonic devices and performance-enhanced plasmonic sensors. We conclude with our perspectives on the upcoming challenges, opportunities, and the possible future directions of the emerging field of plasmofluidics. PMID:26140612

Plasmofluidics: Merging Light and Fluids at the Micro-/Nanoscale.

PubMed

Wang, Mingsong; Zhao, Chenglong; Miao, Xiaoyu; Zhao, Yanhui; Rufo, Joseph; Liu, Yan Jun; Huang, Tony Jun; Zheng, Yuebing

2015-09-16

Plasmofluidics is the synergistic integration of plasmonics and micro/nanofluidics in devices and applications in order to enhance performance. There has been significant progress in the emerging field of plasmofluidics in recent years. By utilizing the capability of plasmonics to manipulate light at the nanoscale, combined with the unique optical properties of fluids and precise manipulation via micro/nanofluidics, plasmofluidic technologies enable innovations in lab-on-a-chip systems, reconfigurable photonic devices, optical sensing, imaging, and spectroscopy. In this review article, the most recent advances in plasmofluidics are examined and categorized into plasmon-enhanced functionalities in microfluidics and microfluidics-enhanced plasmonic devices. The former focuses on plasmonic manipulations of fluids, bubbles, particles, biological cells, and molecules at the micro/nanoscale. The latter includes technological advances that apply microfluidic principles to enable reconfigurable plasmonic devices and performance-enhanced plasmonic sensors. The article is concluded with perspectives on the upcoming challenges, opportunities, and possible future directions of the emerging field of plasmofluidics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estimating the Prevalence of Anxiety and Mood Disorders in an Adolescent General Population: An Evaluation of the GHQ12

ERIC Educational Resources Information Center

Mann, Robert E.; Paglia-Boak, Angela; Adlaf, Edward M.; Beitchman, Joseph; Wolfe, David; Wekerle, Christine; Hamilton, Hayley A.; Rehm, Jurgen

2011-01-01

Anxiety and mood disorders (AMD) may be more common among adolescents than previously thought, and epidemiological research would benefit from an easily-administered measure of AMD. We assessed the ability of the GHQ12 to estimate the prevalence of AMD in a representative sample of Ontario adolescents. Data were based on self-administered…

Knowledge and Use of Low Vision Services Among Persons with Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Casten, Robin J.; Maloney, Eileen K.; Rovner, Barry W.

2005-01-01

Visual impairment (blindness or low vision) is a leading cause of disability among older adults and is most often due to age-related macular degeneration (AMD). It is predicted that 2.95 million people will have AMD by 2020 (Eye Diseases Prevalence Research Group, 2004). Unfortunately, there is no cure for AMD, nor can lost vision be restored.…

The potential effect of population development, smoking and antioxidant supplementation on the future epidemiology of age-related macular degeneration in Switzerland.

PubMed

Bauer, P; Barthelmes, D; Kurz, M; Fleischhauer, J C; Sutter, F K

2008-05-01

Due to the predicted age shift of the population an increase in the number of patients with late AMD is expected. At present smoking represents the only modifiable risk factor. Supplementation of antioxidants in patients at risk is the sole effective pharmacological prevention. The aim of this study is to estimate the future epidemiological development of late AMD in Switzerland and to quantify the potential effects of smoking and antioxidants supplementation. The modelling of the future development of late AMD cases in Switzerland was based on a meta-analysis of the published data on AMD-prevalence and on published Swiss population development scenarios until 2050. Three different scenarios were compared: low, mean and high. The late AMD cases caused by smoking were calculated using the "population attributable fraction" formula and data on the current smoking habits of the Swiss population. The number of potentially preventable cases was estimated using the data of the Age-Related Eye Disease Study (AREDS). According to the mean population development scenario, late AMD cases in Switzerland will rise from 37 200 cases in 2005 to 52 500 cases in 2020 and to 93 200 cases in 2050. Using the "low" and the "high" scenarios the late AMD cases may range from 49 500 to 56 000 in 2020 and from 73 700 to 118 400 in 2050, respectively. Smoking is responsible for approximately 7 % of all late AMD cases, i. e., 2600 cases in 2005, 3800 cases in 2020, 6600 cases in 2050 ("mean scenario"). With future antioxidant supplementation to all patients at risk another 3100 cases would be preventable until 2020 and possibly 23 500 cases until 2050. Due to age shift in the population a 2.5-fold increase in late AMD cases until 2050 is expected, representing a socioeconomic challenge. Cessation of smoking and supplementation of antioxidants to all patients at risk has the potential to reduce this number. Unfortunately, public awareness is low. These data may support health-care providers and public opinion leaders when developing public education and prevention strategies.

Cost-Effectiveness of Screening for Intermediate Age-Related Macular Degeneration during Diabetic Retinopathy Screening.

PubMed

Chan, Christina K W; Gangwani, Rita A; McGhee, Sarah M; Lian, JinXiao; Wong, David S H

2015-11-01

To determine whether screening for age-related macular degeneration (AMD) during a diabetic retinopathy (DR) screening program would be cost effective in Hong Kong. We compared and evaluated the impacts of screening, grading, and vitamin treatment for intermediate AMD compared with no screening using a Markov model. It was based on the natural history of AMD in a cohort with a mean age of 62 years, followed up until 100 years of age or death. Subjects attending a DR screening program were recruited. A cost-effectiveness analysis was undertaken from a public provider perspective. It included grading for AMD using the photographs obtained for DR screening and treatment with vitamin therapy for those with intermediate AMD. The measures of effectiveness were obtained largely from a local study, but the transition probabilities and utility values were from overseas data. Costs were all from local sources. The main assumptions and estimates were tested in sensitivity analyses. The outcome was cost per quality-adjusted life year (QALY) gained. Both costs and benefits were discounted at 3%. All costs are reported in United States dollars ($). The cost per QALY gained through screening for AMD and vitamin treatment for appropriate cases was $12,712 after discounting. This would be considered highly cost effective based on the World Health Organization's threshold of willingness to pay (WTP) for a QALY, that is, less than the annual per capita gross domestic product of $29,889. Because of uncertainty regarding the utility value for those with advanced AMD, we also tested an extreme, conservative value for utility under which screening remained cost effective. One-way sensitivity analyses revealed that, besides utility values, the cost per QALY was most sensitive to the progression rate from intermediate to advanced AMD. The cost-effectiveness acceptability curve showed a WTP for a QALY of $29,000 or more has a more than 86% probability of being cost effective compared with no screening. Our analysis demonstrated that AMD screening carried out simultaneously with DR screening for patients with diabetes would be cost effective in a Hong Kong public healthcare setting. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2013-01-01

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

Difference between age-related macular degeneration and polypoidal choroidal vasculopathy in the hereditary contribution of the A69S variant of the age-related maculopathy susceptibility 2 gene (ARMS2).

PubMed

Yanagisawa, Suiho; Kondo, Naoshi; Miki, Akiko; Matsumiya, Wataru; Kusuhara, Sentaro; Tsukahara, Yasutomo; Honda, Shigeru; Negi, Akira

2011-01-01

To investigate whether the A69S variant of the age-related maculopathy susceptibility 2 gene (ARMS2) has a different hereditary contribution in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). We initially conducted a comparative genetic analysis of neovascular AMD and PCV, genotyping the ARMS2 A69S variant in 181 subjects with neovascular AMD, 198 subjects with PCV, and 203 controls in a Japanese population. Genotyping was conducted using TaqMan technology. Results were then integrated into a meta-analysis of previous studies representing an assessment of the association between the ARMS2 A69S variant and neovascular AMD and/or PCV, comprising a total of 3,828 subjects of Asian descent. The Q-statistic test was used to assess between-study heterogeneity. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a fixed effects model. The genetic effect of the A69S variant was stronger in neovascular AMD (allelic summary OR=3.09 [95% CI, 2.71-3.51], fixed effects p<0.001) than in PCV (allelic summary OR=2.13 [95% CI, 1.91-2.38], fixed effects p<0.001). The pooled risk allele frequency was significantly higher in neovascular AMD (64.7%) than in PCV (55.6%). The population attributable risks for the variant allele were estimated to be 43.9% (95% CI, 39.0%-48.4%) and 29.7% (95% CI, 25.4%-34.0%) for neovascular AMD and PCV, respectively. No significant between-study heterogeneity was observed in any statistical analysis in this meta-analysis. Our meta-analysis provides substantial evidence that the ARMS2 A69S variant confers a significantly higher risk of neovascular AMD than PCV. Furthermore, there is compelling evidence that the risk attributable to the A69S variant differs between geographic atrophy and neovascular AMD. Together with defining the molecular basis of susceptibility, understanding the relationships between this genomic region and disease subtypes will yield important insights, elucidating the biologic architecture of this phenotypically heterogeneous disorder.

Risk factors for exudative age-related macular degeneration in a large French case-control study.

PubMed

Zerbib, Jennyfer; Delcourt, Cécile; Puche, Nathalie; Querques, Giuseppe; Cohen, Salomon Yves; Sahel, José; Korobelnik, Jean-François; Le Goff, Mélanie; Souied, Eric H

2014-06-01

The purpose of the CAP (Creteil AMD PHRC-funded) Study was to analyze risk factors of exudative age-related macular degeneration (AMD) in a large French case-control population. One thousand and twenty-four patients with exudative AMD and 275 controls were recruited. Information about lifestyle, medical history, and dietary intake were collected. Associations of risk factors were estimated using logistic regression. After multivariate adjustment, CFH Y402H and ARMS2 A69S polymorphisms were associated with very high risk for exudative AMD (OR = 6.21 and OR = 11.7, respectively, p < 0.0001). Risk for exudative AMD was increased in current smokers (OR = 3.79, p = 0.0003) and former smokers having quitted since less than 20 years ago (OR = 2.30, p = 0.002), but not in former smokers having quitted since 20 years or more ago (OR = 0.81, p = 0.43). Heavy smokers (at least 25 pack-years) were particularly at risk (OR = 3.61, p < 0.0001). Use of cooking oils rich in omega 3 fatty acids was significantly associated with a reduced risk of exudative AMD (OR = 0.55, 95 % CI: 0.36-0.84, p = 0.006), as well as a high consumption of fruits (OR = 0.60, 95 % CI: 0.37-0.98, p = 0.04), but not the consumption of fish, vegetables or oils rich in omega 6. High waist circumference was associated with increased risk for exudative AMD (OR = 2.53, p < 0.0001), but not hypercholesterolemia, hypertension, or body mass index. The CAP Study confirms major genetic risk factors for exudative AMD. It further documents the high risk in heavy smokers and the long persistence of risk after smoking cessation, and the associations with waist circumference and fruit consumption. Furthermore, we observed an inverse correlation between AMD and cooking oils harboring a beneficial omega-3 fatty acid profile.

Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study

PubMed Central

2013-01-01

Background Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly, Caucasian populations. There is strong evidence that mitochondrial dysfunction and oxidative stress play a role in the cell death found in AMD retinas. The purpose of this study was to examine the association of the Caucasian mitochondrial JTU haplogroup cluster with AMD. We also assessed for gender bias and additive risk with known high risk nuclear gene SNPs, ARMS2/LOC387715 (G > T; Ala69Ser, rs10490924) and CFH (T > C; Try402His, rs1061170). Methods Total DNA was isolated from 162 AMD subjects and 164 age-matched control subjects located in Los Angeles, California, USA. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the J, U, T, and H mitochondrial haplogroups and the ARMS2-rs10490924 and CFH-rs1061170 SNPs. PCR amplified products were sequenced to verify the nucleotide substitutions for the haplogroups and ARMS2 gene. Results The JTU haplogroup cluster occurred in 34% (55/162) of AMD subjects versus 15% (24/164) of normal (OR = 2.99; p = 0.0001). This association was slightly greater in males (OR = 3.98, p = 0.005) than the female population (OR = 3.02, p = 0.001). Assuming a dominant effect, the risk alleles for the ARMS2 (rs10490924; p = 0.00001) and CFH (rs1061170; p = 0.027) SNPs were significantly associated with total AMD populations. We found there was no additive risk for the ARMS2 (rs10490924) or CFH (rs1061170) SNPs on the JTU haplogroup background. Conclusions There is a strong association of the JTU haplogroup cluster with AMD. In our Southern California population, the ARMS2 (rs10490924) and CFH (rs1061170) genes were significantly but independently associated with AMD. SNPs defining the JTU mitochondrial haplogroup cluster may change the retinal bioenergetics and play a significant role in the pathogenesis of AMD. PMID:23302509

Parylene as a new membrane material for BioMEMS applications

NASA Astrophysics Data System (ADS)

Lu, Bo

The work in this thesis aims to use MEMS and microfabrication technologies to develop two types of parylene membrane devices for biomedical applications. The first device is the parylene membrane filter for cancer detection. The presence of circulating tumor cells (CTC) in patient blood is an important sign of cancer metastasis. However, currently there are two big challenges for CTC detection. First, CTCs are extremely rare, especially at the early stage of cancer metastasis. Secondly, CTCs are very fragile, and are very likely to be damaged during the capturing process. By using size-based membrane filtration through the specially designed parylene filters, together with a constant-pressure filtration system, we are able to capture the CTCs from patient blood with high capture efficiency, high viability, moderate enrichment, and high throughput. Both immunofluorescence enumeration and telomerase activity detection have been used to detect and differentiate the captured CTCs. The feasibility of further cell culture of the captured CTCs has also been demonstrated, which could be a useful way to increase the number of CTCs for future studies. Models of the time-dependent cell membrane damage are developed to predict and prevent CTC damage during this detection process. The results of clinical trials further demonstrate that the parylene membrane filter is a promising device for cancer detection. The second device is the parylene artificial Bruch's membrane for age-related macular degeneration (AMD). AMD is usually characterized by an impaired Bruch's membrane with much lowered permeability, which impedes the transportation of nutrients from choroid vessels to nourish the retinal pigment epithelial (RPE) cells and photoreceptors. Parylene is selected as a substitute material because of its good mechanical properties, transparency, biocompatibility, and machinability. More importantly, it is found that the permeability of submicron parylene is very similar to that of healthy human Bruch's membrane. A mesh-supported submicron parylene membrane structure has been designed and its feasibility as an artificial Bruch's membrane has been demonstrated by diffusion experiments, cell perfusion culture, and pressure deflection tests. RPE cells are able to adhere, proliferate and develop into normal in vivo-like morphology and functions. Currently this artificial membrane is under clinical trials.

Sputtered highly oriented PZT thin films for MEMS applications

NASA Astrophysics Data System (ADS)

Kalpat, Sriram S.

