Management of diabetic macular edema in Japan: a review and expert opinion.

PubMed

Terasaki, Hiroko; Ogura, Yuichiro; Kitano, Shigehiko; Sakamoto, Taiji; Murata, Toshinori; Hirakata, Akito; Ishibashi, Tatsuro

2018-01-01

Diabetic retinopathy is a frequent cause of visual impairment in working-age adults (≥ 30 years) and in Japan is most commonly observed in those aged 50-69 years. Diabetic macular edema (DME) is one of the main causes of vision disturbance in diabetic retinopathy, which is a clinically significant microvascular complication of diabetes. Anti-vascular endothelial growth factor (VEGF) therapy is becoming the mainstay of treatment for DME. However, to achieve sustained long-term improvement in visual acuity, conventional laser photocoagulation, vitrectomy and steroid therapy are also expected to play a role in the treatment of DME. This review summarizes the epidemiology and pathology of diabetic retinopathy and DME, evaluates the findings regarding the diagnosis and treatment of DME, and underscores the importance of systemic management of the disease in the context of the current health care situation in Japan. Finally, the unmet needs of patients with DME and prospects for research are discussed. The weight of evidence suggests that it is important to establish a multipronged treatment strategy centered on anti-VEGF therapy.

Surgical Versus Medical Treatment for Diabetic Macular Edema: A Review.

PubMed

Crim, Nicolás; Velez-Montoya, Raúl; Morales-Canton, Virgilio

2017-01-01

We aimed to compare the results of pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling, an alternative therapeutic strategy, with those of medical treatment for chronic macular edema. We conducted a review of the literature on the microscopic, anatomical, and functional reasons for performing PPV with ILM peeling in patients with diabetic macular edema (DME). We searched the PubMed database for articles published between 2000 and 2017. We used the medical subject heading "vitrectomy diabetic macular edema" and the keywords "diabetic macular edema", "internal limiting membrane peeling", "pars plana vitrectomy", "diabetic retinopathy", and "optical coherence tomography". Analysis of the literature revealed that cytokines, vascular endothelial growth factor, reactive oxygen species (ROS), and advanced glycation end-products (AGEs) play a unique role in DME. The vitreous cavity serves as a physiological reservoir for all inflammatory molecules. AGE receptors are localized at the footplates of Müller cells and the external limiting membrane (ELM). The footplates of Müller cells are in contact with the ILM, which suggests that they might be responsible for the structural damage (i.e., thickening) observed in the ILM of patients with DME. Therefore, PPV could allow a reduction of cytokines and pro-inflammatory molecules from the vitreous cavity. ILM peeling could eliminate not only the physical traction of a thickened structure, but also the natural reservoir of AGEs, ROS, and inflammatory molecules. PPV with ILM peeling is a surgical option that should be considered when treating patients with chronic DME.

Diabetic Macular Edema: Options for Adjunct Therapy.

PubMed

Calvo, Pilar; Abadia, Beatriz; Ferreras, Antonio; Ruiz-Moreno, Oscar; Verdes, Guayente; Pablo, Luis E

2015-09-01

Diabetes mellitus (DM) is a chronic disease that affects 387 million people worldwide. Diabetic retinopathy (DR), a common complication of DM, is the main cause of blindness in the active population. Diabetic macular edema (DME) may occur at any stage of DR, and is characterized by vascular hyperpermeability accompanied by hard exudates within the macula. Medical and surgical therapies have dramatically reduced the progression of DR, and timely intervention can reduce the risk of severe vision loss by more than 90 %. In 2012, intravitreal ranibizumab became the first antivascular endothelial growth factor (anti-VEGF) agent approved for DME and, since then, many reports of the use of ranibizumab for DME have been promising. Randomized, prospective, multicenter clinical trials-most notably, RESOLVE, READ-2, RISE/RIDE, RESTORE, DRCR.net protocol I, and RETAIN-reported improvements in best-corrected visual acuity and decreased central retinal thickness as measured with optical coherence tomography in patients with DME. Similar treatment benefits have also been noted in clinical trials evaluating intravitreal aflibercept and bevacizumab (DAVINCI, VISTA/VIVID, and BOLT) and more recently DRCR.net protocol T. Intravitreal steroids (dexamethasone intravitreal implant and fluocinolone acetonide), particularly in refractory cases, also play a significant role in the management of DME (MEAD/CHAMPLAIN and FAMOUS/FAME studies). In summary, over the last 5 years, blocking VEGF and inflammation has been shown to improve visual outcomes in patients with macular edema due to DM, revolutionizing the treatment of center-involved DME and establishing a new standard of care.

Impact of estimated glomerular filtration rate on diabetic macular edema.

PubMed

Temkar, Shreyas; Karuppaiah, Nishanthini; Takkar, Brijesh; Bhowmik, Dipankar; Tripathi, Manjari; Ramakrishnan, Sivasubramanian; Sharma, Yog Raj; Vohra, Rajpal; Chawla, Rohan; Venkatesh, Pradeep

2018-06-01

Diabetic macular edema (DME) is a major cause of visual impairment in patients with diabetes and is influenced by various systemic factors. This study evaluates the effect of renal status on DME using estimated glomerular filtration rate (eGFR) as a study marker. This was a prospective observational cross-sectional study. One hundred and ninety-five patients of diabetic retinopathy (DR) were included. Group 1 had patients of DR without DME (n = 100), and group 2 had patients of DR with DME (n = 95). All patients were evaluated for DR/DME-related risk factors. eGFR was calculated in all patients. Spectral domain optical coherence tomography (SDOCT) was done to identify the various patterns and severity of DME. Group 2 patients had significantly higher comorbidities than those in group 1 (p < 0.001). Hba1c, total cholesterol, triglycerides, LDL/HDL ratio, systolic and diastolic blood pressures were significantly higher in group II (p < 0.001 in each). There was no significant difference between the groups in terms of blood urea, serum creatinine or eGFR. eGFR did not show a significant association with a specific SDOCT pattern or severity of DME. Comorbidities are more common and more severe in patients with DME. However, eGFR as a marker was not useful in predicting either the severity or pattern of DME. eGFR, in its present form, may not be useful in the evaluation and management of patients with DME.

Oral minocycline for the treatment of diabetic macular edema (DME): results of a phase I/II clinical study.

PubMed

Cukras, Catherine A; Petrou, Philip; Chew, Emily Y; Meyerle, Catherine B; Wong, Wai T

2012-06-22

Inflammation contributes significantly to the pathogenesis of diabetic macular edema (DME). In particular, retinal microglia demonstrate increased activation and aggregation in areas of DME. Study authors investigated the safety and potential efficacy of oral minocycline, a drug capable of inhibiting microglial activation, in the treatment of DME. A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with fovea-involving DME who received oral minocycline 100 mg twice daily for 6 months. Main outcome measurements included best-corrected visual acuity (BCVA), central retinal subfield thickness (CST), and central macular volume using spectral domain optical coherence tomography (SD-OCT) and late leakage on fluorescein angiography (FA). Findings indicated that the study drug was well tolerated and not associated with significant safety issues. In study eyes, mean BCVA improved continuously from baseline at 1, 2, 4, and 6 months by +1.0, +4.0, +4.0, and +5.8 letters, respectively, while mean retinal thickness (CST) on OCT decreased by -2.9%, -5.7%, -13.9, and -8.1% for the same time points. At month 6, mean area of late leakage on FA decreased by -34.4% in study eyes. Mean changes in contralateral fellow eyes also demonstrated similar trends. Improvements in outcome measures were not correlated with concurrent changes in systemic factors. In this pilot proof-of-concept study of DME, minocycline as primary treatment was associated with improved visual function, central macular edema, and vascular leakage, comparing favorably with historical controls from previous studies. Microglial inhibition with oral minocycline may be a promising therapeutic strategy targeting the inflammatory etiology of DME. (ClinicalTrials.gov number, NCT01120899.).

Comorbidity and health care visit burden in working-age commercially insured patients with diabetic macular edema.

PubMed

Kiss, Szilárd; Chandwani, Hitesh S; Cole, Ashley L; Patel, Vaishali D; Lunacsek, Orsolya E; Dugel, Pravin U

2016-01-01

To examine the comorbidity profile and update estimates of health care resource utilization for commercially insured, working-age adults with diabetic macular edema (DME) relative to a matched comparison group of diabetic adults without DME. Additional comparisons were made in the subgroup of pseudophakic patients. A retrospective matched-cohort study of commercially insured diabetic adults aged 18-63 years was conducted using medical and outpatient pharmacy claims (July 1, 2008-June 30, 2013). Outcomes included diabetes-related and ocular comorbidities and health care resource utilization (any health care visit days, outpatient visit days, inpatient visit days, emergency room visits, eye care-related visit days, unique medications) in the 12-month post-index period. All diabetes-related and ocular comorbidities were significantly more prevalent in DME cases versus non-DME controls ( P <0.05). A significantly greater proportion of DME cases utilized eye care-related visits compared with non-DME controls ( P <0.001). DME cases had almost twice the mean number of total health care visit days compared to non-DME controls (28.6 vs 16.9 days, P <0.001), with a minority of visit days being eye care-related (mean 5.1 vs 1.5 days, P <0.001). Similar trends were observed in pseudophakic cohorts. This working-age DME population experienced a mean of 29 health care visit days per year. Eye care-related visit days were a minority of the overall visit burden (mean 5 days) emphasizing the trade-offs DME patients face between managing DME and their overall diabetic disease. Insights into the complex comorbidity profile and health care needs of diabetic patients with DME will better inform treatment decisions and help optimize disease management.

Multifractal geometry in analysis and processing of digital retinal photographs for early diagnosis of human diabetic macular edema.

PubMed

Tălu, Stefan

2013-07-01

The purpose of this paper is to determine a quantitative assessment of the human retinal vascular network architecture for patients with diabetic macular edema (DME). Multifractal geometry and lacunarity parameters are used in this study. A set of 10 segmented and skeletonized human retinal images, corresponding to both normal (five images) and DME states of the retina (five images), from the DRIVE database was analyzed using the Image J software. Statistical analyses were performed using Microsoft Office Excel 2003 and GraphPad InStat software. The human retinal vascular network architecture has a multifractal geometry. The average of generalized dimensions (Dq) for q = 0, 1, 2 of the normal images (segmented versions), is similar to the DME cases (segmented versions). The average of generalized dimensions (Dq) for q = 0, 1 of the normal images (skeletonized versions), is slightly greater than the DME cases (skeletonized versions). However, the average of D2 for the normal images (skeletonized versions) is similar to the DME images. The average of lacunarity parameter, Λ, for the normal images (segmented and skeletonized versions) is slightly lower than the corresponding values for DME images (segmented and skeletonized versions). The multifractal and lacunarity analysis provides a non-invasive predictive complementary tool for an early diagnosis of patients with DME.

The prevalence and systemic risk factors of diabetic macular edema: a cross-sectional study from Turkey.

PubMed

Acan, Durgul; Calan, Mehmet; Er, Duygu; Arkan, Tugba; Kocak, Nilufer; Bayraktar, Firat; Kaynak, Suleyman

2018-04-12

The aim of this study was to evaluate the prevalence of diabetic macular edema (DME) utilizing optical coherence tomography (OCT), and to clarify the effects of the systemic findings and risk factors on the development of DME. This cross-sectional study was conducted in the departments of ophthalmology and endocrinology at the Dokuz Eylul University School of Medicine in Izmir, Turkey. The demographics, type and duration of diabetes mellitus, treatment modality, smoking and alcohol consumption habits, as well as the systemic blood pressure, renal functional tests, hemoglobulin A1c level, serum lipid profile, and 24-h urine albumin level were noted and statistically analyzed. The relationships between the systemic findings and DME were studied. Four-hundred and thirteen eyes of 413 diabetic patients who were examined between January 2011 and July 2012 were enrolled in this study. The prevalence of DME was 15.3% among the patients. The males exhibited DME significantly more frequently than the females (p = 0.031), and the duration of diabetes was significantly longer in those patients with DME (p < 0.001). Those patients without DME frequently used antihyperlipidemic drugs and had a higher level of high density lipoprotein cholesterol (p = 0.040 and p = 0.046, respectively). The patient's alcohol consumption, nephropathy, neuropathy, previous cataract surgery, severity of diabetic retinopathy, and insulin usage were statistically significant factors with regard to the DME prevalence. This study demonstrated the prevalence of DME in Turkey by utilizing OCT. The development of DME can be avoided or limited and the response to treatment may be improved by the regulation of the DME risk factors.

Persistent Macular Thickening After Ranibizumab Treatment for Diabetic Macular Edema With Vision Impairment

PubMed Central

Bressler, Susan B.; Ayala, Allison R.; Bressler, Neil M.; Melia, Michele; Qin, Haijing; Ferris, Frederick L.; Flaxel, Christina J.; Friedman, Scott M.; Glassman, Adam R.; Jampol, Lee M.; Rauser, Michael E.

2016-01-01

IMPORTANCE The prevalence of persistent diabetic macular edema (DME) after months of anti–vascular endothelial growth factor therapy and its effect on visual acuity are unknown. OBJECTIVE To assess subsequent outcomes of eyes with DME persisting for 24 weeks after initiating treatment with 0.5 mg of ranibizumab. DESIGN, SETTING, AND PARTICIPANTS We performed post hoc, exploratory analyses of a randomized clinical trial from March 20, 2007, through January 29, 2014, from 117 of 296 eyes (39.5%) randomly assigned to receive ranibizumab with persistent DME (central subfield thickness ≥250 μm on time domain optical coherence tomography) through the 24-week visit. INTERVENTIONS Four monthly intravitreous injections of ranibizumab and then as needed per protocol. MAIN OUTCOMES AND MEASURES Cumulative 3-year probabilities of chronic persistent DME (failure to achieve a central subfield thickness <250 μm and at least a 10% reduction from the 24-week visit on at least 2 consecutive study visits) determined by life-table analyses, and at least 10 letter (≥2 line) gain or loss of visual acuity among those eyes. RESULTS The probability of chronic persistent DME among eyes with persistent DME at the 24-week visit decreased from 100% at the 32-week visit to 81.1% (99% CI, 69.6%-88.6%), 55.8% (99% CI, 42.9%-66.9%), and 40.1% (99% CI, 27.4%-52.4%) at the 1-, 2-, and 3-year visits, respectively. At 3 years, visual acuity improved in eyes with and without chronic persistent DME through the follow-up period, respectively, by a mean of 7 letters and 13 letters from baseline. Among 40 eyes with chronic persistent edema through 3 years, 17 (42.5%) (99% CI, 23.1%-63.7%) gained 10 letters or more from baseline, whereas 5 (12.5%) (99% CI, 2.8%-31.5%) lost 10 letters or more from baseline. CONCLUSIONS AND RELEVANCE These data suggest less than half of eyes treated for DME with intravitreous ranibizumab have persistent central-involved DME through 24 weeks after initiating treatment. Among the 40% that then have chronic persistent central-involved DME through 3 years, longer-term visual acuity outcomes appear to be slightly worse than in the 60% in which DME does not persist. Nevertheless, when following the treatment protocol used in this trial among eyes with vision impairment from DME, long-term improvement in visual acuity from baseline is typical and substantial (≥2-line) loss of visual acuity is likely uncommon through 3 years, even when central-involved DME chronically persists. PMID:26746868

Fully Automatic Segmentation of Fluorescein Leakage in Subjects With Diabetic Macular Edema

PubMed Central

Rabbani, Hossein; Allingham, Michael J.; Mettu, Priyatham S.; Cousins, Scott W.; Farsiu, Sina

2015-01-01

Purpose. To create and validate software to automatically segment leakage area in real-world clinical fluorescein angiography (FA) images of subjects with diabetic macular edema (DME). Methods. Fluorescein angiography images obtained from 24 eyes of 24 subjects with DME were retrospectively analyzed. Both video and still-frame images were obtained using a Heidelberg Spectralis 6-mode HRA/OCT unit. We aligned early and late FA frames in the video by a two-step nonrigid registration method. To remove background artifacts, we subtracted early and late FA frames. Finally, after postprocessing steps, including detection and inpainting of the vessels, a robust active contour method was utilized to obtain leakage area in a 1500-μm-radius circular region centered at the fovea. Images were captured at different fields of view (FOVs) and were often contaminated with outliers, as is the case in real-world clinical imaging. Our algorithm was applied to these images with no manual input. Separately, all images were manually segmented by two retina specialists. The sensitivity, specificity, and accuracy of manual interobserver, manual intraobserver, and automatic methods were calculated. Results. The mean accuracy was 0.86 ± 0.08 for automatic versus manual, 0.83 ± 0.16 for manual interobserver, and 0.90 ± 0.08 for manual intraobserver segmentation methods. Conclusions. Our fully automated algorithm can reproducibly and accurately quantify the area of leakage of clinical-grade FA video and is congruent with expert manual segmentation. The performance was reliable for different DME subtypes. This approach has the potential to reduce time and labor costs and may yield objective and reproducible quantitative measurements of DME imaging biomarkers. PMID:25634978

Automatic Diabetic Macular Edema Detection in Fundus Images Using Publicly Available Datasets

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

Giancardo, Luca; Meriaudeau, Fabrice; Karnowski, Thomas Paul

2011-01-01

Diabetic macular edema (DME) is a common vision threatening complication of diabetic retinopathy. In a large scale screening environment DME can be assessed by detecting exudates (a type of bright lesions) in fundus images. In this work, we introduce a new methodology for diagnosis of DME using a novel set of features based on colour, wavelet decomposition and automatic lesion segmentation. These features are employed to train a classifier able to automatically diagnose DME. We present a new publicly available dataset with ground-truth data containing 169 patients from various ethnic groups and levels of DME. This and other two publiclymore » available datasets are employed to evaluate our algorithm. We are able to achieve diagnosis performance comparable to retina experts on the MESSIDOR (an independently labelled dataset with 1200 images) with cross-dataset testing. Our algorithm is robust to segmentation uncertainties, does not need ground truth at lesion level, and is very fast, generating a diagnosis on an average of 4.4 seconds per image on an 2.6 GHz platform with an unoptimised Matlab implementation.« less

Considerations for management of patients with diabetic macular edema: Optimizing treatment outcomes and minimizing safety concerns through interdisciplinary collaboration.

PubMed

Strain, W David; Cos, Xavier; Prünte, Christian

2017-04-01

Diabetes is a growing worldwide epidemic and a leading cause of blindness in working-age people around the world. Diabetic retinopathy (DR) and diabetic macular edema (DME) are common causes of visual impairment in people with diabetes and often indicate the presence of diabetes-associated preclinical micro- and macrovascular complications. As such, patients with DR and DME often display complex, highly comorbid profiles. Several treatments are currently available for the treatment of DME, including anti-vascular endothelial growth factor (VEGF) agents, which are administered via intravitreal injection. While the safety profiles of approved ocular anti-VEGF therapies have been reassuring, the high-risk nature of the DME patient population means that treatment must be carefully considered and a holistic approach to disease management should be taken. This requires multidisciplinary, collaborative care involving all relevant specialties to ensure that patients not only receive prompt treatment for DME but also appropriate consideration is taken of any systemic comorbidities to evaluate and minimize potentially serious safety issues. Copyright © 2017. Published by Elsevier B.V.

Three-Dimensional Enhanced Imaging of Vitreoretinal Interface in Diabetic Retinopathy Using Swept-Source Optical Coherence Tomography.

PubMed

Adhi, Mehreen; Badaro, Emmerson; Liu, Jonathan J; Kraus, Martin F; Baumal, Caroline R; Witkin, Andre J; Hornegger, Joachim; Fujimoto, James G; Duker, Jay S; Waheed, Nadia K

2016-02-01

To analyze the vitreoretinal interface in diabetic eyes using 3-dimensional wide-field volumes acquired using high-speed, long-wavelength swept-source optical coherence tomography (SSOCT). Prospective cross-sectional study. Fifty-six diabetic patients (88 eyes) and 11 healthy nondiabetic controls (22 eyes) were recruited. Up to 8 SSOCT volumes were acquired for each eye. A registration algorithm removed motion artifacts and merged multiple SSOCT volumes to improve signal. Vitreous visualization was enhanced using vitreous windowing method. Of 88 diabetic eyes, 20 eyes had no retinopathy, 21 eyes had nonproliferative diabetic retinopathy (NPDR) without macular edema, 20 eyes had proliferative diabetic retinopathy (PDR) without macular edema, and 27 eyes had diabetic macular edema (DME) with either NPDR or PDR. Thick posterior hyaloid relative to healthy nondiabetic controls was observed in 0 of 20 (0%) diabetic eyes without retinopathy, 4 of 21 (19%) eyes with NPDR, 11 of 20 (55%) eyes with PDR, and 11 of 27 (41%) eyes with DME (P = .0001). Vitreoschisis was observed in 6 of 22 (27%) healthy nondiabetic eyes, 9 of 20 (45%) diabetic eyes without retinopathy, 10 of 21 (48%) eyes with NPDR, 13 of 20 (65%) eyes with PDR, and 17 of 27 (63%) eyes with DME (P = .007). While no healthy nondiabetic controls and diabetic eyes without retinopathy had adhesions/pegs between detached posterior hyaloid and retina, 1 of 21 (4%), 11 of 20 (55%), and 11 of 27 (41%) eyes with NPDR, PDR, and DME, respectively, demonstrated this feature (P = .0001). SSOCT with motion-correction and vitreous windowing provides wide-field 3-dimensional information of vitreoretinal interface in diabetic eyes. This may be useful in assessing progression of retinopathy, planning diabetic vitreous surgery, and predicting treatment outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Association Between Diabetic Macular Edema and Cardiovascular Events in Type 2 Diabetes Patients: A Multicenter Observational Study.

PubMed

Leveziel, Nicolas; Ragot, Stéphanie; Gand, Elise; Lichtwitz, Olivier; Halimi, Jean Michel; Gozlan, Julien; Gourdy, Pierre; Robert, Marie-Françoise; Dardari, Dured; Boissonnot, Michèle; Roussel, Ronan; Piguel, Xavier; Dupuy, Olivier; Torremocha, Florence; Saulnier, Pierre-Jean; Maréchaud, Richard; Hadjadj, Samy

2015-08-01

Diabetic macular edema (DME) is the main cause of visual loss associated with diabetes but any association between DME and cardiovascular events is unclear.This study aims to describe the possible association between DME and cardiovascular events in a multicenter cross-sectional study of patients with type 2 diabetes.Two thousand eight hundred seven patients with type 2 diabetes were recruited from diabetes and nephrology clinical institutional centers participating in the DIAB 2 NEPHROGENE study focusing on diabetic complications. DME (presence/absence) and diabetic retinopathy (DR) classification were based on ophthalmological report and/or on 30° color retinal photographs. DR was defined as absent, nonproliferative (background, moderate, or severe) or proliferative. Cardiovascular events were stroke, myocardial infarction, and lower limb amputation.Details regarding associations between DME and cardiovascular events were evaluated.The study included 2807 patients with type 2 diabetes, of whom 355 (12.6%) had DME. DME was significantly and independently associated with patient age, known duration of diabetes, HbA1c, systolic blood pressure, and DR stage. Only the prior history of lower limb amputation was strongly associated with DME in univariate and multivariate analyses, whereas no association was found with regard to myocardial infarction or stroke. Moreover, both major (n = 32) and minor lower limb (n = 96) amputations were similarly associated with DME, with respective odds ratio of 3.7 (95% confidence interval [CI], 1.77-7.74; P = 0.0012) and of 4.29 (95% CI, 2.79-6.61; P < 0.001).DME is strongly and independently associated with lower limb amputation in type 2 diabetic patients.

Association Between Diabetic Macular Edema and Cardiovascular Events in Type 2 Diabetes Patients

PubMed Central

Leveziel, Nicolas; Ragot, Stéphanie; Gand, Elise; Lichtwitz, Olivier; Halimi, Jean Michel; Gozlan, Julien; Gourdy, Pierre; Robert, Marie-Françoise; Dardari, Dured; Boissonnot, Michèle; Roussel, Ronan; Piguel, Xavier; Dupuy, Olivier; Torremocha, Florence; Saulnier, Pierre-Jean; Maréchaud, Richard; Hadjadj, Samy

2015-01-01

Abstract Diabetic macular edema (DME) is the main cause of visual loss associated with diabetes but any association between DME and cardiovascular events is unclear. This study aims to describe the possible association between DME and cardiovascular events in a multicenter cross-sectional study of patients with type 2 diabetes. Two thousand eight hundred seven patients with type 2 diabetes were recruited from diabetes and nephrology clinical institutional centers participating in the DIAB 2 NEPHROGENE study focusing on diabetic complications. DME (presence/absence) and diabetic retinopathy (DR) classification were based on ophthalmological report and/or on 30° color retinal photographs. DR was defined as absent, nonproliferative (background, moderate, or severe) or proliferative. Cardiovascular events were stroke, myocardial infarction, and lower limb amputation. Details regarding associations between DME and cardiovascular events were evaluated. The study included 2807 patients with type 2 diabetes, of whom 355 (12.6%) had DME. DME was significantly and independently associated with patient age, known duration of diabetes, HbA1c, systolic blood pressure, and DR stage. Only the prior history of lower limb amputation was strongly associated with DME in univariate and multivariate analyses, whereas no association was found with regard to myocardial infarction or stroke. Moreover, both major (n = 32) and minor lower limb (n = 96) amputations were similarly associated with DME, with respective odds ratio of 3.7 (95% confidence interval [CI], 1.77–7.74; P = 0.0012) and of 4.29 (95% CI, 2.79–6.61; P < 0.001). DME is strongly and independently associated with lower limb amputation in type 2 diabetic patients. PMID:26287408

Fully automatic segmentation of fluorescein leakage in subjects with diabetic macular edema.

PubMed

Rabbani, Hossein; Allingham, Michael J; Mettu, Priyatham S; Cousins, Scott W; Farsiu, Sina

2015-01-29

To create and validate software to automatically segment leakage area in real-world clinical fluorescein angiography (FA) images of subjects with diabetic macular edema (DME). Fluorescein angiography images obtained from 24 eyes of 24 subjects with DME were retrospectively analyzed. Both video and still-frame images were obtained using a Heidelberg Spectralis 6-mode HRA/OCT unit. We aligned early and late FA frames in the video by a two-step nonrigid registration method. To remove background artifacts, we subtracted early and late FA frames. Finally, after postprocessing steps, including detection and inpainting of the vessels, a robust active contour method was utilized to obtain leakage area in a 1500-μm-radius circular region centered at the fovea. Images were captured at different fields of view (FOVs) and were often contaminated with outliers, as is the case in real-world clinical imaging. Our algorithm was applied to these images with no manual input. Separately, all images were manually segmented by two retina specialists. The sensitivity, specificity, and accuracy of manual interobserver, manual intraobserver, and automatic methods were calculated. The mean accuracy was 0.86 ± 0.08 for automatic versus manual, 0.83 ± 0.16 for manual interobserver, and 0.90 ± 0.08 for manual intraobserver segmentation methods. Our fully automated algorithm can reproducibly and accurately quantify the area of leakage of clinical-grade FA video and is congruent with expert manual segmentation. The performance was reliable for different DME subtypes. This approach has the potential to reduce time and labor costs and may yield objective and reproducible quantitative measurements of DME imaging biomarkers. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Subthreshold micropulse laser reduces anti-VEGF injection burden in patients with diabetic macular edema.

PubMed

Moisseiev, Elad; Abbassi, Sam; Thinda, Sumeer; Yoon, Joseph; Yiu, Glenn; Morse, Lawrence S

2018-01-01

To evaluate the efficacy of micropulse laser in the early treatment of diabetic macular edema (DME) and its associated burden of anti-vascular endothelial growth factor (VEGF) injections. This retrospective comparative study compared a group of 19 eyes with DME treated with micropulse laser to a matched control group of 19 eyes with DME treated with ranibizumab injections without micropulse laser. Recorded parameters included previous medical and ocular history, previous and subsequent ranibizumab injections administered for DME, visual acuity (VA), central macular thickness throughout the follow-up period, and the occurrence of any complications. The improvement in VA was comparable in both groups, at 12 months and at the final follow-up. Patients treated with micropulse laser required significantly fewer ranibizumab injections than their controls, both at 12 months (1.7 ± 2.3 vs 5.6 ± 2.1) and by the end of the follow-up (2.6 ± 3.3 vs 9.3 ± 5.1) (p<0.001 for both). No complications related to the micropulse laser were encountered. Micropulse laser is a safe and effective treatment for DME, which may achieve comparable improvement in VA along with a significant reduction in the burden of anti-VEGF injections. We suggest a treatment approach for its inclusion in the early stages of DME.

77 FR 36548 - Dermatologic and Ophthalmic Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-19

... edema (DME). Ranibizumab injection is currently approved for the treatment of neovascular (wet) age-related macular degeneration (AMD) and macular edema following retinal vein occlusion (RVO). During the...

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

Fully automated macular pathology detection in retina optical coherence tomography images using sparse coding and dictionary learning

NASA Astrophysics Data System (ADS)

Sun, Yankui; Li, Shan; Sun, Zhongyang

2017-01-01

We propose a framework for automated detection of dry age-related macular degeneration (AMD) and diabetic macular edema (DME) from retina optical coherence tomography (OCT) images, based on sparse coding and dictionary learning. The study aims to improve the classification performance of state-of-the-art methods. First, our method presents a general approach to automatically align and crop retina regions; then it obtains global representations of images by using sparse coding and a spatial pyramid; finally, a multiclass linear support vector machine classifier is employed for classification. We apply two datasets for validating our algorithm: Duke spectral domain OCT (SD-OCT) dataset, consisting of volumetric scans acquired from 45 subjects-15 normal subjects, 15 AMD patients, and 15 DME patients; and clinical SD-OCT dataset, consisting of 678 OCT retina scans acquired from clinics in Beijing-168, 297, and 213 OCT images for AMD, DME, and normal retinas, respectively. For the former dataset, our classifier correctly identifies 100%, 100%, and 93.33% of the volumes with DME, AMD, and normal subjects, respectively, and thus performs much better than the conventional method; for the latter dataset, our classifier leads to a correct classification rate of 99.67%, 99.67%, and 100.00% for DME, AMD, and normal images, respectively.

Fully automated macular pathology detection in retina optical coherence tomography images using sparse coding and dictionary learning.

PubMed

Sun, Yankui; Li, Shan; Sun, Zhongyang

2017-01-01

We propose a framework for automated detection of dry age-related macular degeneration (AMD) and diabetic macular edema (DME) from retina optical coherence tomography (OCT) images, based on sparse coding and dictionary learning. The study aims to improve the classification performance of state-of-the-art methods. First, our method presents a general approach to automatically align and crop retina regions; then it obtains global representations of images by using sparse coding and a spatial pyramid; finally, a multiclass linear support vector machine classifier is employed for classification. We apply two datasets for validating our algorithm: Duke spectral domain OCT (SD-OCT) dataset, consisting of volumetric scans acquired from 45 subjects—15 normal subjects, 15 AMD patients, and 15 DME patients; and clinical SD-OCT dataset, consisting of 678 OCT retina scans acquired from clinics in Beijing—168, 297, and 213 OCT images for AMD, DME, and normal retinas, respectively. For the former dataset, our classifier correctly identifies 100%, 100%, and 93.33% of the volumes with DME, AMD, and normal subjects, respectively, and thus performs much better than the conventional method; for the latter dataset, our classifier leads to a correct classification rate of 99.67%, 99.67%, and 100.00% for DME, AMD, and normal images, respectively.

Subconjunctival sirolimus in the treatment of diabetic macular edema

PubMed Central

Krishnadev, Nupura; Forooghian, Farzin; Cukras, Catherine; Wong, Wai; Saligan, Leorey; Chew, Emily Y.; Nussenblatt, Robert; Ferris, Frederick

2011-01-01

Background Diabetic macular edema (DME) is a leading cause of blindness in the developed world. Sirolimus has been shown to inhibit the production, signaling, and activity of many growth factors relevant to the development of diabetic retinopathy. This phase I/II study assesses the safety of multiple subconjunctival sirolimus injections for the treatment of DME, with some limited efficacy data. Methods In this phase I/II prospective, open-label pilot study, five adult participants with diabetic macular edema involving the center of the fovea and best-corrected ETDRS visual acuity score of ≤74 letters (20/32 or worse) received 20 μl (440 μg) of subconjunctival sirolimus at baseline, month 2 and every 2 months thereafter, unless there was resolution of either retinal thickening on OCT or leakage on fluorescein angiography. Main outcome measures included best-corrected visual acuity and central retinal thickness on OCT at 6 months and 1 year, as well as safety outcomes. Results Repeated subconjunctival sirolimus injections were well-tolerated, with no significant drug-related adverse events. There was no consistent treatment effect related to sirolimus; one participant experienced a 2-line improvement in visual acuity and 2 log unit decrease in retinal thickness at 6 months and 1 year, two remained essentially stable, one had stable visual acuity but improvement of central retinal thickness of 1 and 3 log units at 6 months and 1 year respectively, and one had a 2-line worsening of visual acuity and a 1 log unit increase in retinal thickness at 6 months and 1 year. Results in the fellow eyes with diabetic macular edema, not treated with sirolimus, were similar. Conclusions Subconjunctival sirolimus appears safe to use in patients with DME. Assessment of possible treatment benefit will require a randomized trial. PMID:21567211

Neural Retinal Disorganization as a Robust Marker of Visual Acuity in Current and Resolved Diabetic Macular Edema

PubMed Central

Radwan, Salma H.; Soliman, Ahmed Z.; Lammer, Jan; Lin, Michael M.; Prager, Sonja G.; Silva, Paolo S.; Aiello, Lloyd Bryce; Aiello, Lloyd Paul

2015-01-01

Despite treatment advances, diabetic eye disease remains a leading cause of visual acuity (VA) loss worldwide. No methods to prospectively determine which patients will gain or lose vision exist, limiting individualized risk assessment and management. We investigated whether noninvasive, readily obtainable spectral domain optical coherence tomography parameters were correlated with VA in eyes with current or resolved center-involved diabetic macular edema (DME). Images were evaluated for disorganization of the retinal inner layers (DRIL), cysts, epiretinal membranes, microaneurysms, subretinal fluid, and outer layer disruption/reflectivity. DRIL affecting ≥50% of the 1-mm central retinal zone was associated with worse VA in all eyes, eyes with current edema, and eyes with resolved edema. Furthermore, early 4-month change in DRIL extent predicted VA change from baseline to 1 year. These data suggest that DRIL is a robust predictor of VA in eyes with present or previous DME and more highly correlated with VA than other widely used measures, such as retinal thickness. If further studies confirm DRIL as a predictive biomarker of future VA, physicians would gain a new tool of substantial clinical and investigative importance that could significantly change the approach to ophthalmic counseling and therapeutic management in patients with diabetes. PMID:25633419

Diabetic Macular Edema.

PubMed

Gundogan, Fatih C; Yolcu, Umit; Akay, Fahrettin; Ilhan, Abdullah; Ozge, Gokhan; Uzun, Salih

2016-01-01

Diabetic macular edema (DME), one the most prevalent causes of visual loss in industrialized countries, may be diagnosed at any stage of diabetic retinopathy. The diagnosis, treatment, and follow up of DME have become straightforward with recent developments in fundus imaging, such as optical coherence tomography. Laser photocoagulation, intravitreal injections, and pars plana vitrectomy surgery are the current treatment modalities; however, the positive effects of currently available intravitreally injected agents are temporary. At this point, further treatment choices are needed for a permanent effect. The articles published between 1985-2015 years on major databases were searched and most appropriate 40 papers were used to write this review article.

Efficacy of Intravitreal Anti-vascular Endothelial Growth Factor or Steroid Injection in Diabetic Macular Edema According to Fluid Turbidity in Optical Coherence Tomography

PubMed Central

Lee, Kyungmin; Chung, Heeyoung; Park, Youngsuk

2014-01-01

Purpose To determine if short term effects of intravitreal anti-vascular endothelial growth factor or steroid injection are correlated with fluid turbidity, as detected by spectral domain optical coherence tomography (SD-OCT) in diabetic macular edema (DME) patients. Methods A total of 583 medical records were reviewed and 104 cases were enrolled. Sixty eyes received a single intravitreal bevacizumab injection (IVB) on the first attack of DME and 44 eyes received triamcinolone acetonide treatment (IVTA). Intraretinal fluid turbidity in DME patients was estimated with initialintravitreal SD-OCT and analyzed with color histograms from a Photoshop program. Central macular thickness and visual acuity using a logarithm from the minimum angle of resolution chart, were assessed at the initial period and 2 months after injections. Results Visual acuity and central macular thickness improved after injections in both groups. In the IVB group, visual acuity and central macular thickness changed less as the intraretinal fluid became more turbid. In the IVTA group, visual acuity underwent less change while central macular thickness had a greater reduction (r = -0.675, p = 0.001) as the intraretinal fluid was more turbid. Conclusions IVB and IVTA injections were effective in reducing central macular thickness and improving visual acuity in DME patients. Further, fluid turbidity, which was detected by SD-OCT may be one of the indexes that highlight the influence of the steroid-dependent pathogenetic mechanism. PMID:25120338

Comparison of Standardized Clinical Classification with Fundus Photograph Grading for the assessment of Diabetic Retinopathy and Diabetic Macular Edema Severity

PubMed Central

Gangaputra, Sapna; Lovato, James F.; Hubbard, Larry; Davis, Matthew D; Esser, Barbara A; Ambrosius, Walter T.; Chew, Emily Y.; Greven, Craig; Perdue, Letitia H; Wong, Wai T.; Condren, Audree; Wilkinson, Charles P.; Agrón, Elvira; Adler, Sharon; Danis, Ronald P

2013-01-01

Purpose To compare evaluation by clinical examination with image grading at a reading center (RC) for the classification of diabetic retinopathy (DR) and diabetic macular edema (DME). Methods ACCORD and FIND had similar methods of clinical and fundus photograph evaluation. For analysis purposes the photographic grading scales were condensed to correspond to the clinical scales and agreement between clinicians and reading center classification were compared. Results 6902 eyes of ACCORD participants and 3638 eyes of FIND participants were analyzed for agreement (percent, kappa) on DR on a 5 level scale. Exact agreement between clinicians and RC on DR severity category was 69% in ACCORD and 74% in FIND (Kappa 0.42 and 0.65). Sensitivity of the clinical grading to identify presence of mild nonproliferative retinopathy or worse was 0.53 in ACCORD and 0.84 in FIND. Specificities were 0.97 and 0.96, respectively. DME agreement in 6649 eyes of ACCORD participants and 3366 eyes of FIND participants was similar in both studies (Kappa 0.35 and 0.41). Sensitivities of the clinical grading to identify DME were 0.44 and 0.53 and specificities were 0.99 and 0.94, respectively. Conclusion Our results support the use of clinical information for defining broad severity categories, but not for documenting small to moderate changes in DR over time. PMID:23615341

Diabetic Macular Edema: From Old Concepts to New Therapeutic Avenues

PubMed Central

Mansour, Ahmad M; Pulido, Jose S; Arevalo, J Fernando

2015-01-01

Diabetic macular edema (DME) is a significant cause of blindness in the working population and is currently challenging to treat. Current interventions include focal laser or intravitreal injections. This article outlines a new treatment protocol based on the theory that peripheral ischemia is the precursor to angiogenesis, which will ultimately gather its momentum at the fovea. Extreme peripheral light laser panretinal photocoagulation (PRP) back to the equator reduces excessive production of the vascular endothelial growth factor (VEGF) in the eye. This decreases VEGF-induced DME and provides long-term protection against the development of neovascularization. Initial exacerbation of DME often accompanies PRP. Therefore, injections of anti-VEGF agents (with or without dexamethasone implants) initially can forestall worsening of DME and prevent loss of vision. However, on the other hand, applying peripheral PRP and intraocular injections can induce posterior vitreous detachment (PVD). This could help release vitreomacular adhesions (VMA) and vitreomacular traction (VMT), thereby decreasing DME severity and improving the response to intravitreal injections. In the current approach, peripheral retinal photocoagulation should stop the drive for VEGF release; moreover, laser ablation should produce secondary, accidental, and beneficial PVD. This approach precludes focal laser therapy and paves the path for prolonged intervals between anti-VEGF therapy. PMID:27800500

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

PubMed

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

2017-08-01

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

A Review of Ranibizumab for the Treatment of Diabetic Retinopathy.

PubMed

Stewart, Michael W

2017-06-01

Laser photocoagulation has been the standard treatment for diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) for several decades. The discovery of vascular endothelial growth factor (VEGF) and the subsequent determination of its critical role in the development DME and PDR has led to the development of VEGF inhibitory drugs. Ranibizumab was the first anti-VEGF drug approved for the treatment of both DME and diabetic retinopathy in eyes with DME. Medline searches with the keywords "ranibizumab," "diabetic macular edema," and "proliferative diabetic retinopathy" were performed to identify pertinent pre-clinical studies and clinical trials. Top-line data, with emphasis on pivotal trials, was identified and incorporated into this manuscript. Findings from small uncontrolled trials were generally not used unless they filled important gaps in our understanding of anti-VEGF therapy. Ranibizumab is a recombinant humanized antibody fragment that binds all isoforms of VEGF-A with high affinity. Three parallel lines of clinical research have produced level I evidence supporting the superiority of ranibizumab over laser photocoagulation for the treatment of DME. Regular injections also lead to improvement in diabetic retinopathy severity scores in a large minority of eyes. Ranibizumab is effective for PDR and produces less visual field loss than laser photocoagulation. It has an excellent safety profile, with low incidence of ocular and systemic adverse events. Ranibizumab has become a frequently used first-line therapy for the treatment of DME. Emerging data suggest that it may become an important treatment for DR and PDR.

Diabetic Macular Edema

PubMed Central

Gundogan, Fatih C.; Yolcu, Umit; Akay, Fahrettin; Ilhan, Abdullah; Ozge, Gokhan; Uzun, Salih

2016-01-01

Diabetic macular edema (DME), one the most prevalent causes of visual loss in industrialized countries, may be diagnosed at any stage of diabetic retinopathy. The diagnosis, treatment, and follow up of DME have become straightforward with recent developments in fundus imaging, such as optical coherence tomography. Laser photocoagulation, intravitreal injections, and pars plana vitrectomy surgery are the current treatment modalities; however, the positive effects of currently available intravitreally injected agents are temporary. At this point, further treatment choices are needed for a permanent effect. Sources of data selection: The articles published between 1985-2015 years on major databases were searched and most appropriate 40 papers were used to write this review article. PMID:27182271

Machine learning techniques for diabetic macular edema (DME) classification on SD-OCT images.

PubMed

Alsaih, Khaled; Lemaitre, Guillaume; Rastgoo, Mojdeh; Massich, Joan; Sidibé, Désiré; Meriaudeau, Fabrice

2017-06-07

Spectral domain optical coherence tomography (OCT) (SD-OCT) is most widely imaging equipment used in ophthalmology to detect diabetic macular edema (DME). Indeed, it offers an accurate visualization of the morphology of the retina as well as the retina layers. The dataset used in this study has been acquired by the Singapore Eye Research Institute (SERI), using CIRRUS TM (Carl Zeiss Meditec, Inc., Dublin, CA, USA) SD-OCT device. The dataset consists of 32 OCT volumes (16 DME and 16 normal cases). Each volume contains 128 B-scans with resolution of 1024 px × 512 px, resulting in more than 3800 images being processed. All SD-OCT volumes are read and assessed by trained graders and identified as normal or DME cases based on evaluation of retinal thickening, hard exudates, intraretinal cystoid space formation, and subretinal fluid. Within the DME sub-set, a large number of lesions has been selected to create a rather complete and diverse DME dataset. This paper presents an automatic classification framework for SD-OCT volumes in order to identify DME versus normal volumes. In this regard, a generic pipeline including pre-processing, feature detection, feature representation, and classification was investigated. More precisely, extraction of histogram of oriented gradients and local binary pattern (LBP) features within a multiresolution approach is used as well as principal component analysis (PCA) and bag of words (BoW) representations. Besides comparing individual and combined features, different representation approaches and different classifiers are evaluated. The best results are obtained for LBP[Formula: see text] vectors while represented and classified using PCA and a linear-support vector machine (SVM), leading to a sensitivity(SE) and specificity (SP) of 87.5 and 87.5%, respectively.

Distribution of Nonperfusion Area on Ultra-widefield Fluorescein Angiography in Eyes With Diabetic Macular Edema: DAVE Study.

PubMed

Fan, Wenying; Wang, Kang; Ghasemi Falavarjani, Khalil; Sagong, Min; Uji, Akihito; Ip, Michael; Wykoff, Charles C; Brown, David M; van Hemert, Jano; Sadda, SriniVas R

2017-08-01

To explore the distribution of nonperfusion area (NPA) in eyes with diabetic macular edema (DME) and its relationship with the severity of DME. Prospective, observational case series. Forty eyes of 29 patients with treatment-naïve DME who participated in the DAVE study (NCT01552408) were included. Ultra-widefield fluorescein angiography images were sent to the Doheny Image Reading Center, where they were montaged and corrected using stereographic projection to adjust for peripheral distortion. Two experienced, independent/masked certified graders manually segmented the NPA and the total visible retinal area (TRA), and computed the NPA and TRA in square millimeters (mm 2 ). The ischemic index (ISI) was calculated. The distributions of NPA and ISI within different retinal zones were correlated with the severity of DME. In 40 eyes with treatment-naïve DME (mean age, 55.8 years) visual acuity (VA) (mean 59.6 EDTRS letters) was correlated with central macular thickness (CMT) (mean 536.9 μm, R = -0.418, P = .008) and macular volume (MV) (mean 11.9 mm 3 , R = -0.449, P = .004). The NPA and ISI among the different retinal zones were significantly different (NPA: P < .001; ISI: P = .005). The NPA and ISI in the midperiphery were negatively associated with CMT (NPA: P = .04; ISI: P = .02). However, the global NPA and ISI for the entire retina were not associated with CMT or MV (P > .05). In eyes with DME, the ISI increases with increasing distance from the fovea. The severity of DME does not appear to correlate with global NPA and ISI. Copyright © 2017 Elsevier Inc. All rights reserved.

Interdigitation Zone Band Restoration After Treatment of Diabetic Macular Edema.

PubMed

Serizawa, Satoshi; Ohkoshi, Kishiko; Minowa, Yuko; Soejima, Kumiko

2016-09-01

To investigate whether the integrity of the interdigitation zone band, the ellipsoid zone band, and the external limiting membrane are reliable markers of treatment outcome in diabetic macular edema (DME). In this retrospective study, we examined 41 treatment-naïve eyes (38 patients) with DME that were treated with laser therapy, pharmacotherapy, and/or vitrectomy. Best-corrected visual acuity and the integrity of the interdigitation zone band, the ellipsoid zone band, and the external limiting membrane were assessed before treatment and at 3, 6, and 12 months after DME treatment. One year after treatment, the external limiting membrane, ellipsoid zone band, and interdigitation zone band were completely visible in 30 (73.2%), 24 (58.5%), and 2 (4.9%) eyes, respectively. Interdigitation zone band status improved significantly (P = 0.005) 1 year after treatment. The interdigitation zone did not improve in the absence of the ellipsoid zone band. Likewise, ellipsoid zone status did not improve in the absence of the external limiting membrane at any time after treatment. The results of this study show that restoration of the interdigitation zone band constitutes a very sensitive marker of DME treatment outcome when the ellipsoid zone band is visible before treatment.

Exudate-based diabetic macular edema detection in fundus images using publicly available datasets

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

Giancardo, Luca; Meriaudeau, Fabrice; Karnowski, Thomas Paul

2011-01-01

Diabetic macular edema (DME) is a common vision threatening complication of diabetic retinopathy. In a large scale screening environment DME can be assessed by detecting exudates (a type of bright lesions) in fundus images. In this work, we introduce a new methodology for diagnosis of DME using a novel set of features based on colour, wavelet decomposition and automatic lesion segmentation. These features are employed to train a classifier able to automatically diagnose DME through the presence of exudation. We present a new publicly available dataset with ground-truth data containing 169 patients from various ethnic groups and levels of DME.more » This and other two publicly available datasets are employed to evaluate our algorithm. We are able to achieve diagnosis performance comparable to retina experts on the MESSIDOR (an independently labelled dataset with 1200 images) with cross-dataset testing (e.g., the classifier was trained on an independent dataset and tested on MESSIDOR). Our algorithm obtained an AUC between 0.88 and 0.94 depending on the dataset/features used. Additionally, it does not need ground truth at lesion level to reject false positives and is computationally efficient, as it generates a diagnosis on an average of 4.4 s (9.3 s, considering the optic nerve localization) per image on an 2.6 GHz platform with an unoptimized Matlab implementation.« less

Classification of SD-OCT volumes for DME detection: an anomaly detection approach

NASA Astrophysics Data System (ADS)

Sankar, S.; Sidibé, D.; Cheung, Y.; Wong, T. Y.; Lamoureux, E.; Milea, D.; Meriaudeau, F.

2016-03-01

Diabetic Macular Edema (DME) is the leading cause of blindness amongst diabetic patients worldwide. It is characterized by accumulation of water molecules in the macula leading to swelling. Early detection of the disease helps prevent further loss of vision. Naturally, automated detection of DME from Optical Coherence Tomography (OCT) volumes plays a key role. To this end, a pipeline for detecting DME diseases in OCT volumes is proposed in this paper. The method is based on anomaly detection using Gaussian Mixture Model (GMM). It starts with pre-processing the B-scans by resizing, flattening, filtering and extracting features from them. Both intensity and Local Binary Pattern (LBP) features are considered. The dimensionality of the extracted features is reduced using PCA. As the last stage, a GMM is fitted with features from normal volumes. During testing, features extracted from the test volume are evaluated with the fitted model for anomaly and classification is made based on the number of B-scans detected as outliers. The proposed method is tested on two OCT datasets achieving a sensitivity and a specificity of 80% and 93% on the first dataset, and 100% and 80% on the second one. Moreover, experiments show that the proposed method achieves better classification performances than other recently published works.

Rationale for the Diabetic Retinopathy Clinical Research Network Treatment Protocol for Center-involved Diabetic Macular Edema

PubMed Central

Aiello, Lloyd Paul; Beck, Roy W; Bressler, Neil M.; Browning, David J.; Chalam, KV; Davis, Matthew; Ferris, Frederick L; Glassman, Adam; Maturi, Raj; Stockdale, Cynthia R.; Topping, Trexler

2011-01-01

Objective Describe the underlying principles used to develop a web-based algorithm that incorporated intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy Clinical Research Network (DRCR.net) randomized clinical trial. Design Discussion of treatment protocol for DME. Participants Subjects with vision loss from DME involving the center of the macula. Methods The DRCR.net created an algorithm incorporating anti-VEGF injections in a comparative effectiveness randomized clinical trial evaluating intravitreal ranibizumab with prompt or deferred (≥24 weeks) focal/grid laser in eyes with vision loss from center-involved DME. Results confirmed that intravitreal ranibizumab with prompt or deferred laser provides superior visual acuity outcomes, compared with prompt laser alone through at least 2 years. Duplication of this algorithm may not be practical for clinical practice. In order to share their opinion on how ophthalmologists might emulate the study protocol, participating DRCR.net investigators developed guidelines based on the algorithm's underlying rationale. Main Outcome Measures Clinical guidelines based on a DRCR.net protocol. Results The treatment protocol required real time feedback from a web-based data entry system for intravitreal injections, focal/grid laser, and follow-up intervals. Guidance from this system indicated whether treatment was required or given at investigator discretion and when follow-up should be scheduled. Clinical treatment guidelines, based on the underlying clinical rationale of the DRCR.net protocol, include repeating treatment monthly as long as there is improvement in edema compared with the previous month, or until the retina is no longer thickened. If thickening recurs or worsens after discontinuing treatment, treatment is resumed. Conclusions Duplication of the approach used in the DRCR.net randomized clinical trial to treat DME involving the center of the macula with intravitreal ranibizumab may not be practical in clinical practice, but likely can be emulated based on an understanding of the underlying rationale for the study protocol. Inherent differences between a web-based treatment algorithm and a clinical approach may lead to differences in outcomes that are impossible to predict. The closer the clinical approach is to the algorithm used in the study, the more likely the outcomes will be similar to those published. PMID:22136692

Optical Coherence Tomography Measurements and Analysis Methods in Optical Coherence Tomography Studies of Diabetic Macular Edema

PubMed Central

Browning, David J.; Glassman, Adam R.; Aiello, Lloyd P.; Bressler, Neil M.; Bressler, Susan; Danis, Ronald P.; Davis, Matthew D.; Ferris, Frederick L.; Huang, Suber S.; Kaiser, Peter K.; Kollman, Craig; Sadda, Srinavas; Scott, Ingrid U.; Qin, Haijing

2009-01-01

Objective To evaluate optical coherence tomography (OCT) measurements and methods of analysis of OCT data in studies of diabetic macular edema (DME). Design Associations of pairs of OCT variables and results of three analysis methods using data from two studies of DME. Participants Two hundred sixty-three subjects from a study of modified Early Treatment of Diabetic Retinopathy Study (mETDRS) versus modified macular grid (MMG) photocoagulation for DME and 96 subjects from a study of diurnal variation of DME. Methods Correlations were calculated for pairs of OCT variables at baseline and for changes in the variables over time. Distribution of OCT measurement changes, predictive factors for OCT measurement changes, and treatment group outcomes were compared when three measures of change in macular thickness were analyzed: absolute change in retinal thickness, relative change in retinal thickness, and relative change in retinal thickening. Main Outcome Measures Concordance of results using different OCT variables and analysis methods. Results Center point thickness correlated highly with central subfield mean thickness (CSMT) at baseline (0.98–0.99). The distributions of changes in CSMT were approximately normally distributed for absolute change in retinal thickness and relative change in retinal thickness, but not for relative change in retinal thickening. The macular thinning in the mETDRS group was significantly greater than in the MMG group when absolute change in retinal thickness was used, but not when relative change in thickness and relative change in thickening were used. Relative change in macular thickening provides unstable data in eyes with mild degrees of baseline thickening, unlike the situation with absolute or relative change in retinal thickness. Conclusions Central subfield mean thickness is the preferred OCT measurement for the central macula because of its higher reproducibility and correlation with other measurements of the central macula. Total macular volume may be preferred when the central macula is less important. Absolute change in retinal thickness is the preferred analysis method in studies involving eyes with mild macular thickening. Relative change in thickening may be preferable when retinal thickening is more severe. PMID:18675696

Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA).