Recently there has been an explosion of interest in the field of micro-electro-mechanical systems (MEMS). MEMS device technology has become critical in the growth of various fields like medical, automotive, chemical, and space technology. Among the many applications of ferroelectric thin films in MEMS devices, microfluidics is a field that has drawn considerable amount of research from bio-technology industries as well as chemical and semiconductor manufacturing industries. PZT thin films have been identified as best suited materials for micro-actuators and micro-sensors used in MEMS devices. A promising application for piezoelectric thin film based MEMS devices is disposable drug delivery systems that are capable of sensing biological parameters, mixing and delivering minute and precise amounts of drugs using micro-pumps or micro mixers. These devices call for low driving voltages, so that they can be battery operated. Improving the performance of the actuator material is critical in achieving battery operated disposal drug delivery systems. The device geometry and power consumption in MEMS devices largely depends upon the piezoelectric constant of the films, since they are most commonly used to convert electrical energy into a mechanical response of a membrane or cantilever and vice versa. Phenomenological calculation on the crystal orientation dependence of piezoelectric coefficients for PZT single crystal have reported a significant enhancement of the piezoelectric d33 constant by more than 3 times along [001] in the rhombohedral phase as compared to the conventionally used orientation PZT(111) since [111] is the along the spontaneous polarization direction. This could mean considerable improvement in the MEMS device performance and help drive the operating voltages lower. The motivation of this study is to investigate the crystal orientation dependence of both dielectric and piezoelectric coefficients of PZT thin films in order to select the appropriate orientation that could improve the MEMS device performance. Potential application of these devices is as battery operated disposable drug delivery systems. This work will also investigate the fabrication of a flexural plate wave based microfluidic device using the PZT thin film of appropriate orientation that would enhance the device performance. (Abstract shortened by UMI.)

Micro-field evoked potentials recorded from the porcine sub-dural cortical surface utilizing a microelectrode array.

PubMed

Kitzmiller, Joseph P; Hansford, Derek J; Fortin, Linda D; Obrietan, Karl H; Bergdall, Valerie K; Beversdorf, David Q

2007-05-15

A sub-dural surface microelectrode array designed to detect micro-field evoked potentials has been developed. The device is comprised of an array of 350-microm square gold contacts, with bidirectional spacing of 150 microm, contained within a polyimide Kapton material. Cytotoxicity testing suggests that the device is suitable for use with animal and human patients. Implementation of the device in animal studies revealed that reliable evoked potentials could be acquired. Further work will be needed to determine how these micro-field potentials, which demonstrate selectivity for one eye, relate to the distribution of the ocular dominance columns of the occipital cortex.

Markers of inflammation, oxidative stress, and endothelial dysfunction and the 20-year cumulative incidence of early age-related macular degeneration: the Beaver Dam Eye Study.

PubMed

Klein, Ronald; Myers, Chelsea E; Cruickshanks, Karen J; Gangnon, Ronald E; Danforth, Lorraine G; Sivakumaran, Theru A; Iyengar, Sudha K; Tsai, Michael Y; Klein, Barbara E K

2014-04-01

IMPORTANCE Modifying levels of factors associated with age-related macular degeneration (AMD) may decrease the risk for visual impairment in older persons. OBJECTIVE To examine the relationships of markers of inflammation, oxidative stress, and endothelial dysfunction to the 20-year cumulative incidence of early AMD. DESIGN, SETTING, AND PARTICIPANTS This longitudinal population-based cohort study involved a random sample of 975 persons in the Beaver Dam Eye Study without signs of AMD who participated in the baseline examination in 1988-1990 and up to 4 follow-up examinations in 1993-1995, 1998-2000, 2003-2005, and 2008-2010. EXPOSURES Serum markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor-α receptor 2, interleukin-6, and white blood cell count), oxidative stress (8-isoprostane and total carbonyl content), and endothelial dysfunction (soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1) were measured. Interactions with complement factor H (rs1061170), age-related maculopathy susceptibility 2 (rs10490924), complement component 3 (rs2230199), and complement component 2/complement factor B (rs4151667) were examined using multiplicative models. Age-related macular degeneration was assessed from fundus photographs. MAIN OUTCOMES AND MEASURES Early AMD defined by the presence of any size drusen and the presence of pigmentary abnormalities or by the presence of large-sized drusen (≥125-μm diameter) in the absence of late AMD. RESULTS The 20-year cumulative incidence of early AMD was 23.0%. Adjusting for age, sex, and other risk factors, high-sensitivity C-reactive protein (odds ratio comparing fourth with first quartile, 2.18; P = .005), tumor necrosis factor-α receptor 2 (odds ratio, 1.78; P = .04), and interleukin-6 (odds ratio, 1.78; P = .03) were associated with the incidence of early AMD. Increased incidence of early AMD was associated with soluble vascular cell adhesion molecule-1 (odds ratio per SD on the logarithmic scale, 1.21; P = .04). CONCLUSIONS AND RELEVANCE We found modest evidence of relationships of serum high-sensitivity C-reactive protein, tumor necrosis factor-α receptor 2, interleukin-6, and soluble vascular cell adhesion molecule-1 to the 20-year cumulative incidence of early AMD independent of age, smoking status, and other factors. It is not known whether these associations represent a cause and effect relationship or whether other unknown confounders accounted for the findings. Even if inflammatory processes are a cause of early AMD, it is not known whether interventions that reduce systemic inflammatory processes will reduce the incidence of early AMD.

Mechanics of Multifunctional Materials & Microsystems

DTIC Science & Technology

2012-03-09

Mechanics of Materials; Life Prediction (Materials & Micro-devices); Sensing, Precognition & Diagnosis; Multifunctional Design of Autonomic...Life Prediction (Materials & Micro-devices); Sensing, Precognition & Diagnosis; Multifunctional Design of Autonomic Systems; Multifunctional...release; distribution is unlimited. 7 VISION: EXPANDED • site specific • autonomic AUTONOMIC AEROSPACE STRUCTURES • Sensing & Precognition • Self

The Optimization dispatching of Micro Grid Considering Load Control

NASA Astrophysics Data System (ADS)

Zhang, Pengfei; Xie, Jiqiang; Yang, Xiu; He, Hongli

2018-01-01

This paper proposes an optimization control of micro-grid system economy operation model. It coordinates the new energy and storage operation with diesel generator output, so as to achieve the economic operation purpose of micro-grid. In this paper, the micro-grid network economic operation model is transformed into mixed integer programming problem, which is solved by the mature commercial software, and the new model is proved to be economical, and the load control strategy can reduce the charge and discharge times of energy storage devices, and extend the service life of the energy storage device to a certain extent.

Passive micromixer using by convection and surface tension effects with air-liquid interface.

PubMed

Ju, Jongil; Warrick, Jay

2013-12-01

This article describes a passive micromixer that utilizes an air-liquid interface and surface tension effects to enhance fluid mixing via convection and Marangoni effects. Performance of the microfluidic component is tested within a passive-pumping-based device that consists of three microchannels connected in succession using passive micro-mixers. Mixing was quantified at 5 key points along the length of the device using microscope images of patterned streams of Alexa 488 fluorescent-dyed water and pure DI water flowing through the device. The passive micro-mixer mixed fluid 15-20 times more effectively than diffusion between laminar flow streams alone and is a novel micro-mixer embodiment that provides an additional strategy for removing external components from microscale devices for simpler, autonomous operation.

Passive micromixer using by convection and surface tension effects with air-liquid interface

PubMed Central

Ju, Jongil; Warrick, Jay

2014-01-01

This article describes a passive micromixer that utilizes an air-liquid interface and surface tension effects to enhance fluid mixing via convection and Marangoni effects. Performance of the microfluidic component is tested within a passive-pumping-based device that consists of three microchannels connected in succession using passive micro-mixers. Mixing was quantified at 5 key points along the length of the device using microscope images of patterned streams of Alexa 488 fluorescent-dyed water and pure DI water flowing through the device. The passive micro-mixer mixed fluid 15–20 times more effectively than diffusion between laminar flow streams alone and is a novel micro-mixer embodiment that provides an additional strategy for removing external components from microscale devices for simpler, autonomous operation. PMID:25104979

Review of Polyimides Used in the Manufacturing of Micro Systems

NASA Technical Reports Server (NTRS)

Wilson, William C.; Atkinson, Gary M.

2007-01-01

Since their invention, polyimides have found numerous uses in MicroElectroMechanical Systems (MEMS) technology. Polyimides can act as photoresist, sacrificial layers, structural layers, and even as a replacement for silicon as the substrate during MEMS fabrication. They enable fabrication of both low and high aspect ratio devices. Polyimides have been used to fabricate expendable molds and reusable flexible molds. Development of a variety of devices that employ polyimides for sensor applications has occurred. Micro-robotic actuator applications include hinges, thermal actuators and residual stress actuators. Currently, polyimides are being used to create new sensors and devices for aerospace applications. This paper presents a review of some of the many uses of polyimides in the development of MEMS devices, including a new polyimide based MEMS fabrication process.

The effect of micro-ECoG substrate footprint on the meningeal tissue response

NASA Astrophysics Data System (ADS)

Schendel, Amelia A.; Nonte, Michael W.; Vokoun, Corinne; Richner, Thomas J.; Brodnick, Sarah K.; Atry, Farid; Frye, Seth; Bostrom, Paige; Pashaie, Ramin; Thongpang, Sanitta; Eliceiri, Kevin W.; Williams, Justin C.

2014-08-01

Objective. There is great interest in designing implantable neural electrode arrays that maximize function while minimizing tissue effects and damage. Although it has been shown that substrate geometry plays a key role in the tissue response to intracortically implanted, penetrating neural interfaces, there has been minimal investigation into the effect of substrate footprint on the tissue response to surface electrode arrays. This study investigates the effect of micro-electrocorticography (micro-ECoG) device geometry on the longitudinal tissue response. Approach. The meningeal tissue response to two micro-ECoG devices with differing geometries was evaluated. The first device had each electrode site and trace individually insulated, with open regions in between, while the second device had a solid substrate, in which all 16 electrode sites were embedded in a continuous insulating sheet. These devices were implanted bilaterally in rats, beneath cranial windows, through which the meningeal tissue response was monitored for one month after implantation. Electrode site impedance spectra were also monitored during the implantation period. Main results. It was observed that collagenous scar tissue formed around both types of devices. However, the distribution of the tissue growth was different between the two array designs. The mesh devices experienced thick tissue growth between the device and the cranial window, and minimal tissue growth between the device and the brain, while the solid device showed the opposite effect, with thick tissue forming between the brain and the electrode sites. Significance. These data suggest that an open architecture device would be more ideal for neural recording applications, in which a low impedance path from the brain to the electrode sites is critical for maximum recording quality.

Automated Age-related Macular Degeneration screening system using fundus images.

PubMed

Kunumpol, P; Umpaipant, W; Kanchanaranya, N; Charoenpong, T; Vongkittirux, S; Kupakanjana, T; Tantibundhit, C

2017-07-01

This work proposed an automated screening system for Age-related Macular Degeneration (AMD), and distinguishing between wet or dry types of AMD using fundus images to assist ophthalmologists in eye disease screening and management. The algorithm employs contrast-limited adaptive histogram equalization (CLAHE) in image enhancement. Subsequently, discrete wavelet transform (DWT) and locality sensitivity discrimination analysis (LSDA) were used to extract features for a neural network model to classify the results. The results showed that the proposed algorithm was able to distinguish between normal eyes, dry AMD, or wet AMD with 98.63% sensitivity, 99.15% specificity, and 98.94% accuracy, suggesting promising potential as a medical support system for faster eye disease screening at lower costs.

An Empirical Study on Operator Interface Design for Handheld Devices to Control Micro Aerial Vehicles

DTIC Science & Technology

2010-10-01

An Empirical Study on Operator Interface Design for Handheld Devices to Control Micro Aerial Vehicles Ming Hou...Report DRDC Toronto TR 2010-075 October 2010 An Empirical Study on Operator Interface Design for Handheld Devices to...drives the need for a small and light controller which will not hinder a soldier carrying it. This requirement brings an issue of designing an

Observing the Sun with micro-interferometric devices: a didactic experiment

NASA Astrophysics Data System (ADS)

Defrère, D.; Absil, O.; Hanot, C.; Riaud, P.; Magette, A.; Marion, L.; Wertz, O.; Finet, F.; Steenackers, M.; Habraken, S.; Surdej, A.; Surdej, J.

2014-04-01

Measuring the angular diameter of celestial bodies has long been the main purpose of stellar interferometry and was its historical motivation. Nowadays, stellar interferometry is widely used for various other scientific purposes that require very high angular resolution measurements. In terms of angular spatial scales probed, observing distant stars located 10 to 100~pc away with a large hectometric interferometer is equivalent to observing our Sun with a micrometric baseline. Based on this idea, we have manufactured a set of micro-interferometric devices and tested them on the sky. The micro-interferometers consist of a chrome layer deposited on a glass plate that has been drilled by laser lithography to produce micron-sized holes with configurations corresponding to proposed interferometer projects such as CARLINA, ELSA, KEOPS, and OVLA. In this paper, we describe these interferometric devices and present interferometric observations of the Sun made in the framework of Astrophysics lectures being taught at the Liège University. By means of a simple photographic camera placed behind a micro-interferometric device, we observed the Sun and derived its angular size. This experiment provides a very didactic way to easily obtain fringe patterns similar to those that will be obtained with future large imaging arrays. A program written in C also allows to reproduce the various point spread functions and fringe patterns observed with the micro-interferometric devices for different types of sources, including the Sun.

Micromirror array nanostructures for anticounterfeiting applications

NASA Astrophysics Data System (ADS)

Lee, Robert A.

2004-06-01

The optical characteristics of pixellated passive micro mirror arrays are derived and applied in the context of their use as reflective optically variable device (OVD) nanostructures for the protection of documents from counterfeiting. The traditional design variables of foil based diffractive OVDs are shown to be able to be mapped to a corresponding set of design parameters for reflective optical micro mirror array (OMMA) devices. The greatly increased depth characteristics of micro mirror array OVDs provides an opportunity for directly printing the OVD microstructure onto the security document in-line with the normal printing process. The micro mirror array OVD architecture therefore eliminates the need for hot stamping foil as the carrier of the OVD information, thereby reducing costs. The origination of micro mirror array devices via a palette based data format and a combination electron beam lithography and photolithography techniques is discussed via an artwork example and experimental tests. Finally the application of the technology to the design of a generic class of devices which have the interesting property of allowing for both application and customer specific OVD image encoding and data encoding at the end user stage of production is described. Because of the end user nature of the image and data encoding process these devices are particularly well suited to ID document applications and for this reason we refer this new OVD concept as biometric OVD technology.

Optimal micro-mirror tilt angle and sync mark design for digital micro-mirror device based collinear holographic data storage system.

PubMed

Liu, Jinpeng; Horimai, Hideyoshi; Lin, Xiao; Liu, Jinyan; Huang, Yong; Tan, Xiaodi

2017-06-01

The collinear holographic data storage system (CHDSS) is a very promising storage system due to its large storage capacities and high transfer rates in the era of big data. The digital micro-mirror device (DMD) as a spatial light modulator is the key device of the CHDSS due to its high speed, high precision, and broadband working range. To improve the system stability and performance, an optimal micro-mirror tilt angle was theoretically calculated and experimentally confirmed by analyzing the relationship between the tilt angle of the micro-mirror on the DMD and the power profiles of diffraction patterns of the DMD at the Fourier plane. In addition, we proposed a novel chess board sync mark design in the data page to reduce the system bit error rate in circumstances of reduced aperture required to decrease noise and median exposure amount. It will provide practical guidance for future DMD based CHDSS development.

Micro-Organ Devices

NASA Technical Reports Server (NTRS)

Gonda, Steven R.; Leslie, Julia; Chang, Robert C.; Starly, Binil; Sun, Wei; Culbertson, Christopher; Holtorf, Heidi

2009-01-01

Micro-organ devices (MODs) are being developed to satisfy an emerging need for small, lightweight, reproducible, biological-experimentati on apparatuses that are amenable to automated operation and that imp ose minimal demands for resources (principally, power and fluids). I n simplest terms, a MOD is a microfluidic device containing a variety of microstructures and assemblies of cells, all designed to mimic a complex in vivo microenvironment by replicating one or more in vivo micro-organ structures, the architectures and composition of the extr acellular matrices in the organs of interest, and the in vivo fluid flows. In addition to microscopic flow channels, a MOD contains one or more micro-organ wells containing cells residing in microscopic e xtracellular matrices and/or scaffolds, the shapes and compositions o f which enable replication of the corresponding in vivo cell assembl ies and flows.

The effect of coolants on the performance of magnetic micro-refrigerators.

PubMed

Silva, D J; Bordalo, B D; Pereira, A M; Ventura, J; Oliveira, J C R E; Araújo, J P

2014-06-01

Magnetic refrigeration is an alternative cooling technique with envisaged technological applications on micro- and opto-electronic devices. Here, we present a magnetic micro-refrigerator cooling device with embedded micro-channels and based on the magnetocaloric effect. We studied the influence of the coolant fluid in the refrigeration process by numerically simulating the heat transfer processes using the finite element method. This allowed us to calculate the cooling power of the device. Our results show that gallium is the most efficient coolant fluid and, when used with Gd5Si2Ge2, a maximum power of 11.2 W/mm3 at a working frequency of -5 kHz can be reached. However, for operation frequencies around 50 Hz, water is the most efficient fluid with a cooling power of 0.137 W/mm3.

Role of the vitreous in age-related macular degeneration.

PubMed

Ondeş, F; Yilmaz, G; Acar, M A; Unlü, N; Kocaoğlan, H; Arsan, A K

2000-01-01

To investigate the relationship between posterior vitreous detachment (PVD) and age-related macular degeneration (AMD). The condition of the vitreous was examined by slit-lamp funduscopy and ultrasonography in 93 eyes of 50 patients with AMD (exudative or dry) and 100 eyes of 50 controls. There was complete PVD in 31 of the 93 eyes (33.3%) of 50 patients with AMD and the posterior vitreous was attached in 62 of these eyes (66.6%). In the control group, in 50 eyes (50%) of 50 subjects there was posterior vitreous detachment. The prevalence of PVD in eyes with macular degeneration was significantly lower (P < .05). There was no statistically significant difference between the exudative and the nonexudative groups in respect to PVD. PVD may have a protective role against the development of AMD. Chronic vitreomacular traction and/or continuous exposure to free radicals and cytokines may possibly be one of the causes of AMD in eyes with attached vitreous.

Genetic studies of age-related macular degeneration: lessons, challenges, and opportunities for disease management.

PubMed

Priya, Rinki Ratna; Chew, Emily Y; Swaroop, Anand

2012-12-01

Age-related macular degeneration (AMD) is a common cause of visual impairment in individuals >55 years of age worldwide. The varying clinical phenotypes of AMD result from contributions of genetic, epigenetic, and nongenetic (environmental) factors. Genetic studies of AMD have come of age as a direct result of tremendous gains from the human genome project, genome-wide association studies, and identification of numerous susceptibility loci. These findings have implicated immune response, high-density lipoprotein cholesterol metabolism, extracellular matrix, and angiogenesis signaling pathways in disease pathophysiology. Herein, we address how the wealth of genetic findings in AMD is expected to impact the practice of medicine, providing opportunities for improved risk assessment, molecular diagnosis, preventive, and therapeutic intervention. We propose that the potential of using genetic variants for monitoring treatment response (pharmacogenetics) may usher in a new era of personalized medicine in the clinical management of AMD. Proprietary or commercial disclosures may be found after the references. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Application of acid mine drainage for coagulation/flocculation of microalgal biomass.

PubMed

Salama, El-Sayed; Kim, Jung Rae; Ji, Min-Kyu; Cho, Dong-Wan; Abou-Shanab, Reda A I; Kabra, Akhil N; Jeon, Byong-Hun

2015-06-01

A novel application of acid mine drainage (AMD) for biomass recovery of two morphologically different microalgae species with respect to AMD dosage, microalgal cell density and pH of medium was investigated. Optimal flocculation of Scenedesmus obliquus and Chlorella vulgaris occurred with 10% dosage of AMD at an initial pH 9 for both 0.5 and 1.0 g/L cell density. The flocculation efficiency was 89% for S. obliquus and 93% for C. vulgaris. Zeta potential (ZP) was increased from -10.66 to 1.77 and -13.19 to 1.33 for S. obliquus and C. vulgaris, respectively. Scanning electron microscope with energy-dispersive X-ray of the microalgae floc confirmed the sweeping floc formation mechanism upon the addition of AMD. Application of AMD for the recovery of microalgae biomass is a cost-effective method, which might further allow reuse of flocculated medium for algal cultivation, thereby contributing to the economic production of biofuel from microalgal biomass. Copyright © 2015 Elsevier Ltd. All rights reserved.

Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

PubMed Central

Yang, Shiqi; Zhao, Jingke; Sun, Xiaodong

2016-01-01

As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance. PMID:27330279

Efficacy of vitrectomy and epiretinal membrane peeling in eyes with dry age-related macular degeneration.

PubMed

Mason, John O; Patel, Shyam A

2015-01-01

To study the efficacy of epiretinal membrane (ERM) peeling in eyes with dry age-related macular degeneration (AMD). We retrospectively analyzed patient charts on 17 eyes (16 patients) that underwent ERM peeling with a concurrent diagnosis of dry AMD. Eyes with concurrent dry AMD and with a good preoperative best-corrected visual acuity (BCVA) (better than or equal to 20/50) had a statistically significant mean BCVA improvement at 6 months after ERM peeling. There was a statistical increase in mean BCVA from 20/95 to 20/56 in dry AMD eyes, and no eyes showed worsening in BCVA at 6 months or at most recent follow-up. Five/seventeen (29.4%) eyes had cataract formation or progression. There were no other complications, reoperations, or reoccurrences. ERM peeling in eyes with dry AMD may show significant improvement, especially in eyes with good preoperative BCVA. The procedure is relatively safe with low complications and reoccurrences.

Unrealistic representations of "the self": A cognitive neuroscience assessment of anosognosia for memory deficit.

PubMed

Berlingeri, Manuela; Ravasio, Alessandra; Cranna, Silvia; Basilico, Stefania; Sberna, Maurizio; Bottini, Gabriella; Paulesu, Eraldo

2015-12-01

Three cognitive components may play a crucial role in both memory awareness and in anosognosia for memory deficit (AMD): (1) a personal data base (PDB), i.e., a memory store that contains "semantic" representations about the self, (2) monitoring processes (MPs) and (3) an explicit evaluation system (EES), or comparator, that assesses and binds the representations stored in the PDB with information obtained from the environment. We compared both the behavior and the functional connectivity (as assessed by resting-state fMRI) of AMD patients with aware patients and healthy controls. We found that AMD is associated with an impoverished PDB, while MPs are necessary to successfully update the PDB. AMD was associated with reduced functional connectivity within both the default-mode network and in a network that includes the left lateral temporal cortex, the hippocampus and the insula. The reduced connectivity between the hippocampus and the insular cortex was correlated with AMD severity. Copyright © 2015 Elsevier Inc. All rights reserved.

Measurements of the force fields within an acoustic standing wave using holographic optical tweezers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bassindale, P. G.; Drinkwater, B. W.; Phillips, D. B.

2014-04-21

Direct measurement of the forces experienced by micro-spheres in an acoustic standing wave device have been obtained using calibrated optical traps generated with holographic optical tweezers. A micro-sphere, which is optically trapped in three dimensions, can be moved through the acoustic device to measure forces acting upon it. When the micro-sphere is subjected to acoustic forces, it's equilibrium position is displaced to a position where the acoustic forces and optical forces are balanced. Once the optical trapping stiffness has been calibrated, observation of this displacement enables a direct measurement of the forces acting upon the micro-sphere. The measured forces aremore » separated into a spatially oscillating component, attributed to the acoustic radiation force, and a constant force, attributed to fluid streaming. As the drive conditions of the acoustic device were varied, oscillating forces (>2.5 pN{sub pp}) and streaming forces (<0.2 pN) were measured. A 5 μm silica micro-sphere was used to characterise a 6.8 MHz standing wave, λ = 220 μm, to a spatial resolution limited by the uncertainty in the positioning of the micro-sphere (here to within 2 nm) and with a force resolution on the order of 10 fN. The results have application in the design and testing of acoustic manipulation devices.« less

Declines in arrestin and rhodopsin in the macula with progression of age-related macular degeneration.

PubMed

Ethen, Cheryl M; Feng, Xiao; Olsen, Timothy W; Ferrington, Deborah A

2005-03-01

Biochemical analysis of age-related macular degeneration (AMD) at distinct stages of the disease will help further understanding of the molecular events associated with disease progression. This study was conducted to determine the ability of a new grading system for eye bank eyes, the Minnesota Grading System (MGS), to discern distinct stages of AMD so that retinal region-specific changes in rod photoreceptor protein expression from donors could be determined. Donor eyes were assigned to a specific level of AMD by using the MGS. Expression of the rod photoreceptor proteins rhodopsin and arrestin was evaluated by Western immunoblot analysis in the macular and peripheral regions of the neurosensory retina from donors at different stages of AMD. A significant linear decline in both arrestin and rhodopsin content correlated with progressive MGS levels in the macula. In contrast, the peripheral region showed no significant correlation between MGS level and the content of either protein. The statistically significant relationship between decreasing macular rod photoreceptor proteins and progressive MGS levels of AMD demonstrates the utility of the clinically based MGS to correspond with specific protein changes found at known, progressive stages of degeneration. Future biochemical analysis of clinically characterized donor eyes will further understanding of the pathobiochemistry of AMD.

Characterization of Fe(II) oxidizing bacterial activities and communities at two acidic Appalachian coalmine drainage-impacted sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Senko, John M.; Wanjugi, Pauline; Lucas, Melanie

2008-06-12

We characterized the microbiologically mediated oxidative precipitation of Fe(II) from coalminederived acidic mine drainage (AMD) along flow-paths at two sites in northern Pennsylvania. At the Gum Boot site, dissolved Fe(II) was efficiently removed from AMD whereas minimal Fe(II) removal occurred at the Fridays-2 site. Neither site received human intervention to treat the AMD. Culturable Fe(II) oxidizing bacteria were most abundant at sampling locations along the AMD flow path corresponding to greatest Fe(II) removal and where overlying water contained abundant dissolved O2. Rates of Fe(II) oxidation determined in laboratory-based sediment incubations were also greatest at these sampling locations. Ribosomal RNA intergenicmore » spacer analysis and sequencing of partial 16S rRNA genes recovered from sediment bacterial communities revealed similarities among populations at points receiving regular inputs of Fe(II)-rich AMD and provided evidence for the presence of bacterial lineages capable of Fe(II) oxidation. A notable difference between bacterial communities at the two sites was the abundance of Chloroflexi-affiliated 16S rRNA gene sequences in clone libraries derived from the Gum Boot sediments. Our results suggest that inexpensive and reliable AMD treatment strategies can be implemented by mimicking the conditions present at the Gum Boot field site.« less

ABSORPTION MEASURE DISTRIBUTION IN Mrk 509

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adhikari, T. P.; Różańska, A.; Sobolewska, M.

2015-12-20

In this paper we model the observed absorption measure distribution (AMD) in Mrk 509, which spans three orders of magnitude in ionization level with a single-zone absorber in pressure equilibrium. AMD is usually constructed from observations of narrow absorption lines in radio-quiet active galaxies with warm absorbers. We study the properties of the warm absorber in Mrk 509 using recently published broadband spectral energy distribution observed with different instruments. This spectrum is an input in radiative transfer computations with full photoionization treatment using the titan code. We show that the simplest way to fully reproduce the shape of AMD is tomore » assume that the warm absorber is a single zone under constant total pressure. With this assumption, we found theoretical AMD that matches the observed AMD determined on the basis of the 600 ks reflection grating spectrometer XMM-Newton spectrum of Mrk 509. The softness of the source spectrum and the important role of the free–free emission breaks the usual degeneracy in the ionization state calculations, and the explicit dependence of the depths of AMD dips on density open a new path to the density diagnostic for the warm absorber. In Mrk 509, the implied density is of the order of 10{sup 8} cm{sup −3}.« less

Ground-state properties of neutron-rich Mg isotopes

NASA Astrophysics Data System (ADS)

Watanabe, S.; Minomo, K.; Shimada, M.; Tagami, S.; Kimura, M.; Takechi, M.; Fukuda, M.; Nishimura, D.; Suzuki, T.; Matsumoto, T.; Shimizu, Y. R.; Yahiro, M.

2014-04-01

We analyze recently measured total reaction cross sections for 24-38Mg isotopes incident on 12C targets at 240 MeV/nucleon by using the folding model and antisymmetrized molecular dynamics (AMD). The folding model well reproduces the measured reaction cross sections, when the projectile densities are evaluated by the deformed Woods-Saxon (def-WS) model with AMD deformation. Matter radii of 24-38Mg are then deduced from the measured reaction cross sections by fine tuning the parameters of the def-WS model. The deduced matter radii are largely enhanced by nuclear deformation. Fully microscopic AMD calculations with no free parameter well reproduce the deduced matter radii for 24-36Mg, but still considerably underestimate them for 37,38Mg. The large matter radii suggest that 37,38Mg are candidates for deformed halo nucleus. AMD also reproduces other existing measured ground-state properties (spin parity, total binding energy, and one-neutron separation energy) of Mg isotopes. Neutron-number (N) dependence of deformation parameter is predicted by AMD. Large deformation is seen from 31Mg with N =19 to a drip-line nucleus 40Mg with N =28, indicating that both the N =20 and 28 magicities disappear. N dependence of neutron skin thickness is also predicted by AMD.