PubMed

Schmidt-Erfurth, Ursula; Garcia-Arumi, Jose; Bandello, Francesco; Berg, Karina; Chakravarthy, Usha; Gerendas, Bianca S; Jonas, Jost; Larsen, Michael; Tadayoni, Ramin; Loewenstein, Anat

2017-01-01

Diabetic retinal disease is envisioned to become the plague of the coming decades with a steep increase of worldwide diabetes incidence followed by a substantial rise in retinal disease. Improvements in diagnostic and therapeutic care have to cope with this dilemma in a clinically and socioeconomically efficient manner. Laser treatment has found a less destructive competitor in pharmacological treatments. As a consequence of recent rigorous clinical trials, laser photocoagulation is no longer recommended for the treatment of diabetic macular edema (DME), and anti-vascular endothelial growth factor therapy has emerged as first-line therapy. Steroids have maintained a role in the management of chronically persistent DME. The paradigm shifts in therapy are accompanied by a substantial break-through in diagnostics. The following guidance for the management of DME has been composed from the best updated knowledge of leading experts in Europe and represents another volume in the series of EURETINA recommendations for the management of retinal disease. © 2017 S. Karger AG, Basel.

Association of Diabetic Macular Edema and Proliferative Diabetic Retinopathy With Cardiovascular Disease: A Systematic Review and Meta-analysis.

PubMed

Xie, Jing; Ikram, M Kamran; Cotch, Mary Frances; Klein, Barbara; Varma, Rohit; Shaw, Jonathan E; Klein, Ronald; Mitchell, Paul; Lamoureux, Ecosse L; Wong, Tien Yin

2017-06-01

Previous studies on the relationship between diabetic retinopathy (DR) and cardiovascular disease (CVD) focused on the early stages of DR. Understanding whether patients with type 2 diabetes and severe stages of DR (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]) have a higher risk of CVD will allow physicians to more effectively counsel patients. To examine the association of severe stages of DR (DME and PDR) with incident CVD in patients with type 2 diabetes. English-language publications were reviewed for articles evaluating the relationship of DR and CVD in MEDLINE, EMBASE, Current Contents, and the Cochrane Library from inception (January 1, 1950) to December 31, 2014, using the search terms diabetic retinopathy OR macular edema AND stroke OR cerebrovascular disease OR coronary artery disease OR heart failure OR myocardial infarction OR angina pectoris OR acute coronary syndrome OR coronary artery disease OR cardiomyopathy. Among 656 studies screened for eligibility, 7604 individuals were included from 8 prospective population-based studies with data on photographic-based DR grading, follow-up visits, and well-defined incident CVD end point. Two independent reviewers conducted a systematic search of the 4 databases, and a single pooled database was developed. Incidence rate ratios (IRRs) were estimated for patients with DME, PDR, and vision-threatening DR, compared with persons without these conditions, by using individual participant data followed by a standard inverse-variance meta-analysis (2-step analysis). The review and analyses were performed from January 1, 2009, to January 1, 2017. Incident CVD, including coronary heart disease, stroke, or death from cardiovascular causes. Among 7604 patients with type 2 diabetes, the prevalence of DME was 4.6% and PDR, 7.4%. After a mean follow-up of 5.9 years (range, 3.2-10.1 years), 1203 incident CVD events, including 916 coronary heart disease cases, were reported. Persons with DME or PDR were more likely to have incident CVD (IRR, 1.39; 95% CI, 1.16-1.67) and fatal CVD (IRR, 2.33; 95% CI, 1.49-3.67) compared with those without DME or PDR. Patients with type 2 diabetes and DME or PDR have an increased risk of incident CVD, which suggests that these persons should be followed up more closely to prevent CVD.

Surgical Versus Medical Treatment for Diabetic Macular Edema: A Review

PubMed Central

CRIM, Nicolás; VELEZ-MONTOYA, Raúl; MORALES-CANTON, Virgilio

2017-01-01

We aimed to compare the results of pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling, an alternative therapeutic strategy, with those of medical treatment for chronic macular edema. We conducted a review of the literature on the microscopic, anatomical, and functional reasons for performing PPV with ILM peeling in patients with diabetic macular edema (DME). We searched the PubMed database for articles published between 2000 and 2017. We used the medical subject heading “vitrectomy diabetic macular edema” and the keywords “diabetic macular edema”, “internal limiting membrane peeling”, “pars plana vitrectomy”, “diabetic retinopathy”, and “optical coherence tomography”. Analysis of the literature revealed that cytokines, vascular endothelial growth factor, reactive oxygen species (ROS), and advanced glycation end-products (AGEs) play a unique role in DME. The vitreous cavity serves as a physiological reservoir for all inflammatory molecules. AGE receptors are localized at the footplates of Müller cells and the external limiting membrane (ELM). The footplates of Müller cells are in contact with the ILM, which suggests that they might be responsible for the structural damage (i.e., thickening) observed in the ILM of patients with DME. Therefore, PPV could allow a reduction of cytokines and pro-inflammatory molecules from the vitreous cavity. ILM peeling could eliminate not only the physical traction of a thickened structure, but also the natural reservoir of AGEs, ROS, and inflammatory molecules. PPV with ILM peeling is a surgical option that should be considered when treating patients with chronic DME. PMID:29560368

Optical coherence tomography measurements and analysis methods in optical coherence tomography studies of diabetic macular edema.

PubMed

Browning, David J; Glassman, Adam R; Aiello, Lloyd P; Bressler, Neil M; Bressler, Susan B; Danis, Ronald P; Davis, Matthew D; Ferris, Frederick L; Huang, Suber S; Kaiser, Peter K; Kollman, Craig; Sadda, Srinavas; Scott, Ingrid U; Qin, Haijing

2008-08-01

To evaluate optical coherence tomography (OCT) measurements and methods of analysis of OCT data in studies of diabetic macular edema (DME). Associations of pairs of OCT variables and results of 3 analysis methods using data from 2 studies of DME. Two hundred sixty-three subjects from a study of modified Early Treatment of Diabetic Retinopathy Study (mETDRS) versus modified macular grid (MMG) photocoagulation for DME and 96 subjects from a study of diurnal variation of DME. Correlations were calculated for pairs of OCT variables at baseline and for changes in the variables over time. Distribution of OCT measurement changes, predictive factors for OCT measurement changes, and treatment group outcomes were compared when 3 measures of change in macular thickness were analyzed: absolute change in retinal thickness, relative change in retinal thickness, and relative change in retinal thickening. Concordance of results using different OCT variables and analysis methods. Center point thickness correlated highly with central subfield mean thickness (CSMT) at baseline (0.98-0.99). The distributions of changes in CSMT were approximately normally distributed for absolute change in retinal thickness and relative change in retinal thickness, but not for relative change in retinal thickening. Macular thinning in the mETDRS group was significantly greater than in the MMG group when absolute change in retinal thickness was used, but not when relative change in thickness and relative change in thickening were used. Relative change in macular thickening provides unstable data in eyes with mild degrees of baseline thickening, unlike the situation with absolute or relative change in retinal thickness. Central subfield mean thickness is the preferred OCT measurement for the central macula because of its higher reproducibility and correlation with other measurements of the central macula. Total macular volume may be preferred when the central macula is less important. Absolute change in retinal thickness is the preferred analysis method in studies involving eyes with mild macular thickening. Relative change in thickening may be preferable when retinal thickening is more severe.

Motion detection and compensation in infrared retinal image sequences.

PubMed

Scharcanski, J; Schardosim, L R; Santos, D; Stuchi, A

2013-01-01

Infrared image data captured by non-mydriatic digital retinography systems often are used in the diagnosis and treatment of the diabetic macular edema (DME). Infrared illumination is less aggressive to the patient retina, and retinal studies can be carried out without pupil dilation. However, sequences of infrared eye fundus images of static scenes, tend to present pixel intensity fluctuations in time, and noisy and background illumination changes pose a challenge to most motion detection methods proposed in the literature. In this paper, we present a retinal motion detection method that is adaptive to background noise and illumination changes. Our experimental results indicate that this method is suitable for detecting retinal motion in infrared image sequences, and compensate the detected motion, which is relevant in retinal laser treatment systems for DME. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cone Photoreceptor Irregularity on Adaptive Optics Scanning Laser Ophthalmoscopy Correlates With Severity of Diabetic Retinopathy and Macular Edema

PubMed Central

Lammer, Jan; Prager, Sonja G.; Cheney, Michael C.; Ahmed, Amel; Radwan, Salma H.; Burns, Stephen A.; Silva, Paolo S.; Sun, Jennifer K.

2016-01-01

Purpose To determine whether cone density, spacing, or regularity in eyes with and without diabetes (DM) as assessed by high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) correlates with presence of diabetes, diabetic retinopathy (DR) severity, or presence of diabetic macular edema (DME). Methods Participants with type 1 or 2 DM and healthy controls underwent AOSLO imaging of four macular regions. Cone assessment was performed by independent graders for cone density, packing factor (PF), nearest neighbor distance (NND), and Voronoi tile area (VTA). Regularity indices (mean/SD) of NND (RI-NND) and VTA (RI-VTA) were calculated. Results Fifty-three eyes (53 subjects) were assessed. Mean ± SD age was 44 ± 12 years; 81% had DM (duration: 22 ± 13 years; glycated hemoglobin [HbA1c]: 8.0 ± 1.7%; DM type 1: 72%). No significant relationship was found between DM, HbA1c, or DR severity and cone density or spacing parameters. However, decreased regularity of cone arrangement in the macular quadrants was correlated with presence of DM (RI-NND: P = 0.04; RI-VTA: P = 0.04), increasing DR severity (RI-NND: P = 0.04), and presence of DME (RI-VTA: P = 0.04). Eyes with DME were associated with decreased density (P = 0.04), PF (P = 0.03), and RI-VTA (0.04). Conclusions Although absolute cone density and spacing don't appear to change substantially in DM, decreased regularity of the cone arrangement is consistently associated with the presence of DM, increasing DR severity, and DME. Future AOSLO evaluation of cone regularity is warranted to determine whether these changes are correlated with, or predict, anatomic or functional deficits in patients with DM. PMID:27926754

Communications between intraretinal and subretinal space on optical coherence tomography of neurosensory retinal detachment in diabetic macular edema

PubMed Central

Gupta, Aditi; Raman, Rajiv; Mohana, KP; Kulothungan, Vaitheeswaran; Sharma, Tarun

2013-01-01

Background: The pathogenesis of development and progression of neurosensory retinal detachment (NSD) in diabetic macular edema (DME) is not yet fully understood. The purpose of this study is to describe the spectral domain optical coherence tomography (SD-OCT) morphological characteristics of NSD associated with DME in the form of outer retinal communications and to assess the correlation between the size of communications and various factors. Materials and Methods: This was an observational retrospective nonconsecutive case series in a tertiary care eye institute. We imaged NSD and outer retinal communications in 17 eyes of 16 patients having NSD associated with DME using SD-OCT. We measured manually the size of the outer openings of these communications and studied its correlation with various factors. Statistical analysis (correlation test) was performed using the Statistical Package for Social Sciences (SPSS) software (version 14.0). The main outcome measures were correlation of the size of communications with dimensions of NSD, presence of subretinal hyper-reflective dots, and best-corrected visual acuity (BCVA). Results: The communications were seen as focal defects of the outer layers of elevated retina. With increasing size of communication, there was increase in height of NSD (r = 0.701, P = 0.002), horizontal diameter of NSD (r = 0.695, P = 0.002), and the number of hyper-reflective dots in the subretinal space (r = 0.729, P = 0.002). The minimum angle of resolution (logMAR) BCVA increased with the increasing size of communications (r = 0.827, P < 0.0001). Conclusions: Outer retinal communications between intra and subretinal space were noted in eyes having NSD associated with DME. The size of communications correlated positively with the size of NSD and subretinal detachment space hyper-reflective dots, and inversely with BCVA. PMID:24379554

A Randomized Trial Comparing Intravitreal Triamcinolone Acetonide and Focal/Grid Photocoagulation for Diabetic Macular Edema

PubMed Central

2009-01-01

Objective To evaluate the efficacy and safety of 1 mg and 4 mg doses of preservative-free intravitreal triamcinolone in comparison with focal/grid photocoagulation for the treatment of diabetic macular edema (DME). Design Multi-center randomized clinical trial Participants 840 study eyes of 693 subjects with DME involving the fovea and visual acuity 20/40 to 20/320 Methods Eyes were randomized to focal/grid photocoagulation (N=330), 1 mg intravitreal triamcinolone (N=256), or 4 mg intravitreal triamcinolone (N=254). Retreatment was given for persistent or new edema at 4-month intervals. The primary outcome was at 2 years. Main Outcome Measures Visual acuity measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) method (primary), optical coherence tomography (OCT)-measured retinal thickness (secondary), and safety. Results At 4 months, mean visual acuity was better in the 4 mg triamcinolone group than in either the laser group (P<0.001) or the 1 mg triamcinolone group (P=0.001). By 1 year, there were no significant differences among groups in mean visual acuity. At the 16-month visit and extending through the primary outcome visit at 2 years, mean visual acuity was better in the laser group than in the other two groups (at 2 years, P=0.02 comparing the laser and 1 mg groups, P=0.002 comparing the laser and 4 mg groups, and P=0.49 comparing the 1mg and 4 mg groups). Treatment group differences in the visual acuity outcome could not be attributed solely to cataract formation. OCT results generally paralleled the visual acuity results. Intraocular pressure was increased from baseline by ≥10 mm Hg at any visit in 4%, 16%, and 33% of eyes in the three treatment groups, respectively, and cataract surgery was performed in 13%, 23%, and 51% of eyes in the three treatment groups, respectively. Conclusions Over a 2-year period, focal/grid photocoagulation is more effective and has fewer side effects than 1 mg or 4 mg doses of preservative-free intravitreal triamcinolone for most patients with DME who have characteristics similar to the cohort in this clinical trial. The results of this study also support that focal/grid photocoagulation currently should be the benchmark against which other treatments are compared in clinical trials of DME. PMID:18662829

New Therapeutic Approaches in Diabetic Retinopathy

PubMed Central

Vaziri, Kamyar; Schwartz, Stephen G.; Relhan, Nidhi; Kishor, Krishna S.; Flynn Jr, Harry W.

2015-01-01

Diabetic retinopathy is a common microvascular complication of diabetes mellitus. It affects a substantial proportion of US adults over age 40. The condition is a leading cause of visual loss. Much attention has been given to expanding the role of current treatments along with investigating various novel therapies and drug delivery methods. In the treatment of diabetic macular edema (DME), intravitreal pharmacotherapies, especially anti-vascular endothelial growth factor (anti-VEGF) agents, have gained popularity. Currently, anti-VEGF agents are often used as first-line agents in center-involved DME, with recent data suggesting that among these agents, aflibercept leads to better visual outcomes in patients with worse baseline visual acuities. While photocoagulation remains the standard treatment for proliferative diabetic retinopathy (PDR), recent FDA approvals of ranibizumab and aflibercept in the management of diabetic retinopathy associated with DME may suggest a potential for pharmacologic treatments of PDR as well. Novel therapies, including small interfering RNAs, chemokines, kallikrein-kinin inhibitors, and various anti-angiogenic agents, are currently being evaluated for the management of diabetic retinopathy and DME. In addition to these strategies, novel drug delivery methods such as sustained-release implants and refillable reservoir implants are either under active evaluation or have recently gained FDA approval. This review provides an update on the novel developments in the treatment of diabetic retinopathy. PMID:26676668

Fully automated detection of diabetic macular edema and dry age-related macular degeneration from optical coherence tomography images

PubMed Central

Srinivasan, Pratul P.; Kim, Leo A.; Mettu, Priyatham S.; Cousins, Scott W.; Comer, Grant M.; Izatt, Joseph A.; Farsiu, Sina

2014-01-01

We present a novel fully automated algorithm for the detection of retinal diseases via optical coherence tomography (OCT) imaging. Our algorithm utilizes multiscale histograms of oriented gradient descriptors as feature vectors of a support vector machine based classifier. The spectral domain OCT data sets used for cross-validation consisted of volumetric scans acquired from 45 subjects: 15 normal subjects, 15 patients with dry age-related macular degeneration (AMD), and 15 patients with diabetic macular edema (DME). Our classifier correctly identified 100% of cases with AMD, 100% cases with DME, and 86.67% cases of normal subjects. This algorithm is a potentially impactful tool for the remote diagnosis of ophthalmic diseases. PMID:25360373

Machine learning based detection of age-related macular degeneration (AMD) and diabetic macular edema (DME) from optical coherence tomography (OCT) images

PubMed Central

Wang, Yu; Zhang, Yaonan; Yao, Zhaomin; Zhao, Ruixue; Zhou, Fengfeng

2016-01-01

Non-lethal macular diseases greatly impact patients’ life quality, and will cause vision loss at the late stages. Visual inspection of the optical coherence tomography (OCT) images by the experienced clinicians is the main diagnosis technique. We proposed a computer-aided diagnosis (CAD) model to discriminate age-related macular degeneration (AMD), diabetic macular edema (DME) and healthy macula. The linear configuration pattern (LCP) based features of the OCT images were screened by the Correlation-based Feature Subset (CFS) selection algorithm. And the best model based on the sequential minimal optimization (SMO) algorithm achieved 99.3% in the overall accuracy for the three classes of samples. PMID:28018716

En Face Doppler Optical Coherence Tomography Measurement of Total Retinal Blood Flow in Diabetic Retinopathy and Diabetic Macular Edema

PubMed Central

Lee, ByungKun; Novais, Eduardo A.; Waheed, Nadia K.; Adhi, Mehreen; de Carlo, Talisa E.; Cole, Emily D.; Moult, Eric M.; Choi, WooJhon; Lane, Mark; Baumal, Caroline R.; Duker, Jay S.; Fujimoto, James G.

2018-01-01

IMPORTANCE Alterations in ocular blood flow play an important role in the pathogenesis and progression of diabetic retinopathy (DR). However, the measurement of retinal blood flow in clinical studies has been challenging. En face Doppler optical coherence tomography (OCT) provides an effective method for measuring total retinal blood flow (TRBF) in the clinic. OBJECTIVE To investigate TRBF in eyes with DR of varying severity, with or without diabetic macular edema (DME), using en face Doppler OCT. DESIGN, SETTING, AND PARTICIPANTS This was a cross-sectional study conducted from May 23, 2014, to January 11, 2016, which analyzed 41 eyes with DR from 31 diabetic patients, 20 eyes without DR from 11 diabetic patients, and 16 eyes from 12 healthy age-matched controls, all at the New England Eye Center in Boston, Massachusetts. MAIN OUTCOMES AND MEASURES Participants were imaged with a high-speed, swept-source OCT prototype at 1050-nm wavelength using repeated en face Doppler OCT raster scans, comprising 600 × 80 axial scans and covering a 1.5 × 2-mm2 area centered at the optic disc. The TRBF was automatically calculated using custom Matlab software. RESULTS This study included 41 eyes with DR from 31 diabetic patients (mean [SD] age, 62.8 [13.4] years; 12 were female patients), 20 eyes without DR from 11 diabetic patients (mean [SD] age, 58.8 [10.1] years; 5 were female patients), and 16 eyes from 12 healthy age-matched controls (mean [SD] age, 57.9 [8.1] years; 8 were female participants). The mean (SD) TRBF was 28.0 (8.5) μL/min in the eyes with DME, 48.8 (13.4) μL/min in the eyes with DR but without DME, 40.1 (7.7) μL/min in the diabetic eyes without retinopathy, and 44.4 (8.3) μL/min in age-matched healthy eyes. A difference in TRBF between the eyes with DME that were treated and the eyes with DME that were not treated was not identified. The TRBF was consistently low in the eyes with DME regardless of DR severity. The eyes with moderate nonproliferative DR but without DME exhibited a wide range of TRBF from 31.1 to 75.0 μL/min, with the distribution being highly skewed. CONCLUSIONS AND RELEVANCE High-speed en face Doppler OCT can measure TRBF in healthy and diabetic eyes. Diabetic eyes with DME exhibited lower TRBF than healthy eyes (P ≤ .001). Further longitudinal studies of TRBF in eyes with DR would be helpful to determine whether reduced TRBF is a risk factor for DME. PMID:28196198

Genome-wide association studies for diabetic macular edema and proliferative diabetic retinopathy.

PubMed

Graham, Patricia S; Kaidonis, Georgia; Abhary, Sotoodeh; Gillies, Mark C; Daniell, Mark; Essex, Rohan W; Chang, John H; Lake, Stewart R; Pal, Bishwanath; Jenkins, Alicia J; Hewitt, Alex W; Lamoureux, Ecosse L; Hykin, Philip G; Petrovsky, Nikolai; Brown, Matthew A; Craig, Jamie E; Burdon, Kathryn P

2018-05-08

Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are sight-threatening complications of diabetes mellitus and leading causes of adult-onset blindness worldwide. Genetic risk factors for diabetic retinopathy (DR) have been described previously, but have been difficult to replicate between studies, which have often used composite phenotypes and been conducted in different populations. This study aims to identify genetic risk factors for DME and PDR as separate complications in Australians of European descent with type 2 diabetes. Caucasian Australians with type 2 diabetes were evaluated in a genome-wide association study (GWAS) to compare 270 DME cases and 176 PDR cases with 435 non-retinopathy controls. All participants were genotyped by SNP array and after data cleaning, cases were compared to controls using logistic regression adjusting for relevant covariates. The top ranked SNP for DME was rs1990145 (p = 4.10 × 10 - 6 , OR = 2.02 95%CI [1.50, 2.72]) on chromosome 2. The top-ranked SNP for PDR was rs918519 (p = 3.87 × 10 - 6 , OR = 0.35 95%CI [0.22, 0.54]) on chromosome 5. A trend towards association was also detected at two SNPs reported in the only other reported GWAS of DR in Caucasians; rs12267418 near MALRD1 (p = 0.008) in the DME cohort and rs16999051 in the diabetes gene PCSK2 (p = 0.007) in the PDR cohort. This study has identified loci of interest for DME and PDR, two common ocular complications of diabetes. These findings require replication in other Caucasian cohorts with type 2 diabetes and larger cohorts will be required to identify genetic loci with statistical confidence. There is considerable overlap in the patient cohorts with each retinopathy subtype, complicating the search for genes that contribute to PDR and DME biology.

Multimodal Imaging in Diabetic Macular Edema.

PubMed

Acón, Dhariana; Wu, Lihteh

2018-01-01

Throughout ophthalmic history it has been shown that progress has gone hand in hand with technological breakthroughs. In the past, fluorescein angiography and fundus photographs were the most commonly used imaging modalities in the management of diabetic macular edema (DME). Today, despite the moderate correlation between macular thickness and functional outcomes, spectral domain optical coherence tomography (SD-OCT) has become the DME workhorse in clinical practice. Several SD-OCT biomarkers have been looked at including presence of epiretinal membrane, vitreomacular adhesion, disorganization of the inner retinal layers, central macular thickness, integrity of the ellipsoid layer, and subretinal fluid, among others. Emerging imaging modalities include fundus autofluorescence, macular pigment optical density, fluorescence lifetime imaging ophthalmoscopy, OCT angiography, and adaptive optics. Technological advances in imaging of the posterior segment of the eye have enabled ophthalmologists to develop hypotheses about pathological mechanisms of disease, monitor disease progression, and assess response to treatment. Spectral domain OCT is the most commonly performed imaging modality in the management of DME. However, reliable biomarkers have yet to be identified. Machine learning may provide treatment algorithms based on multimodal imaging. Copyright 2018 Asia-Pacific Academy of Ophthalmology.

Visual Impairment and Blindness Avoided with Ranibizumab in Hispanic and Non-Hispanic Whites with Diabetic Macular Edema in the United States.

PubMed

Varma, Rohit; Bressler, Neil M; Doan, Quan V; Danese, Mark; Dolan, Chantal M; Lee, Abraham; Turpcu, Adam

2015-05-01

To estimate visual impairment (VI) and blindness avoided with intravitreal ranibizumab 0.3 mg treatment for central-involved diabetic macular edema (DME) among Hispanic and non-Hispanic white individuals in the United States. Population-based model simulating visual acuity (VA) outcomes over 2 years after diagnosis and treatment of DME. Visual acuity changes with and without ranibizumab were based on data from the RISE, RIDE, and DRCR Network trials. For the better-seeing eye, VA outcomes included VI, defined as worse than 20/40 in the better-seeing eye, and blindness, defined as VA of 20/200 or worse in the better-seeing eye. Incidence of 1 or both eyes with central-involved DME in 2010 were estimated based on the 2010 United States population, prevalence of diabetes mellitus, and 1-year central-involved DME incidence rate. Sixty-one percent of incident individuals had bilateral DME and 39% had unilateral DME, but DME could develop in the fellow eye. Cases of VI and blindness avoided with ranibizumab treatment. Among approximately 102 million Hispanic and non-Hispanic white individuals in the United States 45 years of age and older in 2010, an estimated 37 274 had central-involved DME and VI eligible for ranibizumab treatment. Compared with no ranibizumab treatment, the model predicted that ranibizumab 0.3 mg every 4 weeks would reduce the number of individuals with VI from 11 438 (95% simulation interval [SI], 7249-16 077) to 6304 (95% SI, 3921-8981), a 45% (95% SI, 36%-53%) reduction at 2 years. Ranibizumab would reduce the number of incident eyes with VA worse than 20/40 from 16 910 (95% SI, 10 729-23 577) to 9361 (95% SI, 5839-13 245), a 45% (95% SI, 38%-51%) reduction. Ranibizumab was estimated to reduce the number of individuals with legal blindness by 75% (95% SI, 58%-88%) and the number of incident eyes with VA of 20/200 or worse by 76% (95% SI, 63%-87%). This model suggests that ranibizumab 0.3 mg every 4 weeks substantially reduces prevalence of VI and legal blindness 2 years after initiating treatment among Hispanic and non-Hispanic white individuals in the United States with central-involved DME that has caused vision loss. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Subconjunctival sirolimus in the treatment of diabetic macular edema.

PubMed

Krishnadev, Nupura; Forooghian, Farzin; Cukras, Catherine; Wong, Wai; Saligan, Leorey; Chew, Emily Y; Nussenblatt, Robert; Ferris, Frederick; Meyerle, Catherine

2011-11-01

Diabetic macular edema (DME) is a leading cause of blindness in the developed world. Sirolimus has been shown to inhibit the production, signaling, and activity of many growth factors relevant to the development of diabetic retinopathy. This phase I/II study assesses the safety of multiple subconjunctival sirolimus injections for the treatment of DME, with some limited efficacy data. In this phase I/II prospective, open-label pilot study, five adult participants with diabetic macular edema involving the center of the fovea and best-corrected ETDRS visual acuity score of ≤74 letters (20/32 or worse) received 20 μl (440 μg) of subconjunctival sirolimus at baseline, month 2 and every 2 months thereafter, unless there was resolution of either retinal thickening on OCT or leakage on fluorescein angiography. Main outcome measures included best-corrected visual acuity and central retinal thickness on OCT at 6 months and 1 year, as well as safety outcomes. Repeated subconjunctival sirolimus injections were well-tolerated, with no significant drug-related adverse events. There was no consistent treatment effect related to sirolimus; one participant experienced a 2-line improvement in visual acuity and 2 log unit decrease in retinal thickness at 6 months and 1 year, two remained essentially stable, one had stable visual acuity but improvement of central retinal thickness of 1 and 3 log units at 6 months and 1 year respectively, and one had a 2-line worsening of visual acuity and a 1 log unit increase in retinal thickness at 6 months and 1 year. Results in the fellow eyes with diabetic macular edema, not treated with sirolimus, were similar. Subconjunctival sirolimus appears safe to use in patients with DME. Assessment of possible treatment benefit will require a randomized trial.

Cost-effectiveness of treatment of diabetic macular edema.

PubMed

Pershing, Suzann; Enns, Eva A; Matesic, Brian; Owens, Douglas K; Goldhaber-Fiebert, Jeremy D

2014-01-07

Macular edema is the most common cause of vision loss among patients with diabetes. To determine the cost-effectiveness of different treatments of diabetic macular edema (DME). Markov model. Published literature and expert opinion. Patients with clinically significant DME. Lifetime. Societal. Laser treatment, intraocular injections of triamcinolone or a vascular endothelial growth factor (VEGF) inhibitor, or a combination of both. Discounted costs, gains in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). All treatments except laser monotherapy substantially reduced costs, and all treatments except triamcinolone monotherapy increased QALYs. Laser treatment plus a VEGF inhibitor achieved the greatest benefit, gaining 0.56 QALYs at a cost of $6975 for an ICER of $12 410 per QALY compared with laser treatment plus triamcinolone. Monotherapy with a VEGF inhibitor achieved similar outcomes to combination therapy with laser treatment plus a VEGF inhibitor. Laser monotherapy and triamcinolone monotherapy were less effective and more costly than combination therapy. VEGF inhibitor monotherapy was sometimes preferred over laser treatment plus a VEGF inhibitor, depending on the reduction in quality of life with loss of visual acuity. When the VEGF inhibitor bevacizumab was as effective as ranibizumab, it was preferable because of its lower cost. Long-term outcome data for treated and untreated diseases are limited. The most effective treatment of DME is VEGF inhibitor injections with or without laser treatment. This therapy compares favorably with cost-effective interventions for other conditions. Agency for Healthcare Research and Quality.

Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema

PubMed Central

Fong, Angie HC; Lai, Timothy YY

2013-01-01

Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various important clinical trials on the long-term efficacy and safety of ranibizumab in the treatment of neovascular AMD and DME. The pharmacological properties of ranibizumab, its cost effectiveness, and impact on quality of life will also be discussed. PMID:23766636

An anomaly detection approach for the identification of DME patients using spectral domain optical coherence tomography images.

PubMed

Sidibé, Désiré; Sankar, Shrinivasan; Lemaître, Guillaume; Rastgoo, Mojdeh; Massich, Joan; Cheung, Carol Y; Tan, Gavin S W; Milea, Dan; Lamoureux, Ecosse; Wong, Tien Y; Mériaudeau, Fabrice

2017-02-01

This paper proposes a method for automatic classification of spectral domain OCT data for the identification of patients with retinal diseases such as Diabetic Macular Edema (DME). We address this issue as an anomaly detection problem and propose a method that not only allows the classification of the OCT volume, but also allows the identification of the individual diseased B-scans inside the volume. Our approach is based on modeling the appearance of normal OCT images with a Gaussian Mixture Model (GMM) and detecting abnormal OCT images as outliers. The classification of an OCT volume is based on the number of detected outliers. Experimental results with two different datasets show that the proposed method achieves a sensitivity and a specificity of 80% and 93% on the first dataset, and 100% and 80% on the second one. Moreover, the experiments show that the proposed method achieves better classification performance than other recently published works. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of intravitreal injection of ranibizumab on choroidal structure and blood flow in eyes with diabetic macular edema.

PubMed

Okamoto, Masahiro; Yamashita, Mariko; Ogata, Nahoko

2018-05-01

To determine the effects of an intravitreal injection of ranibizumab (IVR) on the choroidal structure and blood flow in eyes with diabetic macular edema (DME). Twenty-eight consecutive patients with DME who received an IVR and 20 non-diabetic, age-matched controls were followed for 1 month. The eyes with DME were divided into those with prior panretinal photocoagulation (PRP, n = 16) and those without prior PRP (no-PRP, n = 12). The enhanced depth imaging optical coherence tomography (EDI-OCT) scans and Niblack's image binarization were performed to determine the choroidal structure. The choroidal blood flow was determined by laser speckle flowgraphy. The subfoveal choroidal thickness at the baseline was significantly thicker in the no-PRP group than in the PRP-treated group. After IVR, the best-corrected visual acuity (BCVA) and central retinal thickness in eyes with DME were significantly improved compared to the baseline values. There were significant differences in the choroidal thickness, total choroidal area, and choroidal vascularity index between the groups after IVR. Choroidal vascular index and choroidal blood flow were significantly reduced only in the no-PRP group and not in the PRP-treated group. In addition, the correlation between the central retinal thickness and the choroidal blood flow was significant in the no-PRP group (r = 0.47, P < 0.05). A single IVR will reduce the central retinal thickness and improve the BCVA in eyes with DME in both the no-PRP and PRP-treated group. IVR affected the choroidal vasculature and blood flow significantly, and a significant correlation was found between the central retinal thickness and the choroidal blood flow in eyes without PRP.

A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema.

PubMed

2008-09-01

To evaluate the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone in comparison with focal/grid photocoagulation for the treatment of diabetic macular edema (DME). Multicenter, randomized clinical trial. Eight hundred forty study eyes of 693 subjects with DME involving the fovea and with visual acuity of 20/40 to 20/320. Eyes were randomized to focal/grid photocoagulation (n = 330), 1 mg intravitreal triamcinolone (n = 256), or 4 mg intravitreal triamcinolone (n = 254). Retreatment was given for persistent or new edema at 4-month intervals. The primary outcome was evaluated at 2 years. Visual acuity measured with the electronic Early Treatment Diabetic Retinopathy Study method (primary), optical coherence tomography-measured retinal thickness (secondary), and safety. At 4 months, mean visual acuity was better in the 4-mg triamcinolone group than in either the laser group (P<0.001) or the 1-mg triamcinolone group (P = 0.001). By 1 year, there were no significant differences among groups in mean visual acuity. At the 16-month visit and extending through the primary outcome visit at 2 years, mean visual acuity was better in the laser group than in the other 2 groups (at 2 years, P = 0.02 comparing the laser and 1-mg groups, P = 0.002 comparing the laser and 4-mg groups, and P = 0.49 comparing the 1-mg and 4-mg groups). Treatment group differences in the visual acuity outcome could not be attributed solely to cataract formation. Optical coherence tomography results generally paralleled the visual acuity results. Intraocular pressure increased from baseline by 10 mmHg or more at any visit in 4%, 16%, and 33% of eyes in the 3 treatment groups, respectively, and cataract surgery was performed in 13%, 23%, and 51% of eyes in the 3 treatment groups, respectively. Over a 2-year period, focal/grid photocoagulation is more effective and has fewer side effects than 1-mg or 4-mg doses of preservative-free intravitreal triamcinolone for most patients with DME who have characteristics similar to the cohort in this clinical trial. The results of this study also support that focal/grid photocoagulation currently should be the benchmark against which other treatments are compared in clinical trials of DME.

Comparison of Film and Digital Fundus Photographs in Eyes of Individuals with Diabetes Mellitus

PubMed Central

Gangaputra, Sapna; Glassman, Adam R.; Aiello, Lloyd Paul; Bressler, Neil; Bressler, Susan B.; Danis, Ronald P.; Davis, Matthew D.

2011-01-01

Purpose. To compare grading of diabetic retinopathy (DR) and diabetic macular edema (DME) from stereoscopic film versus stereoscopic digital photographs obtained from a subset of Diabetic Retinopathy Clinical Research Network (DRCR.net) participants. Methods. In this photographic media comparison study, digital and film images were obtained at a single study visit from some of the subjects enrolled in active DRCR.net clinical study protocols. Digital camera systems and digital and film photographers were certified to obtain images according to standard procedures. Images were graded for DR severity and DME in a masked fashion by Fundus Photograph Reading Center (Madison, WI) graders. Agreement between gradings was assessed by calculating the percentage of agreement and κ statistics. Results. Images obtained with both film and digital media were submitted for 155 eyes of 96 study participants. On a nine-step Early Treatment Diabetic Retinopathy study DR severity scale, grading agreed exactly in 74%, and was within one step of agreement in 93%, with a weighted κ statistic of 0.82 (95% confidence interval [CI], 0.71–0.92). On a nine-step DME severity scale and three-step clinically significant macular edema (CSME) scale, grading agreed exactly in 39% and 88%, respectively, and within one step in 70% and 92% (weighted κ statistic, 0.44 [95% Cl, 0.34–0.54] and 0.72 [95% Cl, 0.55–0.90], respectively). Conclusions. Among clinical sites participating in the DRCR.net, agreement between film and digital images was substantial to almost perfect for DR severity level and moderate to substantial for DME and CSME severity levels, respectively. Replacement of film fundus images with digital images for DR severity level should not adversely affect clinical trial quality. (ClinicalTrials.gov numbers, NCT00367133, NCT00369486, NCT00444600, NCT00445003, NCT00709319.) PMID:21571677

Efficacy of intravitreal anti-vascular endothelial growth factor or steroid injection in diabetic macular edema according to fluid turbidity in optical coherence tomography.

PubMed

Lee, Kyungmin; Chung, Heeyoung; Park, Youngsuk; Sohn, Joonhong

2014-08-01

To determine if short term effects of intravitreal anti-vascular endothelial growth factor or steroid injection are correlated with fluid turbidity, as detected by spectral domain optical coherence tomography (SD-OCT) in diabetic macular edema (DME) patients. A total of 583 medical records were reviewed and 104 cases were enrolled. Sixty eyes received a single intravitreal bevacizumab injection (IVB) on the first attack of DME and 44 eyes received triamcinolone acetonide treatment (IVTA). Intraretinal fluid turbidity in DME patients was estimated with initial intravitreal SD-OCT and analyzed with color histograms from a Photoshop program. Central macular thickness and visual acuity using a logarithm from the minimum angle of resolution chart, were assessed at the initial period and 2 months after injections. Visual acuity and central macular thickness improved after injections in both groups. In the IVB group, visual acuity and central macular thickness changed less as the intraretinal fluid became more turbid. In the IVTA group, visual acuity underwent less change while central macular thickness had a greater reduction (r = -0.675, p = 0.001) as the intraretinal fluid was more turbid. IVB and IVTA injections were effective in reducing central macular thickness and improving visual acuity in DME patients. Further, fluid turbidity, which was detected by SD-OCT may be one of the indexes that highlight the influence of the steroid-dependent pathogenetic mechanism.

Basis and Design of a Randomized Clinical Trial to Evaluate the Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema.

PubMed

Robles-Osorio, Ma Ludivina; García-Franco, Renata; Núñez-Amaro, Carlos D; Mira-Lorenzo, Ximena; Ramírez-Neria, Paulina; Hernández, Wendy; López-Star, Ellery; Bertsch, Thomas; Martínez de la Escalera, Gonzalo; Triebel, Jakob; Clapp, Carmen

2018-01-01

Diabetic retinopathy (DR) and diabetic macular edema (DME) are potentially blinding, microvascular retinal diseases in people with diabetes mellitus. Preclinical studies support a protective role of the hormone prolactin (PRL) due to its ocular incorporation and conversion to vasoinhibins, a family of PRL fragments that inhibit ischemia-induced retinal angiogenesis and diabetes-derived retinal vasopermeability. Here, we describe the protocol of an ongoing clinical trial investigating a new therapy for DR and DME based on elevating the circulating levels of PRL with the prokinetic, dopamine D2 receptor blocker, levosulpiride. It is a prospective, randomized, double-blind, placebo-controlled trial enrolling male and female patients with type 2 diabetes having DME, non-proliferative DR (NPDR), proliferative DR (PDR) requiring vitrectomy, and DME plus standard intravitreal therapy with the antiangiogenic agent, ranibizumab. Patients are randomized to receive placebo (lactose pill, orally TID) or levosulpiride (75 mg/day orally TID) for 8 weeks (DME and NPDR), 1 week (the period before vitrectomy in PDR), or 12 weeks (DME plus ranibizumab). In all cases the study medication is taken on top of standard therapy for diabetes, blood pressure control, or other medical conditions. Primary endpoints in groups 1 and 2 (DME: placebo and levosulpiride), groups 3 and 4 (NPDR: placebo and levosulpiride), and groups 7 and 8 (DME plus ranibizumab: placebo and levosulpiride) are changes from baseline in visual acuity, retinal thickness assessed by optical coherence tomography, and retinal microvascular abnormalities evaluated by fundus biomicroscopy and fluorescein angiography. Changes in serum PRL levels and of PRL and vasoinhibins levels in the vitreous between groups 5 and 6 (PDR undergoing vitrectomy: placebo and levosulpiride) serve as proof of principle that PRL enters the eye to counteract disease progression. Secondary endpoints are changes during the follow-up of health and metabolic parameters (blood pressure, glycated hemoglobin, and serum levels of glucose and creatinine). A total of 120 patients are being recruited. This trial will provide important knowledge on the potential benefits and safety of elevating circulating and intraocular PRL levels with levosulpiride in patients with DR and DME. Ethics approval has been obtained from the Ethics Committees of the National University of Mexico (UNAM) and the Instituto Mexicano de Oftalmología, I.A.P. Dissemination will include submission to peer-reviewed scientific journals and presentation at congresses. Registered at www.ClinicalTrials.gov, ID: NCT03161652 on May 18, 2017.

Recent clinically relevant highlights from the Diabetic Retinopathy Clinical Research Network.

PubMed

Krick, Tracy W; Bressler, Neil M

2018-05-01

To present some recent clinically relevant results from Diabetic Retinopathy Clinical Research (DRCR) Network trials that may guide management of diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR). Among eyes with DME and visual acuity 20/50 or worse, aflibercept, on average, had greater improvement in visual acuity over 2 years compared with bevacizumab or ranibizumab. Aflibercept is associated with higher rates of improvements in diabetic retinopathy severity among eyes with PDR and vision-impairing DME at baseline compared with bevacizumab or ranibizumab. Among eyes with persistent central-involved DME after at least six antivascular endothelial growth factor (anti-VEGF) injections, no difference in mean visual acuity improvement was observed between eyes that received continued ranibizumab and sham injections versus ranibizumab and intravitreous sustained dexamethasone drug-delivery system, especially for phakic eyes. For eyes with PDR, ranibizumab was associated with lower rates of developing PDR-worsening events compared with panretinal photocoagulation, especially among eyes that did not receive ranibizumab for central-involved DME at baseline. Ranibizumab is cost-effective for PDR for eyes with, not without, vision-impairing central-involved DME, highlighting challenges when safety and efficacy results are at odds with cost-effectiveness results. Aflibercept for DME, in certain circumstances, is more likely to have superior visual acuity and anatomical outcomes compared with bevacizumab or ranibizumab. No vision benefits are apparent, especially for phakic eyes, by adding intravitreous corticosteroids for persistent DME following anti-VEGF injections.

Comparison of Modified-ETDRS and Mild Macular Grid Laser Photocoagulation Strategies for Diabetic Macular Edema

PubMed Central

2008-01-01

Purpose To compare two laser photocoagulation techniques for treatment of diabetic macular edema (DME): modified-ETDRS direct/grid photocoagulation (mETDRS) and a, potentially milder, but potentially more extensive, mild macular grid (MMG) laser technique in which small mild burns are placed throughout the macula, whether or not edema is present, and microaneurysms are not treated directly. Methods 263 subjects (mean age 59 years) with previously untreated DME were randomly assigned to receive laser photocoagulation by mETDRS (N=162 eyes) or MMG (N=161 eyes) technique. Visual acuity, fundus photographs and OCT measurements were obtained at baseline and after 3.5, 8, and 12 months. Treatment was repeated if DME persisted. Main Outcome Measure Change in OCT measures at 12-months follow up. Results From baseline to 12 months, among eyes with baseline central subfield thickness ≥ 250 microns, central subfield thickening decreased by an average of 88 microns in the mETDRS group and decreased by 49 microns in the MMG group (adjusted mean difference: 33 microns, 95% confidence interval 5 to 61 microns, P=0.02). Weighted inner zone thickening by OCT decreased by 42 and 28 microns, respectively (adjusted mean difference: 14 microns, 95% confidence interval 1 to 27 microns, P=0.04), maximum retinal thickening (maximum of the central and four inner subfields) decreased by 66 and 39 microns, respectively (adjusted mean difference: 27 microns, 95% confidence interval 6 to 47 microns, P=0.01), and retinal volume decreased by 0.8 and 0.4 mm3, respectively (adjusted mean difference: 0.3 mm3, 95% confidence interval 0.02 to 0.53 mm3, P=0.03). At 12 months, the mean change in visual acuity was 0 letters in the mETDRS group and 2 letters worse in the MMG group (adjusted mean difference: 2 letters, 95% confidence interval −0.5 to 5 letters, P=0.10). Conclusions At 12 months after treatment, the MMG technique is less effective at reducing OCT measured retinal thickening than the more extensively evaluated current mETDRS laser photocoagulation approach. However, the visual acuity outcome with both approaches is not substantially different. Given these findings a larger long-term trial of the MMG technique is not justified. Application to Clinical Practice Modified ETDRS focal photocoagulation should continue as a standard approach for treating diabetic macular edema. PMID:17420366

Rationale for the diabetic retinopathy clinical research network treatment protocol for center-involved diabetic macular edema.

PubMed

Aiello, Lloyd Paul; Beck, Roy W; Bressler, Neil M; Browning, David J; Chalam, K V; Davis, Matthew; Ferris, Frederick L; Glassman, Adam R; Maturi, Raj K; Stockdale, Cynthia R; Topping, Trexler M

2011-12-01

To describe the underlying principles used to develop a web-based algorithm that incorporated intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy Clinical Research Network (DRCR.net) randomized clinical trial. Discussion of treatment protocol for DME. Subjects with vision loss resulting from DME involving the center of the macula. The DRCR.net created an algorithm incorporating anti-VEGF injections in a comparative effectiveness randomized clinical trial evaluating intravitreal ranibizumab with prompt or deferred (≥24 weeks) focal/grid laser treatment in eyes with vision loss resulting from center-involved DME. Results confirmed that intravitreal ranibizumab with prompt or deferred laser provides superior visual acuity outcomes compared with prompt laser alone through at least 2 years. Duplication of this algorithm may not be practical for clinical practice. To share their opinion on how ophthalmologists might emulate the study protocol, participating DRCR.net investigators developed guidelines based on the algorithm's underlying rationale. Clinical guidelines based on a DRCR.net protocol. The treatment protocol required real-time feedback from a web-based data entry system for intravitreal injections, focal/grid laser treatment, and follow-up intervals. Guidance from this system indicated whether treatment was required or given at investigator discretion and when follow-up should be scheduled. Clinical treatment guidelines, based on the underlying clinical rationale of the DRCR.net protocol, include repeating treatment monthly as long as there is improvement in edema compared with the previous month or until the retina is no longer thickened. If thickening recurs or worsens after discontinuing treatment, treatment is resumed. Duplication of the approach used in the DRCR.net randomized clinical trial to treat DME involving the center of the macula with intravitreal ranibizumab may not be practical in clinical practice, but likely can be emulated based on an understanding of the underlying rationale for the study protocol. Inherent differences between a web-based treatment algorithm and a clinical approach may lead to differences in outcomes that are impossible to predict. The closer the clinical approach is to the algorithm used in the study, the more likely the outcomes will be similar to those published. Proprietary or commercial disclosure may be found after the references. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Quantitative evaluation of hard exudates in diabetic macular edema after short-term intravitreal triamcinolone, dexamethasone implant or bevacizumab injections.

PubMed

Shin, Yong Un; Hong, Eun Hee; Lim, Han Woong; Kang, Min Ho; Seong, Mincheol; Cho, Heeyoon

2017-10-03

To quantitatively compare short-term hard exudates (HEs) alteration in patients with diabetic macular edema (DME) after intravitreal triamcinolone, dexamethasone implant or bevacizumab injections. This retrospective study enrolled DME eyes with HEs that underwent a single-dose intravitreal injection of triamcinolone (25 eyes), dexamethasone implant (20 eyes), or three monthly injections of bevacizumab (25 eyes) and completed at least three months of follow-up. All patients were examined before and after 1, 2 and 3 months of injections. Using color fundus photographs, the amount of HEs was quantified by two masked graders. The difference in HEs area between baseline and each follow-up visit was compared among the three groups. After three months, HEs area was reduced to 52.9 ± 4.21% (P < 0.001) in the triamcinolone group, 63.6 ± 6.08% (P = 0.002) in the dexamethasone implant group, and 85.2 ± 5.07% (P = 0.198) in the bevacizumab group. A significant reduction in HEs appeared at one month in the triamcinolone group (53.5 ± 4.91%, P < 0.001) and at two months in the dexamethasone implant group (70.1 ± 5.21%, P = 0.039). Our study suggests intravitreal steroids (triamcinolone, dexamethasone implants) significantly reduce HEs in DME patients on short-term follow-up, whereas intravitreal bevacizumab does not. Therefore, intravitreal steroids may be useful in DME with HEs in the fovea.

Early Retinal and Choroidal Coat Thickness Changes After Intravitreal Dexamethasone Implant Injection for Diabetic Macular Edema.

PubMed

Horozoğlu, Fatih; Sever, Özkan

2018-06-05

Intravitreal steroid injection is one of the treatment choices in diabetic macular edema (DME). Dexamethasone (Dx) implant is the most novel form of intravitreal steroid therapy. Macular thickness improvement is well known effect of Dx implant however; subfoveal choroidal coat thickness (SFCT) changes need to be investigated. To evaluate the early central macular thickness (CMT) and SFCT alterations after single dose dexamethasone implant injection in DME. Retrospective cross-sectional study. We identified 29 patients with DME (29 eyes) who underwent optical coherence tomography (OCT) and fundus fluoroscein angiography (FFA). All patients received a single dose intravitreal Dx implant and were followed for CMT and SFCT alterations for the post-injection first hour, first day, first week, first month and third month. The preoperative mean CMT and SFCT measurements were 592.3±122.3 (412-879) μm and 264.8±53.7 (165-397) μm, respectively. CMT measurements significantly decreased from the first hour (p<0.050) and kept decreasing till 3 month (p<0.001); while SFCT decrement was just significant at the first day (p<0.05). When we compared the decrease in SFCT and CMT, 1 hour was similar, however not significant, 1.5% SFCT and 5% CMT decrease was, respectively (p>0.050). CMT decrease rate was significantly higher than SFCT at 1 day, 1 week, 1 month and 3 month (p<0.001). Intravitreal Dx implant has got a meaningful effect on CMT in patients with DME while SFCT decreases significantly at first hour and first day.

Platform-Independent Cirrus and Spectralis Thickness Measurements in Eyes with Diabetic Macular Edema Using Fully Automated Software

PubMed Central

Willoughby, Alex S.; Chiu, Stephanie J.; Silverman, Rachel K.; Farsiu, Sina; Bailey, Clare; Wiley, Henry E.; Ferris, Frederick L.; Jaffe, Glenn J.

2017-01-01

Purpose We determine whether the automated segmentation software, Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP), can measure, in a platform-independent manner, retinal thickness on Cirrus and Spectralis spectral domain optical coherence tomography (SD-OCT) images in eyes with diabetic macular edema (DME) under treatment in a clinical trial. Methods Automatic segmentation software was used to segment the internal limiting membrane (ILM), inner retinal pigment epithelium (RPE), and Bruch's membrane (BM) in SD-OCT images acquired by Cirrus and Spectralis commercial systems, from the same eye, on the same day during a clinical interventional DME trial. Mean retinal thickness differences were compared across commercial and DOCTRAP platforms using intraclass correlation (ICC) and Bland-Altman plots. Results The mean 1 mm central subfield thickness difference (standard error [SE]) comparing segmentation of Spectralis images with DOCTRAP versus HEYEX was 0.7 (0.3) μm (0.2 pixels). The corresponding values comparing segmentation of Cirrus images with DOCTRAP versus Cirrus software was 2.2 (0.7) μm. The mean 1 mm central subfield thickness difference (SE) comparing segmentation of Cirrus and Spectralis scan pairs with DOCTRAP using BM as the outer retinal boundary was −2.3 (0.9) μm compared to 2.8 (0.9) μm with inner RPE as the outer boundary. Conclusions DOCTRAP segmentation of Cirrus and Spectralis images produces validated thickness measurements that are very similar to each other, and very similar to the values generated by the corresponding commercial software in eyes with treated DME. Translational Relevance This software enables automatic total retinal thickness measurements across two OCT platforms, a process that is impractical to perform manually. PMID:28180033

Fully Automatic Software for Retinal Thickness in Eyes With Diabetic Macular Edema From Images Acquired by Cirrus and Spectralis Systems

PubMed Central

Lee, Joo Yong; Chiu, Stephanie J.; Srinivasan, Pratul P.; Izatt, Joseph A.; Toth, Cynthia A.; Farsiu, Sina; Jaffe, Glenn J.