Nature and nurture- genes and environment- predict onset and progression of macular degeneration.

PubMed

Sobrin, Lucia; Seddon, Johanna M

2014-05-01

Age-related macular degeneration (AMD) is a common cause of irreversible visual loss and the disease burden is rising world-wide as the population ages. Both environmental and genetic factors contribute to the development of this disease. Among environmental factors, smoking, obesity and dietary factors including antioxidants and dietary fat intake influence onset and progression of AMD. There are also several lines of evidence that link cardiovascular, immune and inflammatory biomarkers to AMD. The genetic etiology of AMD has been and continues to be an intense and fruitful area of investigation. Genome-wide association studies have revealed numerous common variants associated with AMD and sequencing is increasing our knowledge of how rare genetic variants strongly impact disease. Evidence for interactions between environmental, therapeutic and genetic factors is emerging and elucidating the mechanisms of this interplay remains a major challenge in the field. Genotype-phenotype associations are evolving. The knowledge of non-genetic, modifiable risk factors along with information about heritability and genetic risk variants for this disease acquired over the past 25 years have greatly improved patient management and our ability to predict which patients will develop or progress to advanced forms of AMD. Personalized medicine and individualized prevention and treatment strategies may become a reality in the near future. Copyright © 2014. Published by Elsevier Ltd.

Generation of Transplantable Retinal Pigmented Epithelial (RPE) Cells for Treatment of Age-Related Macular Degeneration (AMD).

PubMed

Surendran, Harshini; Rathod, Reena J; Pal, Rajarshi

2018-06-13

Age-related macular degeneration (AMD) is the foremost cause of blindness in people over the age of 60 worldwide. Clinically, this disease starts with distortion in central vision eventually leading to legal blindness. Vision loss has a significant impact on quality of life and incurs a substantial cost to the economy. Furthermore, AMD is a complex and progressive neurodegenerative disorder that triggers visual impairment due to the loss of retinal pigmented epithelium (RPE) and the light-sensitive photoreceptors that they support, protect and provide nutrition. Currently, there is no curative treatment for the most common form of this disease, i.e., dry AMD. A novel approach to treat AMD involves the transplantation of RPE cells derived from human induced pluripotent stem cells (iPSCs) in the outer retina. These iPSC-derived RPE cells not only show characteristics similar to native RPE but also could replace as well as regenerate damaged pathologic RPE and produce supportive growth factors and cytokines. Several clinical trials are being conducted taking advantage of a variety of cell- and tissue engineering-based approaches. Here, we present a simple, cost effective, and scalable cell-culture model for generation of purified RPE thus providing the foundation for developing an allogeneic cell therapy for AMD.

Mechanism of Inflammation in Age-Related Macular Degeneration

PubMed Central

Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

2012-01-01

Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

Recent developments in age-related macular degeneration: a review

PubMed Central

Al-Zamil, Waseem M; Yassin, Sanaa A

2017-01-01

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

Physical activity and the 15-year incidence of age-related macular degeneration.

PubMed

Gopinath, Bamini; Liew, Gerald; Burlutsky, George; Mitchell, Paul

2014-11-11

There is uncertainty in the published literature as to whether physical activity should be advocated for age-related macular degeneration (AMD) prevention. We aimed to assess prospectively the association between physical activity and the 15-year incidence of AMD in older adults. We assessed AMD from retinal photographs. Participants provided details of walking exercise and the performance of moderate or vigorous activities, which were used to calculate metabolic equivalents (METs). After adjusting for age, adults aged ≥ 75 years in the highest tertile (the most physically active) compared to those in the lowest tertile (least physically active) were 79% less likely to have incident late AMD over the 15 years (odds ratio [OR], 0.21; 95% confidence intervals [CI], 0.05-0.95). However, after further adjusting for sex, body mass index, smoking, fish consumption, and white cell count, this association was no longer statistically significant (OR, 0.26; 95% CI, 0.06-1.28). Significant associations were not found in those aged <75 or with the 15-year cumulative incidence of early AMD. Physical activity did not influence the risk of AMD over 15 years in older adults, independent of diet, smoking, white cell count, and body mass index. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Device and nondestructive method to determine subsurface micro-structure in dense materials

DOEpatents

Sun, Jiangang [Westmont, IL

2006-05-09

A method and a device to detect subsurface three-dimensional micro-structure in a sample by illuminating the sample with light of a given polarization and detecting light emanating from the sample that has a different direction of polarization by means of a confocal optical system.

Micro-device for coupling, multiplexing and demultiplexing using elliptical-core two-mode fiber

NASA Technical Reports Server (NTRS)

Wang, A.; Murphy, K. A.; Wang, G. Z.; Vengsarkar, A. M.; Claus, R. O.

1990-01-01

We propose and demonstrate experimentally a fiber optic micro-device that is capable of tunably splitting, multiplexing, and demultiplexing optical signals using elliptical-core two-mode optical fiber. A crosstalk of 15 dB with an insertion loss of 1.2 dB was obtained.

Sequestration of phosphorus by acid mine drainage floc

USGS Publications Warehouse

Adler, P.R.; Sibrell, P.L.

2003-01-01

Solubilization and transport of phosphorus (P) to the water environment is a critical environmental issue. Flocs resulting from neutralizing acid mine drainage (AMD) were tested as a possible lowcost amendment to reduce the loss of soluble P from agricultural fields and animal wastewater. Flocs were prepared by neutralizing natural and synthetic solutions of AMD with limestone, lime, ammonium hydroxide, and sodium hydroxide. Phosphorus sequestration was tested in three distinct environments: water, soil, and manure storage basins. In water, flocs prepared from AMD adsorbed 10 to 20 g P kg-1 dry floc in equilibrium with 1 mg L-1 soluble P. Similar results were observed for both Fe-based and A1-based synthetic flocs. A local soil sample adsorbed about 0.1 g P kg-1, about two orders of magnitude less. The AMD-derived flocs were mixed with a highP soil at 5 to 80 g floc kg-1 soil, followed by water and acid (Mehlich1) extractions. All flocs performed similarly. About 70% of the waterextractable P was sequestered by the floc when applied at a rate of 20 g floc kg-1 soil, whereas plant-available P only decreased by about 30%. Under anaerobic conditions simulating manure storage basins, all AMD flocs reduced soluble P by greater than 95% at a rate of 0.2 g floc g-1 rainbow trout (Oncorhynchus mykiss) manure. These findings indicate that AMD flocs could be an effective agent for preventing soluble P losses from soil and manure to the water environment, while at the same time decreasing the costs associated with AMD treatment.

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

PubMed

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

2017-01-01

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

Are Lung Disease and Function Related to Age-related Macular Degeneration?

PubMed Central

Moorthy, Sonia; Cheung, Ning; Klein, Ronald; Shahar, E; Wong, Tien Y

2010-01-01

Purpose To describe the relationship of lung disease and function with early age-related macular degeneration (AMD) in a population-based study. Design A population-based, cross-sectional study of 12,596 middle-aged participants from the Atherosclerosis Risk in Communities Study. Methods Lung function was assessed by spirometry. Physician diagnosis of asthma and lung disease was ascertained from a standardized questionnaire. AMD signs were graded from fundus photographs according to the Wisconsin grading protocol. Results Of our study population, 587 (4.7%) had early AMD, 638 (5.1%) had asthma and 581 (4.6%) had lung disease. After adjusting for age, gender, smoking and hypertension, each litre increase in predicted forced expiratory volume in one second (FEV1) (odds ratio [OR]: 1.27; 95% confidence interval [CI]: 0.89, 1.80), forced vital capacity (FVC) (OR 1.18; 95% CI: 0.93, 1.51) and peak expiratory flow rate (OR 1.12; 95% CI: 0.95, 1.33) were not significantly associated with early AMD. FEV1/FVC ratio (second quartile OR 1.61; 95%CI 0.88–2.93, third quartile OR 1.65; CI 0.90–3.03, fourth quartile OR 1.28; 95%CI 0.68–2.40) was not significantly associated with early AMD. Similarly, asthma (OR 1.06; 95% CI: 0.86, 1.27) and other lung diseases (OR 1.08; 95% CI: 0.90, 1.29) were not associated with early AMD. Conclusion Our data do not support a cross-sectional association between lung disease and risk of early AMD. PMID:21168814

Hydrogeochemical features of surface water and groundwater contaminated with acid mine drainage (AMD) in coal mining areas: a case study in southern Brazil.

PubMed

Galhardi, Juliana Aparecida; Bonotto, Daniel Marcos

2016-09-01

Effects of acid mine drainage (AMD) were investigated in surface waters (Laranjinha River and Ribeirão das Pedras stream) and groundwaters from a coal mining area sampled in two different seasons at Figueira city, Paraná State, Brazil. The spatial data distribution indicated that the acid effluents favor the chemical elements leaching and transport from the tailings pile into the superficial water bodies or aquifers, modifying their quality. The acid groundwaters in both sampling periods (dry: pH 2.94-6.04; rainy: pH 3.25-6.63) were probably due to the AMD generation and infiltration, after the oxidation of sulfide minerals. Such acid effluents cause an increase of the solubilization rate of metals, mainly iron and aluminum, contributing to both groundwater and surface water contamination. Sulfate in high levels is a result of waters' pollution due to AMD. In some cases, high sulfate and low iron contents, associated with less acidic pH values, could indicate that AMD, previously generated, is nowadays being neutralized. The chemistry of the waters affected by AMD is controlled by the pH, sulfide minerals' oxidation, oxygen, iron content, and microbial activity. It is also influenced by seasonal variations that allow the occurrence of dissolution processes and the concentration of some chemical elements. Under the perspective of the waters' quality evaluation, the parameters such as conductivity, dissolved sodium, and sulfate concentrations acted as AMD indicators of groundwaters and surface waters affected by acid effluents.

[Influence of the lutein-rich products consumption on its supply in diet of individuals with age-related macular degeneration (AMD)].

PubMed

Włodarek, Dariusz; Głabska, Dominika

2011-01-01

The aim of the study was analysis of the influence of the lutein-rich products consumption on its supply in diet of individuals with age-related macular degeneration The object of conducted analysis were 127 nutrition questionnaires from 64 individuals with AMD (44 female, 20 male) and 63 without AMD--control group (49 female, 14 male). The age of participants was 50-88. The nutrition questionnaire concerned: AMD and its course, consumption of lutein-rich products and lutein supplementation. Lutein supply was assessed on the base of most often consumed products and lutein content in typical servings as well as on the base of applied supplementation. Patients with AMD, in comparison with control group, were significantly more often choosing green bean, parsley, dill (Anethum graveolens) and young beetroot leaves, as well as were consuming more diversified lutein-rich products. Lutein supply from diet was significanly increased in case of spinach consumption (very high in lutein) and broccoli consumption (high in lutein and chosen relatively often). Other products did not cause increase of lutein supply from diet, even if they evoked increase of lutein content in the typical serving or of quantity of servings. Patients with AMD, in comparison with healthy individuals, more often consume lutein-rich products, but lutein supply from diet in both groups do not differ. Significant increase of lutein supply may be achieved only by consumption of products characterized by the highest content of it. Patients with AMD, in comparison with healthy individuals, more often apply lutein supplementation, that influences lutein daily supply.

Combining macula clinical signs and patient characteristics for age-related macular degeneration diagnosis: a machine learning approach.

PubMed

Fraccaro, Paolo; Nicolo, Massimo; Bonetto, Monica; Giacomini, Mauro; Weller, Peter; Traverso, Carlo Enrico; Prosperi, Mattia; OSullivan, Dympna

2015-01-27

To investigate machine learning methods, ranging from simpler interpretable techniques to complex (non-linear) "black-box" approaches, for automated diagnosis of Age-related Macular Degeneration (AMD). Data from healthy subjects and patients diagnosed with AMD or other retinal diseases were collected during routine visits via an Electronic Health Record (EHR) system. Patients' attributes included demographics and, for each eye, presence/absence of major AMD-related clinical signs (soft drusen, retinal pigment epitelium, defects/pigment mottling, depigmentation area, subretinal haemorrhage, subretinal fluid, macula thickness, macular scar, subretinal fibrosis). Interpretable techniques known as white box methods including logistic regression and decision trees as well as less interpreitable techniques known as black box methods, such as support vector machines (SVM), random forests and AdaBoost, were used to develop models (trained and validated on unseen data) to diagnose AMD. The gold standard was confirmed diagnosis of AMD by physicians. Sensitivity, specificity and area under the receiver operating characteristic (AUC) were used to assess performance. Study population included 487 patients (912 eyes). In terms of AUC, random forests, logistic regression and adaboost showed a mean performance of (0.92), followed by SVM and decision trees (0.90). All machine learning models identified soft drusen and age as the most discriminating variables in clinicians' decision pathways to diagnose AMD. Both black-box and white box methods performed well in identifying diagnoses of AMD and their decision pathways. Machine learning models developed through the proposed approach, relying on clinical signs identified by retinal specialists, could be embedded into EHR to provide physicians with real time (interpretable) support.

Detection of Early Loss of Color Vision in Age-Related Macular Degeneration - With Emphasis on Drusen and Reticular Pseudodrusen.

PubMed

Vemala, Roopa; Sivaprasad, Sobha; Barbur, John L

2017-05-01

To evaluate chromatic sensitivity in patients with age-related macular degeneration (AMD) characterized by drusen and reticular pseudodrusen. To investigate whether the severity of color vision loss can distinguish between various stages of AMD and hence be used as an index of progression toward advanced AMD. Chromatic sensitivity was measured by using the Color Assessment and Diagnosis (CAD) test in asymptomatic individuals with early and intermediate AMD and compared to normative data. All study participants had logMAR visual acuity of 0.3 or better. The CAD thresholds measured in eyes with and without reticular pseudodrusen were also compared and related to central macular thickness (CMT). Student's t-test P values < 0.05 were considered significant. All early- and intermediate-AMD eyes (n = 90) had chromatic sensitivity loss in either RG (red/green) or YB (yellow/blue), or both (P < 0.0001) as compared to age-matched normal subjects. The eyes exhibited a range of CAD thresholds affecting both color mechanisms, but YB color thresholds were in general higher than RG thresholds (P < 0.001). Intermediate-AMD patients exhibited large intersubject variability. In general, eyes with reticular pseudodrusen and eyes with CMT < 200 μm had significantly higher CAD thresholds. The anatomic integrity of cone photoreceptors remains relatively unaffected in early and intermediate stages of AMD. The processing of cone signals in the retina can, however, be heavily disrupted with subsequent loss of both YB and RG chromatic sensitivity. The greatest losses were observed in eyes with reticular pseudodrusen.

Visual Function Metrics in Early and Intermediate Dry Age-related Macular Degeneration for Use as Clinical Trial Endpoints.

PubMed

Cocce, Kimberly J; Stinnett, Sandra S; Luhmann, Ulrich F O; Vajzovic, Lejla; Horne, Anupama; Schuman, Stefanie G; Toth, Cynthia A; Cousins, Scott W; Lad, Eleonora M

2018-05-01

To evaluate and quantify visual function metrics to be used as endpoints of age-related macular degeneration (AMD) stages and visual acuity (VA) loss in patients with early and intermediate AMD. Cross-sectional analysis of baseline data from a prospective study. One hundred and one patients were enrolled at Duke Eye Center: 80 patients with early AMD (Age-Related Eye Disease Study [AREDS] stage 2 [n = 33] and intermediate stage 3 [n = 47]) and 21 age-matched, normal controls. A dilated retinal examination, macular pigment optical density measurements, and several functional assessments (best-corrected visual acuity, macular integrity assessment mesopic microperimety, dark adaptometry, low-luminance visual acuity [LLVA] [standard using a log 2.0 neutral density filter and computerized method], and cone contrast test [CCT]) were performed. Low-luminance deficit (LLD) was defined as the difference in numbers of letters read at standard vs low luminance. Group comparisons were performed to evaluate differences between the control and the early and intermediate AMD groups using 2-sided significance tests. Functional measures that significantly distinguished between normal and intermediate AMD were standard and computerized (0.5 cd/m 2 ) LLVA, percent reduced threshold and average threshold on microperimetry, CCTs, and rod intercept on dark adaptation (P < .05). The intermediate group demonstrated deficits in microperimetry reduced threshhold, computerized LLD2, and dark adaptation (P < .05) relative to early AMD. Our study suggests that LLVA, microperimetry, CCT, and dark adaptation may serve as functional measures differentiating early-to-intermediate stages of dry AMD. Copyright © 2018 Elsevier Inc. All rights reserved.

α-Lipoic Acid Treatment Improves Vision-Related Quality of Life in Patients with Dry Age-Related Macular Degeneration.

PubMed

Tao, Yuan; Jiang, Pengfei; Wei, Yuhua; Wang, Ping; Sun, Xiaoling; Wang, Hong

2016-11-01

Dry form of age-related macular degeneration (AMD) constitutes 90% of AMD cases, and it is characterized by the formation of drusen under the retina and the slow breakdown of the light-sensing cells in the macula, which causes a gradual loss of central vision. Since oxidative stress is involved in the pathogenesis of dry AMD, α-lipoic acid (LA) with antioxidant properties was selected, and its effect on anti-oxidative markers and visual quality in patients with dry AMD was assessed. A total of 100 dry AMD patients (60-83 years old) were randomly assigned to LA treatment group (n = 50) and placebo control group (n = 50). We measured the serum superoxide dismutase (SOD) activity, an important marker of antioxidant defense, best-corrected visual acuity (BCVA), contrast sensitivity, and Chinese-Version Low Vision Quality of Life (CLVQOL) before and after LA or placebo intervention. Pearson correlation coefficients were calculated to explore the relationship between contrast sensitivity values and CLVQOL scores. There was a statistically significant increase in serum SOD activity after LA intervention. The CLVQOL score was improved significantly after LA treatment. The contrast sensitivity measured at middle and low spatial frequency was significantly higher after LA treatment. CLVQOL scores were positively correlated with contrast sensitivity at low spatial frequency (3 cyc/degree) in LA-treated group. These results indicate that LA treatment improves vision-related quality of life in patients with dry AMD probably by increasing antioxidant activity. Thus, LA can be regarded as a promising agent for the treatment of AMD.

ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES.

PubMed

Neely, David; Zarubina, Anna V; Clark, Mark E; Huisingh, Carrie E; Jackson, Gregory R; Zhang, Yuhua; McGwin, Gerald; Curcio, Christine A; Owsley, Cynthia

2017-07-01

To examine the association between subretinal drusenoid deposits (SDDs) identified by multimodal retinal imaging and visual function in older eyes with normal macular health or in the earliest phases of age-related macular degeneration (AMD). Age-related macular degeneration status for each eye was defined according to the Age-Related Eye Disease Study (AREDS) 9-step classification system (normal = Step 1, early AMD = Steps 2-4) based on color fundus photographs. Visual functions measured were best-corrected photopic visual acuity, contrast and light sensitivity, mesopic visual acuity, low-luminance deficit, and rod-mediated dark adaptation. Subretinal drusenoid deposits were identified through multimodal imaging (color fundus photographs, infrared reflectance and fundus autofluorescence images, and spectral domain optical coherence tomography). The sample included 1,202 eyes (958 eyes with normal health and 244 eyes with early AMD). In normal eyes, SDDs were not associated with any visual function evaluated. In eyes with early AMD, dark adaptation was markedly delayed in eyes with SDDs versus no SDD (a 4-minute delay on average), P = 0.0213. However, this association diminished after age adjustment, P = 0.2645. Other visual functions in early AMD eyes were not associated with SDDs. In a study specifically focused on eyes in normal macular health and in the earliest phases of AMD, early AMD eyes with SDDs have slower dark adaptation, largely attributable to the older ages of eyes with SDD; they did not exhibit deficits in other visual functions. Subretinal drusenoid deposits in older eyes in normal macular health are not associated with any visual functions evaluated.

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

PubMed

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.

Investigating the CFH Gene Polymorphisms as a Risk Factor for Age-related Macular Degeneration in an Iranian Population.

PubMed

Babanejad, Mojgan; Moein, Hamidreza; Akbari, Mohammad R; Badiei, Azadeh; Yaseri, Mehdi; Soheilian, Masoud; Najmabadi, Hossein

2016-06-01

Age-related macular degeneration (AMD) is a complex disorder which results in irreversible vision loss and progressive impairment of central vision. Disease susceptibility is influenced by multiple genetic and environmental factors. Single nucleotide polymorphisms (SNP) in the complement factor H gene are the most important genetic risk factors. We conducted a case-control study to investigate the association four SNPs (dbSNP ID: rs800292, rs1061170, rs2274700 and rs3753395) of CFH gene with AMD in the Iranian population. We recruited 100 AMD patients and 100 age- and sex-matched normal controls. Direct sequencing for three SNPs (rs800292, rs2274700 and rs3753395) and restriction fragment length polymorphism utilized for rs1061170. Allele and genotype frequencies of SNPs were calculated and tested for departure from Hardy-Weinberg equilibrium using the Chi-square test. An allelic and genotypic association was compared by logistic regression analysis using the SNPassoc. According to our results, the frequencies of risk allele for all SNPs (G, G, A, and C alleles of rs800292, rs2274700, rs3753395 and rs1061170, respectively) were significantly higher in AMD patients (p value < 0.001). AMD individuals who had at least one copy of the C allele of rs1061170 had an increased risk of disease compared with cases with the T allele. Other studied polymorphisms showed the same association. Our results suggest the contribution of all four predicted CFH polymorphisms in AMD susceptibility among the Iranian population. This association with CFH may lead to early detection and new strategies for prevention and treatment of AMD.

Vacuolar transport of the glutathione conjugate of trans-cinnamic acid.

PubMed

Walczak, H A; Dean, J V

2000-02-01

Red beet (Beta vulgaris L.) tonoplast membrane vesicles and [14C]trans-cinnamic acid-glutatione were used to study the vacuolar transport of phynylpropanoid-glutathione conjugates which are formed in peroxidase-mediated reactions. It was determined that the uptake of [14C]trans-cinnamic acid-glutathione into the tonoplast membrane vesicles was MgATP dependent and was 10-fold faster than the uptake of non-conjugated [14C]trans-cinnamic acid. Uptake of the conjugate in the presence of MgATP was not dependent on a trans-tonoblast H+-electrochemical gradient, because uptake was not affected by the addition of NH4Cl (1 mM; 0% inhibition) and was only slightly affected by gramicidin-D (5 microM; 14% inhibition). Uptake of the conjugate was inhibited 92% by the addition of vanadate (1 mM) and 71% by the addition of the model substrate S-(2,4-dinitrophenyl) glutathione (500 microM). Uptake did not occur when a nonhydrolyzable analog of ATP was used in place of MgATP. The calculated Km and Vmax values for uptake were 142 microM amd 5.95 nmol mg(-1) min(-1), respectively. Based on these results, phenylpropanoid-glutation conjugates formed in peroxidase-mediated reactions appear to be transported into the vacuole by the glutathione S-conjugate pump(s) located in the tonoplast membrane.

Removal of sulphates acidity and iron from acid mine drainage in a bench scale biochemical treatment system.

PubMed

Prasad, D; Henry, J G

2009-02-01

The focus of this study was to develop a simple biochemical system to treat acid mine drainage for its safe disposal. Recovery and reuse of the metals removed were not considered. A three-step process for the treatment of acid mine drainage (AMD), proposed earlier, separates sulphate reducing activity from metal precipitation units and from a pH control system. Following our earlier work on the first step (biological reactor), this paper examines the second step (i.e. chemical reactor). The objectives of this study were: (1) to determine the increase in pH and the reduction of iron in the chemical reactor for different proportions of simulated AMD, and (2) to assess the capability of the chemical reactor. A series of experiments was conducted to study the effects of addition of alkaline sulphidogenic liquor (ASL) derived from a batch sulphidogenic biological reactor (operating with activated sludge and a COD/SO4 ratio of 1.6) on the simulated AMD characteristics. At 60-minute contact time, addition of 30% ASL (pH of 7.60-7.76) to the chemical reactor with 70% AMD (pH of 1.65-2.02), increased the pH of the AMD to 6.57 and alkalinity from 0 to 485 mg l(-1) as CaCO3, respectively and precipitated about 97% of the iron present in the simulated AMD. Others have demonstrated that metals in mine drainage can be precipitated by bacterial sulphate reduction. In this study, iron, a common and major component of mine drainage was used as a surrogate for metals in general. The results indicate the feasibility of treating AMD by an engineered sulphidogenic anaerobic reactor followed by a chemical reactor and that our three-step biochemical process has important advantages over other conventional AMD treatment systems.

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

PubMed

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.

Vitamin D Status and Early Age-Related Macular Degeneration in Postmenopausal Women

PubMed Central

Millen, Amy E.; Voland, Rick; Sondel, Sherie A.; Parekh, Niyati; Horst, Ronald L.; Wallace, Robert B.; Hageman, Gregory S.; Chappell, Rick; Blodi, Barbara A.; Klein, Michael L.; Gehrs, Karen M.; Sarto, Gloria E.; Mares, Julie A.

2010-01-01

Objective The relationship between serum 25-hydroxyvitamin D (25(OH)D) concentrations (nmol/L) and the prevalence of early age-related macular degeneration (AMD) was investigated among participants of the Carotenoids in Age-Related Eye Disease Study. Methods Stereoscopic fundus photographs, taken from 2001–2004, assessed AMD status. Baseline (1994–1998) serum samples were available for 25(OH)D assays in 1,313 women with complete ocular and risk factor data. Odds ratios (ORs) and 95% confidence intervals (CIs) for early AMD (n=241), among 1,287 without advanced disease, were estimated with logistic regression and adjusted for age, smoking, iris pigmentation, family history of AMD, cardiovascular disease, diabetes, and hormone therapy use. Results In multivariate models, no significant relationship was observed between early AMD and 25(OH)D (OR for quintile 5 vs. 1=0.79, 95% CI=0.50–1.24; p for trend=0.47). A significant age interaction (p=0.0025) suggested selective mortality bias in women ≥75 years: serum 25(OH)D was associated with decreased odds of early AMD in women <75 years (n=968) and increased odds in women ≥75 years (n=319) (OR for quintile 5 vs. 1=0.52, 95% CI=0.29–0.91; p for trend=0.02 and 1.76, 95% CI=0.77–4.13; p for trend=0.05, respectively). Further adjustment for body mass index and recreational physical activity, predictors of 25(OH)D, attenuated the observed association in women <75 years. Additionally, among women <75 years, intake of vitamin D from foods and supplements was related to decreased odds of early AMD in multivariate models; no relationship was observed with self-reported time spent in direct sunlight. Conclusions High serum 25(OH)D concentrations may protect against early AMD in women <75 years. PMID:21482873

Impairments in Dark Adaptation Are Associated with Age-Related Macular Degeneration Severity and Reticular Pseudodrusen.

PubMed

Flamendorf, Jason; Agrón, Elvira; Wong, Wai T; Thompson, Darby; Wiley, Henry E; Doss, E Lauren; Al-Holou, Shaza; Ferris, Frederick L; Chew, Emily Y; Cukras, Catherine

2015-10-01

We investigate whether ocular and person-based characteristics were associated with dark adaptation (DA). Cross-sectional, single-center, observational study. One hundred sixteen participants older than 50 years of age with a range of age-related macular degeneration (AMD) severity. Participants underwent best-corrected visual acuity (BCVA) testing, ophthalmoscopic examination, and multimodal imaging. Presence of reticular pseudodrusen (RPD) was assessed by masked grading of fundus images and was confirmed with optical coherence tomography. Eyes also were graded for AMD features (drusen, pigmentary changes, late AMD) to generate person-based AMD severity groups. One eye was designated the study eye for DA testing. Nonparametric statistical testing was performed on all comparisons. The primary outcome of this study was the rod intercept time (RIT), which is defined as the time for a participant's visual sensitivity to recover to a stimulus intensity of 5×10(-3) cd/m(2) (a decrease of 3 log units), or until a maximum test duration of 40 minutes was reached. A total of 116 study eyes from 116 participants (mean age, 75.4±9.4 years; 58% female) were analyzed. Increased RIT was associated significantly with increasing AMD severity, increasing age (r = 0.34; P = 0.0002), decreasing BCVA (r = -0.54; P < 0.0001), pseudophakia (P = 0.03), and decreasing subfoveal choroidal thickness (r = -0.27; P = 0.003). Study eyes with RPD (15/116 [13%]) had a significantly greater mean RIT compared with eyes without RPD in any AMD severity group (P < 0.02 for all comparisons), with 80% reaching the DA test ceiling. Impairments in DA increased with age, worse visual acuity, presence of RPD, AMD severity, and decreased subfoveal choroidal thickness. Analysis of covariance found the multivariate model that best fit the data included age, AMD group, and presence of RPD (R(2) = 0.56), with the presence of RPD conferring the largest parameter estimate. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Visual function assessment in simulated real-life situations in patients with age-related macular degeneration compared to normal subjects.