2013-01-01

Purpose. To determine whether a novel automatic segmentation program, the Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP), can be applied to spectral-domain optical coherence tomography (SD-OCT) images obtained from different commercially available SD-OCT in eyes with diabetic macular edema (DME). Methods. A novel segmentation framework was used to segment the retina, inner retinal pigment epithelium, and Bruch's membrane on images from eyes with DME acquired by one of two SD-OCT systems, Spectralis or Cirrus high definition (HD)-OCT. Thickness data obtained by the DOCTRAP software were compared with those produced by Spectralis and Cirrus. Measurement agreement and its dependence were assessed using intraclass correlation (ICC). Results. A total of 40 SD-OCT scans from 20 subjects for each machine were included in the analysis. Spectralis: the mean thickness in the 1-mm central area determined by DOCTRAP and Spectralis was 463.8 ± 107.5 μm and 467.0 ± 108.1 μm, respectively (ICC, 0.999). There was also a high level agreement in surrounding areas (out to 3 mm). Cirrus: the mean thickness in the 1-mm central area was 440.8 ± 183.4 μm and 442.7 ± 182.4 μm by DOCTRAP and Cirrus, respectively (ICC, 0.999). The thickness agreement in surrounding areas (out to 3 mm) was more variable due to Cirrus segmentation errors in one subject (ICC, 0.734–0.999). After manual correction of the errors, there was a high level of thickness agreement in surrounding areas (ICC, 0.997–1.000). Conclusions. The DOCTRAP may be useful to compare retinal thicknesses in eyes with DME across OCT platforms. PMID:24084089

Prevalence of diabetic retinopathy and diabetic macular edema in a primary care-based teleophthalmology program for American Indians and Alaskan Natives.

PubMed

Bursell, Sven-Erik; Fonda, Stephanie J; Lewis, Drew G; Horton, Mark B

2018-01-01

Diabetes and its complications are more common in American Indians and Alaska Natives (AI/AN) than other US racial/ethnic populations. Prior reports of diabetic retinopathy (DR) prevalence in AI/AN are dated, and research on diabetic macular edema (DME) is limited. This study characterizes the recent prevalence of DR and DME in AI/AN using primary care-based teleophthalmology surveillance. This is a multi-site, clinic-based, cross-sectional study of DR and DME. The sample is composed of AI /AN patients with diabetes (n = 53,998), served by the nationally distributed Indian Health Service-Joslin Vision Network Teleophthalmology Program (IHS-JVN) in primary care clinics of US Indian Health Service (IHS), Tribal, and Urban Indian health care facilities (I/T/U) from 1 November 2011 to 31 October 2016. Patients were recruited opportunistically for a retinal examination using the IHS-JVN during their regular diabetes care. The IHS-JVN used clinically validated, non-mydriatic, retinal imaging and retinopathy assessment protocols to identify the severity levels of non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), DME, and sight threatening retinopathy (STR; a composite measure). Key social-demographic (age, gender, IHS area), diabetes-related health (diabetes therapy, duration of diabetes, A1c), and imaging technology variables were examined. The analysis calculated frequencies and percentages of severity levels of disease. Prevalence of any NPDR, PDR, DME, and STR among AI/AN patients undergoing DR teleophthalmology surveillance by IHS-JVN was 17.7%, 2.3%, 2.3%, and 4.2%, respectively. Prevalence was lowest in Alaska and highest among patients with A1c >/ = 8%, duration of diabetes > 10 years, or using insulin. Prevalence of DR in this cohort was approximately half that in previous reports for AI/AN, and prevalence of DME was less than that reported in non-AI/AN populations. A similar reduction in diabetes related end-stage renal disease in the same population and time period has been reported by other researchers. Since these two diabetic complications share a common microvasculopathic mechanism, this coincident change in prevalence may also share a common basis, possibly related to improved diabetes management.

Impact of injection therapy on retinal patients with diabetic macular edema or retinal vein occlusion.

PubMed

Sivaprasad, Sobha; Oyetunde, Sesan

2016-01-01

An important factor in the choice of therapy is the impact it has on the patient's quality of life. This survey aimed to understand treatment burden, treatment-related anxiety and worry, and practical issues such as appointment attendance and work absence in patients receiving injection therapy for diabetic macular edema (DME) or retinal vein occlusion (RVO). A European sample of 131 retinal patients completed a detailed questionnaire to elucidate the impact of injection therapy on individuals with DME or RVO. RVO and DME greatly impact a patient's quality of life. An intensive injection regimen and the requirements for multiple hospital visits place a large practical burden on the patient. Each intravitreal injection appointment (including travel time) was reported to take an average of 4.5 hours, with a total appointment burden over 6 months of 13.5 hours and 20 hours for RVO and DME patients, respectively. This creates a significant burden on patient time and may make appointment attendance difficult. Indeed, 53% of working patients needed to take at least 1 day off work per appointment and 71% of patients required a carer's assistance at the time of the injection appointment, ~6.3 hours per injection. In addition to practical issues, three-quarters of patients reported experiencing anxiety about their most recent injection treatment, with 54% of patients reporting that they were anxious for at least 2 days prior to the injection. Patients' most desired improvement to their treatment regimen was to have fewer injections and to require fewer appointments, to achieve the same visual results. Patients' quality of life is clearly very affected by having to manage an intensive intravitreal injection regimen, with a considerable treatment burden having a large negative effect. Reducing the appointment burden to achieve the same visual outcomes and the provision of additional support for patients to attend appointments would greatly benefit those receiving intravitreal injection therapies for DME and RVO.

Communications between intraretinal and subretinal space on optical coherence tomography of neurosensory retinal detachment in diabetic macular edema.

PubMed

Gupta, Aditi; Raman, Rajiv; Mohana, Kp; Kulothungan, Vaitheeswaran; Sharma, Tarun

2013-09-01

The pathogenesis of development and progression of neurosensory retinal detachment (NSD) in diabetic macular edema (DME) is not yet fully understood. The purpose of this study is to describe the spectral domain optical coherence tomography (SD-OCT) morphological characteristics of NSD associated with DME in the form of outer retinal communications and to assess the correlation between the size of communications and various factors. This was an observational retrospective nonconsecutive case series in a tertiary care eye institute. We imaged NSD and outer retinal communications in 17 eyes of 16 patients having NSD associated with DME using SD-OCT. We measured manually the size of the outer openings of these communications and studied its correlation with various factors. Statistical analysis (correlation test) was performed using the Statistical Package for Social Sciences (SPSS) software (version 14.0). The main outcome measures were correlation of the size of communications with dimensions of NSD, presence of subretinal hyper-reflective dots, and best-corrected visual acuity (BCVA). The communications were seen as focal defects of the outer layers of elevated retina. With increasing size of communication, there was increase in height of NSD (r = 0.701, P = 0.002), horizontal diameter of NSD (r = 0.695, P = 0.002), and the number of hyper-reflective dots in the subretinal space (r = 0.729, P = 0.002). The minimum angle of resolution (logMAR) BCVA increased with the increasing size of communications (r = 0.827, P < 0.0001). Outer retinal communications between intra and subretinal space were noted in eyes having NSD associated with DME. The size of communications correlated positively with the size of NSD and subretinal detachment space hyper-reflective dots, and inversely with BCVA.

Characterization of ischemic index using ultra-widefield fluorescein angiography in patients with focal and diffuse recalcitrant diabetic macular edema.

PubMed

Patel, Ravi D; Messner, Leonard V; Teitelbaum, Bruce; Michel, Kimberly A; Hariprasad, Seenu M

2013-06-01

To explore the association of angiographic nonperfusion in focal and diffuse recalcitrant diabetic macular edema (DME) in diabetic retinopathy (DR). A retrospective, observational case series of patients with the diagnosis of recalcitrant DME for at least 2 years placed into 1 of 4 cohorts based on the degree of DR. A total of 148 eyes of 76 patients met the inclusion criteria at 1 academic institution. Ultra-widefield fluorescein angiography (FA) images and spectral-domain optical coherence tomography (SD OCT) images were obtained on all patients. Ultra-widefield FA images were graded for quantity of nonperfusion, which was used to calculate ischemic index. Main outcome measures were mean ischemic index, mean change in central macular thickness (CMT), and mean number of macular photocoagulation treatments over the 2-year study period. The mean ischemic index was 47% (SD 25%; range 0%-99%). The mean ischemic index of eyes within Cohorts 1, 2, 3, and 4 was 0%, 34% (range 16%-51%), 53% (range 32%-89%), and 65% (range 47%-99%), respectively. The mean percentage decrease in CMT in Cohorts 1, 2, 3, and 4 were 25.2%, 19.1%, 11.6%, and 7.2%, respectively. The mean number of macular photocoagulation treatments in Cohorts 1, 2, 3, and 4 was 2.3, 4.8, 5.3, and 5.7, respectively. Eyes with larger areas of retinal nonperfusion and greater severity of DR were found to have the most recalcitrant DME, as evidenced by a greater number of macular photocoagulation treatments and less reduction in SD OCT CMT compared with eyes without retinal nonperfusion. Areas of untreated retinal nonperfusion may generate biochemical mediators that promote ischemia and recalcitrant DME. Copyright © 2013 Elsevier Inc. All rights reserved.

Cone Photoreceptor Irregularity on Adaptive Optics Scanning Laser Ophthalmoscopy Correlates With Severity of Diabetic Retinopathy and Macular Edema.

PubMed

Lammer, Jan; Prager, Sonja G; Cheney, Michael C; Ahmed, Amel; Radwan, Salma H; Burns, Stephen A; Silva, Paolo S; Sun, Jennifer K

2016-12-01

To determine whether cone density, spacing, or regularity in eyes with and without diabetes (DM) as assessed by high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) correlates with presence of diabetes, diabetic retinopathy (DR) severity, or presence of diabetic macular edema (DME). Participants with type 1 or 2 DM and healthy controls underwent AOSLO imaging of four macular regions. Cone assessment was performed by independent graders for cone density, packing factor (PF), nearest neighbor distance (NND), and Voronoi tile area (VTA). Regularity indices (mean/SD) of NND (RI-NND) and VTA (RI-VTA) were calculated. Fifty-three eyes (53 subjects) were assessed. Mean ± SD age was 44 ± 12 years; 81% had DM (duration: 22 ± 13 years; glycated hemoglobin [HbA1c]: 8.0 ± 1.7%; DM type 1: 72%). No significant relationship was found between DM, HbA1c, or DR severity and cone density or spacing parameters. However, decreased regularity of cone arrangement in the macular quadrants was correlated with presence of DM (RI-NND: P = 0.04; RI-VTA: P = 0.04), increasing DR severity (RI-NND: P = 0.04), and presence of DME (RI-VTA: P = 0.04). Eyes with DME were associated with decreased density (P = 0.04), PF (P = 0.03), and RI-VTA (0.04). Although absolute cone density and spacing don't appear to change substantially in DM, decreased regularity of the cone arrangement is consistently associated with the presence of DM, increasing DR severity, and DME. Future AOSLO evaluation of cone regularity is warranted to determine whether these changes are correlated with, or predict, anatomic or functional deficits in patients with DM.

The Diabetic Retinopathy Barometer Study: Global perspectives on access to and experiences of diabetic retinopathy screening and treatment.

PubMed

Cavan, D; Makaroff, L; da Rocha Fernandes, J; Sylvanowicz, M; Ackland, P; Conlon, J; Chaney, D; Malhi, A; Barratt, J

2017-07-01

To assess the level of awareness, prevention and treatment of Diabetic Eye Disease (DED) comprising Diabetic Retinopathy (DR) and Diabetic Macula Edema (DME) retinopathy among adults with diabetes and health professionals. The Diabetic Retinopathy Barometer Study consisted of a qualitative study, which consisted of semi-structured interviews, and a quantitative study using online surveys for adults with diabetes and for health professionals. A total of 4340 adults with diabetes and 2329 health professionals participated in the surveys. Diabetic eye disease (DED) without macular edema (DME) was reported by 19.5% of adults with diabetes and a further 7.6% reported that they had DME. Although 94% of adults with diabetes saw a health care professional for their diabetes, only 79% had ever had an eye examination for DED, and 23% had not had an eye examination in the last year. Moreover, 65% of the ophthalmologists surveyed reported that most patients presented when visual problems had already occurred. Overall, 62% of people with DED had received treatment. Of these, 74% had laser therapy, 29% surgery and 24% anti-VEGF therapy. Strategic investment is required to enhance patient education and professional training on the importance of regular eye examinations; and in providing accessible DR screening programmes and proactive treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

Retinal Imaging Techniques for Diabetic Retinopathy Screening

PubMed Central

Goh, James Kang Hao; Cheung, Carol Y.; Sim, Shaun Sebastian; Tan, Pok Chien; Tan, Gavin Siew Wei; Wong, Tien Yin

2016-01-01

Due to the increasing prevalence of diabetes mellitus, demand for diabetic retinopathy (DR) screening platforms is steeply increasing. Early detection and treatment of DR are key public health interventions that can greatly reduce the likelihood of vision loss. Current DR screening programs typically employ retinal fundus photography, which relies on skilled readers for manual DR assessment. However, this is labor-intensive and suffers from inconsistency across sites. Hence, there has been a recent proliferation of automated retinal image analysis software that may potentially alleviate this burden cost-effectively. Furthermore, current screening programs based on 2-dimensional fundus photography do not effectively screen for diabetic macular edema (DME). Optical coherence tomography is becoming increasingly recognized as the reference standard for DME assessment and can potentially provide a cost-effective solution for improving DME detection in large-scale DR screening programs. Current screening techniques are also unable to image the peripheral retina and require pharmacological pupil dilation; ultra-widefield imaging and confocal scanning laser ophthalmoscopy, which address these drawbacks, possess great potential. In this review, we summarize the current DR screening methods using various retinal imaging techniques, and also outline future possibilities. Advances in retinal imaging techniques can potentially transform the management of patients with diabetes, providing savings in health care costs and resources. PMID:26830491

Retinal Imaging Techniques for Diabetic Retinopathy Screening.

PubMed

Goh, James Kang Hao; Cheung, Carol Y; Sim, Shaun Sebastian; Tan, Pok Chien; Tan, Gavin Siew Wei; Wong, Tien Yin

2016-02-01

Due to the increasing prevalence of diabetes mellitus, demand for diabetic retinopathy (DR) screening platforms is steeply increasing. Early detection and treatment of DR are key public health interventions that can greatly reduce the likelihood of vision loss. Current DR screening programs typically employ retinal fundus photography, which relies on skilled readers for manual DR assessment. However, this is labor-intensive and suffers from inconsistency across sites. Hence, there has been a recent proliferation of automated retinal image analysis software that may potentially alleviate this burden cost-effectively. Furthermore, current screening programs based on 2-dimensional fundus photography do not effectively screen for diabetic macular edema (DME). Optical coherence tomography is becoming increasingly recognized as the reference standard for DME assessment and can potentially provide a cost-effective solution for improving DME detection in large-scale DR screening programs. Current screening techniques are also unable to image the peripheral retina and require pharmacological pupil dilation; ultra-widefield imaging and confocal scanning laser ophthalmoscopy, which address these drawbacks, possess great potential. In this review, we summarize the current DR screening methods using various retinal imaging techniques, and also outline future possibilities. Advances in retinal imaging techniques can potentially transform the management of patients with diabetes, providing savings in health care costs and resources. © 2016 Diabetes Technology Society.

United States comparative costs and absenteeism of diabetic ophthalmic conditions.

PubMed

Brook, Richard A; Kleinman, Nathan L; Patel, Sunil; Smeeding, Jim E; Beren, Ian A; Turpcu, Adam

2015-06-01

This retrospective cohort study examined the impact of diabetic macular edema (DME), diabetic retinopathy (DR), or diabetes on annual health benefit costs and absenteeism in US employees. Claims data from 2001 to 2012 was extracted from the Human Capital Management Services Group Research Reference Database on annual direct/indirect health benefit costs and absences for employees aged ≥ 18 years. Employees with DME, DR, or diabetes were identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Employees were divided into two groups, drivers or nondrivers, and examined in separate analyses. For drivers and nondrivers, the DME, DR, and diabetes cohorts were compared with their respective control groups (without diabetes). Two-part regression models controlled for demographics and job-related characteristics. A total of 39,702 driver and 426,549 nondriver employees were identified as having ≥ 1 year's continuous health plan enrollment. Direct medical costs for drivers with DME, DR, or diabetes were $6470, $8021, and $5102, respectively (>2.8 times higher and statistically significant compared with driver controls). Nondrivers with DME and DR incurred significantly higher sick leave and short-term disability costs compared with the nondrivers with diabetes and nondriver controls. In drivers with DME, the majority of days of absence were for short- and long-term disability (12.41 and 11.43 days, respectively). In drivers with DR, the majority of days of absence were for short-term disability (10.70 days). In nondrivers with DME and nondrivers with DR, the majority of days of absence were for sick leave (5.74 and 4.93 days, respectively) and short-term disability (5.08 and 4.93 days, respectively). DME and DR are associated with substantial direct medical cost and absenteeism in this real-world sample of medically insured employees. This research highlights the negative impact of DME and DR on annual costs and absenteeism and may assist employers in assessing the impact of these conditions on employees.

Navigated macular laser decreases retreatment rate for diabetic macular edema: a comparison with conventional macular laser.

PubMed

Neubauer, Aljoscha S; Langer, Julian; Liegl, Raffael; Haritoglou, Christos; Wolf, Armin; Kozak, Igor; Seidensticker, Florian; Ulbig, Michael; Freeman, William R; Kampik, Anselm; Kernt, Marcus

2013-01-01

The purpose of this study was to evaluate and compare clinical outcomes and retreatment rates using navigated macular laser versus conventional laser for the treatment of diabetic macular edema (DME). In this prospective, interventional pilot study, 46 eyes from 46 consecutive patients with DME were allocated to receive macular laser photocoagulation using navigated laser. Best corrected visual acuity and retreatment rate were evaluated for up to 12 months after treatment. The control group was drawn based on chart review of 119 patients treated by conventional laser at the same institutions during the same time period. Propensity score matching was performed with Stata, based on the nearest-neighbor method. Propensity score matching for age, gender, baseline visual acuity, and number of laser spots yielded 28 matched patients for the control group. Visual acuity after navigated macular laser improved from a mean 0.48 ± 0.37 logMAR by a mean +2.9 letters after 3 months, while the control group showed a mean -4.0 letters (P = 0.03). After 6 months, navigated laser maintained a mean visual gain of +3.3 letters, and the conventional laser group showed a slower mean increase to +1.9 letters versus baseline. Using Kaplan-Meier analysis, the laser retreatment rate showed separation of the survival curves after 2 months, with fewer retreatments in the navigated group than in the conventional laser group during the first 8 months (18% versus 31%, respectively, P = 0.02). The short-term results of this pilot study suggest that navigated macular photocoagulation is an effective technique and could be considered as a valid alternative to conventional slit-lamp laser for DME when focal laser photocoagulation is indicated. The observed lower retreatment rates with navigated retinal laser therapy in the first 8 months suggest a more durable treatment effect.

Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

PubMed Central

Arevalo, J. Fernando; Sanchez, Juan G.; Lasave, Andres F.; Wu, Lihteh; Maia, Mauricio; Bonafonte, Sergio; Brito, Miguel; Alezzandrini, Arturo A.; Restrepo, Natalia; Berrocal, Maria H.; Saravia, Mario; Farah, Michel Eid; Fromow-Guerra, Jans; Morales-Canton, Virgilio

2011-01-01

This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy. PMID:21584260

Changes in vision related quality of life in patients with diabetic macular edema: ranibizumab or laser treatment?

PubMed

Turkoglu, Elif Betul; Celık, Erkan; Aksoy, Nilgun; Bursalı, Ozlem; Ucak, Turgay; Alagoz, Gursoy

2015-01-01

To compare the changes in vision related quality of life (VR-QoL) in patients with diabetic macular edema (DME) undergoing intravitreal ranibizumab (IVR) injection or focal/grid laser. In this prospective study, 70 patients with clinically significant macular edema (CSME) were randomized to undergo IVR injection (n=35) and focal/grid laser (n=35). If necessary, the laser or ranibizumab injections were repeated. Distance and near visual acuities, central retinal thickness (CRT) and The 25-item Visual Function Questionnaire (VFQ-25) were used to measure the effectiveness of treatments and VR-QoL before and after 6 months following IVR or laser treatment. The demographic and clinical findings before the treatments were similar in both main groups. The improvements in distance and near visual acuities were higher in IVR group than the laser group (p<0.01). The reduction in CRT in IVR group was higher than that in laser treatment group (p<0.01). In both groups, the VFQ-25 composite score tended to improve from baseline to 6 months. And at 6th month, the changes in composite score were significantly higher in IVR group than in laser group (p<0.05). The improvements in overall composite scores were 6.3 points for the IVR group compared with 3.0 points in the laser group. Patients treated with IVR and laser had large improvements in composite scores, general vision, near and distance visual acuities in VFQ-25 at 6 months, in comparison with baseline scores, and also mental health subscale in IVR group. Our study revealed that IVR improved not only visual acuity or CRT, but also vision related quality of life more than laser treatment in DME. And these patient-reported outcomes may play an important role in the treatment choice in DME for clinicians. Copyright © 2015 Elsevier Inc. All rights reserved.

Randomized Trial Evaluating Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema

PubMed Central

Elman, Michael J.; Aiello, Lloyd Paul; Beck, Roy W.; Bressler, Neil M.; Bressler, Susan B.; Edwards, Allison R.; Ferris, Frederick L.; Friedman, Scott M.; Glassman, Adam R.; Miller, Kellee M.; Scott, Ingrid U.; Stockdale, Cynthia R.; Sun, Jennifer K.

2010-01-01

Objective Evaluate intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). Design Multicenter, randomized clinical trial. Participants A total of 854 study eyes of 691 participants with visual acuity (approximate Snellen equivalent) of 20/32 to 20/320 and DME involving the fovea. Methods Eyes were randomized to sham injection + prompt laser (n=293), 0.5 mg ranibizumab + prompt laser (n=187), 0.5 mg ranibizumab + deferred (≥24 weeks) laser (n=188), or 4 mg triamcinolone + prompt laser (n=186). Retreatment followed an algorithm facilitated by a web-based, real-time data-entry system. Main Outcome Measures Best-corrected visual acuity and safety at 1 year. Results The 1-year mean change (±standard deviation) in the visual acuity letter score from baseline was significantly greater in the ranibizumab + prompt laser group (+9±11, P<0.001) and ranibizumab + deferred laser group (+9±12, P<0.001) but not in the triamcinolone + prompt laser group (+4±13, P=0.31) compared with the sham + prompt laser group (+3±13). Reduction in mean central subfield thickness in the triamcinolone + prompt laser group was similar to both ranibizumab groups and greater than in the sham + prompt laser group. In the subset of pseudophakic eyes at baseline (n=273), visual acuity improvement in the triamcinolone + prompt laser group appeared comparable to that in the ranibizumab groups. No systemic events attributable to study treatment were apparent. Three eyes (0.8%) had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. Two-year visual acuity outcomes were similar to 1-year outcomes. Conclusions Intravitreal ranibizumab with prompt or deferred laser is more effective through at least 1 year compared with prompt laser alone for the treatment of DME involving the central macula. Ranibizumab as applied in this study, although uncommonly associated with endophthalmitis, should be considered for patients with DME and characteristics similar to those in this clinical trial. In pseudophakic eyes, intravitreal triamcinolone + prompt laser seems more effective than laser alone but frequently increases the risk of intraocular pressure elevation. PMID:20427088

Multifocal electroretinography changes at the 1-year follow-up in a cohort of diabetic macular edema patients treated with ranibizumab.

PubMed

Baget-Bernaldiz, Marc; Romero-Aroca, Pedro; Bautista-Perez, Angel; Mercado, Joaquin

2017-10-01

To determine the changes in the multifocal electroretinogram (mfERG) at 1 year in a clinical series of diabetic macular edema (DME) patients treated with ranibizumab (RNBZ) using a pro re nata protocol. We analyzed a clinical series of 35 eyes of 35 patients with DME at baseline and after treating them with RNBZ over 1 year, in order to determine the change in the macular function, which was assessed by means of the response density and the implicit time of the first-order kernel (FOK) P1 wave of the mfERG at the foveola (R1), fovea (R2) and parafovea (R3). These electrophysiological parameters were studied taking into account different independent variables, such as DME type, degree of diabetic retinopathy (DR), level of preservation of both the ellipsoid zone (IS/OS) and the external limiting membrane (ELM) and changes in central retinal thickness (CRT) and total macular volume (TMV). We also studied the relationship between the response density and the best-corrected visual acuity (BCVA). Eyes with cystic and spongiform DME showed better response density with respect to the serous type (p < 0.001) at baseline. Similarly, eyes with high IS/OS and ELM preservation rates showed higher initial response density compared to the others (p < 0.001). Eyes with moderate DR had better response density compared to those with severe and proliferative DR (p = 0.001). At the beginning of the study, those eyes with proliferative and severe DR showed longer implicit times with respect to those with moderate DR (p = 0.04). The response density significantly increased in eyes that anatomically restored the IS/OS and the ELM after being treated with RNBZ (both p < 0.001). Similarly, eyes with spongiform DME further improved the response density with respect to those with cystic and serous DME (p < 0.001). On the contrary, eyes with hard exudates showed less improvement in their response density at the end of the study (p < 0.001). We observed a significant relationship between BCVA and the response density achieved at the end of the study (p = 0.012). Eyes with severe and proliferative DR significantly shortened implicit time compared to those with moderate DR (p = 0.04). The multifocal electroretinogram allowed us to differentiate groups of eyes with DME according to their electrophysiological profile, both initially and after being treated with RNBZ. Ranibizumab increased the response density in all DME types included in the study, with a maximum response in those eyes with spongiform type. Once treated with RNBZ, the macular electrophysiological activity improved in eyes that had a well-preserved ellipsoid zone and ELM. The presence of hard exudates was a limitation to the response density achieved at the foveola.

Correlation between retinal sensitivity and cystoid space characteristics in diabetic macular edema.

PubMed

Velaga, Swetha B; Nittala, Muneeswar G; Parinitha, B; Sadda, S R; Chhablani, Jay Kumar

2016-06-01

To evaluate the correlation between retinal sensitivity and cystoid space characteristics in eyes with diabetic macular edema (DME). Prospective cross-sectional study of 22 subjects with DME (32 treatment-naïve eyes). All study subjects underwent complete ophthalmic examination, including slit-lamp biomicroscopy and dilated fundus examination. All subjects underwent spectral domain optical coherence tomography (SD-OCT) and microperimetry (MP). Intraretinal cystoid space (ICS) volume was generated after manual delineation of cystoid space boundaries using the three-dimensional-OCT software. Various SD-OCT parameters, including retinal thickness, retinal volume, cystoid space volume, cystoid space intensity, and outer retinal structure integrity, were correlated with MP parameters and best-corrected visual acuity (BCVA). Subject's mean age was 57 ± 9 years. The mean logarithm of minimum angle of resolution BCVA was 0.4 ± 0.2. The intraclass correlation coefficient for inter- and intra-grader assessment of cystoid space volume by manual delineation was 0.99 and 0.99, respectively. Mean total ICS volume was 0.4 ± 0.4 mm 3 and for the foveal center, subfield was 0.1 ± 0.1 mm 3 . Mean retinal sensitivity was 12.89 ± 10 dB; however, foveal retinal sensitivity was 12.3 ± 11.1 dB. We found no significant correlation between BCVA and total cystoid space volume (r = 0.33, P = 0.06). Correlation between total retinal sensitivity and total ICS was negative and nonsignificant (r = -0.17, P = 0.36). Correlation between foveal retinal sensitivity and foveal cystoid space intensity was moderate and marginally significant (r = -0.43, P = 0.05). Total cystoid space volume was not significantly correlated with BCVA or total retinal sensitivity in subjects with DME. Foveal cystoid space optical intensity was negatively correlated with foveal retinal sensitivity. These findings suggest further investigation of cystoid space characteristics in the setting of DME may be of value.

Impact of insulin treatment in diabetic macular edema therapy in type 2 diabetes.

PubMed

Matsuda, Simone; Tam, Tiffany; Singh, Rishi P; Kaiser, Peter K; Petkovsek, Daniel; Zanella, Maria Teresa; Ehlers, Justis P

2015-02-01

To evaluate the impact of insulin therapy on the outcomes of diabetic macular edema (DME) treatment with vascular endothelial growth factor (VEGF) inhibitors in people with type 2 diabetes. A retrospective consecutive case series of 95 patients with type 2 diabetes and DME who were treated with anti-VEGF therapy. We examined 2 cohorts: patients taking only oral antidiabetic agents and patients on insulin therapy. The main outcome measures were change in visual acuity and change in central subfield macular thickness measured by spectral-domain optical coherence tomography. The additional variables analyzed included glycated hemoglobin (A1C), creatinine, blood pressure and body mass index and their correlations with clinical findings. Both groups had a statistically significant improvement in visual acuity (oral antidiabetic agents group: 20/61 to 20/49, p=0.003; insulin therapy group: 20/76 to 20/56, p=0.005). There was no difference between groups at initial or 12-month examination (p=0.239 and p=0.489, respectively). From an anatomic standpoint, central subfield macular thickness also improved significantly in both groups: from 454.7 μm to 354.9 μm (p<0.001) in the oral antidiabetic agents group and from 471.5 μm to 368.4 μm (p<0.001) in the insulin therapy group. Again, there was no significant difference between groups at initial or 12-month follow-up examinations (p=0.586 and p=0.591, respectively). Mean A1C levels remained relatively stable during the follow up in both groups. Anti-VEGF therapy is a useful treatment for DME. This study suggests that chronic insulin therapy, compared with oral antidiabetic agents, does not modify the anatomic or functional effectiveness of DME treatment. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Individuals' Perspectives on Coping with Vision Loss from Diabetic Retinopathy.

PubMed

Sturrock, Bonnie A; Rees, Gwyneth; Lamoureux, Ecosse L; Wong, Tien Y; Holloway, Edith; Fenwick, Eva K

2018-04-01

People with vision loss from diabetic retinopathy (DR) and diabetic macular edema (DME) use problem-focused and emotion-regulation strategies that may influence their short- and longer-term adaptation and psychological outcomes. Our findings can assist the development of models of adjustment to DR/DME-related vision loss and treatments focused on adaptation. To qualitatively determine the coping strategies used by participants with vision loss resulting from DR/DME. Fifty-seven participants with DR/DME engaged in one of eight focus groups or one of 18 semistructured interviews. Participants were mostly older than 55 years (mean, 58.7 years) and male (68%) and had type 2 diabetes (74%; median duration, 17 years). Almost 50% had proliferative DR, 95% had undergone laser treatment, and 42% had DME; 68%, 14% and 14% had none, mild (<0.3 logarithm of the minimum angle of resolution ≤ 0.48), and moderate-severe vision impairment (>0.48 logarithm of the minimum angle of resolution) in the better eye. Focus groups/interviews were transcribed verbatim and iteratively analyzed using the constant comparative method. Qualitative software NVivo 2008 was used to sort/store the data. Our top-down and bottom-up approach to conceptualize the data was informed by the Transactional Model of Stress and Coping. Coping efforts were mostly problem focused (64%) with seven subthemes: problem solving, passive coping, changing activities to suit a new ability level, active coping, rehearsing alternative outcomes, maintaining independence, and information seeking. Emotion-regulation strategies were distraction, acceptance, alternative adaptive thinking, avoidance, expressing emotions, denial, and changing emotions. Meaning-based coping strategies included mindfulness and engaging in meaningful activities. Themes relating to adaptation and moderators to coping (e.g., dispositional optimism) are outlined. Participants described a variety of ways to cope. Some strategies are likely to improve functioning and decrease distress, whereas others are expected to reduce immediate distress while perpetuating this in the longer term. Our findings may assist researchers to develop models of adjustment to DR/DME-related vision loss and psychosocial/educational interventions focused on adaptation.

Association between characteristics of foveal cystoid spaces and short-term responsiveness to ranibizumab for diabetic macular edema.

PubMed

Murakami, Tomoaki; Suzuma, Kiyoshi; Uji, Akihito; Yoshitake, Shin; Dodo, Yoko; Fujimoto, Masahiro; Yoshitake, Tatsuya; Miwa, Yuko; Yoshimura, Nagahisa

2018-05-01

To investigate the association between the characteristics of foveal cystoid spaces and short-term responsiveness to ranibizumab treatment for diabetic macular edema (DME) at 3 months from the initial injection. We retrospectively reviewed 66 eyes of 61 patients with center-involved DME who received three consecutive ranibizumab injections and following as-needed administrations. We evaluated the relationship between visual improvement at 3 months and the preoperative optical coherence tomography (OCT) parameters including hyperreflective foci, heterogeneous OCT reflectivity, mean levels of OCT reflectivity and height of foveal cystoid spaces. Twenty-three eyes without preoperative hyperreflective foci in the foveal cystoid spaces had significantly greater improvement in the logarithm of the minimum angle of resolution visual acuity (logMAR VA) at 3 months than 43 eyes with foci (P = 0.006). That was similar to the greater reduction in CSF thickness in eyes without lesions after treatment at the same time point (P < 0.001). VA improvement at 3 months was not associated with the height (R = 0.215, P = 0.083) or the reflectivity levels (R = -0.079, P = 0.538) of foveal cystoid spaces. There were no differences in VA changes between eyes with and without heterogeneous reflectivity in foveal cystoid spaces (P = 0.297). Multivariate analyses showed that logMAR VA and the absence of hyperreflective foci in foveal cystoid spaces were associated with VA improvement at 3 months. Hyperreflective foci in foveal cystoid spaces at baseline predict poorer short-term responsiveness to ranibizumab injections for DME.

Longitudinal Study of Sustained-Release Dexamethasone Intravitreal Implant in Patients with Diabetic Macular Edema.

PubMed

Aknin, Isabelle; Melki, Laurent

2016-01-01

Observational studies are needed to confirm the long-term efficacy and safety of Ozurdex® intravitreal implant in real life. Among 29 patients with persistent diabetic macular edema (DME), of whom 14 (48%) patients did not have any previous treatments and 22 (76%) any previous antivascular endothelial growth factor (anti-VEGF) injections, significant visual acuity (VA) improvement was observed with a mean gain of 13.8 letters at month 6 (p < 0.0001), 12.7 letters at month 12 (p = 0.0032) and 16.5 letters at month 18 (p = 0.0313). During the follow-up, a total of 17 (59%) patients had a VA improvement of ≥15 letters. Significant central macular thickness decrease was observed with a mean reduction of 159.07 μm at month 6 (p < 0.0001), 181.8 μm at month 12 (p < 0.0001) and 236.17 μm at month 18 (p = 0.0313). No serious adverse events were reported. With a good efficacy and safety, manageable adverse events and an injection rate much lower compared to that of anti-VEGF, this study confirms the use of Ozurdex® for the treatment of persistent DME. © 2016 S. Karger AG, Basel.

A Crossover Design for Comparative Efficacy: A 36-Week Randomized Trial of Bevacizumab and Ranibizumab for Diabetic Macular Edema.

PubMed

Wiley, Henry E; Thompson, Darby J S; Bailey, Clare; Chew, Emily Y; Cukras, Catherine A; Jaffe, Glenn J; Lee, Richard W J; Loken, Erin K; Meyerle, Catherine B; Wong, Wai; Ferris, Frederick L

2016-04-01

To investigate the comparative efficacy of bevacizumab (Avastin) and ranibizumab (Lucentis; both Genentech, Inc, South San Francisco, CA) for diabetic macular edema (DME) using a crossover study design. Randomized, double-masked, 36-week, 3-period crossover clinical trial. Fifty-six subjects with DME involving the center of the macula in one or both eyes. Monthly intravitreous injections of bevacizumab (1.25 mg) or ranibizumab (0.3 mg). Comparison of mean changes in visual acuity and central retinal thickness, tested using a linear mixed-effects model. Based on the linear mixed-effects model, the 3-month estimated mean improvement in visual acuity was 5.3 letters for bevacizumab and 6.6 letters for ranibizumab (difference, 1.3 letters; P = 0.039). Estimated change in optical coherence tomography (OCT) central subfield mean thickness (CSMT) was -89 μm for bevacizumab and -137 μm for ranibizumab (difference, 48 μm; P < 0.001). Incorporating cumulative treatment benefit, the model yielded a predicted 36-week (9-month) average improvement in visual acuity of 7.1 letters (95% confidence interval [CI], 5.0-9.2) for bevacizumab and 8.4 letters (95% CI, 6.3-10.5) for ranibizumab, and a change in OCT CSMT of -128 μm (95% CI, -155 to -100) for bevacizumab and -176 μm (95% CI, -202 to -149) for ranibizumab. There was no significant treatment-by-period interaction (i.e., treatment difference was constant in all 3 periods), nor was there a significant differential carryover effect from one period to the next. This trial demonstrated a statistically significant but small relative clinical benefit of ranibizumab compared with bevacizumab for treatment of DME, using a markedly reduced sample size relative to a full comparative efficacy study. The effects on visual acuity and central retinal thickness for the 2 drugs are consistent with those reported at 1 year for the concurrent parallel-group trial by the Diabetic Retinopathy Clinical Research Network testing bevacizumab, ranibizumab, and aflibercept for DME. The 3-period crossover design allowed for meaningful and efficient comparison, suggesting that this approach may be useful for future comparative efficacy studies of anti-vascular endothelial growth factor drugs for DME. Published by Elsevier Inc.

The Relationship between OCT-measured Central Retinal Thickness and Visual Acuity in Diabetic Macular Edema

PubMed Central

2008-01-01

Objective To compare optical coherence tomography (OCT)-measured retinal thickness and visual acuity in eyes with diabetic macular edema (DME) both before and after macular laser photocoagulation. Design Cross-sectional and longitudinal study. Participants 210 subjects (251 eyes) with DME enrolled in a randomized clinical trial of laser techniques. Methods Retinal thickness was measured with OCT and visual acuity was measured with the electronic-ETDRS procedure. Main Outcome Measures OCT-measured center point thickness and visual acuity Results The correlation coefficients for visual acuity versus OCT center point thickness were 0.52 at baseline and 0.49, 0.36, and 0.38 at 3.5, 8, and 12 months post-laser photocoagulation. The slope of the best fit line to the baseline data was approximately 4.4 letters (95% C.I.: 3.5, 5.3) better visual acuity for every 100 microns decrease in center point thickness at baseline with no important difference at follow-up visits. Approximately one-third of the variation in visual acuity could be predicted by a linear regression model that incorporated OCT center point thickness, age, hemoglobin A1C, and severity of fluorescein leakage in the center and inner subfields. The correlation between change in visual acuity and change in OCT center point thickening 3.5 months after laser treatment was 0.44 with no important difference at the other follow-up times. A subset of eyes showed paradoxical improvements in visual acuity with increased center point thickening (7–17% at the three time points) or paradoxical worsening of visual acuity with a decrease in center point thickening (18%–26% at the three time points). Conclusions There is modest correlation between OCT-measured center point thickness and visual acuity, and modest correlation of changes in retinal thickening and visual acuity following focal laser treatment for DME. However, a wide range of visual acuity may be observed for a given degree of retinal edema and paradoxical increases in center point thickening with increases in visual acuity as well as paradoxical decreases in center point thickening with decreases in visual acuity were not uncommon. Thus, although OCT measurements of retinal thickness represent an important tool in clinical evaluation, they cannot reliably substitute as a surrogate for visual acuity at a given point in time. This study does not address whether short-term changes on OCT are predictive of long-term effects on visual acuity. PMID:17123615

Targeted Retinal Photocoagulation for Diabetic Macular Edema with Peripheral Retinal Nonperfusion: Three-Year Randomized DAVE Trial.

PubMed

Brown, David M; Ou, William C; Wong, Tien P; Kim, Rosa Y; Croft, Daniel E; Wykoff, Charles C

2018-05-01

To evaluate the effect of targeted retinal photocoagulation (TRP) on visual and anatomic outcomes and treatment burden in eyes with diabetic macular edema (DME). Phase I/II prospective, randomized, controlled clinical trial. Forty eyes of 29 patients with center-involved macular edema secondary to diabetes mellitus. Eyes with center-involved DME and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) between 20/32 and 20/320 (Snellen equivalent) were randomized 1:1 to monotherapy with 0.3 mg ranibizumab (Lucentis, Genentech, South San Francisco, CA) or combination therapy with 0.3 mg ranibizumab and TRP guided by widefield fluorescein angiography. All eyes received 4 monthly ranibizumab injections followed by monthly examinations and pro re nata (PRN) re-treatment through 36 months. Targeted retinal photocoagulation was administered outside the macula to areas of retinal capillary nonperfusion plus a 1-disc area margin in the combination therapy arm at week 1, with re-treatment at months 6, 18, and 25, if indicated. Mean change in ETDRS BCVA from baseline and number of intravitreal injections administered. At baseline, mean age was 55 years, mean BCVA was 20/63 (Snellen equivalent), and mean central retinal subfield thickness (CRT) was 530 μm. Thirty-four eyes (85%) completed month 36, at which point mean BCVA improved 13.9 and 8.2 letters (P = 0.20) and mean CRT improved 302 and 152 μm (P = 0.03) in the monotherapy and combination therapy arms, respectively. The mean number of injections administered through month 36 was 24.4 (range, 10-34) and 27.1 (range, 12-36), with 73% (362/496) and 80% (433/538) of PRN injections administered (P = 0.004) in the monotherapy and combination therapy arms, respectively. Goldmann visual field isopter III-4e area decreased by 2% and 18% in the monotherapy and combination therapy arms, respectively (P = 0.30). In this 3-year randomized trial of 40 eyes with DME, there was no evidence that combination therapy with ranibizumab and TRP improved visual outcomes or reduced treatment burden compared with ranibizumab alone. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Vision Outcomes Following Anti-Vascular Endothelial Growth Factor Treatment of Diabetic Macular Edema in Clinical Practice.

PubMed

Holekamp, Nancy M; Campbell, Joanna; Almony, Arghavan; Ingraham, Herbert; Marks, Steven; Chandwani, Hitesh; Cole, Ashley L; Kiss, Szilárd

2018-04-20

To determine monitoring and treatment patterns, and vision outcomes in real-world patients initiating anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME). Retrospective interventional cohort study. SETTING: Electronic medical record analysis of Geisinger Health System data. 110 patients (121 study eyes) initiating intravitreal ranibizumab or bevacizumab for DME during January 2007‒May 2012, with baseline corrected visual acuity of 20/40‒20/320, and ≥1 ophthalmologist visits during follow-up. Intravitreal injections per study eye during the first 12 months; corrected visual acuity, change in corrected visual acuity from baseline, proportions of eyes with ≥10 or ≥15 approxEarly Treatment Diabetic Retinopathy Study letter gain/loss at 12 months; number of ophthalmologist visits. Over 12 months, mean number of ophthalmologist visits was 9.2; mean number of intravitreal injections was 3.1 (range, 1-12), with most eyes (68.6%) receiving ≤3 injections. At 12 months, mean corrected visual acuity change was +4.7 letters (mean 56.9 letters at baseline); proportions of eyes gaining ≥10 or ≥15 letters were 31.4% and 24.0%, respectively; proportions of eyes losing ≥10 or ≥15 letters were 10.8% and 8.3%, respectively. Eyes receiving adjunctive laser during the first 6 months (n = 33) showed similar change in corrected visual acuity to non-laser-treated eyes (n = 88) (+3.1 vs +5.3 letters at 12 months). DME patients receiving anti-VEGF therapy in clinical practice undergo less frequent monitoring and intravitreal injections, and achieve inferior vision outcomes to patients in landmark clinical trials. Copyright © 2018. Published by Elsevier Inc.

Bevacizumab and Panretinal photocoagulation protect against ocular hypertension after posterior subtenon injection of triamcinolone acetonide for diabetic macular edema.

PubMed

Hsieh, Yi-Ting; Yang, Chung-May; Chang, Shu-Hui

2017-08-01

To analyze the prognostic factors for ocular hypertension after posterior subtenon injection of triamcinolone acetonide (PSTA) for the treatment of diabetic macular edema (DME). Patients who received PSTA for DME from January 2006 to December 2011 were enrolled retrospectively and were followed until December 2012 in one hospital. Modified Cox regression models were used to analyze the factors associated with ocular hypertension, which was defined as an intraocular pressure>21 mmHg after PSTA. A total of 180 PSTA injections were given to 114 eyes from 73 adults with DME. During a mean follow-up of 50.4 weeks after each injection, ocular hypertension occurred in 20.6% of injections (28.1% of eyes). Treatment-naïve patients with proliferative diabetic retinopathy (PDR) had a higher risk of ocular hypertension after PSTA than those with nonproliferative diabetic retinopathy (NPDR) [hazard ratio (HR)=3.255, p=0.030]. Intravitreal injection of bevacizumab (IVB) before PSTA had a significant effect in lowering the risk of ocular hypertension after PSTA in patients with PDR who had received panretinal photocoagulation (PRP) (HR=0.107, p=0.035). Both prompt PRP and IVB following PSTA had a protective effect against ocular hypertension in treatment-naïve patients with PDR (HR=0.086, p=0.0002 and HR=0.155, p=0.049, respectively). Treatment-naïve patients with PDR had a higher risk of ocular hypertension after PSTA than those with NPDR. Bevacizumab and prompt PRP both had a protective effect against ocular hypertension after PSTA in patients with PDR. Copyright © 2016. Published by Elsevier B.V.

Real-World Cost Savings Demonstrated by Switching Patients with Refractory Diabetic Macular Edema to Intravitreal Fluocinolone Acetonide (Iluvien): A Retrospective Cost Analysis Study.

PubMed

Ch'ng, Soon W; Brent, Alexander J; Empeslidis, Theodoros; Konidaris, Vasileios; Banerjee, Somnath

2018-06-01

It is hypothesized that using fluocinolone acetonide (FAc) implants such as Iluvien for the treatment of diabetic macular edema (DME) may reduce the total number of intravitreal injections and clinic visits, resulting in an overall treatment cost reduction. The primary aim of this study is to identify the real-world cost savings achievable in a tertiary National Health Service (NHS) hospital. A retrospective cost analysis study was conducted. The inclusion criteria were patients with refractory DME who were switched to Iluvien. The average yearly costs were calculated both before and after the switch to Iluvien. All costs including medicines, investigations, clinics, and management of raised intraocular pressure (IOP) were calculated. The cost differences over the 3 years' worth of Iluvien treatment were calculated and analyzed. To ensure non-inferiority of this treatment intervention, the best corrected visual acuity (BCVA) and central retinal thickness (CRT) were also analyzed. Statistical analysis was conducted with a Student t test where appropriate and statistical significance is identified where p < 0.05. Fourteen eyes of 13 patients met the inclusion criteria. Switching patients to Iluvien achieved on average a saving of £2606.17 per patient (p = 0.33) over the 3 years. However, seven cases (50%) had a rise in IOP after Iluvien that warranted medical treatment and two cases (14.3%) required glaucoma surgery. Incorporating the costs of glaucoma management reduced the overall savings over 3 years to £1064.66 per patient. The BCVA and CRT analysis showed a non-inferiority relationship between Iluvien and any previous treatment. The use of Iluvien in refractory DME patients represents a cost- and time-saving procedure, while showing non-inferiority in terms of efficacy.

Anti-Vascular Endothelial Growth Factor Comparative Effectiveness Trial for Diabetic Macular Edema: Additional Efficacy Post Hoc Analyses of a Randomized Clinical Trial.

PubMed

Jampol, Lee M; Glassman, Adam R; Bressler, Neil M; Wells, John A; Ayala, Allison R

2016-12-01

Post hoc analyses from the Diabetic Retinopathy Clinical Research Network randomized clinical trial comparing aflibercept, bevacizumab, and ranibizumab for diabetic macular edema (DME) might influence interpretation of study results. To provide additional outcomes comparing 3 anti-vascular endothelial growth factor (VEGF) agents for DME. Post hoc analyses performed from May 3, 2016, to June 21, 2016, of a randomized clinical trial performed from August 22, 2012, to September 23, 2015, of 660 participants comparing 3 anti-VEGF treatments in eyes with center-involved DME causing vision impairment. Randomization to intravitreous aflibercept (2.0 mg), bevacizumab (1.25 mg), or ranibizumab (0.3 mg) administered up to monthly based on a structured retreatment regimen. Focal/grid laser treatment was added after 6 months for the treatment of persistent DME. Change in visual acuity (VA) area under the curve and change in central subfield thickness (CST) within subgroups based on whether an eye received laser treatment for DME during the study. Post hoc analyses were performed for 660 participants (mean [SD] age, 61 [10] years; 47% female, 65% white, 16% black or African American, 16% Hispanic, and 3% other). For eyes with an initial VA of 20/50 or worse, VA improvement was greater with aflibercept than the other agents at 1 year but superior only to bevacizumab at 2 years. Mean (SD) letter change in VA over 2 years (area under curve) was greater with aflibercept (+17.1 [9.7]) than with bevacizumab (+12.1 [9.4]; 95% CI, +1.6 to +7.3; P < .001) or ranibizumab (+13.6 [8.5]; 95% CI, +0.7 to +6.0; P = .009). When VA was 20/50 or worse at baseline, bevacizumab reduced CST less than the other agents at 1 year, but at 2 years the differences had diminished. In subgroups stratified by baseline VA, anti-VEGF agent, and whether focal/grid laser treatment was performed for DME, the only participants to have a substantial reduction in mean CST between 1 and 2 years were those with a baseline VA of 20/50 or worse receiving bevacizumab and laser treatment (mean [SD], -55 [108] µm; 95% CI, -82 to -28 µm; P < .001). Although post hoc analyses should be viewed with caution given the potential for bias, in eyes with a VA of 20/50 or worse, aflibercept has the greatest improvement in VA over 2 years. Focal/grid laser treatment, ceiling and floor effects, or both may account for mean thickness reductions noted only in bevacizumab-treated eyes between 1 and 2 years. clinicaltrials.gov Identifier NCT01627249.

Intravitreal aflibercept for diabetic macular edema.

PubMed

Korobelnik, Jean-François; Do, Diana V; Schmidt-Erfurth, Ursula; Boyer, David S; Holz, Frank G; Heier, Jeffrey S; Midena, Edoardo; Kaiser, Peter K; Terasaki, Hiroko; Marcus, Dennis M; Nguyen, Quan D; Jaffe, Glenn J; Slakter, Jason S; Simader, Christian; Soo, Yuhwen; Schmelter, Thomas; Yancopoulos, George D; Stahl, Neil; Vitti, Robert; Berliner, Alyson J; Zeitz, Oliver; Metzig, Carola; Brown, David M

2014-11-01

A head-to-head comparison was performed between vascular endothelial growth factor blockade and laser for treatment of diabetic macular edema (DME). Two similarly designed, double-masked, randomized, phase 3 trials, VISTA(DME) and VIVID(DME). We included 872 patients (eyes) with type 1 or 2 diabetes mellitus who presented with DME with central involvement. Eyes received either intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation. The primary efficacy endpoint was the change from baseline in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 52. Secondary efficacy endpoints at week 52 included the proportion of eyes that gained ≥ 15 letters from baseline and the mean change from baseline in central retinal thickness as determined by optical coherence tomography. Mean BCVA gains from baseline to week 52 in the IAI 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (P < 0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (P < 0.0001) in VIVID. The corresponding proportions of eyes gaining ≥ 15 letters were 41.6% and 31.1% versus 7.8% (P < 0.0001) in VISTA, and 32.4% and 33.3% versus 9.1% (P < 0.0001) in VIVID. Similarly, mean reductions in central retinal thickness were 185.9 and 183.1 versus 73.3 μm (P < 0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm (P < 0.0001) in VIVID. Overall incidences of ocular and nonocular adverse events and serious adverse events, including the Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events and vascular deaths, were similar across treatment groups. At week 52, IAI demonstrated significant superiority in functional and anatomic endpoints over laser, with similar efficacy in the 2q4 and 2q8 groups despite the extended dosing interval in the 2q8 group. In general, IAI was well-tolerated. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction.