PubMed

Barteselli, G; Gomez, M L; Doede, A L; Chhablani, J; Gutstein, W; Bartsch, D-U; Dustin, L; Azen, S P; Freeman, W R

2014-10-01

To evaluate visual function variations in eyes with age-related macular degeneration (AMD) compared to normal eyes under different light/contrast conditions using a time-dependent visual acuity testing instrument, the Central Vision Analyzer (CVA). Overall, 37 AMD eyes and 35 normal eyes were consecutively tested with the CVA after assessing best-corrected visual acuity (BCVA) using ETDRS charts. The CVA established visual thresholds for three mesopic environments (M1 (high contrast), M2 (medium contrast), and M3 (low contrast)) and three backlight-glare environments (G1 (high contrast, equivalent to ETDRS), G2 (medium contrast), and G3 (low contrast)) under timed conditions. Vision drop across environments was calculated, and repeatability of visual scores was determined. BCVA significantly reduced with decreasing contrast in all eyes. M1 scores for BCVA were greater than M2 and M3 (P<0.001); G1 scores were greater than G2 and G3 (P<0.01). BCVA dropped more in AMD eyes than in normal eyes between M1 and M2 (P=0.002) and between M1 and M3 (P=0.003). In AMD eyes, BCVA was better using ETDRS charts compared to G1 (P<0.001). The drop in visual function between ETDRS and G1 was greater in AMD eyes compared to normal eyes (P=0.004). Standard deviations of test-retest ranged from 0.100 to 0.139 logMAR. The CVA allowed analysis of the visual complaints that AMD patients experience with different lighting/contrast time-dependent conditions. BCVA changed significantly under different lighting/contrast conditions in all eyes, however, AMD eyes were more affected by contrast reduction than normal eyes. In AMD eyes, timed conditions using the CVA led to worse BCVA compared to non-timed ETDRS charts.

Age-related macular degeneration and modification of systemic complement factor H production through liver transplantation.

PubMed

Khandhadia, Samir; Hakobyan, Svetlana; Heng, Ling Z; Gibson, Jane; Adams, David H; Alexander, Graeme J; Gibson, Jonathan M; Martin, Keith R; Menon, Geeta; Nash, Kathryn; Sivaprasad, Sobha; Ennis, Sarah; Cree, Angela J; Morgan, B Paul; Lotery, Andrew J

2013-08-01

To investigate whether modification of liver complement factor H (CFH) production, by alteration of liver CFH Y402H genotype through liver transplantation (LT), influences the development of age-related macular degeneration (AMD). Multicenter, cross-sectional study. We recruited 223 Western European patients ≥ 55 years old who had undergone LT ≥ 5 years previously. We determined AMD status using a standard grading system. Recipient CFH Y402H genotype was obtained from DNA extracted from recipient blood samples. Donor CFH Y402H genotype was inferred from recipient plasma CFH Y402H protein allotype, measured using enzyme-linked immunosorbent assays. This approach was verified by genotyping donor tissue from a subgroup of patients. Systemic complement activity was ascertained by measuring levels of plasma complement proteins using an enzyme-linked immunosorbent assay, including substrates (C3, C4), activation products (C3a, C4a, and terminal complement complex), and regulators (total CFH, C1 inhibitor). We evaluated AMD status and recipient and donor CFH Y402H genotype. In LT patients, AMD was associated with recipient CFH Y402H genotype (P = 0.036; odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.4) but not with donor CFH Y402H genotype (P = 0.626), after controlling for age, sex, smoking status, and body mass index. Recipient plasma CFH Y402H protein allotype predicted donor CFH Y402H genotype with 100% accuracy (n = 49). Plasma complement protein or activation product levels were similar in LT patients with and without AMD. Compared with previously reported prevalence figures (Rotterdam Study), LT patients demonstrated a high prevalence of both AMD (64.6% vs 37.1%; OR, 3.09; P<0.001) and the CFH Y402H sequence variation (41.9% vs 36.2%; OR, 1.27; P = 0.014). Presence of AMD is not associated with modification of hepatic CFH production. In addition, AMD is not associated with systemic complement activity in LT patients. These findings suggest that local intraocular complement activity is of greater importance in AMD pathogenesis. The high AMD prevalence observed in LT patients may be associated with the increased frequency of the CFH Y402H sequence variation. The authors have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Performance benchmark of LHCb code on state-of-the-art x86 architectures

NASA Astrophysics Data System (ADS)

Campora Perez, D. H.; Neufeld, N.; Schwemmer, R.

2015-12-01

For Run 2 of the LHC, LHCb is replacing a significant part of its event filter farm with new compute nodes. For the evaluation of the best performing solution, we have developed a method to convert our high level trigger application into a stand-alone, bootable benchmark image. With additional instrumentation we turned it into a self-optimising benchmark which explores techniques such as late forking, NUMA balancing and optimal number of threads, i.e. it automatically optimises box-level performance. We have run this procedure on a wide range of Haswell-E CPUs and numerous other architectures from both Intel and AMD, including also the latest Intel micro-blade servers. We present results in terms of performance, power consumption, overheads and relative cost.

Lightweight carbon nanotube-based structural-energy storage devices for micro unmanned systems

NASA Astrophysics Data System (ADS)

Rivera, Monica; Cole, Daniel P.; Hahm, Myung Gwan; Reddy, Arava L. M.; Vajtai, Robert; Ajayan, Pulickel M.; Karna, Shashi P.; Bundy, Mark L.

2012-06-01

There is a strong need for small, lightweight energy storage devices that can satisfy the ever increasing power and energy demands of micro unmanned systems. Currently, most commercial and developmental micro unmanned systems utilize commercial-off-the-shelf (COTS) lithium polymer batteries for their energy storage needs. While COTS lithium polymer batteries are the industry norm, the weight of these batteries can account for up to 60% of the overall system mass and the capacity of these batteries can limit mission durations to the order of only a few minutes. One method to increase vehicle endurance without adding mass or sacrificing payload capabilities is to incorporate multiple system functions into a single material or structure. For example, the body or chassis of a micro vehicle could be replaced with a multifunctional material that would serve as both the vehicle structure and the on-board energy storage device. In this paper we present recent progress towards the development of carbon nanotube (CNT)-based structural-energy storage devices for micro unmanned systems. Randomly oriented and vertically aligned CNT-polymer composite electrodes with varying degrees of flexibility are used as the primary building blocks for lightweight structural-supercapacitors. For the purpose of this study, the mechanical properties of the CNT-based electrodes and the charge-discharge behavior of the supercapacitor devices are examined. Because incorporating multifunctionality into a single component often degrades the properties or performance of individual structures, the performance and property tradeoffs of the CNT-based structural-energy storage devices will also be discussed.

Pre-stressed piezoelectric bimorph micro-actuators based on machined 40 µm PZT thick films: batch scale fabrication and integration with MEMS

NASA Astrophysics Data System (ADS)

Wilson, S. A.; Jourdain, R. P.; Owens, S.

2010-09-01

The projected force-displacement capability of piezoelectric ceramic films in the 20-50 µm thickness range suggests that they are well suited to many micro-fluidic and micro-pneumatic applications. Furthermore when they are configured as bending actuators and operated at ~ 1 V µm - 1 they do not necessarily conform to the high-voltage, very low-displacement piezoelectric stereotype. Even so they are rarely found today in commercial micro-electromechanical devices, such as micro-pumps and micro-valves, and the main barriers to making them much more widely available would appear to be processing incompatibilities rather than commercial desirability. In particular, the issues associated with integration of these devices into MEMS at the production level are highly significant and they have perhaps received less attention in the mainstream than they deserve. This paper describes a fabrication route based on ultra-precision ceramic machining and full-wafer bonding for cost-effective batch scale production of thick film PZT bimorph micro-actuators and their integration with MEMS. The resulting actuators are pre-stressed (ceramic in compression) which gives them added performance, they are true bimorphs with bi-directional capability and they exhibit full bulk piezoelectric ceramic properties. The devices are designed to integrate with ancillary systems components using transfer-bonding techniques. The work forms part of the European Framework 6 Project 'Q2M—Quality to Micro'.

Microbiological challenge of four protective devices for the reconstitution of cytotoxic agents.

PubMed

De Prijck, K; D'Haese, E; Vandenbroucke, J; Coucke, W; Robays, H; Nelis, H J

2008-12-01

To evaluate the susceptibility to microbial contamination that occurs during simulated handling of protective devices for the preparation of cytotoxic drug solutions. Four devices, i.e. Chemoprotect spike, Clave connector, PhaSeal and Securmix were challenged with low and high inocula of micro-organisms. The cells, transferred to the connected vials during repeated manipulations of the devices were counted by means of solid-phase cytometry. Of the four devices, PhaSeal afforded the lowest transfer of micro-organisms. Secondly, the efficiency of procedures for the disinfection of an artificially contaminated rubber stopper was compared prior to connection of the vial to the PhaSeal device. Spraying or swabbing alone was inadequate, as opposed to a combination of spraying [0.5% or 2.0% (w/v) chlorhexidine in isopropanol] and swabbing [70% (v/v) isopropanol]. Although Phaseal afforded the lowest transfer of micro-organisms, adequate disinfection of the vial prior to connection remains required. Unlike aspects of operator protection, which are well documented, the microbiological safety of protective devices for the preparation of cytotoxic drugs has not been addressed in the literature. This study estimates the susceptibility to microbial contamination during handling of four commonly used devices.

X-82 to Treat Age-related Macular Degeneration

ClinicalTrials.gov

2018-05-30

Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

[Anti-VEGF therapy resistance in neovascular age-related macular degeneration].

PubMed

Budzinskaya, M V; Plyukhova, A A; Sorokin, P A

With account to the increase in the elderly population in most of the developed countries, the WHO defines age-related macular degeneration (AMD) as one of the main causes of blindness in the world. A large percentage of disability is accounted for by exudative, or neovascular, form of AMD. Today, a total of 5 anti-VEGF drugs exist that are recommended for treatment of exudative AMD: pegaptanib, ranibizumab, bevacizumab, aflibercept, and conbercept. Despite significant progress in the treatment of neovascular AMD yielded by the introduction into clinical practice of anti-VEGF drugs, some patients report a lack (down to complete lack) of response with standard treatment patterns and even a decrease in treatment efficacy after repeated intravitreal injections.

Prevention of age-related macular degeneration.

PubMed

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

2011-02-01

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

Fabrication of robust tooling for mass production of polymeric microfluidic devices

NASA Astrophysics Data System (ADS)

Fu, G.; Tor, S. B.; Loh, N. H.; Hardt, D. E.

2010-08-01

Polymer microfluidic devices are gaining popularity for bio-applications. In both commonly used methods for the fabrication of polymer microfluidic devices, i.e. injection molding and hot-embossing, the quality of a mold insert is of high importance. Micro powder injection molding (μPIM) provides a suitable option for metal mold insert fabrication. In this paper, two mold inserts with micro-features of different patterns and sizes were produced using 316L stainless steel powder and an in-house binder system. The mold inserts were successfully used to produce cyclic olefin copolymer (COC, trade name TOPAS) micromixer plates with micro-channels of widths 100 µm and 50 µm. Compared with CNC-machined hot work steel mold inserts, the quality of the micro-channels is better as far as geometrical quality and dimensional tolerance are concerned. However, surface finish and flatness of the μPIM mold inserts are inferior to those of CNC-machined mold inserts.

Eye vision system using programmable micro-optics and micro-electronics

NASA Astrophysics Data System (ADS)

Riza, Nabeel A.; Amin, M. Junaid; Riza, Mehdi N.

2014-02-01

Proposed is a novel eye vision system that combines the use of advanced micro-optic and microelectronic technologies that includes programmable micro-optic devices, pico-projectors, Radio Frequency (RF) and optical wireless communication and control links, energy harvesting and storage devices and remote wireless energy transfer capabilities. This portable light weight system can measure eye refractive powers, optimize light conditions for the eye under test, conduct color-blindness tests, and implement eye strain relief and eye muscle exercises via time sequenced imaging. Described is the basic design of the proposed system and its first stage system experimental results for vision spherical lens refractive error correction.

Micro-machined thermo-conductivity detector

DOEpatents

Yu, Conrad

2003-01-01

A micro-machined thermal conductivity detector for a portable gas chromatograph. The detector is highly sensitive and has fast response time to enable detection of the small size gas samples in a portable gas chromatograph which are in the order of nanoliters. The high sensitivity and fast response time are achieved through micro-machined devices composed of a nickel wire, for example, on a silicon nitride window formed in a silicon member and about a millimeter square in size. In addition to operating as a thermal conductivity detector, the silicon nitride window with a micro-machined wire therein of the device can be utilized for a fast response heater for PCR applications.

Rapid protein concentration, efficient fluorescence labeling and purification on a micro/nanofluidics chip.

PubMed

Wang, Chen; Ouyang, Jun; Ye, De-Kai; Xu, Jing-Juan; Chen, Hong-Yuan; Xia, Xing-Hua

2012-08-07

Fluorescence analysis has proved to be a powerful detection technique for achieving single molecule analysis. However, it usually requires the labeling of targets with bright fluorescent tags since most chemicals and biomolecules lack fluorescence. Conventional fluorescence labeling methods require a considerable quantity of biomolecule samples, long reaction times and extensive chromatographic purification procedures. Herein, a micro/nanofluidics device integrating a nanochannel in a microfluidics chip has been designed and fabricated, which achieves rapid protein concentration, fluorescence labeling, and efficient purification of product in a miniaturized and continuous manner. As a demonstration, labeling of the proteins bovine serum albumin (BSA) and IgG with fluorescein isothiocyanate (FITC) is presented. Compared to conventional methods, the present micro/nanofluidics device performs about 10(4)-10(6) times faster BSA labeling with 1.6 times higher yields due to the efficient nanoconfinement effect, improved mass, and heat transfer in the chip device. The results demonstrate that the present micro/nanofluidics device promises rapid and facile fluorescence labeling of small amount of reagents such as proteins, nucleic acids and other biomolecules with high efficiency.

Wireless thin film transistor based on micro magnetic induction coupling antenna.