PubMed

Haller, Julia A; Qin, Haijing; Apte, Rajendra S; Beck, Roy R; Bressler, Neil M; Browning, David J; Danis, Ronald P; Glassman, Adam R; Googe, Joseph M; Kollman, Craig; Lauer, Andreas K; Peters, Mark A; Stockman, Margaret E

2010-06-01

To evaluate vitrectomy for diabetic macular edema (DME) in eyes with at least moderate vision loss and vitreomacular traction. Prospective cohort study. The primary cohort included 87 eyes with DME and vitreomacular traction based on investigator's evaluation, visual acuity 20/63-20/400, optical coherence tomography (OCT) central subfield >300 microns and no concomitant cataract extraction at the time of vitrectomy. Surgery was performed according to the investigator's usual routine. Follow-up visits were performed after 3 months, 6 months (primary end point), and 1 year. Visual acuity, OCT retinal thickening, and operative complications. At baseline, median visual acuity in the 87 eyes was 20/100 and median OCT thickness was 491 microns. During vitrectomy, additional procedures included epiretinal membrane peeling in 61%, internal limiting membrane peeling in 54%, panretinal photocoagulation in 40%, and injection of corticosteroids at the close of the procedure in 64%. At 6 months, median OCT central subfield thickness decreased by 160 microns, with 43% having central subfield thickness <250 microns and 68% having at least a 50% reduction in thickening. Visual acuity improved by > or =10 letters in 38% (95% confidence interval, 28%-49%) and deteriorated by > or =10 letters in 22% (95% confidence interval, 13%-31%). Postoperative complications through 6 months included vitreous hemorrhage (5 eyes), elevated intraocular pressure requiring treatment (7 eyes), retinal detachment (3 eyes), and endophthalmitis (1 eye). Few changes in results were noted between 6 months and 1 year. After vitrectomy performed for DME and vitreomacular traction, retinal thickening was reduced in most eyes. Between 28% and 49% of eyes with characteristics similar to those included in this study are likely to have improvement of visual acuity, whereas between 13% and 31% are likely to have worsening. The operative complication rate is low and similar to what has been reported for this procedure. These data provide estimates of surgical outcomes and serve as a reference for future studies that might consider vitrectomy for DME in eyes with at least moderate vision loss and vitreomacular traction. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Quantitative assessment of macular contraction and vitreoretinal interface alterations in diabetic macular edema treated with intravitreal anti-VEGF injections.

PubMed

Cetin, Ebru Nevin; Demirtaş, Önder; Özbakış, Nihal Cesur; Pekel, Gökhan

2018-06-20

Macular contraction after anti-vascular endothelial growth factor (anti-VEGF) injections for diabetic macular edema (DME) was evaluated by documenting the displacement of macular capillary vessels and epiretinal membrane (ERM) formation. A total of 130 eyes were included in this retrospective study. The study group consisted of 63 eyes which had intravitreal anti-VEGF injections for DME, and the control group included 67 eyes without central DME. The study and the control groups were well balanced in terms of diabetes duration and HbA1c. The distances between the bifurcation of the macular capillary retinal vessels were measured, and ERM status was evaluated based on spectral-OCT findings on the initial and final visit. In the study group, the mean number of injections was 4.7 ± 2.6 (3-14). The mean follow-up time was 16.7 ± 7.8 months in the study group whereas it was 20.7 ± 10.9 months in the control group (p = 0.132). The change in distance measurements between the reference points on macular capillary vessels was significant in all lines except line c (p < 0.05 for lines a, b, d, e, and f) in the study group whereas it was significant in only line e in the control group (p = 0.007, paired samples test). However, when the change in macular thickness was accounted as a confounding factor, the change in distances between the references points from the initial visit to the final visit lost its significance (repeated measures ANCOVA, p > 0.05). During follow-up, the number of cases with ERM changed from 10 to 12 in the study group whereas it remained three in the control group. There was a displacement of macular capillary vessels which was associated with the change in macular thickness in eyes having anti-VEGF injections for DME. The number of ERM cases did not change significantly during the follow-up.

Non-damaging laser therapy of the macula: Titration algorithm and tissue response

NASA Astrophysics Data System (ADS)

Palanker, Daniel; Lavinsky, Daniel; Dalal, Roopa; Huie, Philip

2014-02-01

Retinal photocoagulation typically results in permanent scarring and scotomata, which limit its applicability to the macula, preclude treatments in the fovea, and restrict the retreatments. Non-damaging approaches to laser therapy have been tested in the past, but the lack of reliable titration and slow treatment paradigms limited their clinical use. We developed and tested a titration algorithm for sub-visible and non-damaging treatments of the retina with pulses sufficiently short to be used with pattern laser scanning. The algorithm based on Arrhenius model of tissue damage optimizes the power and duration for every energy level, relative to the threshold of lesion visibility established during titration (and defined as 100%). Experiments with pigmented rabbits established that lesions in the 50-75% energy range were invisible ophthalmoscopically, but detectable with Fluorescein Angiography and OCT, while at 30% energy there was only very minor damage to the RPE, which recovered within a few days. Patients with Diabetic Macular Edema (DME) and Central Serous Retinopathy (CSR) have been treated over the edematous areas at 30% energy, using 200μm spots with 0.25 diameter spacing. No signs of laser damage have been detected with any imaging modality. In CSR patients, subretinal fluid resolved within 45 days. In DME patients the edema decreased by approximately 150μm over 60 days. After 3-4 months some patients presented with recurrence of edema, and they responded well to retreatment with the same parameters, without any clinically visible damage. This pilot data indicates a possibility of effective and repeatable macular laser therapy below the tissue damage threshold.

Cost-effectiveness of ranibizumab in the treatment of visual impairment due to diabetic macular edema.

PubMed

Haig, Jennifer; Barbeau, Martin; Ferreira, Alberto

2016-07-01

Objective Ranibizumab, an anti-vascular endothelial growth factor designed for ocular use, has been deemed cost-effective in multiple indications by several Health Technology Assessment bodies. This study assessed the cost-effectiveness of ranibizumab monotherapy or combination therapy (ranibizumab plus laser photocoagulation) compared with laser monotherapy for the treatment of visual impairment due to diabetic macular edema (DME). Methods A Markov model was developed in which patients moved between health states defined by best-corrected visual acuity (BCVA) intervals and an absorbing 'death' state. The population of interest was patients with DME due to type 1 or type 2 diabetes mellitus. Baseline characteristics were based on those of participants in the RESTORE study. Main outputs were costs (in 2013 CA$) and health outcomes (in quality-adjusted life-years [QALYs]) and the incremental cost-effectiveness ratio (ICER) was calculated. This cost-utility analysis was conducted from healthcare system and societal perspectives in Quebec. Results From a healthcare system perspective, the ICERs for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$24 494 and CA$36 414 per QALY gained, respectively. The incremental costs per year without legal blindness for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$15 822 and CA$20 616, respectively. Based on the generally accepted Canadian ICER threshold of CA$50 000 per QALY gained, ranibizumab monotherapy and combination therapy were found to be cost-effective compared with laser monotherapy. From a societal perspective, ranibizumab monotherapy and combination therapy provided greater benefits at lower costs than laser monotherapy (ranibizumab therapy dominated laser therapy). Conclusions Ranibizumab monotherapy and combination therapy resulted in increased quality-adjusted survival and time without legal blindness and lower costs from a societal perspective compared with laser monotherapy.

Intravitreal Aflibercept Injection in Eyes With Substantial Vision Loss After Laser Photocoagulation for Diabetic Macular Edema: Subanalysis of the VISTA and VIVID Randomized Clinical Trials.

PubMed

Wykoff, Charles C; Marcus, Dennis M; Midena, Edoardo; Korobelnik, Jean-François; Saroj, Namrata; Gibson, Andrea; Vitti, Robert; Berliner, Alyson J; Williams Liu, Zinaria; Zeitz, Oliver; Metzig, Carola; Schmelter, Thomas; Heier, Jeffrey S

2016-12-22

Information on the effect of anti-vascular endothelial growth factor therapy in eyes with diabetic macular edema (DME) with vision loss after macular laser photocoagulation is clinically valuable. To evaluate visual and anatomic outcomes in a subgroup of macular laser photocoagulation treatment control (hereafter laser control) eyes with substantial vision loss receiving treatment with intravitreal aflibercept injection. This investigation was a post hoc analysis of a subgroup of laser control eyes in 2 phase 3 trials-VISTA (Study of Intravitreal Aflibercept Injection in Patients With Diabetic Macular Edema) and VIVID (Intravitreal Aflibercept Injection in Vision Impairment Due to DME)-in a multicenter setting. One hundred nine laser control eyes with center-involving DME were included. Treatment with intravitreal aflibercept injection (2 mg) every 8 weeks after 5 monthly doses with sham injections on nontreatment visits starting at week 24 was initiated on meeting prespecified criteria of at least a 10-letter visual acuity loss at 2 consecutive visits or at least a 15-letter visual acuity loss from the best previous measurement at 1 visit and vision not better than at baseline. Visual and anatomic outcomes in a subgroup of laser control eyes receiving treatment with intravitreal aflibercept injection. Through week 100, a total of 63 of 154 eyes (40.9%) in VISTA and 46 of 133 eyes (34.6%) in VIVID initially randomized to laser control received treatment with intravitreal aflibercept injection. The median time from week 24 to the first intravitreal aflibercept injection treatment was 34.0 (VISTA) and 83.5 (VIVID) days. In this subgroup, the mean (SD) visual gain from baseline to week 100 was 2.2 (12.5) (VISTA) and 3.8 (10.1) (VIVID) letters. At the time of intravitreal aflibercept injection initiation, these eyes had a mean (SD) loss of 11.0 (10.1) (VISTA) and 10.0 (6.5) (VIVID) letters from baseline, and they subsequently gained a mean (SD) of 17.4 (9.7) (VISTA) and 13.6 (8.6) (VIVID) letters from the initiation of treatment with intravitreal aflibercept injection through week 100. There was a minimal mean change in central subfield thickness from baseline in these eyes at the time of intravitreal aflibercept injection initiation (an increase of 3.9 μm in VISTA and a decrease of 3.0 μm in VIVID), after which further mean (SD) reductions of 285.6 (202.6) μm (VISTA) and 313.4 (181.9) μm (VIVID) occurred through week 100. Intravitreal aflibercept injection improves visual and anatomic outcomes in eyes experiencing substantial vision loss after macular laser photocoagulation treatment for DME. clinicaltrials.gov Identifiers: NCT01363440 and NCT01331681.

Incidence and Progression of Diabetic Retinopathy in Urban India: Sankara Nethralaya-Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS II), Report 1.

PubMed

Raman, Rajiv; Ganesan, Suganeswari; Pal, Swakshyar Saumya; Gella, Laxmi; Kulothungan, Vaitheeswaran; Sharma, Tarun

2017-10-01

To evaluate the 4-year incidence and progression of and risk factors for diabetic retinopathy (DR) in an Indian population. From a cross-sectional study of 1425 subjects with diabetes, 911 (63.9%) returned for 4-year follow-up. After excluding 21 with ungradable retinal images, data from 890 subjects were analyzed. Participants underwent examinations based on a standard protocol, which included grading of retinal photographs. The incidences of DR, diabetic macular edema (DME), and sight-threatening diabetic retinopathy (STDR) were 9.2%, 2.6%, and 5.0%, respectively. In subjects with DR at baseline, the incidence of DME and STDR had increased (11.5% and 22.7%, respectively). 1-step and 2-step progressions of DR were seen in 30.2% and 12.6% of participants, respectively, and 1-step and 2-step regressions were seen in 12.0% and 1.8%, respectively. Incident DR, DME, and STDR were associated with higher systolic blood pressure (odds ratio, OR, 1.21, 2.11 and 1.72, respectively, for every 10 mmHg increase). Incident DR and DME were associated with increasing duration of diabetes (OR 2.29 and 4.77, respectively, for every 10-year increase) and presence of anemia (OR 1.96 and 10.14, respectively). Incident DR was also associated with higher hemoglobin A1c (OR 1.16 for every 1% increase). Variables associated with 1-step progression were every 10 mg/dL increase in serum total cholesterol (OR 15.65) as a risk factor, and 10 mg/dL increase in serum triglyceride (OR 0.52) as a protective factor. The incidences of STDR and DME were higher in people with pre-existing DR than in those without DR at baseline.

Impact of intravitreal pharmacotherapies including antivascular endothelial growth factor and corticosteroid agents on diabetic retinopathy.

PubMed

Wykoff, Charles C

2017-05-01

Diabetic retinopathy is common and increasing in prevalence. Pharmacologic management of diabetic macular edema (DME) has improved tremendously over the last decade with the use of two families of intravitreally administered medications: antivascular endothelial growth factor-specific agents and corticosteroids. Clinical evaluation of these pharmaceuticals has demonstrated that they can have a substantial impact on diabetic retinopathy severity levels and the underlying retinal vasculature itself. Phase 3 trials employing ranibizumab, aflibercept, and fluocinolone acetonide enrolling eyes with center-involving DME causing visual acuity loss have demonstrated impressive alteration of the natural history of progressive diabetic retinopathy worsening over time through blunted progression to proliferative diabetic retinopathy, improving diabetic retinopathy severity levels, and slowing progressive retinal nonperfusion, the underlying disease process central to diabetic retinopathy itself. Accumulating data indicate that the threshold to initiate ocular-specific pharmacologic treatment for diabetic retinopathy, previously predominately limited to eyes with visual loss because of center-involved DME or proliferative diabetic retinopathy, is being lowered to earlier stages of diabetic retinopathy. Ongoing clinical trials and secondary analyses continue to further explore the impact and durability of vascular endothelial growth factor blockade and corticosteroids on modification of diabetic retinopathy and the underlying retinal vasculature itself.

Long-term effect of anti-vascular endothelial growth factor injections on intraocular pressure

PubMed Central

Nariani, Ashiyana; Williams, Blake; Hariprasad, Seenu M

2016-01-01

Objective: There is a substantial debate in the ophthalmology community about whether anti-vascular endothelial growth factor (VEGF) injections result in a long-term increase in intraocular pressure (IOP). Design: We performed a retrospective study to investigate how the number and timing of intravitreal injections in patients with age-related macular degeneration (AMD) and diabetic macular edema (DME) affect IOP over time. Methods: We collected long-term IOP data on patients receiving anti-VEGF injections at our institution. Patients over the age of 40 years who received injections for AMD (n = 76) or DME (n = 55) were included. Patients were grouped according to indication as well as number of injections received (1–3, 4–6, 7–9, or 10+ injections). IOP measurements were then placed into time points (0–6, 6–12, 12–18, 18–24, or 24+ months) and compared to the preinjection average IOP. Results: For patients with DME, average preinjection IOP was 15.7 mmHg. At 24+ months after injection, the average IOP was 15.2 (P = 0.68) for patients receiving 1–3 injections, 16.8 (P = 0.23) for 4–6 injections, and 14.4 (P = 0.66) for 7–9 injections. For patients with AMD, average initial IOP was 15.6 mmHg. At 24+ months after injection, the average IOP was 12.6 (P = 0.97) for 1–3 injections, 14.9 (P = 0.96) for 4–6 injections, 14.8 (P = 0.84) for 7–9 injections, and 15.7 (P = 0.56) for 10+ injections. Conclusions: There was no increase in IOP over time for AMD or DME patients, regardless of how many injections they received. For patients receiving unilateral injections, there was no increase in IOP in the injected eye when compared to the noninjected eye. PMID:27853011

Identification of Diabetic Retinopathy and Ungradable Image Rate with Ultrawide Field Imaging in a National Teleophthalmology Program.

PubMed

Silva, Paolo S; Horton, Mark B; Clary, Dawn; Lewis, Drew G; Sun, Jennifer K; Cavallerano, Jerry D; Aiello, Lloyd Paul

2016-06-01

To compare diabetic retinopathy (DR) identification and ungradable image rates between nonmydriatic ultrawide field (UWF) imaging and nonmydriatic multifield fundus photography (NMFP) in a large multistate population-based DR teleophthalmology program. Multiple-site, nonrandomized, consecutive, cross-sectional, retrospective, uncontrolled imaging device evaluation. Thirty-five thousand fifty-two eyes (17 526 patients) imaged using NMFP and 16 218 eyes (8109 patients) imaged using UWF imaging. All patients undergoing Joslin Vision Network (JVN) imaging with either NMFP or UWF imaging from May 1, 2014, through August 30, 2015, within the Indian Health Service-JVN program, which serves American Indian and Alaska Native communities at 97 sites across 25 states, were evaluated. All retinal images were graded using a standardized validated protocol in a centralized reading center. Ungradable rate for DR and diabetic macular edema (DME). The ungradable rate per patient for DR and DME was significantly lower with UWF imaging compared with NMFP (DR, 2.8% vs. 26.9% [P < 0.0001]; DME, 3.8% vs. 26.2% [P < 0.0001]). Identification of eyes with either DR or referable DR (moderate nonproliferative DR or DME or worse) was increased using UWF imaging from 11.7% to 24.2% (P < 0.0001) and from 6.2% to 13.6% (P < 0.0001), respectively. In eyes with DR imaged with UWF imaging (n = 3926 eyes of 2402 patients), the presence of predominantly peripheral lesions suggested a more severe level of DR in 7.2% of eyes (9.6% of patients). In a large, widely distributed DR ocular telehealth program, as compared with NMFP, nonmydriatic UWF imaging reduced the number of ungradable eyes by 81%, increased the identification of DR nearly 2-fold, and identified peripheral lesions suggesting more severe DR in almost 10% of patients, thus demonstrating significant benefits of this imaging method for large DR teleophthalmology programs. Copyright © 2016 American Academy of Ophthalmology. All rights reserved.

Evaluation of time domain and spectral domain optical coherence tomography in the measurement of diabetic macular edema.

PubMed

Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B; Chew, Emily Y; Wong, Wai T

2008-10-01

To evaluate macular thickness and volume measurements and their intrasession repeatability in two optical coherence tomography (OCT) systems: the Stratus OCT, a time domain system, and the Cirrus HD-OCT, a spectral domain system (both by Carl Zeiss Meditec, Inc., Dublin, CA), in the context of diabetic macular edema (DME). Thirty-three eyes of 33 diabetic patients with clinically significant macular edema (CSME) were scanned in a single session by a single operator on both OCT systems. Macular thickness measurements of nine standard macular subfields and total macular volume were obtained and analyzed. Bland-Altman plots were constructed to assess agreement in macular measurements. Intraclass correlation coefficients (ICCs), coefficients of repeatability (CR(W)), and coefficients of variation (CV(W)) were used to assess intrasession repeatability. Macular thickness in nine retinal subfields and macular volume were significantly higher in the Cirrus HD-OCT system compared with the Stratus OCT system. Subfield thickness and total volume measurements, respectively, were 30 to 55 microm and 3.2 mm(3) greater for the Cirrus HD-OCT system compared with the Stratus OCT system. Both Stratus OCT and Cirrus HD-OCT systems demonstrated high intrasession repeatability, with overlapping ranges for CR(W), CV(W), and ICC. Repeatability measures (CR(W) and CV(W)) differed significantly between systems in only one of nine subfields (outer temporal subfield). Absolute measures of macular thickness and volume in patients with DME differed significantly in magnitude between the Stratus OCT and Cirrus HD-OCT systems. However, both OCT systems demonstrated high intrasessional repeatability. Although the two systems may not be used interchangeably, they appear equally reliable in generating macular measurements for clinical practice and research.

Novel pharmacotherapies in diabetic retinopathy: Current status and what's in the horizon?

PubMed Central

Das, Arup; McGuire, Paul G; Monickaraj, Finny

2016-01-01

The blood–retinal barrier (BRB) alteration is the hallmark feature of diabetic retinopathy. Vascular endothelial growth factor (VEGF) is a potent vasopermeability factor that has been implicated in the pathogenesis of BRB alteration. Inflammation also plays a crucial role in this process with involvement of several chemokines and cytokines. Multiple anti-VEGF drugs are widely used as in the treatment of diabetic macular edema (DME) as well as proliferative diabetic retinopathy. Several clinical trials have proved the beneficial effects of these drugs in improvement of vision and prevention of vision loss. However, the response to anti-VEGF drugs in DME is not complete in a significant number of patients. The effect seems transient in this latter group, and many patients do not show complete resolution of fluid. Potential novel therapies targeting molecules beyond VEGF are being developed and examined in clinical trials. PMID:26953018

Intravitreal steroids for the treatment of retinal diseases.

PubMed

Sarao, Valentina; Veritti, Daniele; Boscia, Francesco; Lanzetta, Paolo

2014-01-01

Diabetic macular edema (DME), pseudophakic cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO), and uveitis are ocular conditions related to severe visual impairment worldwide. Corticosteroids have been widely used in the treatment of these retinal diseases, due to their well-known antiangiogenic, antiedematous, and anti-inflammatory properties. Intravitreal steroids have emerged as novel and essential tools in the ophthalmologist's armamentarium, allowing for maximization of drug efficacy and limited risk of systemic side effects. Recent advances in ocular drug delivery methods led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drug's half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections. The purpose of this review is to provide an update on the use of intravitreal steroids as a treatment option for a variety of retinal diseases and to review the current literature considering their properties, safety, and adverse events.

Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema.

PubMed

Elman, Michael J; Aiello, Lloyd Paul; Beck, Roy W; Bressler, Neil M; Bressler, Susan B; Edwards, Allison R; Ferris, Frederick L; Friedman, Scott M; Glassman, Adam R; Miller, Kellee M; Scott, Ingrid U; Stockdale, Cynthia R; Sun, Jennifer K

2010-06-01

Evaluate intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). Multicenter, randomized clinical trial. A total of 854 study eyes of 691 participants with visual acuity (approximate Snellen equivalent) of 20/32 to 20/320 and DME involving the fovea. Eyes were randomized to sham injection + prompt laser (n=293), 0.5 mg ranibizumab + prompt laser (n=187), 0.5 mg ranibizumab + deferred (> or =24 weeks) laser (n=188), or 4 mg triamcinolone + prompt laser (n=186). Retreatment followed an algorithm facilitated by a web-based, real-time data-entry system. Best-corrected visual acuity and safety at 1 year. The 1-year mean change (+/-standard deviation) in the visual acuity letter score from baseline was significantly greater in the ranibizumab + prompt laser group (+9+/-11, P<0.001) and ranibizumab + deferred laser group (+9+/-12, P<0.001) but not in the triamcinolone + prompt laser group (+4+/-13, P=0.31) compared with the sham + prompt laser group (+3+/-13). Reduction in mean central subfield thickness in the triamcinolone + prompt laser group was similar to both ranibizumab groups and greater than in the sham + prompt laser group. In the subset of pseudophakic eyes at baseline (n=273), visual acuity improvement in the triamcinolone + prompt laser group appeared comparable to that in the ranibizumab groups. No systemic events attributable to study treatment were apparent. Three eyes (0.8%) had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. Two-year visual acuity outcomes were similar to 1-year outcomes. Intravitreal ranibizumab with prompt or deferred laser is more effective through at least 1 year compared with prompt laser alone for the treatment of DME involving the central macula. Ranibizumab as applied in this study, although uncommonly associated with endophthalmitis, should be considered for patients with DME and characteristics similar to those in this clinical trial. In pseudophakic eyes, intravitreal triamcinolone + prompt laser seems more effective than laser alone but frequently increases the risk of intraocular pressure elevation. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Algorithm for the Measure of Vitreous Hyper-Reflective Foci (VHRF) in Optical Coherence Tomography: VHRF Correlates with Diabetic Retinopathy Disease Progression

PubMed Central

Korot, Edward; Comer, Grant; Steffens, Timothy; Antonetti, David A.

2015-01-01

Importance Developing a non-invasive measure of diabetic retinopathy disease progression may provide clinicians information for patient specific intervention. Objective To develop an algorithm to measure vitreous hyper-reflective foci (VHRF) from standard 3-dimensional OCT images in an unbiased manner. This algorithm was applied to OCT scans from controls, patients with diabetes, and with diabetic macular edema to determine whether VHRF score is associated with macular edema and may serve as a non-invasive measure of inflammation. Design, Setting and Participants We retrospectively analyzed the OCT scans from 97 patients that were seen at the University of Michigan. Patients with diabetes without signs of retinopathy and patients with DME were compared to controls. Main Outcomes and Measures An algorithm was developed in order to enhance the vitreous imaging from OCT to allow automated quantification of VHRF and calculation of a VHRF score. This score was compared between controls and patients with diabetic retinopathy. Results VHRF scores were increased in patients with DME by 2.95 fold, (mean (SD): 5.60 (8.65)) compared to control patients (mean (SD): 1.90 (3.42)) 95% CI [0.75, 7.45] (p=0.012) and by 6.83 fold compared to patients with diabetes without retinopathy (mean (SD): 0.82 (1.26)) 95% CI [1.46, 8.82], (p=0.005). Conclusions and Relevance VHRF scores may be obtained from OCT images that include the vitreous and may provide a rapid and non-invasive clinical correlate for ocular inflammation. Limitations include study size, specifically regarding comorbidities affecting VHRF score. Higher VHRF scores in patients with DME as compared to controls and diabetic patients without retinopathy warrant further population based and longitudinal studies to help determine the value of VHRF score in selecting therapeutic intervention. PMID:26502148

[Early efficacy of dexamethasone implant (OZURDEX®) in diabetic macular edema: Real life study].

PubMed

Sarda, V; Fajnkuchen, F; Nghiem-Buffet, S; Grenet, T; Chaine, G; Giocanti-Auregan, A

2017-05-01

To assess early efficacy of dexamethasone intravitreal implant 0.7mg (OZURDEX ® ) at the time of peak efficacy (2 months after injection) in patients with decreased visual acuity secondary to diabetic macular edema (DME). Retrospective monocentric study. Inclusion criteria were best-corrected visual acuity (BCVA)≤70 letters (20/40) due to DME and central retinal thickness (CRT)≥300 microns (Cirrus 2, Carl Zeiss Meditec, Inc, Dublin). Enrolled patients could be treatment naive or not (after failure of laser photocoagulation and/or anti-VEGF therapy). Follow-up was at least 6 months. Our primary endpoint was BCVA gain at M2 after injection. Secondary endpoints were best-corrected visual acuity at 2 and 4 months, central retinal thickness at 2 and 4 months, mean interval between 2 injections, and adverse events. Nineteen eyes of 19 patients were included in this study. The mean age was 67.45 years, sex ratio was 2.17 men/women, and the patients were all type 2 diabetics. Three of 19 patients were treatment naive for anti-VEGF intravitreal injection, and 52.3% were pseudophakic (10/19 patients). The mean gain of BCVA at M2 was +7.7 letters. The mean BCVA was 51.1 ETDRS letters at baseline and 58.8 at M2. Mean CRT was 568.9μm at baseline and 291.2μm at M2. Treatment with dexamethasone implant was mainly a second-line treatment after failure of other treatments (macular laser photocoagulation and/or intravitreal injection of anti-VEGF). Three patients were naive of anti-VEGF treatment. Intraocular pressure≥25mmHg was found in 2 patients, and controlled medically. No glaucoma surgery was performed. The dexamethasone implant (OZURDEX ® ) allows an anatomical and functional improvement in patients suffering from vision loss due to DME. In this series, the implant was well tolerated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Intravitreal bevacizumab and dexamethasone implant for treatment of chronic diabetic macular edema.

PubMed

Güler, Emre; Totan, Yüksel; Betül Güragaç, Fatma

2017-06-01

To evaluate anatomical and functional outcomes of intraviteal bevacizumab (IVB) in patients with chronic diabetic macular edema (DME), and the effectivity and safety of dexamethasone implant in those unresponsive to regular IVB treatment. Thirty-five eyes of 35 patients (16 male and 19 female) with chronic DME (central foveal thickness (CFT)  > 275 μm, duration  > 6 months) received three injections of 2.5 mg IVB with six-week intervals. At 18 weeks, dexamethasone implant was applied to patients unresponsive to IVB. Main outcomes were the change in best corrected visual acuity (BCVA), CFT and ocular and systemic adverse effects for both drugs. The patients responsive to IVB were followed up for 36 weeks and those patients receiving dexamethasone implant were followed up for 24 weeks postoperatively. At 18 weeks, the mean BCVA (0.68 ± 0.40 logMAR, p = 0.45) and CFT (453 ± 169 μm, p = 0.58) did not show any significant change compared to baseline (0.74 ± 0.42 logMAR and 521 ± 151 μm, respectively). In 20 patients (%57.1) responsive to IVB, the CFT was significantly improved from 12 to 36 weeks with the mean value of 295 ± 42 μ (p = 0.01). However, no significant difference was observed for BCVA during this period (p = 0.17). Dexamethasone was implanted in 15 eyes (42.8%) unresponsive to IVB at 18 weeks. Statistically significant improvements were observed in BCVA (at postoperative 4 and 12 weeks) and CFT (at postoperative 4, 12 and 24 weeks). In addition, both parameters significantly worsened at 24 weeks compared to 12 weeks (p < 0.001 and p = 0.01, respectively). Patients with chronic DME should be followed in accordance with a fixed treatment protocol combining anti-VEGF and steroid treatments.

Shall we stay, or shall we switch? Continued anti-VEGF therapy versus early switch to dexamethasone implant in refractory diabetic macular edema.

PubMed

Busch, Catharina; Zur, Dinah; Fraser-Bell, Samantha; Laíns, Inês; Santos, Ana Rita; Lupidi, Marco; Cagini, Carlo; Gabrielle, Pierre-Henry; Couturier, Aude; Mané-Tauty, Valérie; Giancipoli, Ermete; Ricci, Giuseppe D'Amico; Cebeci, Zafer; Rodríguez-Valdés, Patricio J; Chaikitmongkol, Voraporn; Amphornphruet, Atchara; Hindi, Isaac; Agrawal, Kushal; Chhablani, Jay; Loewenstein, Anat; Iglicki, Matias; Rehak, Matus

2018-05-05

To compare functional and anatomical outcomes of continued anti-vascular endothelial growth factor (VEGF) therapy versus dexamethasone (DEX) implant in eyes with refractory diabetic macular edema (DME) after three initial anti-VEGF injections in a real-world setting. To be included in this retrospective multicenter, case-control study, eyes were required: (1) to present with early refractory DME, as defined by visual acuity (VA) gain ≤ 5 letters or reduction in central subfield thickness (CST) ≤ 20%, after a loading phase of anti-VEGF therapy (three monthly injections) and (2) to treat further with (a) anti-VEGF therapy or (b) DEX implant. Main outcome measures were change in visual acuity (VA) and central subfield thickness (CST) at 12 months. Due to imbalanced baseline characteristics, a matched anti-VEGF group was formed by only keeping eyes with similar baseline characteristics as those in the DEX group. A total of 110 eyes from 105 patients were included (anti-VEGF group: 72 eyes, DEX group: 38 eyes). Mean change in VA at 12 months was - 0.4 ± 10.8 letters (anti-VEGF group), and + 6.1 ± 10.6 letters (DEX group) (P = 0.004). Over the same period, mean change in CST was + 18.3 ± 145.9 µm (anti-VEGF group) and - 92.8 ± 173.6 µm (DEX group) (P < 0.001). Eyes in the DEX group were more likely to gain ≥ 10 letters (OR 3.71, 95% CI 1.19-11.61, P = 0.024) at month 12. In a real-world setting, eyes with DME considered refractory to anti-VEGF therapy after three monthly injections which were switched to DEX implant and had better visual and anatomical outcomes at 12 months than those that continued treatment with anti-VEGF therapy.

A meta-analysis of the effect of a dexamethasone intravitreal implant versus intravitreal anti-vascular endothelial growth factor treatment for diabetic macular edema.

PubMed

He, Ye; Ren, Xin-Jun; Hu, Bo-Jie; Lam, Wai-Ching; Li, Xiao-Rong

2018-05-21

This meta-analysis evaluated the effectiveness and safety of dexamethasone (DEX) implant and intravitreal anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). The PubMed, Embase, clinicaltrials.gov website and Cochrane Library databases were comprehensively searched for studies comparing DEX implant with anti-VEGF in patients with DME. Best-corrected visual acuity (BCVA), central subfield thickness (CST) and adverse events were extracted from the final eligible studies. Review Manager (RevMan) 5.3 for Mac was used to analyze the data and GRADE profiler were used to access the quality of outcomes. Based on four randomized clinical trials assessing a total of 521 eyes, the DEX implant can achieve visual acuity improvement for DME at rates similar to those achieved via anti-VEGF treatment (mean difference [MD] = - 0.43, P = 0.35), with superior anatomic outcomes at 6 months (MD = - 86.71 μm, P = 0.02), while requiring fewer injections, in comparison to anti-VEGF treatment. Although the mean reduction in CST did not showed significant difference at 12 months (MD = - 33.77 μm, P = 0.21), the significant in BCVA from baseline to 12 months supported the anti-VEGF treatment (MD = - 3.26, P < 0.00001). No statistically significant differences in terms of the serious adverse events. However, use of the DEX implant has higher risk of intraocular pressure elevation and cataract than anti-VEGF treatment. Compared with anti-VEGF, DEX implant improved anatomical outcomes significantly. However, this did not translate to improved visual acuity, which may be due to the progression of cataract. Therefore, the DEX implant may be recommended as a first chioce for select cases, such as for pseudophakic eyes, anti-VEGF-resistant eyes, or patients reluctant to receive intravitreal injections frequently.

Comparison of Aflibercept, Bevacizumab, and Ranibizumab for Treatment of Diabetic Macular Edema: Extrapolation of Data to Clinical Practice.

PubMed

Heier, Jeffrey S; Bressler, Neil M; Avery, Robert L; Bakri, Sophie J; Boyer, David S; Brown, David M; Dugel, Pravin U; Freund, K Bailey; Glassman, Adam R; Kim, Judy E; Martin, Daniel F; Pollack, John S; Regillo, Carl D; Rosenfeld, Philip J; Schachat, Andrew P; Wells, John A

2016-01-01

The Diabetic Retinopathy Clinical Research Network (DRCR Network), sponsored by the National Eye Institute, reported the results of a comparative effectiveness randomized clinical trial (RCT) evaluating the 3 anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept (2.0 mg), bevacizumab (1.25 mg), and ranibizumab (0.3 mg) for treatment of diabetic macular edema (DME) involving the center of the retina and associated with visual acuity loss. The many important findings of the RCT prompted the American Society of Retina Specialists to convene a group of experts to provide their perspective regarding clinically relevant findings of the study. To describe specific outcomes of the RCT judged worthy of highlighting, to discuss how these and other clinically relevant results should be considered by specialists treating DME, and to identify unanswered questions that merit consideration before treatment. The DRCR Network-authored publication on primary outcomes of the comparative effectiveness RCT at 89 sites in the United States. The study period of the RCT was August 22, 2012, to August 28, 2013. On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and with visual acuity impairment, including mean (SD) improvements by +13.3 (11.1) letters with aflibercept vs +9.7 (10.1) letters with bevacizumab (P < .001) and +11.2 (9.4) letters with ranibizumab (P = .03). Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept (+18.9 [11.5]) over bevacizumab (+11.8 [12.0]) or ranibizumab (14.2 [10.6]) 1 year later (P < .001 for interaction with visual acuity as a continuous variable, and P = .002 for interaction with visual acuity as a categorical variable). It is unknown whether different visual acuity outcomes associated with the use of the 3 anti-VEGF agents would be noted with other treatment regimens or with adequately repackaged bevacizumab, as well as in patients with criteria that excluded them from the RCT, such as persistent DME despite recent anti-VEGF treatment. On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and visual acuity impairment. Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept over bevacizumab or ranibizumab 1 year later. Care needs to be taken when attempting to extrapolate outcomes of this RCT to differing treatment regimens. With access to adequately repackaged bevacizumab, many specialists might initiate therapy with bevacizumab when visual acuity is good (ie, 20/32 to 20/40 as measured in the DRCR Network), recognizing that the cost-effectiveness of bevacizumab outweighs that of aflibercept or ranibizumab.

Nonmydriatic ultrawide field retinal imaging compared with dilated standard 7-field 35-mm photography and retinal specialist examination for evaluation of diabetic retinopathy.

PubMed

Silva, Paolo S; Cavallerano, Jerry D; Sun, Jennifer K; Noble, Jason; Aiello, Lloyd M; Aiello, Lloyd Paul

2012-09-01

To compare nonmydriatic stereoscopic Optomap ultrawide field images with dilated stereoscopic Early Treatment Diabetic Retinopathy Study 7-standard field 35-mm color 30-degree fundus photographs (ETDRS photography) and clinical examination for determining diabetic retinopathy (DR) and diabetic macular edema (DME) severity. Single-site, prospective, comparative, instrument validation study. One hundred three diabetic patients (206 eyes) representing the full spectrum of DR severity underwent nonmydriatic ultrawide field 100-degree and 200-degree imaging, dilated ETDRS photography, and dilated fundus examination by a retina specialist. Two independent readers graded images to determine DR and DME severity. A third masked retina specialist adjudicated discrepancies. Based on ETDRS photography (n = 200), the results were as follows: no DR (n = 25 eyes [12.5%]), mild nonproliferative DR (NPDR; 47 [23.5%]), moderate NPDR (61 [30.5%]), severe NPDR (11 [5.5%]), very severe NPDR (3 [1.5%]), and proliferative DR (52 [2.5%]). One (0.5%) eye was ungradable and 6 eyes did not complete ETDRS photography. No DME was found in 114 eyes (57.0%), DME was found in 28 eyes (14.0%), and clinically significant DME was found in 47 eyes (23.5%), and 11 (5.5%) eyes were ungradable. Exact DR severity agreement between ultrawide field 100-degree imaging and ETDRS photography occurred in 84%, with agreement within 1 level in 91% (K(W) = 0.85; K = 0.79). Nonmydriatic ultrawide field images exactly matched clinical examination results for DR in 70% and were within 1 level in 93% (K(W) = 0.71; K = 0.61). Nonmydriatic ultrawide field imaging acquisition time was less than half that of dilated ETDRS photography (P < .0001). Nonmydriatic ultrawide field images compare favorably with dilated ETDRS photography and dilated fundus examination in determining DR and DME severity; however, they are acquired more rapidly. If confirmed in broader diabetic populations, nonmydriatic ultrawide field imaging may prove to be beneficial in DR evaluation in research and clinical settings. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison of early dexamethasone retreatment versus standard dexamethasone regimen combined with PRN ranibizumab in diabetic macular edema.

PubMed

Arıkan Yorgun, Mücella; Toklu, Yasin; Mutlu, Melek

2017-02-01

The purpose of the study is to evaluate the efficacy and safety of as-needed dexamethasone (DEX) retreatment compared with standard DEX retreatment combined with PRN ranibizumab injections among patients with persistent diabetic macular edema (DME). Twenty-eight patients with persistent macular edema having recurrence earlier than 6 months after initial DEX implantation were included in this retrospective study. Group I consisted of 13 patients retreated using monthly PRN ranibizumab injections combined with standard 6-monthly DEX implantation; Group II consisted of 15 patients retreated with DEX implantation earlier than 6 months on an "as-needed" basis. There was no significant difference between the groups with regarding to age, gender, HbA1C levels, duration of diabetes, duration of macular edema, baseline central macular thickness (CMT), best-corrected visual acuity (BCVA), and intraocular pressure (IOP) values (p > 0.05). The mean follow-up time of the whole study population was 10.13 ± 1.75 months (range 9-15). The mean CMT values were significantly decreased in both groups compared to baseline values except for the 6th-month CMT in Group I (p < 0.05). The mean logMAR BCVA values were not statistically different between groups during the follow-up compared to baseline BCVA values (p > 0.05). However, a significant change in mean BCVA from baseline was seen at 4th, 6th, and 9th months in Group II (p ≤ 0.05). The mean number of total intravitreal treatments was 3.50 ± 0.77 in Group I and 2.53 ± 0.51 in Group II (p = 0.001). During the follow-up period, one patient in Group I and five patients in Group II had increased IOP (≥25 mmHg). Early DEX retreatment improved vision with superior anatomical improvement at 6th month and with fewer intravitreal treatments in eyes with DME. However, improvement in visual acuity is similar with standard DEX retreatment combined with PRN ranibizumab group.

Macular autofluorescence in eyes with cystoid macula edema, detected with 488 nm-excitation but not with 580 nm-excitation.

PubMed

Bessho, Kenichiro; Gomi, Fumi; Harino, Seiyo; Sawa, Miki; Sayanagi, Kaori; Tsujikawa, Motokazu; Tano, Yasuo

2009-06-01

Fundus autofluorescence (AF) derives from lipofuscin in the retinal pigment epithelium (RPE). Because lipofuscin is a by-product of phagocytosis of photoreceptors by RPE, AF imaging is expected to describe some functional aspect of the retina. In this study we report distribution of AF in patients showing macular edema. Three eyes with diabetic macular edema (DME) and 11 with retinal vein occlusion (RVO), associated with macular edema (ME) were examined. ME was determined by standard fundus examination, fluorescein angiography (FA) and optical coherence tomography (OCT). AF was recorded using a Heidelberg confocal scanning laser ophthalmoscope (cSLO) with 488 nm laser exciter (488 nm-AF), and a conventional Topcon fundus camera with halogen lamp exciter and 580 nm band-pass filter (580 nm-AF). Color fundus picture, FA image and these two AF images were analyzed by superimposing all images. All subjects presented cystoid macular edema (CME) with petaloid pattern hyperfluorescence in FA. In 488 nm-AF, all eyes (100%) showed macular autofluorescence of a similar shape to that of the CME in FA. In contrast, in 580 nm-AF only one eye (7%) presented this corresponding petaloid-shaped autofluorescence. In all cases, peripheral retinal edemas did not show autofluorescence corresponding to the leakage in FA. In eyes with CME, analogous hyperautofluorescence to the CME was always observed in 488 nm-AF, while it was rarely observed in 580 nm-AF. Moreover, this CME hyperautofluorescence was only seen in the macular area. We hypothesize that autofluorescence from CME may be considered as a "pseudo" or "relative" autofluorescence, due to macular stretching following CME that may result in lateral displacement of macular pigments (MPs) and subsequent reduction of MPs density, as MPs block 488 nm-AF more intensely than 580 nm-AF. Although this phenomenon may not directly indicate change of RPE function, it may be used as a method to assess or track CME non-invasively.

Intravitreal Steroids for the Treatment of Retinal Diseases

PubMed Central

Veritti, Daniele; Boscia, Francesco

2014-01-01

Diabetic macular edema (DME), pseudophakic cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO), and uveitis are ocular conditions related to severe visual impairment worldwide. Corticosteroids have been widely used in the treatment of these retinal diseases, due to their well-known antiangiogenic, antiedematous, and anti-inflammatory properties. Intravitreal steroids have emerged as novel and essential tools in the ophthalmologist's armamentarium, allowing for maximization of drug efficacy and limited risk of systemic side effects. Recent advances in ocular drug delivery methods led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drug's half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections. The purpose of this review is to provide an update on the use of intravitreal steroids as a treatment option for a variety of retinal diseases and to review the current literature considering their properties, safety, and adverse events. PMID:24526927

Cost-effectiveness of Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema Treatment: Analysis From the Diabetic Retinopathy Clinical Research Network Comparative Effectiveness Trial.

PubMed

Ross, Eric L; Hutton, David W; Stein, Joshua D; Bressler, Neil M; Jampol, Lee M; Glassman, Adam R

2016-08-01

Anti-vascular endothelial growth factor (VEGF) medicines have revolutionized diabetic macular edema (DME) treatment. A recent randomized clinical trial comparing anti-VEGF agents for patients with decreased vision from DME found that at 1 year aflibercept (2.0 mg) achieved better visual outcomes than repackaged (compounded) bevacizumab (1.25 mg) or ranibizumab (0.3 mg); the worse the starting vision, the greater the treatment benefit with aflibercept. However, aflibercept and ranibizumab, respectively, are approximately 31 and 20 times more expensive than bevacizumab. To examine the incremental cost-effectiveness ratios (ICERs) of aflibercept, bevacizumab, and ranibizumab for the treatment of DME. Post hoc analysis of efficacy, safety, and resource utilization data at 1-year follow-up from the Diabetic Retinopathy Clinical Research Network Comparative Effectiveness Trial. Patients were enrolled from August 22, 2012, through August 28, 2013, and analysis was performed from August 21, 2014, through November 7, 2015. The ICERs for all trial participants and subgroups with baseline vision of approximate Snellen equivalent 20/32 to 20/40 (better vision) and baseline vision of approximate Snellen equivalent 20/50 or worse (worse vision). One-year trial data were used to calculate cost-effectiveness for 1 year for the 3 anti-VEGF agents; mathematical modeling was then used to project 10-year cost-effectiveness results. The study included 624 participants (mean [SD] age, 60.6 [10.5] years; 45.7% female; 65.5% white), 209 in the aflibercept group, 207 in the bevacizumab group, and 208 in the ranibizumab group. For all participants, during 1 year, the ICERs of aflibercept and ranibizumab compared with bevacizumab were $1 110 000 per quality-adjusted life-year (QALY) and $1 730 000 per QALY, respectively. During 10 years, they were $349 000 per QALY and $603 000 per QALY, respectively. Compared with ranibizumab, aflibercept's ICER was $648 000 per QALY at 1 year and $203 000 per QALY at 10 years. For the subgroup with worse baseline vision, the 10-year ICERs of aflibercept and ranibizumab compared with bevacizumab were $287 000 per QALY and $817 000 per QALY, respectively. In eyes with decreased vision from DME, treatment costs of aflibercept and ranibizumab would need to decrease by 69% and 80%, respectively, to reach a cost-effectiveness threshold of $100 000 per QALY compared with bevacizumab during a 10-year horizon; for the subgroup with worse baseline vision, the costs would need to decrease by 62% and 84%, respectively. Aflibercept (2.0 mg) and ranibizumab (0.3 mg) are not cost-effective relative to bevacizumab for treatment of DME unless their prices decrease substantially. These results highlight the challenges that physicians, patients, and policymakers face when safety and efficacy results are at odds with cost-effectiveness results.

Dimethyl ether production from methanol and/or syngas

DOEpatents

Dagle, Robert A; Wang, Yong; Baker, Eddie G; Hu, Jianli

2015-02-17

Disclosed are methods for producing dimethyl ether (DME) from methanol and for producing DME directly from syngas, such as syngas from biomass. Also disclosed are apparatus for DME production. The disclosed processes generally function at higher temperatures with lower contact times and at lower pressures than conventional processes so as to produce higher DME yields than do conventional processes. Certain embodiments of the processes are carried out in reactors providing greater surface to volume ratios than the presently used DME reactors. Certain embodiments of the processes are carried out in systems comprising multiple microchannel reactors.

[New perspectives in the approach to diabetic macular edema. Aflibercept therapy].

PubMed

Ruiz-Moreno, J M

2015-03-01

The VISTA and VIVID trials were conducted to compare the safety and efficacy of two intravitreal injection (IVI) regimens of aflibercept versus macular laser photocoagulation for the treatment of diabetic macular edema (DME). These double-masked, phase III clinical trials randomized (461/402) patients with DME to receive either 2mg aflibercept IVI every 4 weeks (2q4) or 2mg aflibercept IVI every 8 weeks (2q8) after 5 initial monthly doses vs macular laser photocoagularion. The primary efficacy endpoint was the mean change in best corrected visual acuity (BCVA) from baseline to week 52. Secondary efficacy endpoints were the change in central retinal thickness (CRT), the proportion of patients who gained ≥10 amd ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and the change in the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) in near and distance vision. The mean BCVA gains in the 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (p<0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (p<0.0001) in VIVID. The proportions of patients gaining ≥ 15 letters and the proportion of patients with an improvement of > 2 levels in the severity of diabetic retinopathy was significant in the treatment groups versus the laser group. Mean reductions in CRT in the 2q4 and 2q8 groups vs the laser group were 185.9 and 183.1 versus 73.3 μm (p<0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm (p<0.0001) in VIVID. The incidences of ocular and nonocular adverse events were similar in all groups. In conclusion, IIV aflibercept demonstrated statistically significant superiority in improvement in BCVA and reduction in DME over laser, with similar efficacy in the 2q4 and 2q8 groups in VISTA and VIVID. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Denoising and segmentation of retinal layers in optical coherence tomography images

NASA Astrophysics Data System (ADS)

Dash, Puspita; Sigappi, A. N.

2018-04-01

Optical Coherence Tomography (OCT) is an imaging technique used to localize the intra-retinal boundaries for the diagnostics of macular diseases. Due to speckle noise, low image contrast and accurate segmentation of individual retinal layers is difficult. Due to this, a method for retinal layer segmentation from OCT images is presented. This paper proposes a pre-processing filtering approach for denoising and segmentation methods for segmenting retinal layers OCT images using graph based segmentation technique. These techniques are used for segmentation of retinal layers for normal as well as patients with Diabetic Macular Edema. The algorithm based on gradient information and shortest path search is applied to optimize the edge selection. In this paper the four main layers of the retina are segmented namely Internal limiting membrane (ILM), Retinal pigment epithelium (RPE), Inner nuclear layer (INL) and Outer nuclear layer (ONL). The proposed method is applied on a database of OCT images of both ten normal and twenty DME affected patients and the results are found to be promising.

Advances in retinal imaging for diabetic retinopathy and diabetic macular edema.

PubMed

Tan, Colin Siang Hui; Chew, Milton Cher Yong; Lim, Louis Wei Yi; Sadda, Srinivas R

2016-01-01

Diabetic retinopathy and diabetic macular edema (DME) are leading causes of blindness throughout the world, and cause significant visual morbidity. Ocular imaging has played a significant role in the management of diabetic eye disease, and the advent of advanced imaging modalities will be of great value as our understanding of diabetic eye diseases increase, and the management options become increasingly varied and complex. Color fundus photography has established roles in screening for diabetic eye disease, early detection of progression, and monitoring of treatment response. Fluorescein angiography (FA) detects areas of capillary nonperfusion, as well as leakage from both microaneurysms and neovascularization. Recent advances in retinal imaging modalities complement traditional fundus photography and provide invaluable new information for clinicians. Ultra-widefield imaging, which can be used to produce both color fundus photographs and FAs, now allows unprecedented views of the posterior pole. The pathologies that are detected in the periphery of the retina have the potential to change the grading of disease severity, and may be of prognostic significance to disease progression. Studies have shown that peripheral ischemia may be related to the presence and severity of DME. Optical coherence tomography (OCT) provides structural detail of the retina, and the quantitative and qualitative features are useful in the monitoring of diabetic eye disease. A relatively recent innovation, OCT angiography, produces images of the fine blood vessels at the macula and optic disc, without the need for contrast agents. This paper will review the roles of each of these imaging modalities for diabetic eye disease.

Advances in retinal imaging for diabetic retinopathy and diabetic macular edema

PubMed Central

Tan, Colin Siang Hui; Chew, Milton Cher Yong; Lim, Louis Wei Yi; Sadda, Srinivas R

2016-01-01

Diabetic retinopathy and diabetic macular edema (DME) are leading causes of blindness throughout the world, and cause significant visual morbidity. Ocular imaging has played a significant role in the management of diabetic eye disease, and the advent of advanced imaging modalities will be of great value as our understanding of diabetic eye diseases increase, and the management options become increasingly varied and complex. Color fundus photography has established roles in screening for diabetic eye disease, early detection of progression, and monitoring of treatment response. Fluorescein angiography (FA) detects areas of capillary nonperfusion, as well as leakage from both microaneurysms and neovascularization. Recent advances in retinal imaging modalities complement traditional fundus photography and provide invaluable new information for clinicians. Ultra-widefield imaging, which can be used to produce both color fundus photographs and FAs, now allows unprecedented views of the posterior pole. The pathologies that are detected in the periphery of the retina have the potential to change the grading of disease severity, and may be of prognostic significance to disease progression. Studies have shown that peripheral ischemia may be related to the presence and severity of DME. Optical coherence tomography (OCT) provides structural detail of the retina, and the quantitative and qualitative features are useful in the monitoring of diabetic eye disease. A relatively recent innovation, OCT angiography, produces images of the fine blood vessels at the macula and optic disc, without the need for contrast agents. This paper will review the roles of each of these imaging modalities for diabetic eye disease. PMID:26953028

Effects of kallidinogenase in patients undergoing vitrectomy for diabetic macular edema.

PubMed

Yoshizumi, Yuki; Ohara, Zaigen; Tabuchi, Hitoshi; Sumino, Hitomi; Maeda, Yukiko; Mochizuki, Hideki; Yamane, Ken; Kiuchi, Yoshiaki

2018-05-12

To evaluate the effectiveness of the combination of vitrectomy with kallidinogenase for diabetic macular edema (DME). This study was designed as a prospective, randomized, multicenter study comparing 19 eyes of 19 patients who received 150 units of kallidinogenase administered a day for 52 weeks from the day after vitrectomy (study group) with 20 eyes of 20 patients who received no kallidinogenase (control group). The main outcome measurements included logMAR visual acuity and central foveal thickness (CFT) before surgery and at 3, 6, 9, and 12 months after vitrectomy. During follow-up, 11 patients dropped out (six in the study group and five in the control group), leaving 28 eyes in 28 patients for analysis (13 in the study group and 15 in the control group). Visual acuity improved significantly at 12 months in both groups compared with before surgery. The degree of improvement did not differ significantly between the groups. At 12 months, the mean CFT decreased significantly in both groups, with no significant difference in the rate of change between the two groups. In the study group, the visual acuity and CFT significantly improved from 3 to 12 months and from 6 to 12 months, whereas these parameters did not continue to improve in the control group after 6 months (for visual acuity) or 3 months (for CFT). After vitrectomy for DME, visual acuity and CFT improved significantly in both groups, but only patients treated with kallidinogenase continued to have significant improvement throughout the study period.

SFOL Pulse: A High Accuracy DME Pulse for Alternative Aircraft Position and Navigation.

PubMed

Kim, Euiho; Seo, Jiwon

2017-09-22

In the Federal Aviation Administration's (FAA) performance based navigation strategy announced in 2016, the FAA stated that it would retain and expand the Distance Measuring Equipment (DME) infrastructure to ensure resilient aircraft navigation capability during the event of a Global Navigation Satellite System (GNSS) outage. However, the main drawback of the DME as a GNSS back up system is that it requires a significant expansion of the current DME ground infrastructure due to its poor distance measuring accuracy over 100 m. The paper introduces a method to improve DME distance measuring accuracy by using a new DME pulse shape. The proposed pulse shape was developed by using Genetic Algorithms and is less susceptible to multipath effects so that the ranging error reduces by 36.0-77.3% when compared to the Gaussian and Smoothed Concave Polygon DME pulses, depending on noise environment.

SFOL Pulse: A High Accuracy DME Pulse for Alternative Aircraft Position and Navigation

PubMed Central

Kim, Euiho

2017-01-01

In the Federal Aviation Administration’s (FAA) performance based navigation strategy announced in 2016, the FAA stated that it would retain and expand the Distance Measuring Equipment (DME) infrastructure to ensure resilient aircraft navigation capability during the event of a Global Navigation Satellite System (GNSS) outage. However, the main drawback of the DME as a GNSS back up system is that it requires a significant expansion of the current DME ground infrastructure due to its poor distance measuring accuracy over 100 m. The paper introduces a method to improve DME distance measuring accuracy by using a new DME pulse shape. The proposed pulse shape was developed by using Genetic Algorithms and is less susceptible to multipath effects so that the ranging error reduces by 36.0–77.3% when compared to the Gaussian and Smoothed Concave Polygon DME pulses, depending on noise environment. PMID:28937615

Comparison of the two techniques for measurement of the density of Demodex folliculorum: standardized skin surface biopsy and direct microscopic examination.

PubMed

Aşkin, U; Seçkin, D

2010-05-01

In daily dermatological practice, many dermatologists do not include demodicosis in their differential diagnoses, or the diagnosis of demodicosis is frequently masked by other skin diseases such as papulopustular or erythematotelangiectatic rosacea, seborrhoeic dermatitis, perioral dermatitis and contact dermatitis. There are two methods for measurement of the density of Demodex folliculorum (Dd): standardized skin surface biopsy (SSSB) and direct microscopic examination of fresh secretions from sebaceous glands (DME). No study has been reported in the literature comparing the diagnostic value of these two techniques. To compare the value of the two techniques, SSSB and DME, for the measurement of Dd in patients with suspected demodicosis. Mite density was investigated using SSSB and DME in 37 patients with facial skin lesions suggesting demodicosis. Two samples, one for SSSB and one for DME, were obtained from a cheek lesion of each patient. Twenty-three (62%) patients were diagnosed with demodicosis according to their clinical manifestations combined with a high Dd (Dd > 5 mites cm(-2)) with SSSB and/or DME. In all the patients, the mean Dd measured with SSSB was higher than that with DME (22.9 +/- 5.9 and 2.2 +/- 0.8, respectively; P = 0.001). Also, among the 23 patients with demodicosis, the mean Dd measured using SSSB was higher than the mean Dd with DME (36.5 +/- 8.3 and 3.4 +/- 1.2, respectively; P = 0.0001). We recommend the use of SSSB for the measurement of Dd as more patients with demodicosis can be diagnosed with this method compared with the DME method.

Identification of factors to increase efficacy of telemedicine screening for diabetic retinopathy in endocrinology practices using the Intelligent Retinal Imaging System (IRIS) platform.

PubMed

Naik, Sapna; Wykoff, Charles C; Ou, William C; Stevenson, Jonathan; Gupta, Sunil; Shah, Ankoor R

2018-06-01

Diabetic retinopathy (DR) and diabetic macular edema (DME) can be evaluated using telemedicine systems, such as the Intelligent Retinal Imaging Systems (IRIS), in patients with Diabetes Mellitus (DM). In an endocrinology-based population utilizing IRIS we determine prevalence rates of DR and DME, and identify associated epidemiologic correlations. This is a multicenter, retrospective chart review using screening data from IRIS. Centers for Disease Control and Prevention (CDC) data on epidemiologic variables (by county) namely, prevalence of DM, incidence of DM, obesity, and time of physical inactivity, were compared against prevalence rates of DR found at screening. A total of 10,223 eyes of 5,242 patients with DM were imaged. DR and DME were noted in 1781 (33.98%) and 226 imaging studies (4.31%) respectively. The coefficient of determination was greatest for incidence of DM (R 2  = 0.92), followed by DM prevalence (R 2  = 0.79), obesity, (R 2  = 0.67), and physical inactivity (R 2  = 0.34). The presence of DR during screening varied significantly by county (p < 0.001). Screening in counties with a higher incidence of DM led to a higher prevalence of identified DR at time of screening. The current work suggests that telemedicine screening in areas known to have a higher incidence of DM may be worthwhile. Copyright © 2018 Elsevier B.V. All rights reserved.

Enhanced Benefit in Diabetic Macular Edema from AKB-9778 Tie2 Activation Combined with Vascular Endothelial Growth Factor Suppression.

PubMed

Campochiaro, Peter A; Khanani, Arshad; Singer, Michael; Patel, Sunil; Boyer, David; Dugel, Pravin; Kherani, Saleema; Withers, Barbara; Gambino, Laura; Peters, Kevin; Brigell, Mitchell

2016-08-01

To assess the effect of AKB-9778 alone or in combination with ranibizumab in subjects with diabetic macular edema (DME). A phase IIa, randomized, placebo- and sham injection-controlled, double-masked clinical trial. Subjects (n = 144) with decreased vision from DME and central subfield thickness (CST) ≥325 μm measured by spectral-domain optical coherence tomography (SD OCT) enrolled at 36 sites. Subjects were randomized to (1) AKB-9778 monotherapy: subcutaneous AKB-9778 15 mg twice per day (BID) + monthly sham intraocular injections; (2) combination therapy: subcutaneous AKB-9778 15 mg BID + monthly 0.3 mg ranibizumab; or (3) ranibizumab monotherapy: subcutaneous placebo injections BID + monthly 0.3 mg ranibizumab. Best-corrected visual acuity (BCVA) and CST were measured at baseline and every 4 weeks. Primary outcome measure was mean change from baseline CST at week 12. Other outcomes included BCVA, safety assessments, and Diabetic Retinopathy Severity Score (DRSS). At week 12, mean change from baseline CST was significantly greater in the combination group (-164.4±24.2 μm) compared with the ranibizumab monotherapy group (-110.4±17.2 μm; P = 0.008) and was 6.2±13.0 μm in the AKB-9778 monotherapy group. Mean CST at week 12 and percentage of eyes with resolved edema was 340.0±11.2 μm and 29.2%, respectively, in the combination group versus 392.1±17.1 μm and 17.0%, respectively, in the ranibizumab monotherapy group. Mean change from baseline BCVA (letters) was 6.3±1.3 in the combination group, 5.7±1.2 in the ranibizumab monotherapy group, and 1.5±1.2 in the AKB-9778 monotherapy group. The percentage of study eyes that gained ≥10 or ≥15 letters was 8.7% and 4.3%, respectively, in the AKB-9778 monotherapy group, 29.8% and 17.0%, respectively, in the ranibizumab monotherapy group, and 35.4% and 20.8%, respectively, in the combination group. Improvements in DRSS in study eyes were similar across groups, and the percentage of qualified fellow eyes with a ≥2-step change was 11.4% in all AKB-9778-treated subjects compared with 4.2% in the ranibizumab monotherapy group. AKB-9778 was well tolerated, with no clear by-treatment differences in adverse events. Activation of Tie2 by subcutaneous injections of AKB-9778 combined with suppression of vascular endothelial growth factor (VEGF) causes a significantly greater reduction in DME than that seen with suppression of VEGF alone. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The DA VINCI Study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema.

PubMed

Do, Diana V; Schmidt-Erfurth, Ursula; Gonzalez, Victor H; Gordon, Carmelina M; Tolentino, Michael; Berliner, Alyson J; Vitti, Robert; Rückert, Rene; Sandbrink, Rupert; Stein, David; Yang, Ke; Beckmann, Karola; Heier, Jeff S

2011-09-01

To determine whether different doses and dosing regimens of intravitreal vascular endothelial growth factor (VEGF) Trap-Eye are superior to focal/grid photocoagulation in eyes with diabetic macular edema (DME). Multicenter, randomized, double-masked, phase 2 clinical trial. A total of 221 diabetic patients with clinically significant macular edema involving the central macula. Patients were assigned to 1 of 5 treatment regimens: 0.5 mg VEGF Trap-Eye every 4 weeks; 2 mg VEGF Trap-Eye every 4 weeks; 2 mg VEGF Trap-Eye for 3 initial monthly doses and then every 8 weeks; 2 mg VEGF Trap-Eye for 3 initial monthly doses and then on an as-needed (PRN) basis; or macular laser photocoagulation. Assessments were completed at baseline and every 4 weeks thereafter. Mean change in visual acuity and central retinal thickness (CRT) at 24 weeks. Patients in the 4 VEGF Trap-Eye groups experienced mean visual acuity benefits ranging from +8.5 to +11.4 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters versus only +2.5 letters in the laser group (P ≤ 0.0085 for each VEGF Trap-Eye group vs. laser). Gains from baseline of 0+, 10+, and 15+ letters were seen in up to 93%, 64%, and 34% of VEGF Trap-Eye groups versus up to 68%, 32%, and 21% in the laser group, respectively. Mean reductions in CRT in the 4 VEGF Trap-Eye groups ranged from -127.3 to -194.5 μm compared with only -67.9 μm in the laser group (P = 0.0066 for each VEGF Trap-Eye group vs. laser). VEGF Trap-Eye was generally well tolerated. Ocular adverse events in patients treated with VEGF Trap-Eye were generally consistent with those seen with other intravitreal anti-VEGF agents. Intravitreal VEGF Trap-Eye produced a statistically significant and clinically relevant improvement in visual acuity when compared with macular laser photocoagulation in patients with DME. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Cost-effectiveness analysis of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema.

PubMed

Dewan, Vinay; Lambert, Dennis; Edler, Joshua; Kymes, Steven; Apte, Rajendra S

2012-08-01

Perform a cost-effectiveness analysis of the treatment of diabetic macular edema (DME) with ranibizumab plus prompt or deferred laser versus triamcinolone plus prompt laser. Data for the analysis were drawn from reports of the Diabetic Retinopathy Clinical Research Network (DRCRnet) Protocol I. Computer simulation based on Protocol I data. Analyses were conducted from the payor perspective. Simulated participants assigned characteristics reflecting those seen in Protocol I. Markov models were constructed to replicate Protocol I's 104-week outcomes using a microsimulation approach to estimation. Baseline characteristics, visual acuity (VA), treatments, and complications were based on Protocol I data. Costs were identified by literature search. One-way sensitivity analysis was performed, and the results were validated against Protocol I data. Direct cost of care for 2 years, change in VA from baseline, and incremental cost-effectiveness ratio (ICER) measured as cost per additional letter gained from baseline (Early Treatment of Diabetic Retinopathy Study). For sham plus laser (S+L), ranibizumab plus prompt laser (R+pL), ranibizumab plus deferred laser (R+dL), and triamcinolone plus laser (T+L), effectiveness through 104 weeks was predicted to be 3.46, 7.07, 8.63, and 2.40 letters correct, respectively. The ICER values in terms of dollars per VA letter were $393 (S+L vs. T+L), $5943 (R+pL vs. S+L), and $20 (R+dL vs. R+pL). For pseudophakics, the ICER value for comparison triamcinolone with laser versus ranibizumab with deferred laser was $14 690 per letter gained. No clinically relevant changes in model variables altered outcomes. Internal validation demonstrated good similarity to Protocol I treatment patterns. In treatment of phakic patients with DME, ranibizumab with deferred laser provided an additional 6 letters correct compared with triamcinolone with laser at an additional cost of $19 216 over 2 years. That would indicate that if the gain in VA seen at 2 years is maintained in subsequent years, then the treatment of phakic patients with DME using ranibizumab may meet accepted standards of cost-effectiveness. For pseudophakic patients, first-line treatment with triamcinolone seems to be the most cost-effective option. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Direct and indirect costs among employees with diabetic retinopathy in the United States.

PubMed

Lee, Lauren J; Yu, Andrew P; Cahill, Kevin E; Oglesby, Alan K; Tang, Jackson; Qiu, Ying; Birnbaum, Howard G

2008-05-01

To examine, from the employer perspective, the direct (healthcare) and indirect (workloss) costs of employees with diabetic retinopathy (DR) compared to control non-DR employees with diabetes, and within DR subgroups. Compared annual costs using claims data from 17 large companies (1999-2004). 'DR employees' (n = 2098) had >or= 1 DR (International Classification of Disease, 9th Revision [ICD-9]) diagnosis; DR subgroups included employees with diabetic macular edema (DME), proliferative DR (PDR), and employees receiving photocoagulation or vitrectomy procedures. Descriptive and multivariate tests were performed. DR employee annual direct costs were $18,218 (indirect = $3548) compared to $11,898 (indirect = $2374) for controls (Delta = $2032 (adjusted); p < 0.0001). Costs differences were larger across DR employee subgroups: DME/non-DME ($28,606/$16,363); PDR/non-PDR ($30,135/$13,445; p < 0.0001); DR with/without photocoagulation ($34,539/$16,041; p < 0.0001); and DR with/without vitrectomy ($63,933/$17,239; p < 0.0001). This study examined the incremental costs of treating DR employees, which may be higher than the incremental costs of DR itself. Some measures of diabetes severity (e.g., duration of diabetes) were not available in the claims data, and were therefore not included in the multivariate models. The cost of photocoagulation and vitrectomy procedures pertain to individuals who underwent these procedures, and not the cost of the procedures themselves. DR employees had significantly higher costs than controls, and larger differences existed within DR subgroups. Indirect costs accounted for about 20% of total cost.

Anti-VEGF aptamer (pegaptanib) therapy for ocular vascular diseases.

PubMed

Ng, Eugene W M; Adamis, Anthony P

2006-10-01

Vascular endothelial growth factor (VEGF) is a central regulator of both physiological and pathological angiogenesis. Pegaptanib, a 28-nucleotide RNA aptamer specific for the VEGF(165) isoform, binds to it in the extracellular space, leaving other isoforms unaffected, and inhibits such key VEGF actions as promotion of endothelial cell proliferation and survival, and vascular permeability. Pegaptanib already has been examined as a treatment for two diseases associated with ocular neovascularization, age-related macular degeneration (AMD) and diabetic macular edema (DME). Preclinical studies have shown that VEGF(165) alone mediates pathological ocular neovascularization and that its inactivation by pegaptanib inhibits the choroidal neovascularization observed in patients with neovascular AMD. In contrast, physiological vascularization, which is supported by the VEGF(121) isoform, is unaffected by this inactivation of VEGF(165). In addition, animal model studies have shown that intravitreous injection of pegaptanib can inhibit the breakdown of the blood-retinal barrier characteristic of diabetes and even can reverse this damage to some degree. These preclinical findings formed the basis for randomized controlled trials examining the efficacy of pegaptanib as a therapy for AMD and DME. The VEGF Inhibition Study in Ocular Neovascularization (VISION) trial comprising two replicate, pivotal phase 3 studies, demonstrated that intravitreous injection of pegaptanib resulted in significant clinical benefit, compared with sham injection, for all prespecified clinical end points, irrespective of patient demographics or angiographic subtype, and led to pegaptanib's approval as a treatment for AMD. A phase 2 trial has provided support for the efficacy of intravitreous pegaptanib in the treatment of DME.

Organizing graduate medical education programs into communities of practice.

PubMed

Bing-You, Robert G; Varaklis, Kalli

2016-01-01

Background A new organizational model of educational administrative support was instituted in the Department of Medical Education (DME) to better meet increasing national accreditation demands. Residency and fellowship programs were organized into four 'Communities of Practice' (CoOPs) based on discipline similarity, number of learners, and geographic location. Program coordinator reporting lines were shifted from individual departments to a centralized reporting structure within the DME. The goal of this project was to assess the impact on those most affected by the change. Methods This was a mixed methods study that utilized structured interviews and the Organizational Culture Assessment Instrument (OCAI). Eleven members of the newly formed CoOPs participated in the study. Results Three major themes emerged after review and coding of the interview transcripts: improved group identity, improved availability of resources, and increased opportunity for professional growth. OCAI results indicated that respondents are committed to the DME and perceived the culture to be empowering. The 'preferred culture' was very similar to the culture at the time of the study, with some indication that DME employees are ready for more creativity and innovation in the future. Conclusion Reorganization within the DME of residency programs into CoOPs was overwhelmingly perceived as a positive change. Improved resources and accountability may position our DME to better handle the increasing complexity of graduate medical education.

Occupational Exposure to Diesel Motor Exhaust and Lung Cancer: A Dose-Response Relationship Hidden by Asbestos Exposure Adjustment? The ICARE Study

PubMed Central

Matrat, Mireille; Guida, Florence; Cénée, Sylvie; Févotte, Joelle; Carton, Matthieu; Cyr, Diane; Menvielle, Gwenn; Paget-Bailly, Sophie; Radoï, Loredana; Schmaus, Annie; Bara, Simona; Velten, Michel; Luce, Danièle; Stücker, Isabelle; The Icare Study Group

2015-01-01

Background. In a French large population-based case-control study we investigated the dose-response relationship between lung cancer and occupational exposure to diesel motor exhaust (DME), taking into account asbestos exposure. Methods. Exposure to DME was assessed by questionnaire. Asbestos was taken into account through a global indicator of exposure to occupational carcinogens or by a specific JEM. Results. We found a crude dose response relationship with most of the indicators of DME exposure, including with the cumulative exposure index. All results were affected by adjustment for asbestos exposure. The dose response relationships between DME and lung cancer were observed among subjects never exposed to asbestos. Conclusions. Exposure to DME and to asbestos is frequently found among the same subjects, which may explain why dose-response relationships in previous studies that adjusted for asbestos exposure were inconsistent. PMID:26425123

A simplified noninvasive method to measure airway blood flow in humans.

PubMed

Wanner, Adam; Mendes, Eliana S; Atkins, Neal D

2006-05-01

Our laboratory has previously developed and validated a noninvasive soluble gas uptake method to measure airway blood flow (Qaw) in humans (Onorato DJ, Demirozu MC, Breitenbücher A, Atkins ND, Chediak AD, and Wanner A. Am J Respir Crit Care Med 149: 1132-1137, 1994; Scuri M, McCaskill V, Chediak AD, Abraham WM, and Wanner A. J Appl Physiol 79: 1386-1390, 1995). The method has the disadvantage of requiring eight breath-hold maneuvers for a single Qaw measurement, a complicated data analysis, and the inhalation of a potentially explosive gas mixture containing dimethylether (DME) and O2. Because of these shortcomings, the method thus far has not been used in other laboratories. We now simplified the method by having the subjects inhale 500 ml of a 10% DME-90% N2 gas mixture to fill the anatomical dead space, followed by a 5- or 15-s breath hold, and measuring the instantaneous DME and N2 concentrations and volume at the airway opening during the subsequent exhalation. From the difference in DME concentration in phase 1 of the expired N2 wash-in curve multiplied by the phase 1 dead space volume and divided by the mean DME concentration and the solubility coefficient for DME in tissue, Qaw can be calculated by using Fick's equation. We compared the new method to the validated old method in 10 healthy subjects and found mean +/- SE Qaw values of 34.6 +/- 2.3 and 34.6 +/- 2.8 microl.min(-1).ml(-1), respectively (r = 0.93; upper and lower 95% confidence limit +2.48 and -2.47). Using the new method, the mean coefficient of variation for two consecutive measurements was 4.4% (range 0-10.4%); inhalation of 1.2 mg albuterol caused a 53 +/- 14% increase in Qaw (P = 0.02) and inhalation of 2.4 mg methoxamine caused a 32 +/- 7% decrease in Qaw (P = 0.07). We conclude that the new method provides reliable values of and detects the expected changes in Qaw with vasoactive drugs. The simplicity and improved safety of the method should improve its acceptability for the noninvasive assessment of Qaw in clinical research.

Comparison of low-light nonmydriatic digital imaging with 35-mm ETDRS seven-standard field stereo color fundus photographs and clinical examination.

PubMed

Silva, Paolo S; Walia, Saloni; Cavallerano, Jerry D; Sun, Jennifer K; Dunn, Cheri; Bursell, Sven-Erik; Aiello, Lloyd M; Aiello, Lloyd Paul

2012-09-01

To compare agreement between diagnosis of clinical level of diabetic retinopathy (DR) and diabetic macular edema (DME) derived from nonmydriatic fundus images using a digital camera back optimized for low-flash image capture (MegaVision) compared with standard seven-field Early Treatment Diabetic Retinopathy Study (ETDRS) photographs and dilated clinical examination. Subject comfort and image acquisition time were also evaluated. In total, 126 eyes from 67 subjects with diabetes underwent Joslin Vision Network nonmydriatic retinal imaging. ETDRS photographs were obtained after pupillary dilation, and fundus examination was performed by a retina specialist. There was near-perfect agreement between MegaVision and ETDRS photographs (κ=0.81, 95% confidence interval [CI] 0.73-0.89) for clinical DR severity levels. Substantial agreement was observed with clinical examination (κ=0.71, 95% CI 0.62-0.80). For DME severity level there was near-perfect agreement with ETDRS photographs (κ=0.92, 95% CI 0.87-0.98) and moderate agreement with clinical examination (κ=0.58, 95% CI 0.46-0.71). The wider MegaVision 45° field led to identification of nonproliferative changes in areas not imaged by the 30° field of ETDRS photos. Field area unique to ETDRS photographs identified proliferative changes not visualized with MegaVision. Mean MegaVision acquisition time was 9:52 min. After imaging, 60% of subjects preferred the MegaVision lower flash settings. When evaluated using a rigorous protocol, images captured using a low-light digital camera compared favorably with ETDRS photography and clinical examination for grading level of DR and DME. Furthermore, these data suggest the importance of more extensive peripheral images and suggest that utilization of wide-field retinal imaging may further improve accuracy of DR assessment.

The Cost-Effectiveness of Ranibizumab for the Treatment of Diabetic Macular Edema.

PubMed

Brown, Gary C; Brown, Melissa M; Turpcu, Adam; Rajput, Yamina

2015-07-01

To assess the incremental, comparative effectiveness (patient value gain) and cost effectiveness (financial value gain) associated with 0.3-mg intravitreal ranibizumab injection therapy versus sham therapy for diabetic macular edema (DME). Value-Based Medicine (Center for Value-Based Medicine, Flourtown, PA) 14-year, cost-utility analysis using patient preferences and 2012 United States real dollars. Published data from the identical Ranibizumab Injection in Subjects with Clinically Significant Macular Edema with Center Involvement Secondary to Diabetes Mellitus (RISE and RIDE) clinical trials. An incremental cost-utility analysis was performed using societal and third-party insurer cost perspectives. Costs and outcomes were discounted with net present value analysis at 3% per annum. The incremental comparative effectiveness was measured in: (1) quality-adjusted life year (QALY) gain and (2) percent patient value (quality-of-life) gain. Cost effectiveness was quantified with the cost-utility ratio (CUR) measured as $/QALY. The 14-year, incremental patient value gain conferred by intravitreal ranibizumab therapy for diabetic maculopathy was 0.9981 QALY, equating to an 11.6% improvement in quality of life. The direct, ophthalmic medical cost for ranibizumab therapy in 1 eye was $30 116, whereas for 2 eyes it was $56 336. The direct, nonophthalmic, medical costs saved from decreased depression, injury, skilled nursing facility admissions, nursing home admissions, and other vision-associated costs totaled $51 758, resulting in an overall direct medical cost of $4578. The net mean societal cost for bilateral ranibizumab therapy was -$30 807. Of this total, decreased caregiver costs accrued a $31 406 savings against the direct medical costs, whereas decreased wage losses accrued a $3978 savings. The third-party insurer CUR for bilateral ranibizumab therapy was $4587/QALY. The societal cost perspective for bilateral therapy was -$30 807/QALY, indicating that ranibizumab therapy dominated sham therapy because it conferred both a positive QALY gain of 0.9981 and a financial value gain (positive financial return on investment) of $30 807 referent to the direct ophthalmic medical costs expended. Intravitreal ranibizumab therapy for the treatment of DME confers considerable patient (human) value gain. It also accrues financial value to patients, public and private insurers, and society. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Cost and Selection of Ophthalmic Anti-Vascular Endothelial Growth Factor Agents.

PubMed

Li, Emily; Greenberg, Paul B; Voruganti, Indu; Krzystolik, Magdalena G

2016-05-02

Anti-vascular endothelial growth factor (anti-VEGF) drugs - ranibizumab, aflibercept, and off-label bevacizumab - are vital to the treatment of common retinal diseases, including exudative age-related macular degeneration (AMD), diabetic macular edema (DME), and macular edema (ME) associated with retinal vein occlusion (RVO). Given the high prevalence of AMD and retinal vascular diseases, anti-VEGF agents represent a large cost burden to the United States (US) healthcare system. Although ranibizumab and aflibercept are 30-fold more expensive per injection than bevacizumab, the two more costly medications are commonly used in the US, even though all three have been shown to be effective and safe for treatment of these retinal diseases. We investigated the availability and content of professional ophthalmic guidelines on cost consideration in the selection of anti-VEGF agents. We found that current professional guidelines were limited in availability and lacked specific guidance on cost-based anti-VEGF drug selection. This represents a missed opportunity to encourage the practice of value-based medicine. [Full article available at http://rimed.org/rimedicaljournal-2016-05.asp, free with no login].

[Management of aflibercept in routine clinical practice].

PubMed

Cabrera López, F

2015-03-01

Aflibercept is a new anti-vegf drug that, unlike ranibizumab and bevacizumab blocks both vegf-A and placental growth factor. Moreover, it binds with much greater strength and affinity to human VEGF-A165 than other endogenous vegf receptors, conferring it with a more extended effect and allowing a lower frequency of intravitreal injections. This facilitates the adoption of fixed treatment regimens other than monthly or individual regimens such as "treat and extend". Aflibercept is indicated for the treatment of neovascular (exudative) age-related macular degeneration (ARMD), visual alteration due to macular edema secondary to central retinal vein occlusion (CRVO) and visual alteration due to diabetic macular edema (DME). The present article reviews the management of aflibercept in routine clinical practice, based on the specifications of its new core data sheet, which includes all the therapeutic indications in which its use has been approved and evaluating the distinct alternatives and treatment regimens after the initial loading doses. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

SU-G-BRC-15: The Potential Clinical Significance of Dose Mapping Error for Intra- Fraction Dose Mapping for Lung Cancer Patients

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

Sayah, N; Weiss, E; Watkins, W

Purpose: To evaluate the dose-mapping error (DME) inherent to conventional dose-mapping algorithms as a function of dose-matrix resolution. Methods: As DME has been reported to be greatest where dose-gradients overlap tissue-density gradients, non-clinical 66 Gy IMRT plans were generated for 11 lung patients with the target edge defined as the maximum 3D density gradient on the 0% (end of inhale) breathing phase. Post-optimization, Beams were copied to 9 breathing phases. Monte Carlo dose computed (with 2*2*2 mm{sup 3} resolution) on all 10 breathing phases was deformably mapped to phase 0% using the Monte Carlo energy-transfer method with congruent mass-mapping (EMCM);more » an externally implemented tri-linear interpolation method with voxel sub-division; Pinnacle’s internal (tri-linear) method; and a post-processing energy-mass voxel-warping method (dTransform). All methods used the same base displacement-vector-field (or it’s pseudo-inverse as appropriate) for the dose mapping. Mapping was also performed at 4*4*4 mm{sup 3} by merging adjacent dose voxels. Results: Using EMCM as the reference standard, no clinically significant (>1 Gy) DMEs were found for the mean lung dose (MLD), lung V20Gy, or esophagus dose-volume indices, although MLD and V20Gy were statistically different (2*2*2 mm{sup 3}). Pinnacle-to-EMCM target D98% DMEs of 4.4 and 1.2 Gy were observed ( 2*2*2 mm{sup 3}). However dTransform, which like EMCM conserves integral dose, had DME >1 Gy for one case. The root mean square RMS of the DME for the tri-linear-to- EMCM methods was lower for the smaller voxel volume for the tumor 4D-D98%, lung V20Gy, and cord D1%. Conclusion: When tissue gradients overlap with dose gradients, organs-at-risk DME was statistically significant but not clinically significant. Target-D98%-DME was deemed clinically significant for 2/11 patients (2*2*2 mm{sup 3}). Since tri-linear RMS-DME between EMCM and tri-linear was reduced at 2*2*2 mm{sup 3}, use of this resolution is recommended for dose mapping. Interpolative dose methods are sufficiently accurate for the majority of cases. J.V. Siebers receives funding support from Varian Medical Systems.« less

Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial.

PubMed

Wells, John A; Glassman, Adam R; Ayala, Allison R; Jampol, Lee M; Bressler, Neil M; Bressler, Susan B; Brucker, Alexander J; Ferris, Frederick L; Hampton, G Robert; Jhaveri, Chirag; Melia, Michele; Beck, Roy W

2016-06-01

To provide 2-year results comparing anti-vascular endothelial growth factor (VEGF) agents for center-involved diabetic macular edema (DME) using a standardized follow-up and retreatment regimen. Randomized clinical trial. Six hundred sixty participants with visual acuity (VA) impairment from DME. Randomization to 2.0-mg aflibercept, 1.25-mg repackaged (compounded) bevacizumab, or 0.3-mg ranibizumab intravitreous injections performed up to monthly using a protocol-specific follow-up and retreatment regimen. Focal/grid laser photocoagulation was added after 6 months if DME persisted. Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable. Change in VA, adverse events, and retreatment frequency. Median numbers of injections were 5, 6, and 6 in year 2 and 15, 16, and 15 over 2 years in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P = 0.08). Focal/grid laser photocoagulation was administered in 41%, 64%, and 52%, respectively (aflibercept vs. bevacizumab, P < 0.001; aflibercept vs. ranibizumab, P = 0.04; bevacizumab vs. ranibizumab, P = 0.01). At 2 years, mean VA improved by 12.8, 10.0, and 12.3 letters, respectively. Treatment group differences varied by baseline VA (P = 0.02 for interaction). With worse baseline VA (20/50 to 20/320), mean improvement was 18.1, 13.3, and 16.1 letters, respectively (aflibercept vs. bevacizumab, P = 0.02; aflibercept vs. ranibizumab, P = 0.18; ranibizumab vs. bevacizumab, P = 0.18). With better baseline VA (20/32 to 20/40), mean improvement was 7.8, 6.8, and 8.6 letters, respectively (P > 0.10, for pairwise comparisons). Anti-Platelet Trialists' Collaboration (APTC) events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with ranibizumab (global P = 0.047; aflibercept vs. bevacizumab, P = 0.34; aflibercept vs. ranibizumab, P = 0.047; ranibizumab vs. bevacizumab, P = 0.20; global P = 0.09 adjusted for potential confounders). All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2. Visual acuity outcomes were similar for eyes with better baseline VA. Among eyes with worse baseline VA, aflibercept had superior 2-year VA outcomes compared with bevacizumab, but superiority of aflibercept over ranibizumab, noted at 1 year, was no longer identified. Higher APTC event rates with ranibizumab over 2 years warrants continued evaluation in future trials. Copyright © 2016 American Academy of Ophthalmology. All rights reserved.

Qualitative and quantitative characteristics of near-infrared autofluorescence in diabetic macular edema.

PubMed

Yoshitake, Shin; Murakami, Tomoaki; Horii, Takahiro; Uji, Akihito; Ogino, Ken; Unoki, Noriyuki; Nishijima, Kazuaki; Yoshimura, Nagahisa

2014-05-01

To study the characteristics of near-infrared autofluorescence (NIR-AF) imaging and its association with spectral-domain optical coherence tomography (SD-OCT) findings and logarithm of the minimal angle of resolution (logMAR) visual acuity (VA) in diabetic macular edema (DME). Retrospective, observational, cross-sectional study. One hundred twenty-one consecutive eyes of 87 patients with center-involved DME for whom NIR-AF and SD-OCT images of sufficient quality were obtained. The NIR-AF images were acquired using Heidelberg Retina Angiograph 2 (Heidelberg Engineering, Heidelberg, Germany), and sectional retinal images were obtained using Spectralis OCT (Heidelberg Engineering). The presence of a mosaic pattern and cystoid signs were determined qualitatively. We quantified the average fluorescence intensity in the central 1-mm subfield. The characteristics of the NIR-AF images were compared with the OCT findings and logMAR VA. Qualitative and quantitative characteristics of the NIR-AF images and their association with SD-OCT findings and logMAR VA. Fifty-seven eyes with a mosaic pattern in the NIR-AF macular images had worse logMAR VA (0.355±0.239 vs. 0.212±0.235; P = 0.001), a thicker central subfield (CSF) (530±143 μm vs. 438±105 μm; P <0.001), and disrupted external limiting membrane (ELM; P <0.001) compared with 64 eyes without these findings. Forty-one eyes with a cystoid sign in the NIR-AF images had worse logMAR VA (0.393±0.233 vs. 0.221±0.234; P <0.001) and a thicker CSF (557±155 μm vs. 443±100 μm; P <0.001) than those without them; there were no significant differences in the ELM status. The relative fluorescence intensity in the central subfield in the NIR-AF images was correlated negatively with the CSF thickness and logMAR VA (R = 0.492, P <0.001 and R = 0.377, P <0.001, respectively). Eyes with foveal serous retinal detachment had lower levels of relative fluorescence intensity than those without it (0.751±0.191 vs. 0.877±0.154; P = 0.007); there was no association with the presence of foveal cystoid spaces, disrupted ELM, or hyperreflective foci in the outer retinal layers. Novel qualitative and quantitative NIR-AF characteristics in the macula indicated the clinical relevance and suggested the pathogenesis in DME. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Comparison of Intravitreal Bevacizumab and Intravitreal Diclofenac in the Treatment of Diabetic Macular Edema: a 6-month Follow-up

PubMed Central

FAGHIHI, Hooshang; YAHYAPOUR, Hanif; MAHMOUDZADEH, Raziyeh; FAGHIHI, Shahin

2017-01-01

The aim of this study was to compare the effect of intravitreal diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with that of bevacizumab, a well-known anti-vascular endothelial growth factor (VEGF) drug, in the treatment of diabetic macular edema (DME). Diclofenac was chosen in this study because it has both features of NSAIDs and corticosteroids by inhibiting the cyclooxygenase (COX) and lipoxygenase pathways, respectively. In this non-randomized comparative interventional case series, 64 eyes from 32 patients with bilateral naïve DME were selected and every eye was randomly assigned to intravitreal injection of bevacizumab (IVB) or diclofenac (IVD). After exclusion of some patients because of short follow-up duration or less than two intravitreal injections, finally, 52 eyes from 26 patients were analyzed. Of those, 26 eyes received 500 µg/0.1 mL IVD and 26 eyes received 1.25 mg IVB. After 6 months of follow-up, the results indicated that visual acuity was significantly improved from 0.50 ± 0.13 in IVB and 0.52 ± 0.12 LogMAR in IVD at baseline to 0.2 ± 0.1 and 0.29 ± 0.07, respectively. Central macular thickness (CMT) and macular volume were measured based on spectral-domain optical coherence tomography (OCT) at month 1, 3, and 6. Both groups showed a significant reduction in CMT and macular volume from baseline but there was no significant difference between the IVB and IVD groups. Interestingly, IVD, but not IVB, decreased intraocular pressure (IOP), which is a desirable effect. There was no serious complication due to injections. This study sheds light into the long-term effects of NSAIDs and may support the idea that inflammation suppression by NSAIDs may have the same results as anti-VEGF administration. PMID:29392145

Comparison of Intravitreal Bevacizumab and Intravitreal Diclofenac in the Treatment of Diabetic Macular Edema: a 6-month Follow-up.

PubMed

Faghihi, Hooshang; Yahyapour, Hanif; Mahmoudzadeh, Raziyeh; Faghihi, Shahin

2017-01-01

The aim of this study was to compare the effect of intravitreal diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with that of bevacizumab, a well-known anti-vascular endothelial growth factor (VEGF) drug, in the treatment of diabetic macular edema (DME). Diclofenac was chosen in this study because it has both features of NSAIDs and corticosteroids by inhibiting the cyclooxygenase (COX) and lipoxygenase pathways, respectively. In this non-randomized comparative interventional case series, 64 eyes from 32 patients with bilateral naïve DME were selected and every eye was randomly assigned to intravitreal injection of bevacizumab (IVB) or diclofenac (IVD). After exclusion of some patients because of short follow-up duration or less than two intravitreal injections, finally, 52 eyes from 26 patients were analyzed. Of those, 26 eyes received 500 µg/0.1 mL IVD and 26 eyes received 1.25 mg IVB. After 6 months of follow-up, the results indicated that visual acuity was significantly improved from 0.50 ± 0.13 in IVB and 0.52 ± 0.12 LogMAR in IVD at baseline to 0.2 ± 0.1 and 0.29 ± 0.07, respectively. Central macular thickness (CMT) and macular volume were measured based on spectral-domain optical coherence tomography (OCT) at month 1, 3, and 6. Both groups showed a significant reduction in CMT and macular volume from baseline but there was no significant difference between the IVB and IVD groups. Interestingly, IVD, but not IVB, decreased intraocular pressure (IOP), which is a desirable effect. There was no serious complication due to injections. This study sheds light into the long-term effects of NSAIDs and may support the idea that inflammation suppression by NSAIDs may have the same results as anti-VEGF administration.

Investigation of alterations in multifractality in optical coherence tomographic images of in vivo human retina

NASA Astrophysics Data System (ADS)

Das, Nandan Kumar; Mukhopadhyay, Sabyasachi; Ghosh, Nirmalya; Chhablani, Jay; Richhariya, Ashutosh; Divakar Rao, Kompalli; Sahoo, Naba Kishore

2016-09-01

Optical coherence tomography (OCT) enables us to monitor alterations in the thickness of the retinal layer as disease progresses in the human retina. However, subtle morphological changes in the retinal layers due to early disease progression often may not lead to detectable alterations in the thickness. OCT images encode depth-dependent backscattered intensity distribution arising due to the depth distributions of the refractive index from tissue microstructures. Here, such depth-resolved refractive index variations of different retinal layers were analyzed using multifractal detrended fluctuation analysis, a special class of multiresolution analysis tools. The analysis extracted and quantified microstructural multifractal information encoded in normal as well as diseased human retinal OCT images acquired in vivo. Interestingly, different layers of the retina exhibited different degrees of multifractality in a particular retina, and the individual layers displayed consistent multifractal trends in healthy retinas of different human subjects. In the retinal layers of diabetic macular edema (DME) subjects, the change in multifractality manifested prominently near the boundary of the DME as compared to the normal retinal layers. The demonstrated ability to quantify depth-resolved information on multifractality encoded in OCT images appears promising for the early diagnosis of diseases of the human eye, which may also prove useful for detecting other types of tissue abnormalities from OCT images.

Translating Benzodiazepine Utilization Data into Meaningful Population Exposure: Integration of Two Metrics for Improved Reporting.

PubMed

Brandt, Jaden; Alkabanni, Wajd; Alessi-Severini, Silvia; Leong, Christine

2018-04-04

Drug utilization research on benzodiazepines remains important for measuring trends in consumption within and across borders over time for the sake of monitoring prescribing patterns and identifying potential population safety concerns. The defined daily dose (DDD) system by the World Health Organization (WHO) remains the internationally accepted standard for measuring drug consumption; however, beyond consumption, DDD-based results are difficult to interpret when individual agents are compared with one another or are pooled into a total class-based estimate. The diazepam milligram equivalent (DME) system provides approximate conversions between benzodiazepines and Z-drugs (i.e. zopiclone, zolpidem, zaleplon) based on their pharmacologic potency. Despite this, conversion of total dispensed benzodiazepine quantities into DME values retains diazepam milligrams as the total unit of measurement, which is also impractical for population-level interpretation. In this paper, we propose the use of an integrated DME-DDD metric to obviate the limitations encountered when the component metrics are used in isolation. Through a case example, we demonstrate significant change in results between the DDD and DME-DDD method. Unlike the DDD method, the integrated DME-DDD metric offers estimation of population pharmacologic exposure, and enables superior interpretation of drug utilization results, especially for drug class summary reporting.

Ultrasound assisted co-precipitation of nanostructured CuO-ZnO-Al2O3 over HZSM-5: effect of precursor and irradiation power on nanocatalyst properties and catalytic performance for direct syngas to DME.

PubMed

Allahyari, Somaiyeh; Haghighi, Mohammad; Ebadi, Amanollah; Hosseinzadeh, Shahin

2014-03-01

Nanostructured CuO-ZnO-Al2O3/HZSM-5 was synthesized from nitrate and acetate precursors using ultrasound assisted co-precipitation method under different irradiation powers. The CuO-ZnO-Al2O3/HZSM-5 nanocatalysts were characterized using XRD, FESEM, BET, FTIR and EDX Dot-mapping analyses. The results indicated precursor type and irradiation power have significant influences on phase structure, morphology, surface area and functional groups. It was observed that the acetate formulated CuO-ZnO-Al2O3/HZSM-5 nanocatalyst have smaller CuO crystals with better dispersion and stronger interaction between components in comparison to nitrate based nanocatalysts. Ultrasound assisted co-precipitation synthesis method resulted in nanocatalyst with more uniform morphology compared to conventional method and increasing irradiation power yields smaller particles with better dispersion and higher surface area. Additionally the crystallinity of CuO is lower at high irradiation powers leading to stronger interaction between metal oxides. The nanocatalysts performance were tested at 200-300 °C, 10-40 bar and space velocity of 18,000-36,000 cm(3)/g h with the inlet gas composition of H2/CO = 2/1 in a stainless steel autoclave reactor. The acetate based nanocatalysts irradiated with higher levels of power exhibited better reactivity in terms of CO conversion and DME yield. While there is an optimal temperature for CO conversion and DME yield in direct synthesis of DME, CO conversion and DME yield both increase with the pressure increase. Furthermore ultrasound assisted co-precipitation method yields more stable CuO-ZnO-Al2O3/HZSM-5 nanocatalyst while conventional precipitated nanocatalyst lost their activity ca. 18% and 58% in terms of CO conversion and DME yield respectively in 24 h time on stream test.

Automatic diagnosis of abnormal macula in retinal optical coherence tomography images using wavelet-based convolutional neural network features and random forests classifier

NASA Astrophysics Data System (ADS)

Rasti, Reza; Mehridehnavi, Alireza; Rabbani, Hossein; Hajizadeh, Fedra

2018-03-01

The present research intends to propose a fully automatic algorithm for the classification of three-dimensional (3-D) optical coherence tomography (OCT) scans of patients suffering from abnormal macula from normal candidates. The method proposed does not require any denoising, segmentation, retinal alignment processes to assess the intraretinal layers, as well as abnormalities or lesion structures. To classify abnormal cases from the control group, a two-stage scheme was utilized, which consists of automatic subsystems for adaptive feature learning and diagnostic scoring. In the first stage, a wavelet-based convolutional neural network (CNN) model was introduced and exploited to generate B-scan representative CNN codes in the spatial-frequency domain, and the cumulative features of 3-D volumes were extracted. In the second stage, the presence of abnormalities in 3-D OCTs was scored over the extracted features. Two different retinal SD-OCT datasets are used for evaluation of the algorithm based on the unbiased fivefold cross-validation (CV) approach. The first set constitutes 3-D OCT images of 30 normal subjects and 30 diabetic macular edema (DME) patients captured from the Topcon device. The second publicly available set consists of 45 subjects with a distribution of 15 patients in age-related macular degeneration, DME, and normal classes from the Heidelberg device. With the application of the algorithm on overall OCT volumes and 10 repetitions of the fivefold CV, the proposed scheme obtained an average precision of 99.33% on dataset1 as a two-class classification problem and 98.67% on dataset2 as a three-class classification task.

Automatic diagnosis of abnormal macula in retinal optical coherence tomography images using wavelet-based convolutional neural network features and random forests classifier.

PubMed

Rasti, Reza; Mehridehnavi, Alireza; Rabbani, Hossein; Hajizadeh, Fedra

2018-03-01

The present research intends to propose a fully automatic algorithm for the classification of three-dimensional (3-D) optical coherence tomography (OCT) scans of patients suffering from abnormal macula from normal candidates. The method proposed does not require any denoising, segmentation, retinal alignment processes to assess the intraretinal layers, as well as abnormalities or lesion structures. To classify abnormal cases from the control group, a two-stage scheme was utilized, which consists of automatic subsystems for adaptive feature learning and diagnostic scoring. In the first stage, a wavelet-based convolutional neural network (CNN) model was introduced and exploited to generate B-scan representative CNN codes in the spatial-frequency domain, and the cumulative features of 3-D volumes were extracted. In the second stage, the presence of abnormalities in 3-D OCTs was scored over the extracted features. Two different retinal SD-OCT datasets are used for evaluation of the algorithm based on the unbiased fivefold cross-validation (CV) approach. The first set constitutes 3-D OCT images of 30 normal subjects and 30 diabetic macular edema (DME) patients captured from the Topcon device. The second publicly available set consists of 45 subjects with a distribution of 15 patients in age-related macular degeneration, DME, and normal classes from the Heidelberg device. With the application of the algorithm on overall OCT volumes and 10 repetitions of the fivefold CV, the proposed scheme obtained an average precision of 99.33% on dataset1 as a two-class classification problem and 98.67% on dataset2 as a three-class classification task. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Organizing graduate medical education programs into communities of practice.

PubMed

Bing-You, Robert G; Varaklis, Kalli

2016-01-01

A new organizational model of educational administrative support was instituted in the Department of Medical Education (DME) to better meet increasing national accreditation demands. Residency and fellowship programs were organized into four 'Communities of Practice' (CoOPs) based on discipline similarity, number of learners, and geographic location. Program coordinator reporting lines were shifted from individual departments to a centralized reporting structure within the DME. The goal of this project was to assess the impact on those most affected by the change. This was a mixed methods study that utilized structured interviews and the Organizational Culture Assessment Instrument (OCAI). Eleven members of the newly formed CoOPs participated in the study. Three major themes emerged after review and coding of the interview transcripts: improved group identity, improved availability of resources, and increased opportunity for professional growth. OCAI results indicated that respondents are committed to the DME and perceived the culture to be empowering. The 'preferred culture' was very similar to the culture at the time of the study, with some indication that DME employees are ready for more creativity and innovation in the future. Reorganization within the DME of residency programs into CoOPs was overwhelmingly perceived as a positive change. Improved resources and accountability may position our DME to better handle the increasing complexity of graduate medical education.

Extraction of Fucoxanthin from Raw Macroalgae excluding Drying and Cell Wall Disruption by Liquefied Dimethyl Ether

PubMed Central

Kanda, Hideki; Kamo, Yuichi; Machmudah, Siti; Wahyudiono; Goto, Motonobu

2014-01-01

Macroalgae are one of potential sources for carotenoids, such as fucoxanthin, which are consumed by humans and animals. This carotenoid has been applied in both the pharmaceutical and food industries. In this study, extraction of fucoxanthin from wet brown seaweed Undaria pinnatifida (water content was 93.2%) was carried out with a simple method using liquefied dimethyl ether (DME) as an extractant in semi-continuous flow-type system. The extraction temperature and absolute pressure were 25 °C and 0.59 MPa, respectively. The liquefied DME was passed through the extractor that filled by U. pinnatifida at different time intervals. The time of experiment was only 43 min. The amount of fucoxanthin could approach to 390 μg/g dry of wet U. pinnatifida when the amount of DME used was 286 g. Compared with ethanol Soxhlet and supercritical CO2 extraction, which includes drying and cell disruption, the result was quite high. Thus, DME extraction process appears to be a good method for fucoxanthin recovery from U. pinnatifida with improved yields. PMID:24796299

FACT complex is required for DNA demethylation at heterochromatin during reproduction in Arabidopsis.

PubMed

Frost, Jennifer M; Kim, M Yvonne; Park, Guen Tae; Hsieh, Ping-Hung; Nakamura, Miyuki; Lin, Samuel J H; Yoo, Hyunjin; Choi, Jaemyung; Ikeda, Yoko; Kinoshita, Tetsu; Choi, Yeonhee; Zilberman, Daniel; Fischer, Robert L

2018-05-15

The DEMETER (DME) DNA glycosylase catalyzes genome-wide DNA demethylation and is required for endosperm genomic imprinting and embryo viability. Targets of DME-mediated DNA demethylation reside in small, euchromatic, AT-rich transposons and at the boundaries of large transposons, but how DME interacts with these diverse chromatin states is unknown. The STRUCTURE SPECIFIC RECOGNITION PROTEIN 1 (SSRP1) subunit of the chromatin remodeler FACT (facilitates chromatin transactions), was previously shown to be involved in the DME-dependent regulation of genomic imprinting in Arabidopsis endosperm. Therefore, to investigate the interaction between DME and chromatin, we focused on the activity of the two FACT subunits, SSRP1 and SUPPRESSOR of TY16 (SPT16), during reproduction in Arabidopsis We found that FACT colocalizes with nuclear DME in vivo, and that DME has two classes of target sites, the first being euchromatic and accessible to DME, but the second, representing over half of DME targets, requiring the action of FACT for DME-mediated DNA demethylation genome-wide. Our results show that the FACT-dependent DME targets are GC-rich heterochromatin domains with high nucleosome occupancy enriched with H3K9me2 and H3K27me1. Further, we demonstrate that heterochromatin-associated linker histone H1 specifically mediates the requirement for FACT at a subset of DME-target loci. Overall, our results demonstrate that FACT is required for DME targeting by facilitating its access to heterochromatin. Copyright © 2018 the Author(s). Published by PNAS.

Diabetic Macular Edema at the time of Cataract Surgery trial: a prospective, randomized clinical trial of intravitreous bevacizumab versus triamcinolone in patients with diabetic macular oedema at the time of cataract surgery - preliminary 6 month results.

PubMed

Lim, Lyndell L; Morrison, Julie L; Constantinou, Marios; Rogers, Sophie; Sandhu, Sukhpal S; Wickremasinghe, Sanjeewa S; Kawasaki, Ryo; Al-Qureshi, Salmaan

2016-05-01

To compare visual and anatomical outcomes between intravitreous bevacizumab (BVB, Avastin) and triamcinolone (TA, Triesence) when administered at the time of cataract surgery in patients with diabetic macular oedema (DME). Prospective, single-masked, randomized clinical trial at The Royal Victorian Eye and Ear Hospital, Melbourne. Patients with clinically significant cataract and either centre-involving DME or DME treated within the previous 24 months. Participants were randomized 1:1 to receive intravitreous BVB 1.25 mg or TA 4 mg during cataract surgery, and at subsequent review if required over 6 months. Change in central macular thickness (CMT) and best corrected visual acuity at 6 months. Forty-one patients (mean age 66.4 years, 73.2% male) were recruited. Visual acuity and CMT were similar between groups at baseline (P > 0.2).After six months, both groups gained vision (mean +21.4 letters in TA group P < 0.0001, +12.5 letters in BVB, P = 0.002), with no significant difference between groups (P = 0.085). In addition, 60.9% of eyes receiving TA achieved a VA of ≥6/12 compared to 73.3% in the BVB group (P = 0.501). However, only TA was associated with a sustained reduction in CMT (-43.8-µm reduction TA vs. +37.3-µm increase BVB, P = 0.006 over 6 months). Following surgery, additional injections were required in 70.6% of participants in the BVB group, compared to 16.7% in the TA group (P < 0.0001). Three patients in the TA group experienced a rise of IOP over 21 mmHg (12.5%) during the 6-month follow-up; BVB had no cases (P = 0.130). There were no cases of endophthalmitis in either group. When administered at the time of cataract surgery in patients with DME, at 6 months both TA and BVB improve visual acuity; however, only TA results in a sustained reduction in CMT. Further follow-up will determine whether this translates into better long-term visual outcomes in the TA group. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

CHOROIDAL THICKNESS IN DIABETIC RETINOPATHY ASSESSED WITH SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY.

PubMed

Laíns, Inês; Talcott, Katherine E; Santos, Ana R; Marques, João H; Gil, Pedro; Gil, João; Figueira, João; Husain, Deeba; Kim, Ivana K; Miller, Joan W; Silva, Rufino; Miller, John B

2018-01-01

To compare the choroidal thickness (CT) of diabetic eyes (different stages of disease) with controls, using swept-source optical coherence tomography. A multicenter, prospective, cross-sectional study of diabetic and nondiabetic subjects using swept-source optical coherence tomography imaging. Choroidal thickness maps, according to the nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields, were obtained using automated software. Mean CT was calculated as the mean value within the ETDRS grid, and central CT as the mean in the central 1 mm. Diabetic eyes were divided into four groups: no diabetic retinopathy (No DR), nonproliferative DR (NPDR), NPDR with diabetic macular edema (NPDR + DME), and proliferative DR (PDR). Multilevel mixed linear models were performed for analyses. The authors included 50 control and 160 diabetic eyes (n = 27 No DR, n = 51 NPDR, n = 61 NPDR + DME, and n = 21 PDR). Mean CT (ß = -42.9, P = 0.022) and central CT (ß = -50.2, P = 0.013) were statistically significantly thinner in PDR eyes compared with controls, even after adjusting for confounding factors. Controlling for age, DR eyes presented a significantly decreased central CT than diabetic eyes without retinopathy (β = -36.2, P = 0.009). Swept-source optical coherence tomography demonstrates a significant reduction of CT in PDR compared with controls. In the foveal region, the choroid appears to be thinner in DR eyes than in diabetic eyes without retinopathy.