PubMed

Jun, Byoung Ok; Lee, Gwang Jun; Kang, Jong Gu; Kim, Seunguk; Choi, Ji-Woong; Cha, Seung Nam; Sohn, Jung Inn; Jang, Jae Eun

2015-12-22

A wireless thin film transistor (TFT) structure in which a source/drain or a gate is connected directly to a micro antenna to receive or transmit signals or power can be an important building block, acting as an electrical switch, a rectifier or an amplifier, for various electronics as well as microelectronics, since it allows simple connection with other devices, unlike conventional wire connections. An amorphous indium gallium zinc oxide (α-IGZO) TFT with magnetic antenna structure was fabricated and studied for this purpose. To enhance the induction coupling efficiency while maintaining the same small antenna size, a magnetic core structure consisting of Ni and nanowires was formed under the antenna. With the micro-antenna connected to a source/drain or a gate of the TFT, working electrical signals were well controlled. The results demonstrated the device as an alternative solution to existing wire connections which cause a number of problems in various fields such as flexible/wearable devices, body implanted devices, micro/nano robots, and sensors for the 'internet of things' (IoT).

Wireless thin film transistor based on micro magnetic induction coupling antenna

PubMed Central

Jun, Byoung Ok; Lee, Gwang Jun; Kang, Jong Gu; Kim, Seunguk; Choi, Ji-Woong; Cha, Seung Nam; Sohn, Jung Inn; Jang, Jae Eun

2015-01-01

A wireless thin film transistor (TFT) structure in which a source/drain or a gate is connected directly to a micro antenna to receive or transmit signals or power can be an important building block, acting as an electrical switch, a rectifier or an amplifier, for various electronics as well as microelectronics, since it allows simple connection with other devices, unlike conventional wire connections. An amorphous indium gallium zinc oxide (α-IGZO) TFT with magnetic antenna structure was fabricated and studied for this purpose. To enhance the induction coupling efficiency while maintaining the same small antenna size, a magnetic core structure consisting of Ni and nanowires was formed under the antenna. With the micro-antenna connected to a source/drain or a gate of the TFT, working electrical signals were well controlled. The results demonstrated the device as an alternative solution to existing wire connections which cause a number of problems in various fields such as flexible/wearable devices, body implanted devices, micro/nano robots, and sensors for the ‘internet of things’ (IoT). PMID:26691929

Wireless thin film transistor based on micro magnetic induction coupling antenna

NASA Astrophysics Data System (ADS)

Jun, Byoung Ok; Lee, Gwang Jun; Kang, Jong Gu; Kim, Seunguk; Choi, Ji-Woong; Cha, Seung Nam; Sohn, Jung Inn; Jang, Jae Eun

2015-12-01

A wireless thin film transistor (TFT) structure in which a source/drain or a gate is connected directly to a micro antenna to receive or transmit signals or power can be an important building block, acting as an electrical switch, a rectifier or an amplifier, for various electronics as well as microelectronics, since it allows simple connection with other devices, unlike conventional wire connections. An amorphous indium gallium zinc oxide (α-IGZO) TFT with magnetic antenna structure was fabricated and studied for this purpose. To enhance the induction coupling efficiency while maintaining the same small antenna size, a magnetic core structure consisting of Ni and nanowires was formed under the antenna. With the micro-antenna connected to a source/drain or a gate of the TFT, working electrical signals were well controlled. The results demonstrated the device as an alternative solution to existing wire connections which cause a number of problems in various fields such as flexible/wearable devices, body implanted devices, micro/nano robots, and sensors for the ‘internet of things’ (IoT).

Micro/Nano Fabricated Solid-State Thermoelectric Generator Devices for Integrated High Voltage Power Sources

NASA Astrophysics Data System (ADS)

Fleurial, J.-P.; Ryan, M. A.; Snyder, G. J.; Huang, C.-K.; Whitacre, J. F.; Patel, J.; Lim, J.; Borshchevsky, A.

2002-01-01

Deep space missions have a strong need for compact, high power density, reliable and long life electrical power generation and storage under extreme temperature conditions. Except for electrochemical batteries and solar cells, there are currently no available miniaturized power sources. Conventional power generators devices become inefficient in extreme environments (such as encountered in Mars, Venus or outer planet missions) and rechargeable energy storage devices can only be operated in a narrow temperature range thereby limiting mission duration. The planned development of much smaller spacecrafts incorporating a variety of micro/nanodevices and miniature vehicles will require novel, reliable power technologies. It is also expected that such micro power sources could have a wide range of terrestrial applications, in particular when the limited lifetime and environmental limitations of batteries are key factors. Advanced solid-state thermoelectric combined with radioisotope or waste heat sources and low profile energy storage devices are ideally suited for these applications. The Jet Propulsion Laboratory has been actively pursuing the development of thermoelectric micro/nanodevices that can be fabricated using a combination of electrochemical deposition and integrated circuit processing techniques. Some of the technical challenges associated with these micro/nanodevice concepts, their expected level of performance and experimental fabrication and testing results to date are presented and discussed.

Prevalence of Subretinal Drusenoid Deposits in Older Persons with and without Age-Related Macular Degeneration, by Multimodal Imaging.

PubMed

Zarubina, Anna V; Neely, David C; Clark, Mark E; Huisingh, Carrie E; Samuels, Brian C; Zhang, Yuhua; McGwin, Gerald; Owsley, Cynthia; Curcio, Christine A

2016-05-01

To assess the prevalence of subretinal drusenoid deposits (SDD) in older adults with healthy maculas and early and intermediate age-related macular degeneration (AMD) using multimodal imaging. Cross-sectional study. A total of 651 subjects aged ≥60 years enrolled in the Alabama Study of Early Age-Related Macular Degeneration from primary care ophthalmology clinics. Subjects were imaged using spectral domain optical coherence tomography (SD OCT) of the macula and optic nerve head (ONH), infrared reflectance, fundus autofluorescence, and color fundus photographs (CFP). Eyes were assessed for AMD presence and severity using the Age-Related Eye Disease Study (AREDS) 9-step scale. Criteria for SDD presence were identification on ≥1 en face modality plus SD OCT or on ≥2 en face modalities if absent on SD OCT. Subretinal drusenoid deposits were considered present at the person level if present in 1 or both eyes. Prevalence of SDD in participants with and without AMD. Overall prevalence of SDD was 32% (197/611), with 62% (122/197) affected in both eyes. Persons with SDD were older than those without SDD (70.6 vs. 68.7 years, P = 0.0002). Prevalence of SDD was 23% in subjects without AMD and 52% in subjects with AMD (P < 0.0001). Among those with early and intermediate AMD, SDD prevalence was 49% and 79%, respectively. After age adjustment, those with SDD were 3.4 times more likely to have AMD than those without SDD (95% confidence interval, 2.3-4.9). By using CFP only for SDD detection per the AREDS protocol, prevalence of SDD was 2% (12/610). Of persons with SDD detected by SD OCT and confirmed by at least 1 en face modality, 47% (89/190) were detected exclusively on the ONH SD OCT volume. Subretinal drusenoid deposits are present in approximately one quarter of older adults with healthy maculae and in more than half of persons with early to intermediate AMD, even by stringent criteria. The prevalence of SDD is strongly associated with AMD presence and severity and increases with age, and its retinal topography including peripapillary involvement resembles that of rod photoreceptors. Consensus on SDD detection methods is recommended to advance our knowledge of this lesion and its clinical and biologic significance. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Geochemical characteristics of dissolved rare earth elements in acid mine drainage from abandoned high-As coal mining area, southwestern China.

PubMed

Li, Xuexian; Wu, Pan

2017-09-01

Acid mine drainage (AMD) represents a major source of water pollution in the small watershed of Xingren coalfield in southwestern Guizhou Province. A detailed geochemical study was performed to investigate the origin, distribution, and migration of REEs by determining the concentrations of REEs and major solutes in AMD samples, concentrations of REEs in coal, bedrocks, and sediment samples, and modeling REEs aqueous species. The results highlighted that all water samples collected in the mining area are identified as low pH, high concentrations of Fe, Al, SO 4 2- and distinctive As and REEs. The spatial distributions of REEs showed a peak in where it is nearby the location of discharging of AMD, and then decrease significantly with distance away from the mining areas. Lots of labile REEs have an origin of coal and bedrocks, whereas the acid produced by the oxidation of pyrite is a prerequisite to cause the dissolution of coal and bedrocks, and then promoting REEs release in AMD. The North American Shale Composite (NASC)-normalized REE patterns of coal and bedrocks are enriched in light REEs (LREEs) and middle REEs (MREEs) relative to heavy REEs (HREEs). Contrary to these solid samples, AMD samples showed slightly enrichment of MREEs compared with LREEs and HREEs. This behavior implied that REEs probably fractionate during acid leaching, dissolution of bedrocks, and subsequent transport, so that the MREEs is primarily enriched in AMD samples. Calculation of REEs inorganic species for AMD demonstrated that sulfate complexes (Ln(SO 4 ) + and Ln(SO 4 ) 2 - ) predominate in these species, accounting for most of proportions for the total REEs species. The high concentrations of dissolved SO 4 2- and low pH play a decisive role in controlling the presence of REEs in AMD, as these conditions are necessary for formation of stable REEs-sulfate complexes in current study. The migration and transportation of REEs in AMD are more likely constrained by adsorption and co-precipitation of Fe-Al hydroxides/hydroxysulfate. In addition, the MREEs is preferentially captured by poorly crystalline Fe-Al hydroxides/hydroxysulfate, which favors that sediments also preserve NASC-normalized patterns with MREEs enrichment in the stream.

Adherence to a Mediterranean diet, genetic susceptibility, and progression to advanced macular degeneration: a prospective cohort study.

PubMed

Merle, Bénédicte M J; Silver, Rachel E; Rosner, Bernard; Seddon, Johanna M

2015-11-01

Adherence to a Mediterranean-type diet is linked to a lower risk of mortality and chronic disease, but the association with the progression of age-related macular degeneration (AMD) and genetic susceptibility is unknown. We examined the association of adherence to the Mediterranean diet and genetic susceptibility with progression to advanced AMD. Among 2525 subjects in the AREDS (Age-Related Eye Disease Study), 1028 eyes progressed to advanced AMD over 13 y. Baseline data for demographic and behavioral covariates were collected by using questionnaires. Dietary data were collected from food-frequency questionnaires. The alternate Mediterranean diet (aMeDi) score (range: 0-9) was constructed from individual intakes of vegetables, fruit, legumes, whole grains, nuts, fish, red and processed meats, alcohol, and the ratio of monounsaturated to saturated fats. Ten genetic loci in 7 genes [complement factor H (CFH), age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 (ARMS2/HTRA1), complement component 2 (C2), complement factor B (CFB), complement component 3 (C3), collagen type VIII α 1 (COL8A1), and RAD51 paralog B (RAD51B)] were examined. Survival analysis was used to assess individual eyes for associations between incident AMD and aMeDi score, as well as interaction effects between aMeDi score and genetic variation on risk of AMD. A high aMeDi score (score of 6-9) was significantly associated with a reduced risk of progression to advanced AMD after adjustment for demographic, behavioral, ocular, and genetic covariates (HR: 0.74; 95% CI: 0.61, 0.91; P-trend = 0.007). The aMeDi score was significantly associated with a lower risk of incident advanced AMD among subjects carrying the CFH Y402H nonrisk (T) allele (P-trend = 0.0004, P-interaction = 0.04). The aMeDi score was not associated with AMD among subjects who were homozygous for the risk (C) allele. Higher adherence to a Mediterranean diet was associated with reduced risk of progression to advanced AMD, which may be modified by genetic susceptibility. This trial was registered at clinicaltrials.gov as NCT00594672. © 2015 American Society for Nutrition.

Analysis of Genetic and Environmental Risk Factors and Their Interactions in Korean Patients with Age-Related Macular Degeneration.

PubMed

Woo, Se Joon; Ahn, Jeeyun; Morrison, Margaux A; Ahn, So Yeon; Lee, Jaebong; Kim, Ki Woong; DeAngelis, Margaret M; Park, Kyu Hyung

2015-01-01

To investigate the association of genetic and environmental factors, and their interactions in Korean patients with exudative age-related macular degeneration (AMD). A total of 314 robustly characterized exudative AMD patients, including 111 PCV (polypoidal choroidal vasculopathy) and 154 typical choroidal neovascularization (CNV), and 395 control subjects without any evidence of AMD were enrolled. Full ophthalmologic examinations including fluorescein angiography (FA), indocyanine green angiography (ICG) and optical coherence tomography (OCT) were done, according to which patients were divided into either PCV or typical CNV. Standardized questionnaires were used to collect information regarding underlying systemic diseases, dietary habits, smoking history and body mass index (BMI). A total of 86 SNPs from 31 candidate genes were analyzed. Genotype association and logistic regression analyses were done and stepwise regression models to best predict disease for each AMD subtype were constructed. Age, spherical equivalent, myopia, and ever smoking were associated with exudative AMD. Age, hypertension, hyperlipidemia, spherical equivalent, and myopia were risk factors for typical CNV, while increased education and ever smoking were significantly associated with PCV (p<.05 for all). Four SNPs, ARMS2/HTRA1 rs10490924, rs11200638, and rs2736911, and CFH rs800292, showed association with exudative AMD. Two of these SNPs, ARMS2/HTRA1 rs10490924 and rs11200638, showed significant association with typical CNV and PCV specifically. There were no significant interactions between environmental and genetic factors. The most predictive disease model for exudative AMD included age, spherical equivalent, smoking, CFH rs800292, and ARMS2 rs10490924 while that for typical CNV included age, hyperlipidemia, spherical equivalent, and ARMS2 rs10490924. Smoking, spherical equivalent, and ARMS2 rs10490924 were the most predictive variables for PCV. When comparing PCV cases to CNV cases, age, BMI, and education were the most predictive risk factors of PCV. Only one locus, the ARMS2/HTRA1 was a significant genetic risk factor for Korean exudative AMD, including its subtypes, PCV and typical CNV. Stepwise regression revealed that CFH was important to risk of exudative AMD in general but not to any specific subtype. While increased education was a unique risk factor to PCV when compared to CNV, this association was independent of refractive error in this homogenous population from South Korea. No significant interactions between environmental and genetic risk factors were observed.

Contents, Followers, and Retweets of the Centers for Disease Control and Prevention's Office of Advanced Molecular Detection (@CDC_AMD) Twitter Profile: Cross-Sectional Study.