Regulation of the Cobalt/Nickel Efflux Operon dmeRF in Agrobacterium tumefaciens and a Link between the Iron-Sensing Regulator RirA and Cobalt/Nickel Resistance

PubMed Central

Dokpikul, Thanittra; Chaoprasid, Paweena; Saninjuk, Kritsakorn; Sirirakphaisarn, Sirin; Johnrod, Jaruwan; Nookabkaew, Sumontha; Mongkolsuk, Skorn

2016-01-01

ABSTRACT The Agrobacterium tumefaciens C58 genome harbors an operon containing the dmeR (Atu0890) and dmeF (Atu0891) genes, which encode a transcriptional regulatory protein belonging to the RcnR/CsoR family and a metal efflux protein belonging to the cation diffusion facilitator (CDF) family, respectively. The dmeRF operon is specifically induced by cobalt and nickel, with cobalt being the more potent inducer. Promoter-lacZ transcriptional fusion, an electrophoretic mobility shift assay, and DNase I footprinting assays revealed that DmeR represses dmeRF transcription through direct binding to the promoter region upstream of dmeR. A strain lacking dmeF showed increased accumulation of intracellular cobalt and nickel and exhibited hypersensitivity to these metals; however, this strain displayed full virulence, comparable to that of the wild-type strain, when infecting a Nicotiana benthamiana plant model under the tested conditions. Cobalt, but not nickel, increased the expression of many iron-responsive genes and reduced the induction of the SoxR-regulated gene sodBII. Furthermore, control of iron homeostasis via RirA is important for the ability of A. tumefaciens to cope with cobalt and nickel toxicity. IMPORTANCE The molecular mechanism of the regulation of dmeRF transcription by DmeR was demonstrated. This work provides evidence of a direct interaction of apo-DmeR with the corresponding DNA operator site in vitro. The recognition site for apo-DmeR consists of 10-bp AT-rich inverted repeats separated by six C bases (5′-ATATAGTATACCCCCCTATAGTATAT-3′). Cobalt and nickel cause DmeR to dissociate from the dmeRF promoter, which leads to expression of the metal efflux gene dmeF. This work also revealed a connection between iron homeostasis and cobalt/nickel resistance in A. tumefaciens. PMID:27235438

Silymarin prevents diabetes-induced hyperpermeability in human retinal endothelial cells.

PubMed

García-Ramírez, Marta; Turch, Mireia; Simó-Servat, Olga; Hernández, Cristina; Simó, Rafael

2018-04-01

Vascular endothelial growth factor (VEGF) plays an essential role in development of diabetic macular edema (DME). While there is evidence suggesting that silymarin, a flavonoid extracted from Silybum marianum, could be useful for prevention and treatment of diabetic nephropathy, no studies have been conducted in diabetic retinopathy (DR). The aim of this study was to assess the effect of silymarin on disruption of inner blood retinal barrier (BRB), the primary cause of DME. Human retinal endothelial cells (HRECs) were cultured under standard (5.5mM D-glucose) and diabetogenic conditions (25mM D-glucose and 25mM D-glucose + recombinant vascular endothelial growth factor [rVEGF, 25mg/mL]). To assess cell viability, three concentrations of silymarin were tested (2, 4 and 10μg/mL). The effect of silymarin on HREC disruption was determined using a dextran (70kD) permeability asssay. No differences were found in the viability of HRECs treated with 2 or 4μg/mL of silymarin as compared to untreated cells, but viability significantly decreased after using 10μg/mL. The concentration of 4 μg/mL was therefore selected. Silymarin (4μg/mL) caused a significant decrease in VEGF-induced permeability in both media with 5.5nM (422±58 vs. 600±72 ng/mL/cm2; p<0.03) and 25nM of D-glucose (354 ± 28 vs. 567 ± 102 ng/mL/cm2; p<0.04). Our results show that silymarin is effective for preventing hyperpermeability induced by diabetic conditions in HRECs. Further studies are needed to assess whether silymarin could be useful to treat DME. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

One-year outcomes of the da Vinci Study of VEGF Trap-Eye in eyes with diabetic macular edema.

PubMed

Do, Diana V; Nguyen, Quan Dong; Boyer, David; Schmidt-Erfurth, Ursula; Brown, David M; Vitti, Robert; Berliner, Alyson J; Gao, Bo; Zeitz, Oliver; Ruckert, Rene; Schmelter, Thomas; Sandbrink, Rupert; Heier, Jeff S

2012-08-01

To compare different doses and dosing regimens of Vascular Endothelial Growth Factor (VEGF) Trap-Eye with laser photocoagulation in eyes with diabetic macular edema (DME). Randomized, double-masked, multicenter, phase 2 clinical trial. Diabetic patients (n = 221) with center-involved DME. Participants were assigned randomly to 1 of 5 treatment regimens: VEGF Trap-Eye 0.5 mg every 4 weeks (0.5q4); 2 mg every 4 weeks (2q4); 2 mg every 8 weeks after 3 initial monthly doses (2q8); or 2 mg dosing as needed after 3 initial monthly doses (2PRN), or macular laser photocoagulation. The change in best-corrected visual acuity (BCVA) at 24 weeks (the primary end point) and at 52 weeks, proportion of eyes that gained 15 letters or more in Early Treatment of Diabetic Retinopathy Study (ETDRS) BCVA, and mean changes in central retinal thickness (CRT) from baseline. As previously reported, mean improvements in BCVA in the VEGF Trap-Eye groups at week 24 were 8.6, 11.4, 8.5, and 10.3 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus 2.5 letters for the laser group (P ≤ 0.0085 versus laser). Mean improvements in BCVA in the VEGF Trap-Eye groups at week 52 were 11.0, 13.1, 9.7, and 12.0 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus -1.3 letters for the laser group (P ≤ 0.0001 versus laser). Proportions of eyes with gains in BCVA of 15 or more ETDRS letters at week 52 in the VEGF Trap-Eye groups were 40.9%, 45.5%, 23.8%, and 42.2% versus 11.4% for laser (P = 0.0031, P = 0.0007, P = 0.1608, and P = 0.0016, respectively, versus laser). Mean reductions in CRT in the VEGF Trap-Eye groups at week 52 were -165.4 μm, -227.4 μm, -187.8 μm, and -180.3 μm versus -58.4 μm for laser (P < 0.0001 versus laser). Vascular Endothelial Growth Factor Trap-Eye generally was well tolerated. The most frequent ocular adverse events with VEGF Trap-Eye were conjunctival hemorrhage, eye pain, ocular hyperemia, and increased intraocular pressure, whereas common systemic adverse events included hypertension, nausea, and congestive heart failure. Significant gains in BCVA from baseline achieved at week 24 were maintained or improved at week 52 in all VEGF Trap-Eye groups. Vascular Endothelial Growth Factor Trap-Eye warrants further investigation for the treatment of DME. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Functional and Expression Analysis of the Metal-Inducible dmeRF System from Rhizobium leguminosarum bv. viciae

PubMed Central

Rubio-Sanz, L.; Prieto, R. I.; Imperial, J.; Brito, B.

2013-01-01

A gene encoding a homolog to the cation diffusion facilitator protein DmeF from Cupriavidus metallidurans has been identified in the genome of Rhizobium leguminosarum UPM791. The R. leguminosarum dmeF gene is located downstream of an open reading frame (designated dmeR) encoding a protein homologous to the nickel- and cobalt-responsive transcriptional regulator RcnR from Escherichia coli. Analysis of gene expression showed that the R. leguminosarum dmeRF genes are organized as a transcriptional unit whose expression is strongly induced by nickel and cobalt ions, likely by alleviating the repressor activity of DmeR on dmeRF transcription. An R. leguminosarum dmeRF mutant strain displayed increased sensitivity to Co(II) and Ni(II), whereas no alterations of its resistance to Cd(II), Cu(II), or Zn(II) were observed. A decrease of symbiotic performance was observed when pea plants inoculated with an R. leguminosarum dmeRF deletion mutant strain were grown in the presence of high concentrations of nickel and cobalt. The same mutant induced significantly lower activity levels of NiFe hydrogenase in microaerobic cultures. These results indicate that the R. leguminosarum DmeRF system is a metal-responsive efflux mechanism acting as a key element for metal homeostasis in R. leguminosarum under free-living and symbiotic conditions. The presence of similar dmeRF gene clusters in other Rhizobiaceae suggests that the dmeRF system is a conserved mechanism for metal tolerance in legume endosymbiotic bacteria. PMID:23934501

Real-life experience of ranibizumab for diabetic macular edema in Taiwan.

PubMed

Tsai, Meng-Ju; Hsieh, Yi-Ting; Peng, Yi-Jie

2018-06-20

To evaluate the visual and anatomical outcomes of intravitreal ranibizumab for diabetic macular edema (DME) in the healthcare system of Taiwan. A total of 39 eyes from 39 patients were retrospectively enrolled in the study. All eyes that fulfilled the key criteria, including a baseline vision between 20 and 70 ETDRS letters and a minimum central macular thickness (CMT) of 300 µm, had at least 3 monthly loading injections of ranibizumab in a year. Macular laser or posterior subtenon injections of triamcinolone acetonide (PSTA) could be performed as supplementary treatments following loading injections. Primary outcomes include best-corrected visual acuity and CMT. Patients' vision improved from 46.5 ± 15.3 letters at baseline to 51.4 ± 16.6 letters at 12 months (p = 0.031). Mean CMT at baseline was 406 ± 105 µm, which decreased to 329 ± 108 µm (p = 0.002). At 12 months, 44.4% of eyes with total injection number < 5 and 42.9% with injection number ≥ 5 achieved a gain in vision that was 10 letters or more. A total of 5 injections or more did not lead to a better visual gain in comparison with only 3-4 injections (p = 0.71), and both had similar number of supplementary treatments (p = 0.43). Monthly reinjections of ranibizumab resulted in a lower likelihood of visual loss of 10 or 15 letters (p = 0.019 and 0.015, respectively, adjusted for age, baseline vision, severity of diabetic retinopathy and the presence of previous treatments); however, supplementary macular lasers, PSTA or ranibizumab without monthly reinjections did not (all p > 0.05). The average number of injections was 4.3 ± 1.0. Treatment for DME with at least three monthly ranibizumab loading injections, with or without other supplementary treatments, is effective at 12 months thereafter. Two monthly reinjections of ranibizumab, while not significantly increasing vision, may have a role in preventing visual loss.

Thrust Evaluation of an Arcjet Thruster Using Dimethyl Ether as a Propellant

NASA Astrophysics Data System (ADS)

Kakami, Akira; Beppu, Shinji; Maiguma, Muneyuki; Tachibana, Takeshi

This paper describes the performance of an arcjet thruster using dimethyl ether (DME) as a propellant. DME, an ether compound, has adequate characteristics for space propulsion systems; DME is storable in a liquid state without a high pressure or cryogenic device and requires no sophisticated temperature management. DME is gasified and liquefied simply by adjusting temperature, whereas hydrazine, a conventional propellant, requires an iridium-based particulate catalyst for its gasification. In this study, thrust of the designed kW-class DME arcjet thruster is measured with a torsional thrust stand. Thrust measurements show that thrust is increased with propellant mass flow rate, and that thrust using DME propellant is higher than when using nitrogen. The prototype DME arcjet thruster yields a specific impulse of 330 s, a thruster efficiency of 0.14, and a thrust of 0.19 N at 60-mg/s DME mass flow rate at 25-A discharge current. The corresponding discharge power and specific power are 2.3 kW and 39 MJ/kg.

Multinuclear NMR Study of the Solid Electrolyte Interface Formed in Lithium Metal Batteries

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

Wan, Chuan; Xu, Suochang; Hu, Mary Y.

The composition of the solid electrolyte interphase (SEI) layers associated with a high performance Cu|Li cell using lithium bis(fluorosulfonyi)imide (LiFSI) in 1,2-dimethoxyethane (DME) as electrolyte is determined by a multinuclear (6Li, 19F, 13C and 1H) solid-state MAS NMR study at high magnetic field (850 MHz). This cell can be cycled at high rates (4 mA•cm-2) for more than 1000 cycles with no increase in the cell impedance at high Columbic efficiency (average of 98.4%) in a highly concentrated LiFSI-DME electrolyte (4 M). LiFSI, LiF, Li2O2 (and/or CH3OLi), LiOH, Li2S and Li2O are observed in the SEI and validated by comparingmore » with the spectra acquired on standard compounds and literature reports. To gain further insight into the role of the solute and its concentration dependence on the formation of SEIs while keeping the solvent of DME unchanged, the SEIs from different concentrations of LiFSI-DME and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI)-DME electrolyte are also investigated. It is found that LiF, a lithiated compound with superior mechanical strength and good Li+ ionic conductivity, is observed in the concentrated 4.0 M LiFSI-DME and the 3.0 M LiTFSI-DME systems but not in the diluted 1.0 M LiFSI-DME system. Li2O exists in both low and high concentration of LiFSI-DME while no Li2O is observed in the LiTFSI system. Furthermore, the dead metallic Li is reduced in the 4 M LiFSI-DME system compared with that in the 1 M LiFSI-DME system. Quantitative 6Li MAS results indicate that the SEI associated with the 4 M LiFSI-DEME is denser or thicker than that of the 1 M LiFSI-DME and the 3 M LiTFSI-DME systems. These findings are likely the reasons for explaining the high electrochemical performance associated with the high concentration LiFSI-DME system.« less

14 CFR 171.321 - DME and marker beacon performance requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false DME and marker beacon performance... (MLS) § 171.321 DME and marker beacon performance requirements. (a) The DME equipment must meet the..._regulations/ibr_locations.html. (b) MLS marker beacon equipment must meet the performance requirements...

DEXAMETHASONE IMPLANT FOR DIABETIC MACULAR EDEMA IN NAIVE COMPARED WITH REFRACTORY EYES: The International Retina Group Real-Life 24-Month Multicenter Study. The IRGREL-DEX Study.

PubMed

Iglicki, Matias; Busch, Catharina; Zur, Dinah; Okada, Mali; Mariussi, Miriana; Chhablani, Jay Kumar; Cebeci, Zafer; Fraser-Bell, Samantha; Chaikitmongkol, Voraporn; Couturier, Aude; Giancipoli, Ermete; Lupidi, Marco; Rodríguez-Valdés, Patricio J; Rehak, Matus; Fung, Adrian Tien-Chin; Goldstein, Michaella; Loewenstein, Anat

2018-04-24

To investigate efficacy and safety of repeated dexamethasone (DEX) implants over 24 months, in diabetic macular edema (DME) eyes that were treatment naive compared with eyes refractory to anti-vascular endothelial growth factor treatment, in a real-life environment. This multicenter international retrospective study assessed best-corrected visual acuity and central subfield thickness (CST) of naive and refractory eyes to anti-vascular endothelial growth factor injections treated with dexamethasone implants. Safety data (intraocular pressure rise and cataract surgery) were recorded. A total of 130 eyes from 125 patients were included. Baseline best-corrected visual acuity and CST were similar for naive (n = 71) and refractory eyes (n = 59). Both groups improved significantly in vision after 24 months (P < 0.001). However, naive eyes gained statistically significantly more vision than refractory eyes (+11.3 ± 10.0 vs. 7.3 ± 2.7 letters, P = 0.01) and were more likely to gain ≥10 letters (OR 3.31, 95% CI 1.19-9.24, P = 0.02). At 6, 12, and 24 months, CST was significantly decreased compared with baseline in both naive and refractory eyes; however, CST was higher in refractory eyes than in naive eyes (CST 279 ± 61 vs. 313 ± 125 μm, P = 0.10). Over a follow-up of 24 months, vision improved in diabetic macular edema eyes after treatment with dexamethasone implants, both in eyes that were treatment naive and eyes refractory to anti-vascular endothelial growth factor treatment; however, improvement was greater in naive eyes.

Local and Systemic Inflammatory Biomarkers of Diabetic Retinopathy: An Integrative Approach.

PubMed

Vujosevic, Stela; Simó, Rafael

2017-05-01

To review the usefulness of local and systemic inflammatory biomarkers of diabetic retinopathy (DR) to implement a more personalized treatment. An integrated research (from ophthalmologist and diabetologist point of view) of most significant literature on serum, vitreous, and aqueous humor (AH) biochemical biomarkers related to inflammation at early and advanced stages of DR (including diabetic macular edema [DME] and proliferative DR) was performed. Moreover, novel imaging retinal biomarkers of local "inflammatory condition" were described. Multiple inflammatory cytokines and chemokines are increased in DR in both serum as well as in the eye (vitreous and AH). Nevertheless, local rather than systemic production of proinflammatory cytokines seems more relevant in the pathogenesis of both DR and DME. In the eye, retinal glia cells (macroglia and microglia) together with RPE are major sources of proinflammatory and angiogenic modulators. Retinal imaging allows for noninvasive clinical evaluation of retinal inflammatory response induced by diabetes mellitus. Proinflammatory cytokines/chemokines play an essential role in the pathogenesis of DR. Therefore, circulating biomarkers and retinal imaging aimed at assessing inflammation have emerged as useful tools for monitoring the onset and progression of DR. In addition, "liquid biopsy" of AH seems a good option in patients with advanced stages of DR requiring intravitreous injections. This strategy may permit us to implement a more personalized treatment with better visual function outcome. Further evaluation and validation of circulating and local biomarkers, as well as multimodal imaging is needed to gain new insights into this issue.

Treatment of diabetic retinopathy: Recent advances and unresolved challenges.

PubMed

Stewart, Michael W

2016-08-25

Diabetic retinopathy (DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor (VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema (DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation (PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies.

Performance Characteristics of a DME Propellant Arcjet Thruster

NASA Astrophysics Data System (ADS)

Kakami, Akira; Beeppu, Shinji; Maiguma, Muneyuki; Tachibana, Takeshi

This paper describes the influence of cathode configuration on performance of an arcjet thruster using dimethyl ether (DME) propellant. DME, an ether compound, has suitable characteristics for a space propulsion system; DME is storable in a liquid state without being kept under a high pressure, and requires no sophisticated temperature management such as a cryogenic device. DME can be gasified and liquefied simply by adjusting temperature whereas hydrazine, a conventional propellant, requires an iridium-based particulate catalyst for its gasification. In this study, thrust of a 1-kW class DME arcjet thruster is measured at a discharge current of 13 A, DME mass flow rates ranging 15 to 60 mg/s under three cathode configurations: flat-tip rods of 2 and 4 mm in diam. and 4-mm-diam. rod having a cavity of 2 mm in diameter. Thrust measurements show that thrust is increased with propellant mass flow rate. Among the tested cathodes, the flat-tip rod of 4 mm in diam. with 55 mg/s DME flow rate yielded the highest performance: specific impulse of 330 s, thrust of 0.18 N, discharge power of 1400 W and specific power of 25 MJ/kg.

Primary Effects of Intravitreal Bevacizumab in Patients with Diabetic Macular Edema

PubMed Central

Tareen, Iftikhar-ul-Haq; Rahman, Azizur; Mahar, P.S; Memon, Muhammad Saleh

2013-01-01

Objective: To evaluate the efficacy of primary intra vitreal bevacizumab (IVB) injection on macular edema in diabetic patients with improvement in best corrected visual acuity (BCVA) and central macular thickness (CMT) on optical coherence tomography (OCT). Methods: This prospective interventional case series study was conducted at Retina Clinic, Al-Ibrahim Eye Hospital, and Isra Postgraduate Institute of Ophthalmology Karachi. Between December 2010 to June 2012. BCVA measurement with Early Treatment in Diabetic Retinopathy Study (ETDRS) charts and ophthalmic examination, including Slit-lamp bio microscopy, indirect ophthalmoscopy, Fundus fluorescein angiography (FFA) and OCT were done at the base line examination. At monthly interval all patients were treated with 3 injections of 0.05 ml intra vitreal injection containing 1.25 mg bevacizumab. Patients were followed up for 6 months and BCVA and OCT were taken at the final visit at 6 month. Results: The mean BCVA at base line was 0.42±0.14 Log Mar units. This improved to 0.34±0.13, 0.25±0.12, 0.17±0.12 and 0.16±0.14 Log Mar units at 1 month after 1st, 2nd 3rd injections and at final visit at 6 months respectively, a difference that was statistically significant (P>0.0001) from base line. The mean 1mm CMT measurement was 452.9 ± 143.1 µm at base line, improving to 279.8 ± 65.2 µm (P<0.0001) on final visit. No serious complications were observed. Conclusions: Primary IVB at a dose of 1.25 mg on monthly interval seems to provide stability and improvement in BCVA and CMT in patient with DME. PMID:24353679

An Investigation of Flow in Nozzle Hole of Dimethyl Ether

NASA Astrophysics Data System (ADS)

Kato, M.; Yokota, T.; Weber, J.; Gill, D.

2015-12-01

For over twenty years, DME has shown itself to be a most promising fuel for diesel combustion. DME is produced by simple synthesis of such common sources as coal, natural gas, biomass, and waste feedstock. DME is a flammable, thermally-stable liquid similar to liquefied petroleum gas (LPG) and can be handled like LPG. However, the physical properties of DME such as its low viscosity, lubricity and bulk modulus have negative effects for the fuel injection system, which have both limited the achievable injection pressures to about 500 bar and DME's introduction into the market. To overcome some of these effects, a common rail fuel injection system was adapted to operate with DME and produce injection pressures of up to 1000 bar. To understand the effect of the high injection pressure, tests were carried out using 2D optically accessed nozzles. This allowed the impact of the high vapour pressure of DME on the onset of cavitation in the nozzle hole to be assessed and improve the flow characteristics.

Setting Priorities for Diabetic Retinopathy Clinical Research and Identifying Evidence Gaps.

PubMed

Le, Jimmy T; Hutfless, Susan; Li, Tianjing; Bressler, Neil M; Heyward, James; Bittner, Ava K; Glassman, Adam; Dickersin, Kay

2017-01-01

Prioritizing comparative effectiveness research may contribute to obtaining answers that clinicians perceive they need and may minimize research that could be considered wasteful. Our objective was to identify evidence gaps and set priorities for new systematic reviews and randomized controlled trials for managing diabetic retinopathy (DR), including diabetic macular edema (DME). Cross-sectional study. Diabetic Retinopathy Clinical Research Network (DRCR.net) investigators. We provided recommendations from the American Academy of Ophthalmology's 2012 Preferred Practice Patterns for Diabetic Retinopathy as 91 answerable clinical research questions about intervention effectiveness to 410 DRCR.net investigators to rate each question's importance from 0 (not important) to 10 (very important) using a 2-round Delphi survey and to suggest additional questions. We considered questions as high priority if at least 75% of respondents to both rounds assigned an importance rating of 5 or more in round 2. We also extracted outcome measures relevant to DR and asked respondents to identify those that must be measured in all studies. We mapped Cochrane reviews published up to March 2016 to high-priority clinical research questions. Ranking of importance of each clinical question. Thirty-two individuals completed rounds 1 and 2 and suggested 15 questions. Among the final list of 106 clinical research questions, 22 questions met our definition of high priority: 9 of 22 concerned the effectiveness of anti-VEGF therapy, and 13 of 22 focused on how often patients should be followed up (re-examination) and treatment effectiveness in patients with specific characteristics (e.g., DME). Outcomes that 75% or more of respondents marked as "must be measured in all studies" included visual acuity and visual loss, death of participants, and intraocular pressure. Only 1 prioritized question was associated with conclusive evidence from a Cochrane systematic review. A limited response rate among DRCR.net members identified 22 comparative effectiveness research questions as high priority for the management of DR, including DME, but few were associated with Cochrane reviews. These results support the need of systematic reviews and randomized controlled trials to address evidence gaps.

Control of DEMETER DNA demethylase gene transcription in male and female gamete companion cells in Arabidopsis thaliana.

PubMed

Park, Jin-Sup; Frost, Jennifer M; Park, Kyunghyuk; Ohr, Hyonhwa; Park, Guen Tae; Kim, Seohyun; Eom, Hyunjoo; Lee, Ilha; Brooks, Janie S; Fischer, Robert L; Choi, Yeonhee

2017-02-21

The DEMETER (DME) DNA glycosylase initiates active DNA demethylation via the base-excision repair pathway and is vital for reproduction in Arabidopsis thaliana DME-mediated DNA demethylation is preferentially targeted to small, AT-rich, and nucleosome-depleted euchromatic transposable elements, influencing expression of adjacent genes and leading to imprinting in the endosperm. In the female gametophyte, DME expression and subsequent genome-wide DNA demethylation are confined to the companion cell of the egg, the central cell. Here, we show that, in the male gametophyte, DME expression is limited to the companion cell of sperm, the vegetative cell, and to a narrow window of time: immediately after separation of the companion cell lineage from the germline. We define transcriptional regulatory elements of DME using reporter genes, showing that a small region, which surprisingly lies within the DME gene, controls its expression in male and female companion cells. DME expression from this minimal promoter is sufficient to rescue seed abortion and the aberrant DNA methylome associated with the null dme-2 mutation. Within this minimal promoter, we found short, conserved enhancer sequences necessary for the transcriptional activities of DME and combined predicted binding motifs with published transcription factor binding coordinates to produce a list of candidate upstream pathway members in the genetic circuitry controlling DNA demethylation in gamete companion cells. These data show how DNA demethylation is regulated to facilitate endosperm gene imprinting and potential transgenerational epigenetic regulation, without subjecting the germline to potentially deleterious transposable element demethylation.

Your Medicare Coverage: Durable Medical Equipment (DME) Coverage

MedlinePlus

... test, item, or service covered? Go Durable medical equipment (DME) coverage How often is it covered? Medicare ... B (Medical Insurance) covers medically necessary durable medical equipment (DME) that your doctor prescribes for use in ...

Different stabilities of liposomes containing saturated and unsaturated lipids toward the addition of cyclodextrins.

PubMed

Ikeda, Atsushi; Funada, Rikushi; Sugikawa, Kouta

2016-06-14

Liposomes composed of unsaturated lipids were more stable than those containing saturated lipids toward DMe-β-CDx, DMe-α-CDx and DMe-β-CDx. The Hill coefficient values (n) indicated that the saturated lipid·DMe-CDx complexes had stoichiometric ratios in the range of 1 : 3-1 : 4, while the unsaturated lipid·DMe-CDx complexes had ratios in the range of 1 : 1.5-1 : 3. That is, a cis alkene group in the unsaturated lipids prevented complexation with a second DMe-CDx in the direction toward each acyl chain. Furthermore, the liposomes composed of the unsaturated lipids were much slower to form precipitates upon the addition of α-CDx than those of the saturated lipids. To the best of our knowledge, this is the first example showing that CDxs interact with unsaturated lipids.

Control of DEMETER DNA demethylase gene transcription in male and female gamete companion cells in Arabidopsis thaliana

PubMed Central

Park, Jin-Sup; Frost, Jennifer M.; Park, Kyunghyuk; Ohr, Hyonhwa; Park, Guen Tae; Kim, Seohyun; Eom, Hyunjoo; Lee, Ilha; Brooks, Janie S.; Fischer, Robert L.; Choi, Yeonhee

2017-01-01

The DEMETER (DME) DNA glycosylase initiates active DNA demethylation via the base-excision repair pathway and is vital for reproduction in Arabidopsis thaliana. DME-mediated DNA demethylation is preferentially targeted to small, AT-rich, and nucleosome-depleted euchromatic transposable elements, influencing expression of adjacent genes and leading to imprinting in the endosperm. In the female gametophyte, DME expression and subsequent genome-wide DNA demethylation are confined to the companion cell of the egg, the central cell. Here, we show that, in the male gametophyte, DME expression is limited to the companion cell of sperm, the vegetative cell, and to a narrow window of time: immediately after separation of the companion cell lineage from the germline. We define transcriptional regulatory elements of DME using reporter genes, showing that a small region, which surprisingly lies within the DME gene, controls its expression in male and female companion cells. DME expression from this minimal promoter is sufficient to rescue seed abortion and the aberrant DNA methylome associated with the null dme-2 mutation. Within this minimal promoter, we found short, conserved enhancer sequences necessary for the transcriptional activities of DME and combined predicted binding motifs with published transcription factor binding coordinates to produce a list of candidate upstream pathway members in the genetic circuitry controlling DNA demethylation in gamete companion cells. These data show how DNA demethylation is regulated to facilitate endosperm gene imprinting and potential transgenerational epigenetic regulation, without subjecting the germline to potentially deleterious transposable element demethylation. PMID:28130550

Guidelines on Diabetic Eye Care: The International Council of Ophthalmology Recommendations for Screening, Follow-up, Referral, and Treatment Based on Resource Settings.

PubMed

Wong, Tien Y; Sun, Jennifer; Kawasaki, Ryo; Ruamviboonsuk, Paisan; Gupta, Neeru; Lansingh, Van Charles; Maia, Mauricio; Mathenge, Wanjiku; Moreker, Sunil; Muqit, Mahi M K; Resnikoff, Serge; Verdaguer, Juan; Zhao, Peiquan; Ferris, Frederick; Aiello, Lloyd P; Taylor, Hugh R

2018-05-24

Diabetes mellitus (DM) is a global epidemic and affects populations in both developing and developed countries, with differing health care and resource levels. Diabetic retinopathy (DR) is a major complication of DM and a leading cause of vision loss in working middle-aged adults. Vision loss from DR can be prevented with broad-level public health strategies, but these need to be tailored to a country's and population's resource setting. Designing DR screening programs, with appropriate and timely referral to facilities with trained eye care professionals, and using cost-effective treatment for vision-threatening levels of DR can prevent vision loss. The International Council of Ophthalmology Guidelines for Diabetic Eye Care 2017 summarize and offer a comprehensive guide for DR screening, referral and follow-up schedules for DR, and appropriate management of vision-threatening DR, including diabetic macular edema (DME) and proliferative DR, for countries with high- and low- or intermediate-resource settings. The guidelines include updated evidence on screening and referral criteria, the minimum requirements for a screening vision and retinal examination, follow-up care, and management of DR and DME, including laser photocoagulation and appropriate use of intravitreal anti-vascular endothelial growth factor inhibitors and, in specific situations, intravitreal corticosteroids. Recommendations for management of DR in patients during pregnancy and with concomitant cataract also are included. The guidelines offer suggestions for monitoring outcomes and indicators of success at a population level. Copyright © 2018 American Academy of Ophthalmology. All rights reserved.

Ischemic index changes in diabetic retinopathy after intravitreal dexamethasone implant using ultra-widefield fluorescein angiography: a pilot study.

PubMed

Querques, Lea; Parravano, Mariacristina; Sacconi, Riccardo; Rabiolo, Alessandro; Bandello, Francesco; Querques, Giuseppe

2017-08-01

To investigate the effect of dexamethasone intravitreal implant on peripheral ischemia in patients affected by diabetic macular edema (DME). Patients with treatment-naïve diabetic retinopathy (DR) undergoing intravitreal dexamethasone implant for DME between October 2015 and March 2017 were enrolled. Patients underwent a comprehensive ocular examination at baseline (<2 weeks before treatment) and 10 ± 2 weeks after dexamethasone implant including best-corrected visual acuity (BCVA), intraocular pressure, optical coherence tomography, ultra-widefield (UWF) retinography and UWF fluorescein angiography (UWFA). Nine eyes of seven consecutive patients (five males; mean age 66.4 ± 6.7 years) were enrolled. Mean duration of DR was 12.3 ± 8.4 years. Mean interval between UWFA acquisitions was 12.1 ± 2.1 weeks, and the mean interval between intravitreal injection and UWFA acquisition was 11.0 ± 1.6 weeks. Mean pre- and post-injection BCVA was 0.30 ± 0.20 and 0.21 ± 0.14 logMAR (p = 0.06), respectively. Mean pre- and post-injection central macular thickness was 449.8 ± 92.5 and 356.3 ± 52.4 μm (p = 0.03), respectively. Mean pre- and post-injection ischemic index was 24.0 ± 25.0 and 9.8 ± 12.1% (p = 0.0427), respectively. Intravitreal dexamethasone implant reduces peripheral retina ischemia in patients with DR.

Integrative understanding of macular morphologic patterns in diabetic retinopathy based on self-organizing map.

PubMed

Murakami, Tomoaki; Ueda-Arakawa, Naoko; Nishijima, Kazuaki; Uji, Akihito; Horii, Takahiro; Ogino, Ken; Yoshimura, Nagahisa

2014-03-28

To integrate parameters on spectral-domain optical coherence tomography (SD-OCT) in diabetic retinopathy (DR) based on the self-organizing map and objectively describe the macular morphologic patterns. A total of 336 consecutive eyes of 216 patients with DR for whom clear SD-OCT images were available were retrospectively reviewed. Eleven OCT parameters and the logarithm of the minimal angle of resolution (logMAR) were measured. These multidimensional data were analyzed based on the self-organizing map on which similar cases were near each other according to the degree of their similarities, followed by the objective clustering. Self-organizing maps indicated that eyes with greater retinal thickness in the central subfield had greater thicknesses in the superior and temporal subfields. Eyes with foveal serous retinal detachment (SRD) had greater thickness in the nasal or inferior subfield. Eyes with foveal cystoid spaces were arranged to the left upper corner on the two-dimensional map; eyes with foveal SRD to the left lower corner; eyes with thickened retinal parenchyma to the lower area. The following objective clustering demonstrated the unsupervised pattern recognition of macular morphologies in diabetic macular edema (DME) as well as the higher-resolution discrimination of DME per se. Multiple regression analyses showed better association of logMAR with retinal thickness in the inferior subfield in eyes with SRD and with external limiting membrane disruption in eyes with foveal cystoid spaces or thickened retinal parenchyma. The self-organizing map facilitates integrative understanding of the macular morphologic patterns and the structural/functional relationship in DR.

Efficacy of Ranibizumab in Eyes with Diabetic Macular Edema and Macular Nonperfusion in RIDE and RISE.

PubMed

Reddy, Rahul K; Pieramici, Dante J; Gune, Shamika; Ghanekar, Avanti; Lu, Na; Quezada-Ruiz, Carlos; Baumal, Caroline R

2018-05-08

To determine whether there are baseline characteristics that distinguish patients with diabetic macular edema (DME) with coexisting macular nonperfusion (MNP) at baseline and assess these patients' potential to achieve favorable visual acuity (VA), anatomic, and diabetic retinopathy (DR) outcomes over 24 months. Post hoc analysis of RIDE/RISE, 2 phase 3, parallel, randomized, multicenter, double-masked trials (ClinicalTrials.gov: NCT00473382; NCT00473330). Study eyes with best-corrected VA (BCVA)/fluorescein angiogram (FA) data at baseline. To measure MNP, the Early Treatment for Diabetic Retinopathy Study (ETDRS) grid was overlaid on FAs of the macula. The MNP area was calculated by estimating the percentage of capillary loss in the central, inner, and outer subfields and converting into disc areas (DAs) using a software algorithm. Summary statistics and P values, respectively, were provided for all outcomes and comparisons of interest. Baseline characteristics; MNP area, BCVA, and central subfield thickness (CST) at months 12 and 24; and incidence of study eyes with ≥2-step DR improvement at months 3, 6, 12, 18, and 24. Baseline MNP was detected in 28.2%, 25.8%, and 26.3% of study eyes in the ranibizumab 0.3 mg (n = 213), ranibizumab 0.5 mg (n = 225), and sham (n = 228) arms, respectively. At baseline, patients with MNP were younger and had shorter diabetes duration, worse vision, increased CST, and worse DR severity (P values < 0.01 vs. those without MNP). In the ranibizumab 0.3 mg arm, eyes with baseline MNP had lower mean baseline BCVA (53.4 vs. 57.2 ETDRS letters for those without baseline MNP; P = 0.05), but mean BCVA gain at month 24 was comparable (+15.6 vs. +13.4 ETDRS letters, respectively; P = 0.2). Eyes with baseline MNP had increased CST at baseline, but experienced a greater decrease in CST by month 24. The proportion of eyes with ≥2-step DR improvement was greater for eyes with versus without baseline MNP in each ranibizumab arm. Despite having worse vision/increased CST versus those without baseline MNP, eyes with concurrent DME and baseline MNP entering RIDE/RISE experienced robust VA and anatomic improvement with ranibizumab and therefore should not be excluded from therapy. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Reproducibility of Spectral Domain Optical Coherence Tomography Retinal Thickness Measurements and Conversion to Equivalent Time Domain Metrics in Diabetic Macular Edema

PubMed Central

Bressler, Susan B.; Edwards, Allison R.; Chalam, Kakarla V.; Bressler, Neil M.; Glassman, Adam R.; Jaffe, Glenn J.; Melia, Michele; Saggau, David D.; Plous, Oren Z.

2014-01-01

Importance Advances in retinal imaging have led to the development of optical coherence tomography (OCT) instruments that incorporate spectral domain (SD) technology. Understanding measurement variability and relationships between retinal thickness measurements obtained on different machines is critical for proper use in clinical trials and clinical settings. Objectives Evaluate reproducibility of retinal thickness measurements from OCT images obtained by time domain (TD) (Zeiss Stratus) and SD (Zeiss Cirrus and Heidelberg Spectralis) instruments and formulate equations to convert retinal thickness measurements from SD-OCT to equivalent values on TD-OCT. Design Cross-sectional observational study. Each study eye underwent two replicate Stratus scans followed by two replicate Cirrus or Spectralis (real time image registration utilized) scans centered on the fovea. Setting Private and institutional practices Participants Diabetic persons with at least one eye with central-involved diabetic macular edema (DME), defined as Stratus central subfield thickness (CST)≥250μm. An additional normative cohort, individuals with diabetes but without DME, was enrolled. Main Outcome Measure(s) OCT CST and macular volume Results The Bland-Altman coefficient of repeatability for relative change in CST (the degree of change that could be expected from measurement variability) was lower on Spectralis compared with Stratus and Cirrus scans (7%, 12–15%, and 14%, respectively). For each cohort, the initial Stratus CST was within 10% of the replicate Stratus measurement 92% of the time; the conversion equations predicted a Stratus CST within 10% of the observed thickness 86% and 89% of the time for Stratus/Cirrus and Stratus/Spectralis groups, respectively. The Bland-Altman limits of agreement for relative change in CST between machines (the degree of change that could be expected from measurement variability, combined within and between instrument variability) were 21% for Cirrus and 19% for Spectralis, comparing predicted versus actual Stratus measurement. Conclusions and Relevance Reproducibility appears better on Spectralis than Cirrus and Stratus. Conversion equations to transform Cirrus or Spectralis measurements to Stratus-equivalent values, within 10% of the observed Stratus thickness values, appear feasible. CST changes beyond 10% when using the same machine or 20% when switching machines, after conversion to Stratus equivalents, are likely due to a change in retinal thickness and not measurement error. PMID:25058482

Cytotoxic, mutagenicity, and genotoxicity effects of guanylhydrazone derivatives.

PubMed

Pinhatti, Valéria Rodrigues; da Silva, Juliana; Martins, Tales Leandro Costa; Moura, Dinara Jaqueline; Rosa, Renato Moreira; Villela, Izabel; Stopiglia, Cheila Denise Ottonelli; da Silva Santos, Selma; Scroferneker, Maria Lúcia; Machado, Carlos Renato; Saffi, Jenifer; Henriques, João Antonio Pêgas

2016-08-01

Several studies have reported that guanylhydrazones display a variety of desirable biological properties, such as antihypertensive, antibacterial, and antimalarial behaviour. They furthermore promote anti-pneumocystosis and anti-trypanosomiasis, exhibit antitumor activity, and show significant cytotoxicity against cancer cell lines. In this work, we have evaluated the cytotoxicity, mutagenicity, and genotoxicity of two guanylhydrazones derivatives, (E)-2-[(2,3-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (2,3-DMeB) and (E)-2-[(3,4-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (3,4-DMeB), in different biological models. Both 2,3-DMeB and 3,4-DMeB induce weak cytotoxic and mutagenic effects in bacteria and yeast. The genotoxicity of these compounds was determined in a fibroblast cell line (V79) using alkaline comet assay, as well as a modified comet assay with bacterial enzymes formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (EndoIII). Both guanylhydrazone derivatives induced DNA damage. Treatment of V79 cells with EndoIII and FPG proteins demonstrated a significant effect of 2,3-DMeB and 3,4-DMeB with respect to oxidized bases. In addition, the derivatives induced a significant increase in the frequency of micronucleated cells at high doses. The antifungal and anti-trypanosomal properties of these guanylhydrazone derivatives were also evaluated, and the obtained results suggest that 2,3-DMeB is more effective than 3,4-DMeB. The biological activity of 2,3-DMeB and 3,4-DMeB may thus be related, at least in part, to their oxidative potential, as well as to their ability to interact with DNA. Considering the previously reported in vitro antitumor activity of guanylhydrazone derivatives in combination with the lack of acute toxicity and the fact that DNA damage is only observed at high doses should render both compounds good candidates for in vivo studies on antitumor activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of low-temperature combustion and dimethyl ether-diesel blends on performance, combustion, and emission characteristics of common rail diesel engine: a CFD study.

PubMed

Lamani, Venkatesh Tavareppa; Yadav, Ajay Kumar; Narayanappa, Kumar Gottekere

2017-06-01

Due to presence of more oxygen, absence of carbon-carbon (C-C) bond in chemical structure, and high cetane number of dimethyl ether (DME), pollution from DME operated engine is less compared to diesel engine. Hence, the DME can be a promising alternative fuel for diesel engine. The present study emphasizes the effect of various exhaust gas recirculation (EGR) rates (0-20%) and DME/Diesel blends (0-20%) on combustion characteristics and exhaust emissions of common rail direct injection (CRDI) engine using three-dimensional computational fluid dynamics (CFD) simulation. Extended coherent flame model-3 zone (ECFM-3Z) is implemented to carry out combustion analysis, and k-ξ-f model is employed for turbulence modeling. Results show that in-cylinder pressure marginally decreases with employing EGR compared to without EGR case. As EGR rate increases, nitrogen oxide (NO) formation decreases, whereas soot increases marginally. Due to better combustion characteristics of DME, indicated thermal efficiency (ITE) increases with the increases in DME/diesel blend ratio. Adverse effect of EGR on efficiency for blends is less compared to neat diesel, because the anoxygenated region created due to EGR is compensated by extra oxygen present in DME. The trade-off among NO, soot, carbon monoxide (CO) formation, and efficiency is studied by normalizing the parameters. Optimum operating condition is found at 10% EGR rate and 20% DME/diesel blend. The maximum indicated thermal efficiency was observed for DME/diesel ratio of 20% in the present range of study. Obtained results are validated with published experimental data and found good agreement.

In-Situ Immobilization of Ni Complex on Amine-Grafted SiO₂ for Ethylene Polymerization.

PubMed

Lee, Sang Yun; Ko, Young Soo

2018-02-01

The results on the In-Situ synthesis of Ni complex on amine-grafted SiO2 and its ethylene polymerization were explained. SiO2/2NS/(DME)NiBr2 and SiO2/3NS/(DME)NiBr2(Ni(II) bromide ethylene glycol dimethyl ether) catalysts were active for ethylene polymerization. The highest activity was shown at the polymerization temperature of 25 °C, and SiO2/2NS/(DME)NiBr2 exhibited higher activity than SiO2/3NS/(DME)NiBr2. The PDI values of SiO2/2NS/(DME)NiBr2 were in the range of 8~18. The aminosilane compounds and Ni were evenly grafted and distributed in the silica. It was proposed that DME ligand was mostly removed during the supporting process, and only NiBr2 was complexed with the amine group of 2NS based on the results of FT-IR and ethylene polymerization.

AEMS implementation cost study for Boeing 727

NASA Technical Reports Server (NTRS)

Allison, R. L.

1977-01-01

Costs for airline operational implementation of a NASA-developed approach energy management system (AEMS) concept, as applied to the 727 airplane, were determined. Estimated costs are provided for airplane retrofit and for installation of the required DME ground stations. Operational costs and fuel cost savings are presented in a cost-of-ownership study. The potential return on the equipment investment is evaluated using a net present value method. Scheduled 727 traffic and existing VASI, ILS, and collocated DME ground station facilities are summarized for domestic airports used by 727 operators.

Sociomateriality: a theoretical framework for studying distributed medical education.

PubMed

MacLeod, Anna; Kits, Olga; Whelan, Emma; Fournier, Cathy; Wilson, Keith; Power, Gregory; Mann, Karen; Tummons, Jonathan; Brown, Peggy Alexiadis

2015-11-01

Distributed medical education (DME) is a type of distance learning in which students participate in medical education from diverse geographic locations using Web conferencing, videoconferencing, e-learning, and similar tools. DME is becoming increasingly widespread in North America and around the world.Although relatively new to medical education, distance learning has a long history in the broader field of education and a related body of literature that speaks to the importance of engaging in rigorous and theoretically informed studies of distance learning. The existing DME literature is helpful, but it has been largely descriptive and lacks a critical "lens"-that is, a theoretical perspective from which to rigorously conceptualize and interrogate DME's social (relationships, people) and material (technologies, tools) aspects.The authors describe DME and theories about distance learning and show that such theories focus on social, pedagogical, and cognitive considerations without adequately taking into account material factors. They address this gap by proposing sociomateriality as a theoretical framework allowing researchers and educators to study DME and (1) understand and consider previously obscured actors, infrastructure, and other factors that, on the surface, seem unrelated and even unimportant; (2) see clearly how the social and material components of learning are intertwined in fluid, messy, and often uncertain ways; and (3) perhaps think differently, even in ways that disrupt traditional approaches, as they explore DME. The authors conclude that DME brings with it substantial investments of social and material resources, and therefore needs careful study, using approaches that embrace its complexity.

Natural abundance 17O, 6Li NMR and molecular modeling studies of the solvation structures of lithium bis(fluorosulfonyl)imide/1,2-dimethoxyethane liquid electrolytes

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

Wan, Chuan; Hu, Mary Y.; Borodin, Oleg

2016-03-01

Natural abundance 17O and 6Li NMR experiments, quantum chemistry and molecular dynamics studies were employed to investigate the solvation structures of Li+ at various concentrations of LiFSI in DME electrolytes in an effort to solve this puzzle. It was found that the chemical shifts of both 17O and 6Li changed with the concentration of LiFSI, indicating the changes of solvation structures with concentration. For the quantum chemistry calculations, the coordinated cluster LiFSI(DME)2 forms at first, and its relative ratio increases with increasing LiFSI concentration to 1 M. Then the solvation structure LiFSI(DME) become the dominant component. As a result, themore » coordination of forming contact ion pairs between Li+ and FSI- ion increases, but the association between Li+ and DME molecule decreases. Furthermore, at LiFSI concentration of 4 M the solvation structures associated with Li+(FSI-)2(DME), Li+2(FSI-)(DME)4 and (LiFSI)2(DME)3 become the dominant components. For the molecular dynamics simulation, with increasing concentration, the association between DME and Li+ decreases, and the coordinated number of FSI- increases, which is in perfect accord with the DFT results. These results provide more insight on the fundamental mechanism on the very high CE of Li deposition in these electrolytes, especially at high current density conditions.« less

The Inverse Relationship between Digital Media Exposure and Childhood Flourishing.

PubMed

Ruest, Stephanie; Gjelsvik, Annie; Rubinstein, Max; Amanullah, Siraj

2018-06-01

To describe the relationship between digital media exposure (DME) and parental perception of childhood flourishing, or overall positive well-being. It is hypothesized that there is an inverse association between parent-reported measures of childhood flourishing and increasing daily DME. Parental responses for children ages 6-17 years (N = 64 464) from the 2011-2012 National Survey of Children's Health were analyzed. Average weekday DME that was not school work related was categorized in 2-hour intervals: 0 to <2, 2 to < 4, 4 to < 6, and ≥6 hours. Bivariate analyses and logistic regression models were used to examine the relationship between DME and parent-reported frequency of 5 childhood flourishing markers: completing homework, caring about academics, finishing tasks, staying calm when challenged, and showing interest in learning. Only 31% reported <2 hours of weekday DME. For the remaining children, daily DME was 2 to <4 hours (36%), 4 to <6 hours (17%), or ≥6 hours (17%). In a model adjusted for age, sex, race, poverty level, primary language spoken at home, and highest maternal education level, there was a dose-dependent decrease in the odds of demonstrating all 5 markers of flourishing as weekday DME increased (test for trend for each outcome P < .001). In stratified analyses, this relationship held true regardless of the child's age group, sex, or poverty level. This study provides evidence that, among school-aged children, increasing weekday DME has an inverse dose-dependent relationship with multiple childhood flourishing markers. Copyright © 2017 Elsevier Inc. All rights reserved.

Simple, Scalable, Script-based, Science Processor for Measurements - Data Mining Edition (S4PM-DME)

NASA Astrophysics Data System (ADS)

Pham, L. B.; Eng, E. K.; Lynnes, C. S.; Berrick, S. W.; Vollmer, B. E.

2005-12-01

The S4PM-DME is the Goddard Earth Sciences Distributed Active Archive Center's (GES DAAC) web-based data mining environment. The S4PM-DME replaces the Near-line Archive Data Mining (NADM) system with a better web environment and a richer set of production rules. S4PM-DME enables registered users to submit and execute custom data mining algorithms. The S4PM-DME system uses the GES DAAC developed Simple Scalable Script-based Science Processor for Measurements (S4PM) to automate tasks and perform the actual data processing. A web interface allows the user to access the S4PM-DME system. The user first develops personalized data mining algorithm on his/her home platform and then uploads them to the S4PM-DME system. Algorithms in C and FORTRAN languages are currently supported. The user developed algorithm is automatically audited for any potential security problems before it is installed within the S4PM-DME system and made available to the user. Once the algorithm has been installed the user can promote the algorithm to the "operational" environment. From here the user can search and order the data available in the GES DAAC archive for his/her science algorithm. The user can also set up a processing subscription. The subscription will automatically process new data as it becomes available in the GES DAAC archive. The generated mined data products are then made available for FTP pickup. The benefits of using S4PM-DME are 1) to decrease the downloading time it typically takes a user to transfer the GES DAAC data to his/her system thus off-load the heavy network traffic, 2) to free-up the load on their system, and last 3) to utilize the rich and abundance ocean, atmosphere data from the MODIS and AIRS instruments available from the GES DAAC.

Dimethyl Sulfide-Dimethyl Ether and Ethylene Oxide-Ethylene Sulfide Complexes Investigated by Fourier Transform Microwave Spectroscopy and AB Initio Calculation

NASA Astrophysics Data System (ADS)

Kawashima, Yoshiyuki; Tatamitani, Yoshio; Mase, Takayuki; Hirota, Eizi

2015-06-01

The ground-state rotational spectra of the dimethyl sulfide-dimethyl ether (DMS-DME) and the ethylene oxide and ethylene sulfide (EO-ES) complexes were observed by Fourier transform microwave spectroscopy, and a-type and c-type transitions were assigned for the normal, 34S, and three 13C species of the DMS-DME and a-type and b-type rotational transitions for the normal, 34S, and two 13C species of the EO-ES. The observed transitions were analyzed by using an S-reduced asymmetric-top rotational Hamiltonian. The rotational parameters thus derived for the DMS-DME were found consistent with a structure of Cs symmetry with the DMS bound to the DME by two C-H(DMS)---O and one S---H-C(DME) hydrogen bonds. The barrier height V3 to internal rotation of the "free" methyl group in the DME was determined to be 915.4 (23) wn, which is smaller than that of the DME monomer, 951.72 (70) wn, and larger than that of the DME dimer, 785.4 (52) wn. For the EO-ES complex the observed data were interpreted in the terms of an antiparallel Cs geometry with the EO bound to the ES by two C-H(ES)---O and two S---H-C(EO) hydrogen bonds. We have applied a natural bond orbital (NBO) analysis to the DMS-DME and EO-ES to calculate the stabilization energy CT (= ΔEσσ*), which were closely correlated with the binding energy EB, as found for other related complexes. Y. Niide and M. Hayashi, J. Mol. Spectrosc. 220, 65-79 (2003). Y. Tatamitani, B. Liu, J. Shimada, T. Ogata, P. Ottaviani, A. Maris, W. Caminati, and J. L. Alonso, J. Am. Chem. Soc. 124, 2739-2743 (2002).

Glomerular Filtration Rate and/or Ratio of Urine Albumin to Creatinine as Markers for Diabetic Retinopathy: A Ten-Year Follow-Up Study

PubMed Central

Baget-Bernaldiz, Marc; Navarro-Gil, Raul; Sagarra-Alamo, Ramon; Barrot-De La Puente, Joan F.; Mundet-Tuduri, Xavier

2018-01-01

Aims To determine the relationship between diabetic nephropathy and diabetic retinopathy on a population of type 2 diabetes mellitus patients. Methods A prospective ten-year follow-up population-based study. We determined differences between estimated glomerular filtration rate (eGFR) using the chronic kidney disease epidemiology collaboration equation and urine albumin to creatinine ratio. Results Annual incidence of any-DR was 8.21 ± 0.60% (7.06%–8.92%), sight-threatening diabetic retinopathy (STDR) was 2.65 ± 0.14% (2.48%–2.88%), and diabetic macular edema (DME) was 2.21 ± 0.18% (2%–2.49%). Renal study results were as follows: UACR > 30 mg/g had an annual incidence of 7.02 ± 0.05% (6.97%–7.09%), eGFR < 60 ml/min/1.73 m2 incidence was 5.89 ± 0.12% (5.70%–6.13%). Cox's proportional regression analysis of DR incidence shows that renal function studied by eGFR < 60 ml/min/1.73 m2 was less significant (p = 0.04, HR 1.223, 1.098–1.201) than UACR ≥ 300 mg/g (p < 0.001, HR 1.485, 1.103–1.548). The study of STDR shows that eGFR < 60 ml/min/1.73 m2 was significant (p = 0.02, HR 1.890, 1.267–2.820), UACR ≥ 300 mg/g (p < 0.001, HR 2.448, 1.595–3.757), and DME shows that eGFR < 60 ml/min/1.73 m2 was significant (p = 0.02, HR 1.920, 1.287–2.864) and UACR ≥ 300 mg/g (p < 0.001, HR 2.432, 1.584–3.732). Conclusions The UACR has a better association with diabetic retinopathy than the eGFR, although both are important risk factors for diabetic retinopathy. PMID:29682579

Study of retinal neurodegeneration and maculopathy in diabetic Meriones shawi: A particular animal model with human-like macula.

PubMed

Hammoum, Imane; Benlarbi, Maha; Dellaa, Ahmed; Szabó, Klaudia; Dékány, Bulcsú; Csaba, Dávid; Almási, Zsuzsanna; Hajdú, Rozina I; Azaiz, Rached; Charfeddine, Ridha; Lukáts, Ákos; Ben Chaouacha-Chekir, Rafika

2017-09-01

The purpose of this work was to evaluate a potentially useful animal model, Meriones shawi (M.sh)-developing metabolic X syndrome, diabetes and possessing a visual streak similar to human macula-in the study of diabetic retinopathy and diabetic macular edema (DME). Type 2 diabetes (T2D) was induced by high fat diet administration in M.sh. Body weights, blood glucose levels were monitored throughout the study. Diabetic retinal histopathology was evaluated 3 and 7 months after diabetes induction. Retinal thickness was measured, retinal cell types were labeled by immunohistochemistry and the number of stained elements were quantified. Apoptosis was determined with TUNEL assay. T2D induced progressive changes in retinal histology. A significant decrease of retinal thickness and glial reactivity was observed without an increase in apoptosis rate. Photoreceptor outer segment degeneration was evident, with a significant decrease in the number of all cones and M-cone subtype, but-surprisingly-an increase in S-cones. Damage of the pigment epithelium was also confirmed. A decrease in the number and labeling intensity of parvalbumin- and calretinin-positive amacrine cells and a loss of ganglion cells was detected. Other cell types showed no evident alterations. No DME-like condition was noticed even after 7 months. M.sh could be a useful model to study the evolution of diabetic retinal pathology and to identify the role of hypertension and dyslipidemia in the development of the reported alterations. Longer follow up would be needed to evaluate the potential use of the visual streak in modeling human macular diseases. © 2017 Wiley Periodicals, Inc.

Progression of diabetic retinopathy severity after treatment with dexamethasone implant: a 24-month cohort study the 'DR-Pro-DEX Study'.

PubMed

Iglicki, Matias; Zur, Dinah; Busch, Catharina; Okada, Mali; Loewenstein, Anat

2018-06-01

Intravitreal anti-vascular endothelial growth factor agents have been shown to reduce diabetic retinopathy (DR) progression; data on the effects of intravitreal corticosteroids on modifying disease severity are limited. This study evaluates the long-term effect of intravitreal dexamethasone implant (DEX) on the severity and progression of non-proliferative DR (NPDR). This was a retrospective cohort study. Sixty eyes from 60 consecutive patients with NPDR and diabetic macular edema (DME) treated with dexamethasone implant (DEX group) and 49 eyes from consecutive 49 patients without DME requiring observation only. Fundus angiography images from baseline and after 24 months were graded by two masked assessors into mild, moderate and severe NPDR and PDR, according to the ETDRS classification. Patients were followed up 1-3 and 4-6 months after each DEX implant. Re-treatment with DEX implant was on a pro re nata basis. Records were reviewed for performance of panretinal photocoagulation. Main outcome was as follows: change of DR ≥ 1 grade and progression to proliferative diabetic retinopathy (PDR). Three eyes (5%) in the DEX group and 43 (87.8%) eyes in the control group progressed to PDR (P < 0.0001). Twenty-five eyes (41.7%) in the DEX group but none in the control group demonstrated an improvement in DR severity (P < 0.0001). This study provides the first long-term evidence that DEX implant has the potential to not only delay progression of DR and PDR development, but may also improve DR severity over 24 months. Better understanding of the effects of corticosteroids will help guide its use in the treatment pathway of DR.

Direct synthesis of ethanol from dimethyl ether and syngas over combined H-Mordenite and Cu/ZnO catalysts.

PubMed

Li, Xingang; San, Xiaoguang; Zhang, Yi; Ichii, Takashi; Meng, Ming; Tan, Yisheng; Tsubaki, Noritatsu

2010-10-25

Ethanol was directly synthesized from dimethyl ether (DME) and syngas with the combined H-Mordenite and Cu/ZnO catalysts that were separately loaded in a dual-catalyst bed reactor. Methyl acetate (MA) was formed by DME carbonylation over the H-Mordenite catalyst. Thereafter, ethanol and methanol were produced by MA hydrogenation over the Cu/ZnO catalyst. With the reactant gas containing 1.0% DME, the optimized temperature for the reaction was at 493 K to reach 100% conversion. In the products, the yield of methanol and ethanol could reach 46.3% and 42.2%, respectively, with a small amount of MA, ethyl acetate, and CO(2). This process is environmentally friendly as the main byproduct methanol can be recycled to DME by a dehydration reaction. In contrast, for the physically mixed catalysts, the low conversion of DME and high selectivity of methanol were observed.

Consider the DME alternative for diesel engines

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

Fleisch, T.H.; Meurer, P.C.

1996-07-01

Engine tests demonstrate that dimethyl ether (DME, CH{sub 3}OCH{sub 3}) can provide an alternative approach toward efficient, ultra-clean and quiet compression ignition (CI) engines. From a combustion point of view, DME is an attractive alternative fuel for CI engines, primarily for commercial applications in urban areas, where ultra-low emissions will be required in the future. DME can resolve the classical diesel emission problem of smoke emissions, which are completely eliminated. With a properly developed DME injection and combustion system, NO{sub x} emissions can be reduced to 40% of Euro II or U.S. 1998 limits, and can meet the future ULEVmore » standards of California. Simultaneously, the combustion noise is reduced by as much as 15 dB(A) below diesel levels. In addition, the classical diesel advantages such as high thermal efficiency, compression ignition, engine robustness, etc., are retained.« less

Outcomes with As-Needed Ranibizumab after Initial Monthly Therapy: Long-Term Outcomes of the Phase III RIDE and RISE Trials.

PubMed

Boyer, David S; Nguyen, Quan Dong; Brown, David M; Basu, Karen; Ehrlich, Jason S

2015-12-01

To determine whether the efficacy and safety achieved with monthly ranibizumab as treatment for diabetic macular edema (DME) can be maintained with less-than-monthly treatment. Open-label extension (OLE) phase of randomized, sham-controlled phase III trials: RIDE (NCT00473382) and RISE (NCT00473330). Five hundred of 582 adults who completed the 36-month randomized core studies elected to enter the OLE. All patients participating in the OLE were eligible to receive 0.5 mg ranibizumab according to predefined re-treatment criteria: Treatment was administered when DME was identified by the investigator on optical coherence tomography or when best-corrected visual acuity (BCVA) worsened by ≥5 Early Treatment Diabetic Retinopathy Study letters versus month 36. Patients were observed at 30-, 60-, or 90-day intervals depending on the need for treatment. The incidence and severity of ocular and nonocular events, proportion of patients with ≥15-letter best-corrected visual acuity (BCVA) gain from baseline, mean BCVA change from month 36 (final core study visit), mean central foveal thickness (CFT), and mean CFT change from month 36. A mean of 4.5 injections were administered over a mean follow-up of 14.1 months. Approximately 25% of patients did not require further treatment based on protocol-defined re-treatment criteria. Mean BCVA was sustained or improved in these patients through the end of follow-up. Approximately 75% of patients received ≥1 criteria-based re-treatment; mean time to first re-treatment was approximately 3 months after the last masked-phase visit. Mean BCVA remained stable in re-treated patients; CFT was generally stable with a trend toward slight thickening in all patients when mandatory monthly therapy was relaxed. Vision gains achieved after 1 or 3 years of monthly ranibizumab therapy were maintained with a marked reduction in treatment frequency; some patients required no additional treatment. These observations are consistent with other studies evaluating induction followed by maintenance ranibizumab therapy for DME. Patients whose treatment was deferred by 2 years (randomized initially to sham) did not ultimately achieve the same BCVA gains as patients who received ranibizumab from baseline. Ranibizumab's safety profile in the OLE appeared similar to that observed in the controlled core studies and other studies. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Data mining of enzymes using specific peptides

PubMed Central

2009-01-01

Background Predicting the function of a protein from its sequence is a long-standing challenge of bioinformatic research, typically addressed using either sequence-similarity or sequence-motifs. We employ the novel motif method that consists of Specific Peptides (SPs) that are unique to specific branches of the Enzyme Commission (EC) functional classification. We devise the Data Mining of Enzymes (DME) methodology that allows for searching SPs on arbitrary proteins, determining from its sequence whether a protein is an enzyme and what the enzyme's EC classification is. Results We extract novel SP sets from Swiss-Prot enzyme data. Using a training set of July 2006, and test sets of July 2008, we find that the predictive power of SPs, both for true-positives (enzymes) and true-negatives (non-enzymes), depends on the coverage length of all SP matches (the number of amino-acids matched on the protein sequence). DME is quite different from BLAST. Comparing the two on an enzyme test set of July 2008, we find that DME has lower recall. On the other hand, DME can provide predictions for proteins regarded by BLAST as having low homologies with known enzymes, thus supplying complementary information. We test our method on a set of proteins belonging to 10 bacteria, dated July 2008, establishing the usefulness of the coverage-length cutoff to determine true-negatives. Moreover, sifting through our predictions we find that some of them have been substantiated by Swiss-Prot annotations by July 2009. Finally we extract, for production purposes, a novel SP set trained on all Swiss-Prot enzymes as of July 2009. This new set increases considerably the recall of DME. The new SP set is being applied to three metagenomes: Sargasso Sea with over 1,000,000 proteins, producing predictions of over 220,000 enzymes, and two human gut metagenomes. The outcome of these analyses can be characterized by the enzymatic profile of the metagenomes, describing the relative numbers of enzymes observed for different EC categories. Conclusions Employing SPs for predicting enzymatic activity of proteins works well once one utilizes coverage-length criteria. In our analysis, L ≥ 7 has led to highly accurate results. PMID:20034383

The Invisible Work of Distributed Medical Education: Exploring the Contributions of Audiovisual Professionals, Administrative Professionals and Faculty Teachers

ERIC Educational Resources Information Center

MacLeod, Anna; Kits, Olga; Mann, Karen; Tummons, Jonathan; Wilson, Keith W.

2017-01-01

Distributed medical education (DME) is becoming increasingly prevalent. Much of the published literature on DME has focused on the experiences of learners in distributed programs; however, our empirical work leads us to believe that DME changes the context significantly, not only for learners, but also for other important members of the…

Improved navigation by combining VOR/DME information with air or inertial data

NASA Technical Reports Server (NTRS)

Bobick, J. C.; Bryson, A. E., Jr.

1972-01-01

The improvement was determined in navigational accuracy obtainable by combining VOR/DME information (from one or two stations) with air data (airspeed and heading) or with data from an inertial navigation system (INS) by means of a maximum-likelihood filter. It was found that the addition of air data to the information from one VOR/DME station reduces the RMS position error by a factor of about 2, whereas the addition of inertial data from a low-quality INS reduces the RMS position error by a factor of about 3. The use of information from two VOR/DME stations with air or inertial data yields large factors of improvement in RMS position accuracy over the use of a single VOR/DME station, roughly 15 to 20 for the air-data case and 25 to 35 for the inertial-data case. As far as position accuracy is concerned, at most one VOR station need be used. When continuously updating an INS with VOR/DME information, the use of a high-quality INS (0.01 deg/hr gyro drift) instead of a low-quality INS (1.0 deg/hr gyro drift) does not substantially improve position accuracy.

A pilot pharmacokinetic study of miroestrol and deoxymiroestrol on rabbit sera using polyclonal antibody-based icELISA analysis.

PubMed

Kitisripanya, Tharita; Udomsin, Orapin; Komaikul, Jukrapun; Inyai, Chadathorn; Limsuwanchote, Supattra; Yusakul, Gorawit; Putalun, Waraporn

2018-02-01

Miroestrol (ME) and deoxymiroestrol (DME) are the most potent phytoestrogens and bioactive markers in Pueraria candollei var. mirifica tuberous roots. To understand their pharmacokinetic profiles, a pharmacokinetic study of ME and DME, at 0.43 and 0.21 mg per kg body weight, respectively, in three rabbits was performed after orally administering a single dose of P. candollei var. mirifica enriched fraction extract. Two established polyclonal antibody-based indirect competitive enzyme-linked immunosorbent assays were validated to determine ME and DME in rabbit sera. In rabbits, the area under the 0- to 48-hr concentration-time curve of ME and DME were 854.92 and 1,692.84 ng·h/ml, respectively. The maximum concentration of ME was measured 1 hr after administration as 69.62 ± 8.28 ng/ml, and the maximum concentration of DME was measured at 3 hr as 81.8 ± 5.43 ng/ml. These results provide an initial approach for designing and studying the relationship between the ME and DME levels and their therapeutic effects based on their pharmacokinetic profiles. Copyright © 2017 John Wiley & Sons, Ltd.

Structural requirements and reaction pathways in dimethyl ether combustion catalyzed by supported Pt clusters.

PubMed

Ishikawa, Akio; Neurock, Matthew; Iglesia, Enrique

2007-10-31

The identity and reversibility of the elementary steps required for catalytic combustion of dimethyl ether (DME) on Pt clusters were determined by combining isotopic and kinetic analyses with density functional theory estimates of reaction energies and activation barriers to probe the lowest energy paths. Reaction rates are limited by C-H bond activation in DME molecules adsorbed on surfaces of Pt clusters containing chemisorbed oxygen atoms at near-saturation coverages. Reaction energies and activation barriers for C-H bond activation in DME to form methoxymethyl and hydroxyl surface intermediates show that this step is more favorable than the activation of C-O bonds to form two methoxides, consistent with measured rates and kinetic isotope effects. This kinetic preference is driven by the greater stability of the CH3OCH2* and OH* intermediates relative to chemisorbed methoxides. Experimental activation barriers on Pt clusters agree with density functional theory (DFT)-derived barriers on oxygen-covered Pt(111). Measured DME turnover rates increased with increasing DME pressure, but decreased as the O2 pressure increased, because vacancies (*) on Pt surfaces nearly saturated with chemisorbed oxygen are required for DME chemisorption. DFT calculations show that although these surface vacancies are required, higher oxygen coverages lead to lower C-H activation barriers, because the basicity of oxygen adatoms increases with coverage and they become more effective in hydrogen abstraction from DME. Water inhibits reaction rates via quasi-equilibrated adsorption on vacancy sites, consistent with DFT results indicating that water binds more strongly than DME on vacancies. These conclusions are consistent with the measured kinetic response of combustion rates to DME, O2, and H2O, with H/D kinetic isotope effects, and with the absence of isotopic scrambling in reactants containing isotopic mixtures of 18O2-16O2 or 12CH3O12CH3-13CH3O13CH3. Turnover rates increased with Pt cluster size, because small clusters, with more coordinatively unsaturated surface atoms, bind oxygen atoms more strongly than larger clusters and exhibit lower steady-state vacancy concentrations and a consequently smaller number of adsorbed DME intermediates involved in kinetically relevant steps. These effects of cluster size and metal-oxygen bond energies on reactivity are ubiquitous in oxidation reactions requiring vacancies on surfaces nearly saturated with intermediates derived from O2.

Approach for a Clinically Useful Comprehensive Classification of Vascular and Neural Aspects of Diabetic Retinal Disease

PubMed Central

Abramoff, Michael D.; Fort, Patrice E.; Han, Ian C.; Jayasundera, K. Thiran; Sohn, Elliott H.; Gardner, Thomas W.

2018-01-01

The Early Treatment Diabetic Retinopathy Study (ETDRS) and other standardized classification schemes have laid a foundation for tremendous advances in the understanding and management of diabetic retinopathy (DR). However, technological advances in optics and image analysis, especially optical coherence tomography (OCT), OCT angiography (OCTa), and ultra-widefield imaging, as well as new discoveries in diabetic retinal neuropathy (DRN), are exposing the limitations of ETDRS and other classification systems to completely characterize retinal changes in diabetes, which we term diabetic retinal disease (DRD). While it may be most straightforward to add axes to existing classification schemes, as diabetic macular edema (DME) was added as an axis to earlier DR classifications, doing so may make these classifications increasingly complicated and thus clinically intractable. Therefore, we propose future research efforts to develop a new, comprehensive, and clinically useful classification system that will identify multimodal biomarkers to reflect the complex pathophysiology of DRD and accelerate the development of therapies to prevent vision-threatening DRD. PMID:29372250

Approach for a Clinically Useful Comprehensive Classification of Vascular and Neural Aspects of Diabetic Retinal Disease.

PubMed

Abramoff, Michael D; Fort, Patrice E; Han, Ian C; Jayasundera, K Thiran; Sohn, Elliott H; Gardner, Thomas W

2018-01-01

The Early Treatment Diabetic Retinopathy Study (ETDRS) and other standardized classification schemes have laid a foundation for tremendous advances in the understanding and management of diabetic retinopathy (DR). However, technological advances in optics and image analysis, especially optical coherence tomography (OCT), OCT angiography (OCTa), and ultra-widefield imaging, as well as new discoveries in diabetic retinal neuropathy (DRN), are exposing the limitations of ETDRS and other classification systems to completely characterize retinal changes in diabetes, which we term diabetic retinal disease (DRD). While it may be most straightforward to add axes to existing classification schemes, as diabetic macular edema (DME) was added as an axis to earlier DR classifications, doing so may make these classifications increasingly complicated and thus clinically intractable. Therefore, we propose future research efforts to develop a new, comprehensive, and clinically useful classification system that will identify multimodal biomarkers to reflect the complex pathophysiology of DRD and accelerate the development of therapies to prevent vision-threatening DRD.

An Agar-Based Method for Plating Marine Protozoan Parasites of the Genus Perkinsus.

PubMed

Cold, Emma R; Freyria, Nastasia J; Martínez Martínez, Joaquín; Fernández Robledo, José A

2016-01-01

The genus Perkinsus includes protozoan parasites of mollusks responsible for losses in the aquaculture industry and hampering the recovery of natural shellfish beds worldwide, and they are a key taxon for understanding intracellular parasitism adaptations. The ability to propagate the parasite in liquid media, in the absence of the host, has been crucial for improving understanding of its biology; however, alternative techniques to grow the parasite are needed to explore other basic aspects of the Perkinsus spp. biology. We optimized a DME: Ham's F12-5% FBS- containing solid agar medium for plating Perkinsus marinus. This solid medium supported trophozoite propagation both by binary fission and schizogony. Colonies were visible to the naked eye 17 days after plating. We tested the suitability of this method for several applications, including the following: 1) Subcloning P. marinus isolates: single discrete P. marinus colonies were obtained from DME: Ham's F12-5% FBS- 0.75% agar plates, which could be further propagated in liquid medium; 2) Subcloning engineered Perkinsus mediterraneus MOE[MOE]: GFP by streaking cultures on plates; 3) Chemical susceptibility: Infusing the DME: Ham's F12-5% FBS- 0.75% agar plates with triclosan resulted in inhibition of the parasite propagation in a dose-dependent manner. Altogether, our plating method has the potential for becoming a key tool for investigating diverse aspects of Perkinsus spp. biology, developing new molecular tools, and for biotechnological applications.

14 CFR 91.161 - Special awareness training required for pilots flying under visual flight rules within a 60...

Code of Federal Regulations, 2012 CFR

2012-01-01

... pilots flying under visual flight rules within a 60-nautical mile radius of the Washington, DC VOR/DME... flight rules within a 60-nautical mile radius of the Washington, DC VOR/DME. (a) Operations within a 60-nautical mile radius of the Washington, DC VOR/DME under visual flight rules (VFR). Except as provided...

14 CFR 91.161 - Special awareness training required for pilots flying under visual flight rules within a 60...

Code of Federal Regulations, 2011 CFR

2011-01-01

... pilots flying under visual flight rules within a 60-nautical mile radius of the Washington, DC VOR/DME... flight rules within a 60-nautical mile radius of the Washington, DC VOR/DME. (a) Operations within a 60-nautical mile radius of the Washington, DC VOR/DME under visual flight rules (VFR). Except as provided...

14 CFR 91.161 - Special awareness training required for pilots flying under visual flight rules within a 60...

Code of Federal Regulations, 2013 CFR

2013-01-01

... pilots flying under visual flight rules within a 60-nautical mile radius of the Washington, DC VOR/DME... flight rules within a 60-nautical mile radius of the Washington, DC VOR/DME. (a) Operations within a 60-nautical mile radius of the Washington, DC VOR/DME under visual flight rules (VFR). Except as provided...

14 CFR 91.161 - Special awareness training required for pilots flying under visual flight rules within a 60...

Code of Federal Regulations, 2014 CFR

2014-01-01

... pilots flying under visual flight rules within a 60-nautical mile radius of the Washington, DC VOR/DME... flight rules within a 60-nautical mile radius of the Washington, DC VOR/DME. (a) Operations within a 60-nautical mile radius of the Washington, DC VOR/DME under visual flight rules (VFR). Except as provided...

In vivo Elimination of Parental Clones in General and Site-directed Mutagenesis

PubMed Central

Holland, Erika G.; Acca, Felicity E.; Belanger, Kristina M.; Bylo, Mary E.; Kay, Brian K.; Weiner, Michael P.; Kiss, Margaret M.

2015-01-01

The Eco29k I restriction endonuclease is a Sac II isoschizomer that recognizes the sequence 5’-CCGCGG-3’ and is encoded, along with the Eco29k I methylase, in the Escherichia coli strain 29k. We have expressed the Eco29k I restriction-methylation system (RM2) in E. coli strain TG1 to produce the strain AXE688. We have developed a directed molecular evolution (DME) mutagenesis method that uses Eco29k I to restrict incoming parental DNA in transformed cells. Using our DME method, we have demonstrated that our AXE688 strain results in mutated directed molecular evolution libraries with diversity greater than 107 from a single transformation and with greater than 90% recombinant clones. PMID:25523926

In vivo elimination of parental clones in general and site-directed mutagenesis.

PubMed

Holland, Erika G; Acca, Felicity E; Belanger, Kristina M; Bylo, Mary E; Kay, Brian K; Weiner, Michael P; Kiss, Margaret M

2015-02-01

The Eco29k I restriction endonuclease is a Sac II isoschizomer that recognizes the sequence 5'-CCGCGG-3' and is encoded, along with the Eco29k I methylase, in the Escherichia coli strain 29k. We have expressed the Eco29k I restriction-methylation system (RM2) in E. coli strain TG1 to produce the strain AXE688. We have developed a directed molecular evolution (DME) mutagenesis method that uses Eco29k I to restrict incoming parental DNA in transformed cells. Using our DME method, we have demonstrated that our AXE688 strain results in mutated directed molecular evolution libraries with diversity greater than 10(7) from a single transformation and with greater than 90% recombinant clones. Copyright © 2014 Elsevier B.V. All rights reserved.

Asymmetric distribution of Echinoid defines the epidermal leading edge during Drosophila dorsal closure

PubMed Central

Laplante, Caroline

2011-01-01

During Drosophila melanogaster dorsal closure, lateral sheets of embryonic epidermis assemble an actomyosin cable at their leading edge and migrate dorsally over the amnioserosa, converging at the dorsal midline. We show that disappearance of the homophilic cell adhesion molecule Echinoid (Ed) from the amnioserosa just before dorsal closure eliminates homophilic interactions with the adjacent dorsal-most epidermal (DME) cells, which comprise the leading edge. The resulting planar polarized distribution of Ed in the DME cells is essential for the localized accumulation of actin regulators and for actomyosin cable formation at the leading edge and for the polarized localization of the scaffolding protein Bazooka/PAR-3. DME cells with uniform Ed fail to assemble a cable and protrude dorsally, suggesting that the cable restricts dorsal migration. The planar polarized distribution of Ed in the DME cells thus provides a spatial cue that polarizes the DME cell actin cytoskeleton, defining the epidermal leading edge and establishing its contractile properties. PMID:21263031

Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema.

PubMed

Boyer, David S; Yoon, Young Hee; Belfort, Rubens; Bandello, Francesco; Maturi, Raj K; Augustin, Albert J; Li, Xiao-Yan; Cui, Harry; Hashad, Yehia; Whitcup, Scott M

2014-10-01

To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME). Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis. Patients (n = 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of ≥300 μm by optical coherence tomography. Patients were randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months for patients treated at month 36) at ≤40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months. The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of ≥15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP). Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg, and sham, respectively. The percentage of patients with ≥15-letter improvement in BCVA from baseline at study end was greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P ≤ 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (-111.6 μm) and DEX implant 0.35 mg (-107.9 μm) than sham (-41.9 μm; P < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy. The DEX implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in BCVA. The safety profile was acceptable and consistent with previous reports. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Direct Numerical Simulations of Autoignition in Stratified Dimethyl-ether (DME)/Air Turbulent Mixtures

DOE PAGES

Bansal, Gaurav; Mascarenhas, Ajith; Chen, Jacqueline H.

2014-10-01

In our paper, two- and three-dimensional direct numerical simulations (DNS) of autoignition phenomena in stratified dimethyl-ether (DME)/air turbulent mixtures are performed. A reduced DME oxidation mechanism, which was obtained using rigorous mathematical reduction and stiffness removal procedure from a detailed DME mechanism with 55 species, is used in the present DNS. The reduced DME mechanism consists of 30 chemical species. This study investigates the fundamental aspects of turbulence-mixing-autoignition interaction occurring in homogeneous charge compression ignition (HCCI) engine environments. A homogeneous isotropic turbulence spectrum is used to initialize the velocity field in the domain. Moreover, the computational configuration corresponds to amore » constant volume combustion vessel with inert mass source terms added to the governing equations to mimic the pressure rise due to piston motion, as present in practical engines. DME autoignition is found to be a complex three-staged process; each stage corresponds to a distinct chemical kinetic pathway. The distinct role of turbulence and reaction in generating scalar gradients and hence promoting molecular transport processes are investigated. Then, by applying numerical diagnostic techniques, the different heat release modes present in the igniting mixture are identified. In particular, the contribution of homogeneous autoignition, spontaneous ignition front propagation, and premixed deflagration towards the total heat release are quantified.« less

Formation of complex organic molecules in cold objects: the role of gas-phase reactions

NASA Astrophysics Data System (ADS)

Balucani, Nadia; Ceccarelli, Cecilia; Taquet, Vianney

2015-04-01

While astrochemical models are successful in reproducing many of the observed interstellar species, they have been struggling to explain the observed abundances of complex organic molecules. Current models tend to privilege grain surface over gas-phase chemistry in their formation. One key assumption of those models is that radicals trapped in the grain mantles gain mobility and react on lukewarm ( ≳ 30 K) dust grains. Thus, the recent detections of methyl formate (MF) and dimethyl ether (DME) in cold objects represent a challenge and may clarify the respective role of grain-surface and gas-phase chemistry. We propose here a new model to form DME and MF with gas-phase reactions in cold environments, where DME is the precursor of MF via an efficient reaction overlooked by previous models. Furthermore, methoxy, a precursor of DME, is also synthesized in the gas phase from methanol, which is desorbed by a non-thermal process from the ices. Our new model reproduces fairly well the observations towards L1544. It also explains, in a natural way, the observed correlation between DME and MF. We conclude that gas-phase reactions are major actors in the formation of MF, DME and methoxy in cold gas. This challenges the exclusive role of grain-surface chemistry and favours a combined grain-gas chemistry.

Dimethylethanolamine does not prevent liver failure in phosphatidylethanolamine N-methyltransferase-deficient mice fed a choline-deficient diet.

PubMed

Waite, Kristin A; Vance, Dennis E

2004-03-22

Mice that lack phosphatidylethanolamine-N-methyltransferase (PEMT) and are fed a choline-deficient (CD) diet suffer severe liver damage and do not survive. Since phosphatidyldimethylethanolamine (PDME) has physical properties similar to those of phosphatidylcholine (PC), we hypothesized that dimethylethanolamine (DME) would be converted into PDME that might substitute for PC, and therefore abrogate the liver damage in the Pemt -/- mice fed a CD diet. We fed Pemt -/- mice either a CD diet, a CD diet supplemented with choline, or a CD diet supplemented with DME (CD + DME). Pemt -/- mice fed the CD diet developed severe liver failure by 4 days while CD + DME-fed mice developed severe liver failure by 5 days. The hepatic PC level in choline-supplemented (CS) mice was 67 +/- 4 nmol/mg protein, whereas the PC content was reduced in CD- and CD + DME-fed mice (49 +/- 3 and 30 +/- 3 nmol/mg protein, respectively). Upon supplementation of the CD diet with DME the amount of hepatic PDME was 81 +/- 9 nmol/mg protein so that the hepatic content of PC + PDME combined was 111 nmol/mg protein. Moreover, plasma apolipoprotein B100 and Al levels were markedly lower in mice fed the CD + DME diet compared to mice fed the CS diet, as was the plasma content of PC. Thus, despite replacement of the deficit in hepatic PC with PDME in Pemt -/- mice fed a CD diet, normal liver function was not restored. We conclude that although PC and PDME exhibit similar physical properties, the three methyl groups of choline are required for hepatic function in mice.

The Rotational Spectrum of Singly and Doubly 13C-SUBSTITUTED Dimethylether

NASA Astrophysics Data System (ADS)

Koerber, Monika; Endres, Christian P.; Lewen, Frank; Giesen, Thomas F.; Schlemmer, Stephan; Pohl, Roland; Klein, Axel

2010-06-01

Dimethylether (DME) is a nearly prolate asymmetric top with two internal rotors (methyl groups) which undergo periodic large amplitude motions and show a complicated torsional splitting of each rotational energy level. Due to its complex spectrum and its high abundance in hot cores such as Orion KL or Sagittarius B2 at temperatures exceeding 100 K, DME is very prominent in astronomical line surveys and contributes to spectral line confusion of such sources. The interpretation of astronomical observations therefore depends on the knowledge of accurate rest frequencies and reliable intensities. Precise predictions for the ground state of DME's main isotopologue are now available up to 2.1 THz In contrast, very little is known about 13C-substituted DME. Only a few data are available on singly 13C-substituted DME, 12CH_3O13CH_3. However, no data are available on doubly 13C-substituted DME, (13CH_3)_2O, yet. While in (13CH_3)_2O the two internal rotating methyl groups are equivalent and the splitting of rotational energy levels into four substates is comparable to the main isotopologue, singly 13C-substituted DME has two non-equivalent internal rotors resulting in torsional splitting of rotational energy levels into five substates. The purpose of our new laboratory measurements is to extend the knowledge on the astrophysically relevant species 12CH_3O13CH_3. To analyze the complicated spectrum resulting from a 13C-enriched sample of DME, containing all different 13C-substituted species as well as the main isotopologue, also precise data on doubly 13C-substituted DME are inevitable. We performed measurements in the frequency region 35-120 GHz using an all solid state spectrometer. Rotational as well as torsional parameters have been obtained for (13CH_3)_2O as well as 12CH_3O13CH_3 by fitting the assigned transitions to an effective rotational Hamiltonian introduced by Peter Groner. C. Comito et al., Astrophys. J. Suppl. Ser. 156, 127-167 (2005) C. P. Endres et al., Astronomy & Astrophysics 504, 635-640 (2009) Y. Niide and M. Hayashi, J. Mol. Spectrosc. 220, 65-79 (2003) P. Groner, J. Chem. Phys. 107, 4483-4498 (1997).

Worldwide Report, Telecommunications Policy, Research and Development, No. 258

DTIC Science & Technology

1983-01-28

3379, December 1979. [20] F. Vatalaro: Caratteristiche di un filtro digitale dpplicato al sistema DME di precisione per MLS, F.U.B., Relazione 43...Spring 1980. [8] F. Chiarini, M. Gori: Possibilitä di miglioramento della precisione di un DME in banda L öfferta da u’n sistema di antenne a...Vecchio, G. Pedrini, F. Vatalaro: Rapporto sul programma per la determinazione delta forma d’onda impulsiva ottima per un sistema DME di precisione in

An Agar-Based Method for Plating Marine Protozoan Parasites of the Genus Perkinsus

PubMed Central

Cold, Emma R.; Freyria, Nastasia J.; Martínez Martínez, Joaquín; Fernández Robledo, José A.

2016-01-01

The genus Perkinsus includes protozoan parasites of mollusks responsible for losses in the aquaculture industry and hampering the recovery of natural shellfish beds worldwide, and they are a key taxon for understanding intracellular parasitism adaptations. The ability to propagate the parasite in liquid media, in the absence of the host, has been crucial for improving understanding of its biology; however, alternative techniques to grow the parasite are needed to explore other basic aspects of the Perkinsus spp. biology. We optimized a DME: Ham’s F12–5% FBS- containing solid agar medium for plating Perkinsus marinus. This solid medium supported trophozoite propagation both by binary fission and schizogony. Colonies were visible to the naked eye 17 days after plating. We tested the suitability of this method for several applications, including the following: 1) Subcloning P. marinus isolates: single discrete P. marinus colonies were obtained from DME: Ham’s F12–5% FBS– 0.75% agar plates, which could be further propagated in liquid medium; 2) Subcloning engineered Perkinsus mediterraneus MOE[MOE]: GFP by streaking cultures on plates; 3) Chemical susceptibility: Infusing the DME: Ham’s F12–5% FBS– 0.75% agar plates with triclosan resulted in inhibition of the parasite propagation in a dose-dependent manner. Altogether, our plating method has the potential for becoming a key tool for investigating diverse aspects of Perkinsus spp. biology, developing new molecular tools, and for biotechnological applications. PMID:27149378

High-activity PtRuPd/C catalyst for direct dimethyl ether fuel cells.

PubMed

Li, Qing; Wen, Xiaodong; Wu, Gang; Chung, Hoon T; Gao, Rui; Zelenay, Piotr

2015-06-22

Dimethyl ether (DME) has been considered as a promising alternative fuel for direct-feed fuel cells but lack of an efficient DME oxidation electrocatalyst has remained the challenge for the commercialization of the direct DME fuel cell. The commonly studied binary PtRu catalyst shows much lower activity in DME than methanol oxidation. In this work, guided by density functional theory (DFT) calculation, a ternary carbon-supported PtRuPd catalyst was designed and synthesized for DME electrooxidation. DFT calculations indicated that Pd in the ternary PtRuPd catalyst is capable of significantly decreasing the activation energy of the CO and CH bond scission during the oxidation process. As evidenced by both electrochemical measurements in an aqueous electrolyte and polymer-electrolyte fuel cell testing, the ternary catalyst shows much higher activity (two-fold enhancement at 0.5 V in fuel cells) than the state-of-the-art binary Pt50 Ru50 /C catalyst (HiSPEC 12100). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Catalyst activity maintenance study for the liquid phase dimethyl ether process

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

Peng, X.D.; Toseland, B.A.; Underwood, R.P.

1995-12-31

The co-production of dimethyl ether (DME) and methanol from syngas is a process of considerable commercial attractiveness. DME coproduction can double the productivity of a LPMEOH process when using coal-derived syngas. This in itself may offer chemical producers and power companies increased flexibility and more profitable operation. DME is also known as a clean burning liquid fuel; Amoco and Haldor-Topsoe have recently announced the use of DME as an alternative diesel fuel. Moreover, DME can be an interesting intermediate in the production of chemicals such as olefins and vinyl acetate. The current APCl liquid phase dimethyl ether (LPDME) process utilizesmore » a physical mixture of a commercial methanol synthesis catalyst and a dehydration catalyst (e.g., {gamma}-alumina). While this arrangement provides a synergy that results in much higher syngas conversion per pass compared to the methanol-only process, the stability of the catalyst system suffers. The present project is aimed at reducing catalyst deactivation both by understanding the cause(s) of catalyst deactivation and by developing modified catalyst systems. This paper describes the current understanding of the deactivation mechanism.« less

Evaluation of Microwave Landing System (MLS) effect on the delivery performance of a fixed-path metering and spacing system

NASA Technical Reports Server (NTRS)

Credeur, L.; Davis, C. M.; Capron, W. R.

1981-01-01

Metering and spacing (M & S) system's algorithms described assume an aircraft two dimensional are navigation capability. The three navigation systems compared were: very high frequency omnidirectional range/distance measuring equipment (VOR/DME) and ILS, VOR/DME and + or - 40 MLS, and VOR/DME and + or - 60 MLS. Other factors studied were M & S tentative schedule point location, route geometry effects, and approach gate location effects. Summarized results are: the MLS offers some improvement over VOR/DME and ILS if all approach routes contain computer assisted turns; pilot reaction to moving the gate closer to the runway threshold may adversely affect M & S performance; and coupling en route metering to terminal scheduling transfers most of the terminal holding to more full efficient, higher altitude en route delay.

Laminar Flame Velocity and Temperature Exponent of Diluted DME-Air Mixture

NASA Astrophysics Data System (ADS)

Naseer Mohammed, Abdul; Anwar, Muzammil; Juhany, Khalid A.; Mohammad, Akram

2017-03-01

In this paper, the laminar flame velocity and temperature exponent diluted dimethyl ether (DME) air mixtures are reported. Laminar premixed mixture of DME-air with volumetric dilutions of carbon dioxides (CO2) and nitrogen (N2) are considered. Experiments were conducted using a preheated mesoscale high aspect-ratio diverging channel with inlet dimensions of 25 mm × 2 mm. In this method, flame velocities are extracted from planar flames that were stabilized near adiabatic conditions inside the channel. The flame velocities are then plotted against the ratio of mixture temperature and the initial reference temperature. A non-linear power law regression is observed suitable. This regression analysis gives the laminar flame velocity at the initial reference temperature and temperature exponent. Decrease in the laminar flame velocity and increase in temperature exponent is observed for CO2 and N2 diluted mixtures. The addition of CO2 has profound influence when compared to N2 addition on both flame velocity and temperature exponent. Numerical prediction of the similar mixture using a detailed reaction mechanism is obtained. The computational mechanism predicts higher magnitudes for laminar flame velocity and smaller magnitudes of temperature exponent compared to experimental data.

Experimental determination of the navigation error of the 4-D navigation, guidance, and control systems on the NASA B-737 airplane

NASA Technical Reports Server (NTRS)

Knox, C. E.

1978-01-01

Navigation error data from these flights are presented in a format utilizing three independent axes - horizontal, vertical, and time. The navigation position estimate error term and the autopilot flight technical error term are combined to form the total navigation error in each axis. This method of error presentation allows comparisons to be made between other 2-, 3-, or 4-D navigation systems and allows experimental or theoretical determination of the navigation error terms. Position estimate error data are presented with the navigation system position estimate based on dual DME radio updates that are smoothed with inertial velocities, dual DME radio updates that are smoothed with true airspeed and magnetic heading, and inertial velocity updates only. The normal mode of navigation with dual DME updates that are smoothed with inertial velocities resulted in a mean error of 390 m with a standard deviation of 150 m in the horizontal axis; a mean error of 1.5 m low with a standard deviation of less than 11 m in the vertical axis; and a mean error as low as 252 m with a standard deviation of 123 m in the time axis.

16 CFR 1500.41 - Method of testing primary irritant substances.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) to slight eschar formations (injuries in depth) 4 Edema formation: No edema 0 Very slight edema (barely perceptible) 1 Slight edema (edges of area well defined by definite raising) 2 Moderate edema (raised approximately 1 millimeter) 3 Severe edema (raised more than 1 millimeter and extending beyond the...

16 CFR 1500.41 - Method of testing primary irritant substances.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) to slight eschar formations (injuries in depth) 4 Edema formation: No edema 0 Very slight edema (barely perceptible) 1 Slight edema (edges of area well defined by definite raising) 2 Moderate edema (raised approximately 1 millimeter) 3 Severe edema (raised more than 1 millimeter and extending beyond the...

The Diabetes Management Education Program in South Texas: An Economic and Clinical Impact Analysis.

PubMed

Kash, Bita A; Lin, Szu-Hsuan; Baek, Juha; Ohsfeldt, Robert L

2017-01-01

Diabetes is a major chronic disease that can lead to serious health problems and high healthcare costs without appropriate disease management and treatment. In the United States, the number of people diagnosed with diabetes and the cost for diabetes treatment has dramatically increased over time. To improve patients' self-management skills and clinical outcomes, diabetes management education (DME) programs have been developed and operated in various regions. This community case study explores and calculates the economic and clinical impacts of expanding a model DME program into 26 counties located in South Texas. The study sample includes 355 patients with type 2 diabetes and a follow-up hemoglobin A1c level measurement among 1,275 individuals who participated in the DME program between September 2012 and August 2013. We used the Gilmer's cost differentials model and the United Kingdom Prospective Diabetes Study (UKPDS) Risk Engine methodology to predict 3-year healthcare cost savings and 10-year clinical benefits of implementing a DME program in the selected 26 Texas counties. Changes in estimated 3-year cost and the estimated treatment effect were based on baseline hemoglobin A1c level. An average 3-year reduction in medical treatment costs per program participant was $2,033 (in 2016 dollars). The total healthcare cost savings for the 26 targeted counties increases as the program participation rate increases. The total projected cost saving ranges from $12 million with 5% participation rate to $185 million with 75% participation rate. A 10-year outlook on additional clinical benefits associated with the implementation and expansion of the DME program at 60% participation is estimated to result in approximately 4,838 avoided coronary heart disease cases and another 392 cases of avoided strokes. The implementation of this model DME program in the selected 26 counties would contribute to substantial healthcare cost savings and clinical benefits. Organizations that provide DME services may benefit from reduction in medical treatment costs and improvement in clinical outcomes for populations with diabetes.

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

Ruther, Rose E.; Sun, Che -Nan; Holliday, Adam

A simple electrolyte consisting of NaPF 6 salt in 1,2-dimethoxyethane (DME) can extend the voltage window of electric double-layer capacitors (EDLCs) to >3.5 V. DME does not passivate carbon electrodes at very negative potentials (near Na/Na +), extending the practical voltage window by about 1.0 V compared to standard, non-aqueous electrolytes based on acetonitrile. The voltage window is demonstrated in two- and three-electrode cells using a combination of electrochemical impedance spectroscopy (EIS), charge-discharge cycling, and measurements of leakage current. DME-based electrolytes cannot match the high conductivity of acetonitrile solutions, but they can satisfy applications that demand high energy density atmore » moderate power. The conductivity of NaPF 6 in DME is comparable to commercial lithium-ion battery electrolytes and superior to most ionic liquids. Lastly, factors that limit the voltage window and EDLC energy density are discussed, and strategies to further boost energy density are proposed.« less

Lipid-lowering medication use is associated with decreased risk of diabetic retinopathy and its treatments in patients with type 2 diabetes: a real-world observational analysis of a health claims database.

PubMed

Kawasaki, Ryo; Konta, Tsuneo; Nishida, Kohji

2018-05-22

Fenofibrate and statins reduced the risk of diabetic retinopathy (DR) related treatment in clinical trials. We aimed to determine whether lipid-lowering medication use reduce the risk of DR and its treatments in patients with type 2 diabetes using a real-world health claims database. This was an observational analysis using a nation-wide health claims database of the Japan Medical Data Center (JMDC). Type 2 diabetes was defined by the ICD-10 codes with glucose-lowering medication use. Lipid-lowering medication use at least one year was confirmed by the Anatomical Therapeutic Chemical Classification System. DR and diabetic macular edema (DME) were determined by ICD-10; DR related treatments were determined by health insurance claims. A propensity score for lipid-lowering medication use was estimated, and a doubly robust estimator using the inverse probability weighting model with regression adjustment was obtained to estimate odds ratios (OR) with 95% confidence interval (95%CI) for cumulative incidence of DR and its treatments over 3 years. There were 69,070 persons with type 2 diabetes at baseline. DR developed in 5,687 persons over 3 years. Lipid-lowering medication use was associated with decreased risk of incidence of DR (OR 0.772, 95%CI 0.720-0.827; p<0.001). Lipid-lowering medication use was also associated with decreased incidence of DME, any treatments for DR, laser photocoagulation, and vitrectomy in patients with DR at baseline. In a population of patients with type 2 diabetes with a variety of risk profile, lipid-lowering medication use reduced the risk of DR and its treatments of laser photocoagulation and vitrectomy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Serological inflammatory factors as biomarkers for anatomic response in diabetic macular edema treated with anti-VEGF.

PubMed

Brito, Pedro; Costa, Jorge; Gomes, Nuno; Costa, Sandra; Correia-Pinto, Jorge; Silva, Rufino

2018-05-11

To study the relationship between systemic pro-inflammatory factors and macular structural response to intravitreal bevacizumab for diabetic macular edema (DME). Prospective study including 30 cases with DME, treated with bevacizumab and a minimum follow-up of 6 months. All cases underwent baseline laboratory testing for cardiovascular risk (high sensitivity C-reactive protein (hsCRP), homocystein), dyslipidemia, renal dysfunction and glucose control. Serum levels of VEGF, soluble ICAM-1, MCP-1 and TNF-α were assessed by enzyme-linked immunosorbent assay kits. Significant associations between systemic factors and quantitative and qualitative spectral-domain optical coherence macular features were analyzed. A mean of 4.82 ± 0.56 intravitreal injections was performed, resulting in significant improvement of central foveal thickness (CFT) (p < 0.001). A significant association with third month CFT decrease <10% was found for hsCRP (3.33 ± 2.01 vs 1.39 ± 1.15 mg/l, p = 0.007) and ICAM1 (975.54 ± 265.49 vs 727.07 ± 336.09 pg/ml, p = 0.012). ROC curve analysis indicated hsCRP and ICAM1 as significant biomarkers for 3rd month reduced anatomic response (area under the curve (AUC) = 0.807, p = 0.009 for hsCRP; AUC = 0.788, p = 0.014 for ICAM1). ROC curve analysis revealed hsCRP as a significant biomarker for 6th month CFT decrease <10% (AUC = 0.903, p < 0.001, cutoff value = 1.81 mg/l). A significant association with 6th month CFT decrease ≥25% was found for serum MCP1 (244.69 ± 49.34 pg/ml vs 319.24 ± 94.88 pg/ml, p = 0.017) and serum VEGF (90.84 ± 37.33 vs 58.28 ± 25.19 pg/ml, p = 0.027). The combined model of serum VEGF and LDL-cholesterol was found to be predictive of 6th month hard exudate severity (p = 0.001, r2 = 0.463). Increased levels of hsCRP and ICAM1 were found to be significant biomarkers for early reduced anatomic response to anti-VEGF treatment. Cases with higher serum levels of such factors had increased CFT values, despite treatment, suggesting inner blood-retinal barrier breakdown that is not adequately responsive to anti-VEGF monotherapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Angiotensin I-converting enzyme (ACE) inhibitory activity of Fucus spiralis macroalgae and influence of the extracts storage temperature-A short report.

PubMed

Paiva, Lisete; Lima, Elisabete; Neto, Ana Isabel; Baptista, José

2016-11-30

Recently, increasing attention has been paid to the marine algae as a natural source of novel angiotensin-I converting enzyme (ACE) inhibitors, such as the phlorotannins that are the predominant polyphenols in brown algae. This study reports, for the first time, the ACE inhibition of methanol extract/fractions from Azorean brown algae Fucus spiralis (Fs) determined by HPLC-UV method, their total phenolic content (TPC) quantified as phloroglucinol equivalents (PE) and the effect of the Fs dry powder methanol extracts (Fs-DME) storage temperature on ACE inhibition. The results indicate that the ACE inhibition of Fs-DME decreased by 28.8% and 78.2% when stored during 15days at -80°C and -13°C, respectively, as compared with the activity of Fs-DME at a refrigerated temperature of 6°C and assayed immediately after extraction that showed a value of 80.1±2.1%. This Fs-DME sample was fractionated by ultrafiltration membranes into three molecular weight ranges (<1kDa, 1-3kDa and >3kDa), presenting the fraction>3kDa remarkably high ACE inhibition (88.8±2.4%), TPC value (156.6±1.4mg PE/g of dry weight fraction) and yield. Furthermore, chromatographic and spectrophotometric analyses corroborate that phenolic compounds were present in Fs methanol extract/fractions, and also revealed that phloroglucinol occurs in Fs. The results seem to suggest that Azorean Fs can be a source of powerful ACE-inhibitory phlorotannins with potential impact on public health, particularly on hypertensive patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessment of early attrition using an ordinary flatbed scanner.

PubMed

Van't Spijker, Arie; Kreulen, Cees M; Bronkhorst, Ewald M; Creugers, Nico H J

2012-07-01

The aim of this study was to assess a two-dimensional method to monitor occlusal tooth wear quantitatively using a commercially available ordinary flatbed scanner. A flatbed scanner, measuring software and gypsum casts were used. In Part I, two observers (A and B) independently traced scans of marked wear facets of ten sets of casts in two sessions (test and retest). In Part II, three other sets of casts were duplicated and two observers (C and D) marked wear facets and traced the scanned images independently. Intra- and inter-observer agreement was determined comparing measured values (mm(2)) in paired T-tests. Duplicate measurement errors (DME) were calculated. In Part I the test and retest values (10 casts, 218 teeth) of observer A and B did not differ significantly (A: p = 0.289; B: p = 0.666); correlation coefficients were 0.998 (A) and 0.999 (B). "Tracing wear facets" showed a DME of 0.30 mm(2) for observer A and 0.15 mm(2) for observer B. In Part II, assessment of 70 teeth resulted in correlation coefficients of 0.994 for observer C and 0.997 for observer D; no differences between test and retest values were found for C (p = 0.061), although D differed significantly (p = 0.000). The DME for "marking and tracing wear facets" was 0.39 mm(2) (C) and 0.27 mm(2) (D). DME for inter-observer agreement were 0.45 mm(2) (test) and 0.42 mm(2) (re-test). We conclude that marking and tracing of occlusal wear facets to assess occlusal tooth wear quantitatively can be done accurately and reproducibly. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cationic Thiolated Poly(aspartamide) Polymer as a Potential Excipient for Artificial Tear Formulations.

PubMed

Budai-Szűcs, Mária; Horvát, Gabriella; Szilágyi, Barnabás Áron; Gyarmati, Benjámin; Szilágyi, András; Berkó, Szilvia; Szabó-Révész, Piroska; Sandri, Giuseppina; Bonferoni, Maria Cristina; Caramella, Carla; Soós, Judit; Facskó, Andrea; Csányi, Erzsébet

2016-01-01

Dry eye disease is a relatively common ocular problem, which causes eye discomfort and visual disorders leading to a decrease in the quality of life. The aim of this study was to find a possible excipient for eye drop formulations, which is able to stabilize the tear film. A cationic thiolated polyaspartamide polymer, poly[(N-mercaptoethylaspartamide)-co-(N-(N',N'-dimethylaminoethyl)aspartamide)] (ThioPASP-DME), was used as a potential vehicle. Besides satisfying the basic requirements, the chemical structure of ThioPASP-DME is similar to those of ocular mucins as it is a protein-like polymer bearing a considerable number of thiol groups. The solution of the polymer is therefore able to mimic the physiological properties of the mucins and it can interact with the mucus layer via disulphide bond formation. The resultant mucoadhesion provides a prolonged residence time and ensures protective effect for the corneal/conjunctival epithelium. ThioPASP-DME also has an antioxidant effect due to the presence of the thiol groups. The applicability of ThioPASP-DME as a potential excipient in eye drops was determined by means of ocular compatibility tests and through examinations of the interactions with the mucosal surface. The results indicate that ThioPASP-DME can serve as a potential eye drop excipient for the therapy of dry eye disease.