PubMed

Fung, Isaac Chun-Hai; Jackson, Ashley M; Mullican, Lindsay A; Blankenship, Elizabeth B; Goff, Mary Elizabeth; Guinn, Amy J; Saroha, Nitin; Tse, Zion Tsz Ho

2018-04-02

The Office of Advanced Molecular Detection (OAMD), Centers for Disease Control and Prevention (CDC), manages a Twitter profile (@CDC_AMD). To our knowledge, no prior study has analyzed a CDC Twitter handle's entire contents and all followers. This study aimed to describe the contents and followers of the Twitter profile @CDC_AMD and to assess if attaching photos or videos to tweets posted by @CDC_AMD would increase retweet frequency. Data of @CDC_AMD were retrieved on November 21, 2016. All followers (N=809) were manually categorized. All tweets (N=768) were manually coded for contents and whether photos or videos were attached. Retweet count for each tweet was recorded. Negative binomial regression models were applied to both the original and the retweet corpora. Among the 809 followers, 26.0% (210/809) were individual health professionals, 11.6% (94/809) nongovernmental organizations, 3.3% (27/809) government agencies' accounts, 3.3% (27/809) accounts of media organizations and journalists, and 0.9% (7/809) academic journals, with 54.9% (444/809) categorized as miscellaneous. A total of 46.9% (360/768) of @CDC_AMD's tweets referred to the Office's website and their current research; 17.6% (135/768) referred to their scientists' publications. Moreover, 80% (69/86) of tweets retweeted by @CDC_AMD fell into the miscellaneous category. In addition, 43.4% (333/768) of the tweets contained photos or videos, whereas the remaining 56.6% (435/768) did not. Attaching photos or videos to original @CDC_AMD tweets increases the number of retweets by 37% (probability ratio=1.37, 95% CI 1.13-1.67, P=.002). Content topics did not explain or modify this association. This study confirms CDC health communicators' experience that original tweets created by @CDC_AMD Twitter profile sharing images or videos (or their links) received more retweets. The current policy of attaching images to tweets should be encouraged. ©Isaac Chun-Hai Fung, Ashley M Jackson, Lindsay A Mullican, Elizabeth B Blankenship, Mary Elizabeth Goff, Amy J Guinn, Nitin Saroha, Zion Tsz Ho Tse. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 02.04.2018.

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

PubMed Central

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

2013-01-01

Background The importance of incorporating quality-of-life (QoL) assessments into medical practice is growing as health care practice shifts from a “disease-based” to a “patient-centered” model. The prevalence of age-related macular degeneration (AMD) is increasing in today’s aging population. The purpose of this paper is: (1) to discuss, by reviewing the current literature, the impact of AMD on patients’ QoL and the utility of QoL assessments in evaluating the impact of AMD and its treatment; and (2) to make a recommendation for incorporating QoL into clinical practice. Methods We conducted a PubMed and an open Internet search to identify publications on the measurement of QoL in AMD, as well as the impact of AMD and the effect of treatment on QoL. A total of 28 articles were selected. Results AMD has been found to cause a severity-dependent decrement in QoL that is comparable to systemic diseases such as cancer, ischemic heart disease, and stroke. QoL impairment manifests as greater social dependence, difficulty with daily living, higher rates of clinical depression, increased risk of falls, premature admission to nursing homes, and suicide. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) is the most widely used eye disease-specific QoL instrument in AMD. It has been shown to correlate significantly with visual acuity (VA). QoL reflects aspects of AMD including psychological well-being, functional capacity, and the ability to perform patients’ valued activities, which are not captured by a single, numerical VA score. Conclusion The literature shows that the adverse impact of AMD on QoL is comparable to serious systemic disease. Eye disease-specific instruments for measuring QoL, such as the NEI VFQ-25, have shown a significant correlation of QoL decrement with measures of disease severity, as well as significant QoL improvement with treatment. The NEI VFQ-25 and other validated instruments provide a wide-ranging assessment of vision-related functioning that is important to patients and complementary to VA measurement. We strongly recommend the incorporation of QoL assessment into routine clinical practice. PMID:23836961

Prevalence of subretinal drusenoid deposits in older persons with and without age-related macular degeneration, by multimodal imaging

PubMed Central

Zarubina, Anna V.; Neely, David C.; Clark, Mark E.; Huisingh, Carrie E.; Samuels, Brian C.; Zhang, Yuhua; McGwin, Gerald; Owsley, Cynthia; Curcio, Christine A.

2015-01-01

Purpose To assess the prevalence of subretinal drusenoid deposits (SDD) in older adults with healthy maculas and early and intermediate age-related macular degeneration (AMD) using multimodal imaging. Design Cross-sectional study. Participants A total of 651 subjects aged ≥60 years enrolled in the Alabama Study of Early Age-Related Macular Degeneration from primary care ophthalmology clinics. Methods Subjects were imaged using spectral domain optical coherence tomography (SD-OCT) of the macula and optic nerve head (ONH), infrared reflectance, fundus autofluorescence, and color fundus photographs (CFP). Eyes were assessed for AMD presence and severity using the AREDS 9-step scale. Criteria for SDD presence were identification on ≥1 en-face modality plus SD-OCT or on ≥2 en-face modalities if absent on SD-OCT. SDD were considered present at the person-level if present in 1 or both eyes. Main outcomes measures Prevalence of SDD in participants with and without AMD. Results Overall prevalence of SDD was 32% (197/611), with 62% (122/197) affected in both eyes. Persons with SDD were older than those without SDD (70.6 vs. 68.7 years, p =0.0002). Prevalence of SDD was 23% in subjects without AMD and 52% in subjects with AMD (p<0.0001). Among those with early and intermediate AMD, SDD prevalence was 49% and 79%, respectively. After age adjustment, those with SDD were 3.4x more likely to have AMD than those without SDD (95% CI 2.3–4.9). By using CFP only for SDD detection per the AREDS protocol, prevalence of SDD was 2% (12/610). Of persons with SDD detected by SD-OCT and confirmed by at least one en-face modality 47% (89/190) were detected exclusively on the ONH SD-OCT volume. Conclusion SDD are present in approximately one quarter of older adults with healthy maculae and in more than half of persons with early to intermediate AMD, even by stringent criteria. The prevalence of SDD is strongly associated with AMD presence and severity and increases with age, and its retinal topography including peripapillary involvement resembles that of rod photoreceptors. Consensus on SDD detection methods is recommended to advance our knowledge of this lesion and its clinical and biologic significance. PMID:26875000

Design, Fabrication, and In Vitro Testing of an Anti-biofouling Glaucoma Micro-shunt.

PubMed

Harake, Ryan S; Ding, Yuzhe; Brown, J David; Pan, Tingrui

2015-10-01

Glaucoma, one of the leading causes of irreversible blindness, is a progressive neurodegenerative disease. Chronic elevated intraocular pressure (IOP), a prime risk factor for glaucoma, can be treated by aqueous shunts, implantable devices, which reduce IOP in glaucoma patients by providing alternative aqueous outflow pathways. Although initially effective at delaying glaucoma progression, contemporary aqueous shunts often lead to numerous complications and only 50% of implanted devices remain functional after 5 years. In this work, we introduce a novel micro-device which provides an innovative platform for IOP reduction in glaucoma patients. The device design features an array of parallel micro-channels to provide precision aqueous outflow resistance control. Additionally, the device's microfluidic channels are composed of a unique combination of polyethylene glycol materials in order to provide enhanced biocompatibility and resistance to problematic channel clogging from biofouling of aqueous proteins. The microfabrication process employed to produce the devices results in additional advantages such as enhanced device uniformity and increased manufacturing throughput. Surface characterization experimental results show the device's surfaces exhibit significantly less non-specific protein adsorption compared to traditional implant materials. Results of in vitro flow experiments verify the device's ability to provide aqueous resistance control, continuous long-term stability through 10-day protein flow testing, and safety from risk of infection due to bacterial ingression.

Evidence for the Stepwise Stress Model: Gambusia holbrooki and Daphnia magna under acid mine drainage and acidified reference water stress.

PubMed

Gerhardt, Almut; Janssens de Bisthoven, Luc; Soares, Amadeu M V

2005-06-01

The Stepwise Stress Model (SSM) states that a cascade of regulative behavioral responses with different intrinsic sensitivities and threshold values offers increased behavioral plasticity and thus a wider range of tolerance for environmental changes or pollutant exposures. We tested the SSM with a widely introduced fish Gambusia holbrooki (Girard) (Pisces, Poeciliidae) and the standard laboratory test species Daphnia magna Straus (Crustacea, Daphniidae). The stress was simulated by short-term exposure to acid mine drainage (AMD) and to acidified reference water (ACID). Recording of behavioral responses with the multispecies freshwater biomonitor (MFB) generated continuous time-dependent dose-response data that were modeled in three-dimensional (3D) surface plots. Both the pH-dependent mortalities and the strong linear correlations between pH and aqueous metals confirmed the toxicity of the AMD and ACID gradients, respectively, for fish and Daphnia, the latter being more sensitive. AMD stress at pH < or = 5.5 amplified circadian rhythmicity in both species, while ACID stress did so only in G. holbrooki. A behavioral stepwise stress response was found in both species: D. magna decreased locomotion and ventilation (first step) (AMD, ACID), followed by increased ventilation (second step) (AMD). G. holbrooki decreased locomotion (first step) (AMD, ACID) and increased ventilation at intermediate pH levels (second step) (AMD). Both species, although from different taxonomic groups and feeding habits, followed the SSM, which might be expanded to a general concept for describing the behavioral responses of aquatic organims to pollution. Stepwise stress responses might be applied in online biomonitors to provide more sensitive and graduated alarm settings, hence optimizing the "early warning" detection of pollution waves.

Prevalence of Early and Late Age-Related Macular Degeneration in India: The INDEYE Study

PubMed Central

Krishnan, Tiruvengada; Ravindran, Ravilla D.; Murthy, Gudlavalleti V. S.; Vashist, Praveen; Fitzpatrick, Kathryn E.; Thulasiraj, R. Duraisami; John, Neena; Maraini, Giovanni; Camparini, Monica; Chakravarthy, Usha

2010-01-01

Purpose. To estimate the prevalence of early and late age-related macular degeneration (AMD) in India. Methods. Of 7518 people aged 60 years and older identified from randomly sampled villages in North and South India, 5853 (78%) attended an eye examination including fundus photography. Fundus images were graded according to the Wisconsin Age-Related Maculopathy Grading System. Results. Fundus images were ungradable in 1587 people, mainly because of cataract. People 80 years of age and older were less likely to attend the eye examination and more likely to have ungradable images. For ages 60 to 79 years, the percent prevalence (95% confidence interval [CI]) were late AMD 1.2 (0.8–1.5); and early AMD: grade 1 (soft distinct drusen or pigmentary irregularities), 39.3 (37.2–41.5); grade 2 (soft distinct drusen with pigmentary irregularities or soft indistinct or reticular drusen), 6.7 (5.8–7.6); and grade 3 (soft indistinct or reticular drusen with pigmentary irregularities), 0.2 (0.1–0.4). For ages 80 and older, the respective percent prevalence was: late AMD, 2.5 (0.4–4.7); and early AMD: grade 1, 43.1(35.7–50.6); grade 2, 8.1 (4.3–12.0); and grade 3, 0.5 (0–1.5). Conclusions. The prevalence of early AMD (grades 1 and 2) is similar to that observed in Western populations, but grade 3 appears to be lower. The prevalence of late AMD is comparable to that in Western populations in the age group 60 to 79 years. It is likely that the prevalence in the 80 and older age group is underestimated. PMID:19696177

Clinical features and long-term progression of reticular pseudodrusen in age-related macular degeneration: findings from a multicenter cohort.

PubMed

Gil, J Q; Marques, J P; Hogg, R; Rosina, C; Cachulo, M L; Santos, A; Staurenghi, G; Chakravarthy, U; Silva, R

2017-03-01

PurposeTo determine whether reticular pseudodrusen (RPD) confer a long-term increased risk of progression to late age-related macular degeneration (AMD) in the fellow eye of patients with unilateral wet-AMD.Patients and methodsThis was a multicenter, combined prospective and retrospective, longitudinal, observational, study. Patients with wet-AMD in one eye were recruited from two centers and evaluated on the risk of progression to late-AMD in the second eye (study eye). A minimum follow-up of 5 years was required, unless progression occurred first. Baseline retinal profile of patients was evaluated using multimodal imaging. Baseline images were graded by two separate centers.ResultsWe recruited 88 patients (48 female) with a mean age of 75.6±7.1 years and mean follow-up of 65.7±20.9 months. Baseline prevalence of RPD was 58% (n=51). There was no statistically significant association of RPD with increased age (P=0.29) or sex distribution (P=0.39). The most sensitive image modality for RPD was IR (93%), followed by FAF (92%), OCT (74%, RF (33%) and CFP (29%). After 5 years, 54.50% (n=48) of the study eyes progressed to late-AMD. Of those, 81.25% (n=39) developed CNV and 18.75% (n=9) geographic atrophy. After correcting for age and sex, the presence of RPD was significantly associated with development of late-stage AMD (OR=2.55, P=0.03).ConclusionA multimodal approach is mandatory for RPD detection. RPD are highly prevalent in the fellow eyes of patients with unilateral neovascular AMD. Presence of RPD is associated with increased long-term risk of progression, highlighting the importance of comprehensive multimodal retinal imaging and careful monitoring of at-risk patients.

Maculoplasty for age-related macular degeneration: reengineering Bruch's membrane and the human macula.

PubMed

Del Priore, Lucian V; Tezel, Tongalp H; Kaplan, Henry J

2006-11-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the western world. Over the last decade, there have been significant advances in the management of exudative AMD with the introduction of anti-VEGF drugs; however, many patients with exudative AMD continue to lose vision and there are no effective treatments for advanced exudative AMD or geographic atrophy. Initial attempts at macular reconstruction using cellular transplantation have not been effective in reversing vision loss. Herein we discuss the current status of surgical attempts to reconstruct damaged subretinal anatomy in advanced AMD. We reinforce the concept of maculoplasty for advanced AMD, which is defined as reconstruction of macular anatomy in patients with advanced vision loss. Successful maculoplasty is a three-step process that includes replacing or repairing damaged cells (using transplantation, translocation or stimulation of autologous cell proliferation); immune suppression (if allografts are used to replace damaged cells); and reconstruction or replacement of Bruch's membrane (to restore the integrity of the substrate for proper cell attachment). In the current article we will review the rationale for maculoplasty in advanced AMD, and discuss the results of initial clinical attempts at macular reconstruction. We will then discuss the role of Bruch's membrane damage in limiting transplant survival and visual recovery, and discuss the effects of age-related changes within human Bruch's membrane on the initial attachment and subsequent proliferation of transplanted cells. We will discuss attempts to repair Bruch's membrane by coating with extracellular matrix ligands, anatomic reconstitution of the inner collagen layer, and the effects of Bruch's membrane reconstruction of ultrastuctural anatomy and subsequent cell behavior. Lastly, we will emphasize the importance of continued efforts required for successful maculoplasty.