Enhanced Cycling Stability of Rechargeable Li-O2 Batteries Using High Concentration Electrolytes

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

Liu, Bin; Xu, Wu; Yan, Pengfei

2016-01-26

The electrolyte stability against reactive reduced-oxygen species is crucial for the development of rechargeable Li-O2 batteries. In this work, we systematically investigated the effect of lithium salt concentration in 1,2-dimethoxyethane (DME)-based electrolytes on the cycling stability of Li-O2 batteries. Cells with high concentration electrolyte illustrate largely enhanced cycling stability under both the full discharge/charge (2.0-4.5 V vs. Li/Li+) and the capacity limited (at 1,000 mAh g-1) conditions. These cells also exhibit much less reaction-residual on the charged air electrode surface, and much less corrosion to the Li metal anode. The density functional theory calculations are conducted on the molecular orbitalmore » energies of the electrolyte components and the Gibbs activation barriers for superoxide radical anion to attack DME solvent and Li+-(DME)n solvates. In a highly concentrated electrolyte, all DME molecules have been coordinated with salt and the C-H bond scission of a DME molecule becomes more difficult. Therefore, the decomposition of highly concentrated electrolyte in a Li-O2 battery can be mitigated and both air-cathodes and Li-metal anodes exhibits much better reversibility. As a results, the cyclability of Li-O2 can be largely improved.« less

Ternary PtRuPd/C catalyst for high-performance, low-temperature direct dimethyl ether fuel cells

DOE PAGES

Dumont, Joseph Henry; Martinez, Ulises; Chung, Hoon T.; ...

2016-08-19

Here, dimethyl ether (DME) is a promising alternative fuel option for direct-feed low-temperature fuel cells. Until recently, DME had not received the same attention as alcohol fuels, such as methanol or ethanol, despite its notable advantages. These advantages include a high theoretical open-cell voltage (1.18 V at 25 °C) that is similar to that of methanol (1.21 V), much lower toxicity than methanol, and no need for the carbon–carbon bond scission that is needed in ethanol oxidation. DME is biodegradable, has a higher energy content than methanol (8.2 vs. 6.1 kWh kg –1), and, like methanol, can be synthesized frommore » recycled carbon dioxide. Although the performance of direct DME fuel cells (DDMEFCs) has progressed over the past few years, DDMEFCs have not been viewed as fully viable. In this work, we report much improved performance from the ternary Pt 55Ru 35Pd 10/C anode catalyst, allowing DDMEFCs to compete directly with direct methanol fuel cells (DMFCs). We also report results involving binary Pt alloys as reference catalysts and an in situ infrared electrochemical study to better understand the mechanism of DME electro-oxidation on ternary PtRuPd/C catalysts.« less

77 FR 14269 - IFR Altitudes; Miscellaneous Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... LIBEL, CO FIX BROCC, CO FIX 16000 BROCC, CO FIX ECHOA, CO FIX 13200 ECHOA, CO FIX *HAYDEN, CO VOR/DME..... E BND 13200 W BND 11500 *11500--MCA HAYDEN, CO VOR/ DME, E BND Sec. 95.6169 VOR Federal Airway V169...

48 CFR 1034.001 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... controlled. (3) (ANSI #3) Provide for the integration of the company's planning, scheduling, budgeting, work... program organizations. Development, Modernization, Enhancement (DME) is the portion of an IT investment... Major IT investments with DME activities, which meet the contract threshold for fully applying FAR 34.2...

48 CFR 1034.001 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... controlled. (3) (ANSI #3) Provide for the integration of the company's planning, scheduling, budgeting, work... program organizations. Development, Modernization, Enhancement (DME) is the portion of an IT investment... Major IT investments with DME activities, which meet the contract threshold for fully applying FAR 34.2...

48 CFR 1034.001 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... controlled. (3) (ANSI #3) Provide for the integration of the company's planning, scheduling, budgeting, work... program organizations. Development, Modernization, Enhancement (DME) is the portion of an IT investment... Major IT investments with DME activities, which meet the contract threshold for fully applying FAR 34.2...

48 CFR 1034.001 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... controlled. (3) (ANSI #3) Provide for the integration of the company's planning, scheduling, budgeting, work... program organizations. Development, Modernization, Enhancement (DME) is the portion of an IT investment... Major IT investments with DME activities, which meet the contract threshold for fully applying FAR 34.2...

Steroid eye drop treatment (difluprednate ophthalmic emulsion) is effective in reducing refractory diabetic macular edema.

PubMed

Nakano, Sakiko; Yamamoto, Teiko; Kirii, Eriko; Abe, Sachi; Yamashita, Hidetoshi

2010-06-01

To evaluate the efficacy of treatment of refractory diabetic macular edema (DME) after vitrectomy with difluprednate ophthalmic emulsion 0.05% (Durezol(TM)), and to compare this treatment with sub-Tenon's injection of triamcinolone (STTA). This study enrolled patients with refractory diabetic macular edema that persisted despite pars plana vitrectomy in our clinic. In all subjects, more than 3 months had passed since prior treatment. Eleven eyes in ten subjects were treated with STTA (STTA group), and 11 eyes in seven subjects were treated with difluprednate ophthalmic emulsion 0.05% (Durezol(TM), Sirion Therapeutics Inc., USA) 4 times daily for the first month and then twice daily for 2 months (eye drop group). In the eye drop group, mean VA (+/- SD) was 0.67 +/- 0.35 logMAR and mean retinal thickness was 500.6 +/- 207.7 mum at baseline. After 3 months of treatment, mean VA was 0.67 +/- 0.29 and mean retinal thickness had decreased to 341.2 +/- 194.8 mum. The mean minimum value of RT during the treatment period was 300.6 +/- 123.2 mum, and significantly lower than that at baseline (Mann-Whitney U test: P = 0.003). In the STTA group, mean VA (+/- SD) was 0.67 +/- 0.35 logMAR, and mean retinal thickness was 543.3 +/- 132.6 mum at baseline. After 3 months of treatment, mean VA was 0.49 +/- 0.67, and mean retinal thickness had decreased to 378.6 +/- 135 mum. The mean minimum value of RT during the treatment period was 349.9 +/- 113.8 mum, and significantly lower than at baseline (Mann-Whitney U test: P = 0.003). The rate of effective improvement in RT did not differ between the eye drop group (73%) and STTA group (84%) (Fisher's exact test: P = 1). Comparable improvements of retinal thickness were observed in the STTA and eye drop groups. Instillation of difluprednate ophthalmic emulsion 0.05% is a safe and effective treatment that does not require surgical intervention and does not produce severe side-effects.

Surface-Mediated Solvent Decomposition in Li–Air Batteries: Impact of Peroxide and Superoxide Surface Terminations

DOE PAGES

Kumar, Nitin; Radin, Maxwell D.; Wood, Brandon C.; ...

2015-04-13

A viable Li/O 2 battery will require the development of stable electrolytes that do not continuously decompose during cell operation. In some recent experiments it is suggested that reactions occurring at the interface between the liquid electrolyte and the solid lithium peroxide (Li 2O 2) discharge phase are a major contributor to these instabilities. To clarify the mechanisms associated with these reactions, a variety of atomistic simulation techniques, classical Monte Carlo, van der Waals-augmented density functional theory, ab initio molecular dynamics, and various solvation models, are used to study the initial decomposition of the common electrolyte solvent, dimethoxyethane (DME), onmore » surfaces of Li 2O 2. Comparisons are made between the two predominant Li 2O 2 surface charge states by calculating decomposition pathways on peroxide-terminated (O 2 2–) and superoxide-terminated (O 2 1–) facets. For both terminations, DME decomposition proceeds exothermically via a two-step process comprised of hydrogen abstraction (H-abstraction) followed by nucleophilic attack. In the first step, abstracted H dissociates a surface O 2 dimer, and combines with a dissociated oxygen to form a hydroxide ion (OH –). In the remaining surface oxygen then attacks the DME, resulting in a DME fragment that is strongly bound to the Li 2O 2 surface. DME decomposition is predicted to be more exothermic on the peroxide facet; nevertheless, the rate of DME decomposition is faster on the superoxide termination. The impact of solvation (explicit vs implicit) and an applied electric field on the reaction energetics are investigated. Finally, our calculations suggest that surface-mediated electrolyte decomposition should out-pace liquid-phase processes such as solvent auto-oxidation by dissolved O 2.« less

Stable electrolyte for high voltage electrochemical double-layer capacitors

DOE PAGES

Ruther, Rose E.; Sun, Che -Nan; Holliday, Adam; ...

2016-12-28

A simple electrolyte consisting of NaPF 6 salt in 1,2-dimethoxyethane (DME) can extend the voltage window of electric double-layer capacitors (EDLCs) to >3.5 V. DME does not passivate carbon electrodes at very negative potentials (near Na/Na +), extending the practical voltage window by about 1.0 V compared to standard, non-aqueous electrolytes based on acetonitrile. The voltage window is demonstrated in two- and three-electrode cells using a combination of electrochemical impedance spectroscopy (EIS), charge-discharge cycling, and measurements of leakage current. DME-based electrolytes cannot match the high conductivity of acetonitrile solutions, but they can satisfy applications that demand high energy density atmore » moderate power. The conductivity of NaPF 6 in DME is comparable to commercial lithium-ion battery electrolytes and superior to most ionic liquids. Lastly, factors that limit the voltage window and EDLC energy density are discussed, and strategies to further boost energy density are proposed.« less

Multivariable model predictive control design of reactive distillation column for Dimethyl Ether production

NASA Astrophysics Data System (ADS)

Wahid, A.; Putra, I. G. E. P.

2018-03-01

Dimethyl ether (DME) as an alternative clean energy has attracted a growing attention in the recent years. DME production via reactive distillation has potential for capital cost and energy requirement savings. However, combination of reaction and distillation on a single column makes reactive distillation process a very complex multivariable system with high non-linearity of process and strong interaction between process variables. This study investigates a multivariable model predictive control (MPC) based on two-point temperature control strategy for the DME reactive distillation column to maintain the purities of both product streams. The process model is estimated by a first order plus dead time model. The DME and water purity is maintained by controlling a stage temperature in rectifying and stripping section, respectively. The result shows that the model predictive controller performed faster responses compared to conventional PI controller that are showed by the smaller ISE values. In addition, the MPC controller is able to handle the loop interactions well.

Sec61α is required for dorsal closure during Drosophila embryogenesis through its regulation of Dpp signaling

PubMed Central

Wang, Xiaochen; Ward, Robert E.

2010-01-01

During dorsal closure in Drosophila, signaling events in the dorsalmost row of epidermal cells (DME cells) direct the migration of lateral epidermal sheets towards the dorsal midline where they fuse to enclose the embryo. A Jun amino-terminal kinase (JNK) cascade in the DME cells induces the expression of Decapentaplegic (Dpp). Dpp signaling then regulates the cytoskeleton in the DME cells and amnioserosa to affect the cell shape changes necessary to complete dorsal closure. We identified a mutation in Sec61α that specifically perturbs dorsal closure. Sec61α encodes the main subunit of the translocon complex for co-translational import of proteins into the ER. JNK signaling is normal in Sec61α mutant embryos, but Dpp signaling is attenuated and the DME cells fail to maintain an actinomyosin cable as epithelial migration fails. Consistent with this model, dorsal closure is rescued in Sec61α mutant embryos by an activated form of the Dpp receptor Thick veins. PMID:20112345

Quantification of the Keto-Hydroperoxide (HOOCH2OCHO) and Other Elusive Intermediates during Low-Temperature Oxidation of Dimethyl Ether.

PubMed

Moshammer, Kai; Jasper, Ahren W; Popolan-Vaida, Denisia M; Wang, Zhandong; Bhavani Shankar, Vijai Shankar; Ruwe, Lena; Taatjes, Craig A; Dagaut, Philippe; Hansen, Nils

2016-10-04

This work provides new temperature-dependent mole fractions of elusive intermediates relevant to the low-temperature oxidation of dimethyl ether (DME). It extends the previous study of Moshammer et al. [ J. Phys. Chem. A 2015 , 119 , 7361 - 7374 ] in which a combination of a jet-stirred reactor and molecular beam mass spectrometry with single-photon ionization via tunable synchrotron-generated vacuum-ultraviolet radiation was used to identify (but not quantify) several highly oxygenated species. Here, temperature-dependent concentration profiles of 17 components were determined in the range of 450-1000 K and compared to up-to-date kinetic modeling results. Special emphasis is paid toward the validation and application of a theoretical method for predicting photoionization cross sections that are hard to obtain experimentally but essential to turn mass spectral data into mole fraction profiles. The presented approach enabled the quantification of the hydroperoxymethyl formate (HOOCH 2 OCH 2 O), which is a key intermediate in the low-temperature oxidation of DME. The quantification of this keto-hydroperoxide together with the temperature-dependent concentration profiles of other intermediates including H 2 O 2 , HCOOH, CH 3 OCHO, and CH 3 OOH reveals new opportunities for the development of a next-generation DME combustion chemistry mechanism.

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

Kanzler, Charlotte R.; Lian, Peng; Trainer, Emma Leverich

Alkylated mercury species (monomethylmercury, MeHg, and dimethylmercury, DMeHg) exhibit significant bioaccumulation, and pose significant risks to ecosystems and human health. Although decades of research have been devoted to understanding MeHg formation and degradation, little is known about the DMeHg formation in aquatic systems. Here, we combine complementary experimental and computational approaches to examine MeHg speciation and DMeHg formation in sulfidic aqueous solutions, with an emphasis on the formation and decomposition of the binuclear bis(methylmercuric(II)) sulfide complex (CH3Hg)2S. Experimental data indicate that the reaction 2CH3Hg+ + HS- = (CH3Hg)2S has a log K = 26.0. Thus, the binuclear (CH3Hg)2S complex ismore » likely to be the dominant MeHg species under high MeHg concentrations typically used in experimental investigations of MeHg degradation by sulfate-reducing bacteria (SRB). Our finding of a significant abiotic removal mechanism for MeHg in sulfidic solutions through the formation of relatively insoluble (CH3Hg)2S suggests careful reexamination of reported “oxidative demethylation” of MeHg by SRB and perhaps other obligate anaerobes. We provide evidence for slow decomposition of (CH3Hg)2S to DMeHg and HgS, with a first-order rate constant k = 1.5 0.4 x 10-6 h-1. Quantum chemical calculations suggest that the reaction proceeds by a novel mechanism involving rearrangement of the (CH3Hg)2S complex facilitated by strong Hg-Hg interactions that activate a methyl group for intramolecular transfer. Predictions of DMeHg formation rates under a variety of field and laboratory conditions indicate that this pathway for DMeHg formation will be significant in laboratory experiments utilizing high MeHg concentrations, favoring (CH3Hg)2S formation. In natural systems with relatively high MeHg/[H2S]T ratios (the oxic/anoxic interface, for example), DMeHg production may be observed, and warrants further investigation.Experimental and computational evidence show that dimethylmercury is produced from decomposition of bis(methylmercury(ii)) sulfide.« less

14 CFR 171.157 - Performance requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Performance requirements. 171.157 Section... Performance requirements. (a) The DME must meet the performance requirements set forth in the “International... functional and performance characteristics of the DME transponder must be conducted in accordance with the...

14 CFR 171.157 - Performance requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Performance requirements. 171.157 Section... Performance requirements. (a) The DME must meet the performance requirements set forth in the “International... functional and performance characteristics of the DME transponder must be conducted in accordance with the...

14 CFR 171.157 - Performance requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Performance requirements. 171.157 Section... Performance requirements. (a) The DME must meet the performance requirements set forth in the “International... functional and performance characteristics of the DME transponder must be conducted in accordance with the...

14 CFR 171.157 - Performance requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Performance requirements. 171.157 Section... Performance requirements. (a) The DME must meet the performance requirements set forth in the “International... functional and performance characteristics of the DME transponder must be conducted in accordance with the...

14 CFR 171.157 - Performance requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Performance requirements. 171.157 Section... Performance requirements. (a) The DME must meet the performance requirements set forth in the “International... functional and performance characteristics of the DME transponder must be conducted in accordance with the...

The Rise of Voltammetry: From Polarography to the Scanning Electrochemical Microscope

ERIC Educational Resources Information Center

Bard, Allen J.

2007-01-01

The drooping mercury electrode (DME) was previously used to carry out electrochemical experiments but invention of polarography technique changed this. Voltammetry with DME was given the term polarography and are used in measurement of current as a function of potential at small electrodes.

Cationic Thiolated Poly(aspartamide) Polymer as a Potential Excipient for Artificial Tear Formulations

PubMed Central

Budai-Szűcs, Mária; Horvát, Gabriella; Szilágyi, Barnabás Áron; Gyarmati, Benjámin; Szilágyi, András; Berkó, Szilvia; Szabó-Révész, Piroska; Sandri, Giuseppina; Bonferoni, Maria Cristina; Caramella, Carla; Soós, Judit; Facskó, Andrea; Csányi, Erzsébet

2016-01-01

Dry eye disease is a relatively common ocular problem, which causes eye discomfort and visual disorders leading to a decrease in the quality of life. The aim of this study was to find a possible excipient for eye drop formulations, which is able to stabilize the tear film. A cationic thiolated polyaspartamide polymer, poly[(N-mercaptoethylaspartamide)-co-(N-(N′,N′-dimethylaminoethyl)aspartamide)] (ThioPASP-DME), was used as a potential vehicle. Besides satisfying the basic requirements, the chemical structure of ThioPASP-DME is similar to those of ocular mucins as it is a protein-like polymer bearing a considerable number of thiol groups. The solution of the polymer is therefore able to mimic the physiological properties of the mucins and it can interact with the mucus layer via disulphide bond formation. The resultant mucoadhesion provides a prolonged residence time and ensures protective effect for the corneal/conjunctival epithelium. ThioPASP-DME also has an antioxidant effect due to the presence of the thiol groups. The applicability of ThioPASP-DME as a potential excipient in eye drops was determined by means of ocular compatibility tests and through examinations of the interactions with the mucosal surface. The results indicate that ThioPASP-DME can serve as a potential eye drop excipient for the therapy of dry eye disease. PMID:27313866

Selective inhibition of ammonium oxidation and nitrification-linked N2O formation by methyl fluoride and dimethyl ether

USGS Publications Warehouse

Miller, L.G.; Coutlakis, M.D.; Oremland, R.S.; Ward, B.B.

1993-01-01

Methyl fluoride (CH3F) and dimethyl ether (DME) inhibited nitrification in washed-cell suspensions of Nitrosomonas europaea and in a variety of oxygenated soils and sediments. Headspace additions of CH3F (10% [vol/vol]) and DME (25% [vol/vol]) fully inhibited NO2- and N2O production from NH4+ in incubations of N. europaea, while lower concentrations of these gases resulted in partial inhibition. Oxidation of hydroxylamine (NH2OH) by N. europaea and oxidation of NO2- by a Nitrobacter sp. were unaffected by CH3F or DME. In nitrifying soils, CH3F and DME inhibited N2O production. In field experiments with surface flux chambers and intact cores, CH3F reduced the release of N2O from soils to the atmosphere by 20- to 30-fold. Inhibition by CH3F also resulted in decreased NO3- + NO2- levels and increased NH4+ levels in soils. CH3F did not affect patterns of dissimilatory nitrate reduction to ammonia in cell suspensions of a nitrate- respiring bacterium, nor did it affect N2O metabolism in denitrifying soils. CH3F and DME will be useful in discriminating N2O production via nitrification and denitrification when both processes occur and in decoupling these processes by blocking NO2- and NO3- production.

77 FR 3091 - IFR Altitudes; Miscellaneous Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-23

... in Part Grand Junction, CO VOR/DME....... *Paces, CO FIX 11500 *13000--MRA *Paces, CO FIX Slolm, CO FIX.. 13000 *13000--MRA MTA V134 NE TO V220 NW 12900 Slolm, CO FIX *Gleno, CO FIX 14000 *16000--MRA *Gleno, CO FIX Red Table, CO VOR/DME... 14000 [[Page 3094

77 FR 9876 - Proposed Modification of VOR Federal Airways V-10, V-12, and V-508 in the Vicinity of Olathe, KS

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-21

... (OJC) VOR/DME navigation aid located on the Johnson County Executive Airport, Olathe, KS, due to poor performance of the navigation aid. The OJC VOR/DME performs poorly due to suburban encroachment into the...

77 FR 67712 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing of Proposed Rule Change To List...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-13

...''), Tokyo Commodity Exchange (``TOCOM''), Dubai Mercantile Exchange (``DME''), and Bursa Malaysia (``Malaysia'') \\9\\ (collectively, ``Futures Contracts'') and (b) if applicable, other Asian commodities... Europe, LME, TOCOM, DME, and Malaysia are each referred to herein as a ``Futures Exchange.'' \\10...

Assessment of edema volume in skin upon injury in a mouse ear model with optical coherence tomography

PubMed Central

Qin, Wan

2017-01-01

Accurate measurement of edema volume is essential for the investigation of tissue response and recovery following a traumatic injury. The measurements must be noninvasive and repetitive over time so as to monitor tissue response throughout the healing process. Such techniques are particularly necessary for the evaluation of therapeutics that are currently in development to suppress or prevent edema formation. In this study, we propose to use optical coherence tomography (OCT) technique to image and quantify edema in a mouse ear model where the injury is induced by a superficial-thickness burn. Extraction of edema volume is achieved by an attenuation compensation algorithm performed on the three-dimensional OCT images, followed by two segmentation procedures. In addition to edema volume, the segmentation method also enables accurate thickness mapping of edematous tissue, which is an important characteristic of the external symptoms of edema. To the best of our knowledge, this is the first method for noninvasively measuring absolute edema volume. PMID:27282161

21 CFR 172.860 - Fatty acids.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... (2) It is free of chick-edema factor: (i) As evidenced during the bioassay method for determining the chick-edema factor as prescribed in paragraph (c)(2) of this section; or (ii) As evidenced by the... the bioassay method prescribed in paragraph (c)(2) of this section for determining chick-edema factor...

21 CFR 172.860 - Fatty acids.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... (2) It is free of chick-edema factor: (i) As evidenced during the bioassay method for determining the chick-edema factor as prescribed in paragraph (c)(2) of this section; or (ii) As evidenced by the... the bioassay method prescribed in paragraph (c)(2) of this section for determining chick-edema factor...

Heterogeneous structure and solvation dynamics of DME/water binary mixtures: A combined spectroscopic and simulation investigation

NASA Astrophysics Data System (ADS)

Das Mahanta, Debasish; Rana, Debkumar; Patra, Animesh; Mukherjee, Biswaroop; Mitra, Rajib Kumar

2018-05-01

Water is often found in (micro)-heterogeneous environments and therefore it is necessary to understand their H-bonded network structure in such altered environments. We explore the structure and dynamics of water in its binary mixture with relatively less polar small biocompatible amphiphilic molecule 1,2-Dimethoxyethane (DME) by a combined spectroscopic and molecular dynamics (MD) simulation study. Picosecond (ps) resolved fluorescence spectroscopy using coumarin 500 as the fluorophore establishes a non-monotonic behaviour of the mixture. Simulation studies also explore the various possible H-bond formations between water and DME. The relative abundance of such different water species manifests the heterogeneity in the mixture.

Antioxidant and cytotoxic activities of Dendrobium moniliforme extracts and the detection of related compounds by GC-MS.

PubMed

Paudel, Mukti Ram; Chand, Mukesh Babu; Pant, Basant; Pant, Bijaya

2018-04-23

The medicinal orchid Dendrobium moniliforme contains water-soluble polysaccharides, phenanthrenes, bibenzyl derivatives, and polyphenol compounds. This study explored the antioxidant and cytotoxic activities of D. moniliforme extracts and detected their bioactive compounds. Plant material was collected from the Daman of Makawanpur district in central Nepal. Plant extracts were prepared from stems using hexane, chloroform, acetone, ethanol and methanol. The total polyphenol content (TPC) in each extract was determined using Folin-Ciocalteu's reagent and the total flavonoid content (TFC) in each extract was determined using the aluminium chloride method. The in vitro antioxidant and cytotoxic activities of each extract were determined using DPPH (2,2-diphenyl-1-picrylhydrazyl) and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays respectively. Gas chromatography and mass spectrometry (GC-MS) analysis was used to detect bioactive compounds. TPC content was highest (116.65 μg GAE/mg of extract) in D. moniliforme chloroform extract (DMC) and TFC content was highest (116.67 μg QE/mg of extract) in D. moniliforme acetone extract (DMA). D. moniliforme hexane extract (DMH) extract showed the highest percentage of DPPH radical scavenging activity (94.48%), followed closely by D. moniliforme ethanol extract (DME) (94.45%), DMA (93.71%) and DMC (94.35%) at 800 μg/ml concentration. The antioxidant capacities of DMC, DMA, DMH and DME, which were measured in IC 50 values, were much lower 42.39 μg/ml, 49.56 μg/ml, 52.68 μg/ml, and 58.77 μg/ml respectively than the IC 50 of D. moniliforme methanol extract (DMM) (223.15 μg/ml). DMM at the concentration of 800 μg/ml most inhibited the growth of HeLa cells (78.68%) and DME at the same concentration most inhibited the growth of U251 cells (51.95%). The cytotoxic capacity (IC 50 ) of DMM against HeLa cells was 155.80 μg/ml of extract and that of DME against the U251 cells was 772.50 μg/ml of extract. A number of bioactive compounds were detected in both DME and DMM. The fact that plant extract of D. moniliforme has a number of bioactive compounds which showed antioxidant and cytotoxic activities suggests the potential pharmacological importance of this plant.

An enhanced in vivo stable isotope labeling by amino acids in cell culture (SILAC) model for quantification of drug metabolism enzymes.

PubMed

MacLeod, A Kenneth; Fallon, Padraic G; Sharp, Sheila; Henderson, Colin J; Wolf, C Roland; Huang, Jeffrey T-J

2015-03-01

Many of the enzymes involved in xenobiotic metabolism are maintained at a low basal level and are only synthesized in response to activation of upstream sensor/effector proteins. This induction can have implications in a variety of contexts, particularly during the study of the pharmacokinetics, pharmacodynamics, and drug-drug interaction profile of a candidate therapeutic compound. Previously, we combined in vivo SILAC material with a targeted high resolution single ion monitoring (tHR/SIM) LC-MS/MS approach for quantification of 197 peptide pairs, representing 51 drug metabolism enzymes (DME), in mouse liver. However, as important enzymes (for example, cytochromes P450 (Cyp) of the 1a and 2b subfamilies) are maintained at low or undetectable levels in the liver of unstimulated metabolically labeled mice, quantification of these proteins was unreliable. In the present study, we induced DME expression in labeled mice through synchronous ligand-mediated activation of multiple upstream nuclear receptors, thereby enhancing signals for proteins including Cyps 1a, 2a, 2b, 2c, and 3a. With this enhancement, 115 unique, lysine-containing, Cyp-derived peptides were detected in the liver of a single animal, as opposed to 56 in a pooled sample from three uninduced animals. A total of 386 peptide pairs were quantified by tHR/SIM, representing 68 Phase I, 30 Phase II, and eight control proteins. This method was employed to quantify changes in DME expression in the hepatic cytochrome P450 reductase null (HRN) mouse. We observed compensatory induction of several enzymes, including Cyps 2b10, 2c29, 2c37, 2c54, 2c55, 2e1, 3a11, and 3a13, carboxylesterase (Ces) 2a, and glutathione S-transferases (Gst) m2 and m3, along with down-regulation of hydroxysteroid dehydrogenases (Hsd) 11b1 and 17b6. Using DME-enhanced in vivo SILAC material with tHR/SIM, therefore, permits the robust analysis of multiple DME of importance to xenobiotic metabolism, with improved utility for the study of drug pharmacokinetics, pharmacodynamics, and of chemically treated and genetically modified mouse models. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Method of synthesis of anhydrous thorium(IV) complexes

DOEpatents

Kiplinger, Jaqueline L; Cantat, Thibault

2013-04-30

Method of producing anhydrous thorium(IV) tetrahalide complexes, utilizing Th(NO.sub.3).sub.4(H.sub.2O).sub.x, where x is at least 4, as a reagent; method of producing thorium-containing complexes utilizing ThCl.sub.4(DME).sub.2 as a precursor; method of producing purified ThCl.sub.4(ligand).sub.x compounds, where x is from 2 to 9; and novel compounds having the structures: ##STR00001##

Important characteristics of a director of medical education.

PubMed

Powell, V D; George, R J

1993-11-01

In osteopathic graduate medical education programs, the Director of Medical Education (DME) plays the key leadership role. This article outlines critical characteristics and skills that the DME should possess to successfully perform in this role. Central to this success is a passionate commitment to osteopathic medical education and a commitment to justice and fairness.

Assessment of Novel Routes of Biomethane Utilization in a Life Cycle Perspective

PubMed Central

Moghaddam, Elham Ahmadi; Ahlgren, Serina; Nordberg, Åke

2016-01-01

Biomethane, as a replacement for natural gas, reduces the use of fossil-based sources and supports the intended change from fossil to bio-based industry. The study assessed different biomethane utilization routes for production of methanol, dimethyl ether (DME), and ammonia, as fuel or platform chemicals and combined heat and power (CHP). Energy efficiency and environmental impacts of the different pathways was studied in a life cycle perspective covering the technical system from biomass production to the end product. Among the routes studied, CHP had the highest energy balance and least environmental impact. DME and methanol performed competently in energy balance and environmental impacts in comparison with the ammonia route. DME had the highest total energy output, as fuel, heat, and steam, among the different routes studied. Substituting the bio-based routes for fossil-based alternatives would give a considerable reduction in environmental impacts such as global warming potential and acidification potential for all routes studied, especially CHP, DME, and methanol. Eutrophication potential was mainly a result of biomass and biomethane production, with marginal differences between the different routes. PMID:28066762

Study of emissions for a compression ignition engine fueled with a mix of DME and diesel

NASA Astrophysics Data System (ADS)

Jurchiş, Bogdan; Nicolae, Burnete; Călin, Iclodean; Nicolae Vlad, Burnete

2017-10-01

Currently, there is a growing demand for diesel engines, primarily due to the relatively low fuel consumption compared to spark-ignition engines. However, these engines have a great disadvantage in terms of pollution because they produce solid particles that ultimately form particulate matter (PM), which has harmful effects on human health and also on the environment. The toxic emissions from the diesel engine exhaust, like particulate matter (PM) and NOx, generated by the combustion of fossil fuels, lead to the necessity to develop green fuels which on one hand should be obtained from regenerative resources and on the other hand less polluting. In this paper, the authors focused on the amount of emissions produced by a diesel engine when running with a fuel mixture consisting of diesel and DME. Dimethyl ether (DME) is developed mainly by converting natural gas or biomass to synthesis gas (syngas). It is an extremely attractive resource for the future used in the transport industry, given that it can be obtained at low costs from renewable resources. Using DME mixed with diesel for the combustion process, besides the fact that it produces less smoke, the emission levels of particulate matter is reduced compared to diesel and in some situations, NOx emissions may decrease. DME has a high enough cetane number to perform well as a compression-ignition fuel but due to the poor lubrication and viscosity, it is difficult to be used as the main fuel for combustion

77 FR 44721 - Medicare Program; Revisions to Payment Policies Under the Physician Fee Schedule, DME Face to...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-30

... Classification of Diseases IMRT Intensity Modulated Radiation Therapy IOM Internet-only Manual IPCI Indirect... RIA Regulatory impact analysis RVU Relative value unit SBRT Stereotactic body radiation therapy SGR... adjust the payment rates for two common radiation oncology treatment delivery methods, intensity...

Elucidating electrolyte decomposition under electron-rich environments at the lithium-metal anode

DOE PAGES

Camacho-Forero, Luis E.; Balbuena, Perla B.

2017-11-07

The lithium metal anode is one of the key components of the lithium–sulfur (Li–S) batteries, which are considered one of the most promising candidates for the next generation of battery systems. However, one of the main challenges that have prevented Li-metal anodes from becoming feasible to be used in commercial batteries is the continuous decomposition of the electrolyte due to its high reactivity, which leads to the formation of solid–electrolyte interphase (SEI) layers. The properties of the SEI can dramatically affect the performance of the batteries. Thus, a rigorous understanding of the electrolyte decomposition is crucial to elucidate improvements inmore » performance of the Li–S technology. Here, in this work, using density functional theory (DFT) and ab initio molecular dynamics simulations (AIMD), we investigate the effect of electron-rich environments on the decomposition mechanism of electrolyte species in pure 1,2-dimethoxyethane (DME) solvent and 1 M lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and lithium bis(fluorosulfonyl)imide (LiFSI) salt solutions. It is found that systems with pure DME require an average environment of at least ~0.9 |e| per molecule for a DME to decompose into CH 3O - and C 2H 4 2-via a 4-electron transfer. In the case of mixtures, the salts are very prone to react with any excess of electrons. In addition, DME dehydrogenation due to reactions with fragments coming from the salt decompositions was detected. Formation of oligomer anionic species from DME and salt fragments were also identified from the AIMD simulations. Finally, the thermodynamics and kinetics of the most relevant electrolyte decomposition reactions were characterized. DME decomposition reactions predicted from the AIMD simulations were found to be thermodynamically favorable under exposure to Li atoms and/or by reactions with salt fragments. Lastly, in most cases, these reactions were shown to have low to moderate activation barriers.« less

Elucidating electrolyte decomposition under electron-rich environments at the lithium-metal anode

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

Camacho-Forero, Luis E.; Balbuena, Perla B.

The lithium metal anode is one of the key components of the lithium–sulfur (Li–S) batteries, which are considered one of the most promising candidates for the next generation of battery systems. However, one of the main challenges that have prevented Li-metal anodes from becoming feasible to be used in commercial batteries is the continuous decomposition of the electrolyte due to its high reactivity, which leads to the formation of solid–electrolyte interphase (SEI) layers. The properties of the SEI can dramatically affect the performance of the batteries. Thus, a rigorous understanding of the electrolyte decomposition is crucial to elucidate improvements inmore » performance of the Li–S technology. Here, in this work, using density functional theory (DFT) and ab initio molecular dynamics simulations (AIMD), we investigate the effect of electron-rich environments on the decomposition mechanism of electrolyte species in pure 1,2-dimethoxyethane (DME) solvent and 1 M lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and lithium bis(fluorosulfonyl)imide (LiFSI) salt solutions. It is found that systems with pure DME require an average environment of at least ~0.9 |e| per molecule for a DME to decompose into CH 3O - and C 2H 4 2-via a 4-electron transfer. In the case of mixtures, the salts are very prone to react with any excess of electrons. In addition, DME dehydrogenation due to reactions with fragments coming from the salt decompositions was detected. Formation of oligomer anionic species from DME and salt fragments were also identified from the AIMD simulations. Finally, the thermodynamics and kinetics of the most relevant electrolyte decomposition reactions were characterized. DME decomposition reactions predicted from the AIMD simulations were found to be thermodynamically favorable under exposure to Li atoms and/or by reactions with salt fragments. Lastly, in most cases, these reactions were shown to have low to moderate activation barriers.« less

Elucidating electrolyte decomposition under electron-rich environments at the lithium-metal anode.

PubMed

Camacho-Forero, Luis E; Balbuena, Perla B

2017-11-22

The lithium metal anode is one of the key components of the lithium-sulfur (Li-S) batteries, which are considered one of the most promising candidates for the next generation of battery systems. However, one of the main challenges that have prevented Li-metal anodes from becoming feasible to be used in commercial batteries is the continuous decomposition of the electrolyte due to its high reactivity, which leads to the formation of solid-electrolyte interphase (SEI) layers. The properties of the SEI can dramatically affect the performance of the batteries. Thus, a rigorous understanding of the electrolyte decomposition is crucial to elucidate improvements in performance of the Li-S technology. In this work, using density functional theory (DFT) and ab initio molecular dynamics simulations (AIMD), we investigate the effect of electron-rich environments on the decomposition mechanism of electrolyte species in pure 1,2-dimethoxyethane (DME) solvent and 1 M lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and lithium bis(fluorosulfonyl)imide (LiFSI) salt solutions. It is found that systems with pure DME require an average environment of at least ∼0.9 |e| per molecule for a DME to decompose into CH 3 O - and C 2 H 4 2- via a 4-electron transfer. In the case of mixtures, the salts are very prone to react with any excess of electrons. In addition, DME dehydrogenation due to reactions with fragments coming from the salt decompositions was detected. Formation of oligomer anionic species from DME and salt fragments were also identified from the AIMD simulations. Finally, the thermodynamics and kinetics of the most relevant electrolyte decomposition reactions were characterized. DME decomposition reactions predicted from the AIMD simulations were found to be thermodynamically favorable under exposure to Li atoms and/or by reactions with salt fragments. In most cases, these reactions were shown to have low to moderate activation barriers.

Antiangiogenic Therapy for Ischemic Retinopathies

PubMed Central

Al-Latayfeh, Motasem; Silva, Paolo S.; Sun, Jennifer K.; Aiello, Lloyd Paul

2012-01-01

Neovascularization is a common pathological process in various retinal vascular disorders including diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinal vein occlusion (RVO). The development of neovascular vessels may lead to complications such as vitreous hemorrhage, fibrovascular tissue formation, and traction retinal detachments. Ultimately, irreversible vision loss may result. Various proangiogenic factors are involved in these complex processes. Different antiangiogenic drugs have been formulated in an attempt treat these vascular disorders. One factor that plays a major role in the development of retinal neovascularization is vascular endothelial growth factor (VEGF). Anti-VEGF agents are currently FDA approved for the treatment of AMD and RVO. They are also extensively used as an off-label treatment for diabetic macular edema (DME), proliferative DR, and neovascular glaucoma. However, at this time, the long-term safety of chronic VEGF inhibition has not been extensively evaluated. A large and rapidly expanding body of research on angiogenesis is being conducted at multiple centers across the globe to determine the exact contributions and interactions among a variety of angiogenic factors in an effort to determine the therapeutic potential of antiangiogenic agent in the treatment of a variety of retinal diseases. PMID:22675660

Molecular Mechanisms of Diabetic Retinopathy, General Preventive Strategies, and Novel Therapeutic Targets

PubMed Central

Safi, Sher Zaman; Kumar, Selva; Ismail, Ikram Shah Bin

2014-01-01

The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors. PMID:25105142

77 FR 65256 - IFR Altitudes; Miscellaneous Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-26

... FEDERAL AIRWAY V263 Is Amended To Read in Part HUGO, CO VOR/DME *LIMEX, CO FIX **10000 *10000--MRA **8500--MOCA **9000--GNSS MEA *LIMEX, CO FIX AKRON, CO VOR/DME....... **8500 *10000--MRA **7200--MOCA Sec. 95... V611 Is Amended To Read in Part JEFEL, CO FIX *LIMEX, CO FIX 85 00 [[Page 65260

14 CFR 91.711 - Special rules for foreign civil aircraft.

Code of Federal Regulations, 2010 CFR

2010-01-01

... crewmember of that aircraft is able to conduct two-way radio communications in the English language and is on... is able to conduct two-way radiotelephone communications in the English language and that crewmember... approved DME or a suitable RNAV system. When the DME or RNAV system required by this paragraph fails at and...

42 CFR 409.50 - Coinsurance for durable medical equipment (DME) furnished as a home health service.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Coinsurance for durable medical equipment (DME) furnished as a home health service. 409.50 Section 409.50 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM HOSPITAL INSURANCE BENEFITS Home Health...

78 FR 22190 - Modification of Area Navigation (RNAV) Route T-266; AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

...; AK AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action... modifying RNAV route T-266 in Alaska. T-266 is currently defined by the Coghland Island, AK, NDB, the Fredericks Point, AK, NDB and the Annette Island, AK, VOR/DME. The Annette Island VOR/DME remains as one end...

Experimental and Modeling Investigation of the Low-Temperature Oxidation of Dimethyl Ether.

PubMed

Rodriguez, Anne; Frottier, Ophélie; Herbinet, Olivier; Fournet, René; Bounaceur, Roda; Fittschen, Christa; Battin-Leclerc, Frédérique

2015-07-16

The oxidation of dimethyl ether (DME) was studied using a jet-stirred reactor over a wide range of conditions: temperatures from 500 to 1100 K; equivalence ratios of 0.25, 1, and 2; residence time of 2 s; pressure of 106.7 kPa (close to the atmospheric pressure); and an inlet fuel mole fraction of 0.02 (with high dilution in helium). Reaction products were quantified using two analysis methods: gas chromatography and continuous wave cavity ring-down spectroscopy (cw-CRDS). cw-CRDS enabled the quantification of formaldehyde, which is one of the major products from DME oxidation, as well as that of hydrogen peroxide, which is an important branching agent in low-temperature oxidation chemistry. Experimental data were compared with data computed using models from the literature with important deviations being observed for the reactivity at low-temperature. A new detailed kinetic model for the oxidation of DME was developed in this study. Kinetic parameters used in this model were taken from literature or calculated in the present work using quantum calculations. This new model enables a better prediction of the reactivity in the low-temperature region. Under the present JSR conditions, error bars on predictions were given. Simulations were also successfully compared with experimental flow reactor, jet-stirred reactor, shock tube, rapid compression machine, and flame data from literature. The kinetic analysis of the model enabled the highlighting of some specificities of the oxidation chemistry of DME: (1) the early reactivity which is observed at very low-temperature (e.g., compared to propane) is explained by the absence of inhibiting reaction of the radical directly obtained from the fuel (by H atom abstraction) with oxygen yielding an olefin + HO2·; (2) the low-temperature reactivity is driven by the relative importance of the second addition to O2 (promoting the reactivity through branching chain) and the competitive decomposition reactions with an inhibiting effect.

New V and V Tools for Diagnostic Modeling Environment (DME)

NASA Technical Reports Server (NTRS)

Pecheur, Charles; Nelson, Stacy; Merriam, Marshall (Technical Monitor)

2002-01-01

The purpose of this report is to provide correctness and reliability criteria for verification and validation (V&V) of Second Generation Reusable Launch Vehicle (RLV) Diagnostic Modeling Environment, describe current NASA Ames Research Center tools for V&V of Model Based Reasoning systems, and discuss the applicability of Advanced V&V to DME. This report is divided into the following three sections: (1) correctness and reliability criteria; (2) tools for V&V of Model Based Reasoning; and (3) advanced V&V applicable to DME. The Executive Summary includes an overview of the main points from each section. Supporting details, diagrams, figures, and other information are included in subsequent sections. A glossary, acronym list, appendices, and references are included at the end of this report.

Adapting the forms of yesterday to the functions of today and the needs of tomorrow: a genealogical case study of clinical teaching units in Canada.

PubMed

Schrewe, Brett; Pratt, Daniel D; McKellin, William H

2016-05-01

Emergent discourses of social responsibility and accountability have in part fuelled the expansion of distributed medical education (DME). In addition to its potential for redressing physician maldistribution, DME has conferred multiple unexpected educational benefits. In several countries, its recent rise has occurred around the boundaries of traditional medical education practices. Canada has been no exception, with DME proliferating against a backdrop of its longstanding central node, the clinical teaching unit (CTU). The CTU first appeared just over 50 years ago with its position in Canadian health care largely taken-for-granted. Given the increasing prominence of DME, however, it is timely to reconsider what the place of tertiary centre-based practices such as the CTU might be in shifting medical education systems. From a genealogical perspective, it becomes clear that the CTU did not just "happen". Rather, its creation was made possible by multiple interrelated cultural, social, and political changes in Canadian society that, while subtle, are powerfully influential. Making them visible offers a better opportunity to harmonize the benefits of longstanding entities such as the CTU with novel practices such as DME. In so doing, the medical education field may sidestep the pitfalls of investing significant resources that may only produce superficial changes while unwittingly obstructing deeper transformations and improvements. Although this work is refracted through a Canadian prism, reconceptualizing the overall design of medical education systems to take advantage of both tradition and innovation is a persistent challenge across the international spectrum, resistant to tests of time and constraints of context.

Microscopically based energy density functionals for nuclei using the density matrix expansion: Implementation and pre-optimization

NASA Astrophysics Data System (ADS)

Stoitsov, M.; Kortelainen, M.; Bogner, S. K.; Duguet, T.; Furnstahl, R. J.; Gebremariam, B.; Schunck, N.

2010-11-01

In a recent series of articles, Gebremariam, Bogner, and Duguet derived a microscopically based nuclear energy density functional by applying the density matrix expansion (DME) to the Hartree-Fock energy obtained from chiral effective field theory two- and three-nucleon interactions. Owing to the structure of the chiral interactions, each coupling in the DME functional is given as the sum of a coupling constant arising from zero-range contact interactions and a coupling function of the density arising from the finite-range pion exchanges. Because the contact contributions have essentially the same structure as those entering empirical Skyrme functionals, a microscopically guided Skyrme phenomenology has been suggested in which the contact terms in the DME functional are released for optimization to finite-density observables to capture short-range correlation energy contributions from beyond Hartree-Fock. The present article is the first attempt to assess the ability of the newly suggested DME functional, which has a much richer set of density dependencies than traditional Skyrme functionals, to generate sensible and stable results for nuclear applications. The results of the first proof-of-principle calculations are given, and numerous practical issues related to the implementation of the new functional in existing Skyrme codes are discussed. Using a restricted singular value decomposition optimization procedure, it is found that the new DME functional gives numerically stable results and exhibits a small but systematic reduction of our test χ2 function compared to standard Skyrme functionals, thus justifying its suitability for future global optimizations and large-scale calculations.

Legal and Regulatory Challenges Currently Facing Diabetes Treatment Providers and Related Durable Medical Equipment Suppliers

PubMed Central

Liles, Robert

2013-01-01

It has been estimated that 24 million Americans have diabetes, many of whom are Medicare beneficiaries. These individuals carefully monitor their blood glucose levels primarily through the use of in-home blood glucose testing kits. Although the test is relatively simple, the cumulative expense of providing glucose test strips and lancets to patients is ever increasing, both to the Medicare program and to uninsured individuals who must pay out-of-pocket for these testing supplies. This article discusses the diabetes durable medical equipment (DME) coverage under Part B Medicare, the establishment and role of DME Medicare administrative contractors, and national and local coverage requirements for diabetes DME suppliers. This article also discusses the federal government’s ongoing concerns regarding the improper billing of diabetes testing supplies. To protect the Medicare Trust Fund, the federal government has contracted with multiple private entities to conduct reviews and audits of questionable Medicare claims. These private sector contractors have conducted unannounced site visits of DME supplier offices, interviewed patients and their families, placed suppliers on prepayment review, and conducted extensive postpayment audits of prior paid Medicare claims. In more egregious administrative cases, Medicare contractors have recommended that problematic providers and/or DME suppliers have their Medicare numbers suspended or, in some instances, revoked. More serious infractions can lead to civil or criminal liability. In the final part of this article, we will examine the future of enforcement efforts by law enforcement and Medicare contractors and the importance of understanding and complying with federal laws when ordering and supplying diabetes testing strips and lancets. PMID:23566989

Epigenetic role for the conserved Fe-S cluster biogenesis protein AtDRE2 in Arabidopsis thaliana.

PubMed

Buzas, Diana Mihaela; Nakamura, Miyuki; Kinoshita, Tetsu

2014-09-16

On fertilization in Arabidopsis thaliana, one maternal gamete, the central cell, forms a placenta-like tissue, the endosperm. The DNA glycosylase DEMETER (DME) excises 5-methylcytosine via the base excision repair pathway in the central cell before fertilization, creating patterns of asymmetric DNA methylation and maternal gene expression across DNA replications in the endosperm lineage (EDL). Active DNA demethylation in the central cell is essential for transcriptional activity in the EDL of a set of genes, including FLOWERING WAGENINGEN (FWA). A DME-binding motif for iron-sulfur (Fe-S) cluster cofactors is indispensable for its catalytic activity. We used an FWA-GFP reporter to find mutants defective in maternal activation of FWA-GFP in the EDL, and isolated an allele of the yeast Dre2/human antiapoptotic factor CIAPIN1 homolog, encoding an enzyme previously implicated in the cytosolic Fe-S biogenesis pathway (CIA), which we named atdre2-2. We found that AtDRE2 acts in the central cell to regulate genes maternally activated in the EDL by DME. Furthermore, the FWA-GFP expression defect in atdre2-2 was partially suppressed genetically by a mutation in the maintenance DNA methyltransferase MET1; the DNA methylation levels at four DME targets increased in atdre2-2 seeds relative to WT. Although atdre2-2 shares zygotic seed defects with CIA mutants, it also uniquely manifests dme phenotypic hallmarks. These results demonstrate a previously unidentified epigenetic function of AtDRE2 that may be separate from the CIA pathway.

Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review

PubMed Central

Umar, Musa Usman; Abdullahi, Aminu Taura

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect. PMID:27335511

Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review.

PubMed

Umar, Musa Usman; Abdullahi, Aminu Taura

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect.

76 FR 13438 - AccessTel, Inc., American Asset Management Corp., DME Interactive Holdings, Inc., DocuPort, Inc...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-11

... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] AccessTel, Inc., American Asset Management Corp., DME Interactive Holdings, Inc., DocuPort, Inc., and iCarbon Corp., Order of Suspension of Trading March 8, 2011. It appears to the Securities and Exchange Commission that there is a lack of current and accurate information concerning the...

76 FR 28171 - Standard Instrument Approach Procedures, and Takeoff Minimums and Obstacle Departure Procedures...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-16

...-Clyde Ice Field, Takeoff Minimum and Obstacle DP, Amdt 1 Gladewater, TX, Gladewater Muni, Takeoff... Field, VOR/DME RWY 12, Amdt 4 Devil's Lake, ND, Devil's Lake Rgnl, ILS OR LOC/DME RWY 31, Amdt 2 Devil's Lake, ND, Devil's Lake Rgnl, RNAV (GPS) RWY 3, Amdt 1 Ely, NV, Ely Airport-Yelland Field, Takeoff...

Adapting the Forms of Yesterday to the Functions of Today and the Needs of Tomorrow: A Genealogical Case Study of Clinical Teaching Units in Canada

ERIC Educational Resources Information Center

Schrewe, Brett; Pratt, Daniel D.; McKellin, William H.

2016-01-01

Emergent discourses of social responsibility and accountability have in part fuelled the expansion of distributed medical education (DME). In addition to its potential for redressing physician maldistribution, DME has conferred multiple unexpected educational benefits. In several countries, its recent rise has occurred around the boundaries of…

77 FR 24369 - Standard Instrument Approach Procedures, and Takeoff Minimums and Obstacle Departure Procedures...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-24

..., VOR-A, Amdt 7 Washington, DC, Ronald Reagan Washington National, COPTER ILS OR LOC/DME RWY 1, Amdt 1 Washington, DC, Ronald Reagan Washington National, ILS OR LOC/DME RWY 1, ILS RWY 1 (SA CAT I), ILS RWY 1 (CAT II), Amdt 41 Washington, DC, Ronald Reagan Washington National, RNAV (RNP) RWY 1, Amdt 1 Washington...

14 CFR 91.161 - Special awareness training required for pilots flying under visual flight rules within a 60...

Code of Federal Regulations, 2010 CFR

2010-01-01

... pilots flying under visual flight rules within a 60-nautical mile radius of the Washington, DC VOR/DME... Rules Visual Flight Rules § 91.161 Special awareness training required for pilots flying under visual...-nautical mile radius of the Washington, DC VOR/DME under visual flight rules (VFR). Except as provided...

Dimethyl ether (DME) as an alternative fuel

NASA Astrophysics Data System (ADS)

Semelsberger, Troy A.; Borup, Rodney L.; Greene, Howard L.

With ever growing concerns on environmental pollution, energy security, and future oil supplies, the global community is seeking non-petroleum based alternative fuels, along with more advanced energy technologies (e.g., fuel cells) to increase the efficiency of energy use. The most promising alternative fuel will be the fuel that has the greatest impact on society. The major impact areas include well-to-wheel greenhouse gas emissions, non-petroleum feed stocks, well-to-wheel efficiencies, fuel versatility, infrastructure, availability, economics, and safety. Compared to some of the other leading alternative fuel candidates (i.e., methane, methanol, ethanol, and Fischer-Tropsch fuels), dimethyl ether appears to have the largest potential impact on society, and should be considered as the fuel of choice for eliminating the dependency on petroleum. DME can be used as a clean high-efficiency compression ignition fuel with reduced NO x, SO x, and particulate matter, it can be efficiently reformed to hydrogen at low temperatures, and does not have large issues with toxicity, production, infrastructure, and transportation as do various other fuels. The literature relevant to DME use is reviewed and summarized to demonstrate the viability of DME as an alternative fuel.

The use of gaseous fuels mixtures for SI engines propulsion

NASA Astrophysics Data System (ADS)

Flekiewicz, M.; Kubica, G.

2016-09-01

Paper presents results of SI engine tests, carried on for different gaseous fuels. Carried out analysis made it possible to define correlation between fuel composition and engine operating parameters. Tests covered various gaseous mixtures: of methane and hydrogen and LPG with DME featuring different shares. The first group, considered as low carbon content fuels can be characterized by low CO2 emissions. Flammability of hydrogen added in those mixtures realizes the function of combustion process activator. That is why hydrogen addition improves the energy conversion by about 3%. The second group of fuels is constituted by LPG and DME mixtures. DME mixes perfectly with LPG, and differently than in case of other hydrocarbon fuels consists also of oxygen makes the stoichiometric mixture less oxygen demanding. In case of this fuel an improvement in engine volumetric and overall engine efficiency has been noticed, when compared to LPG. For the 11% DME share in the mixture an improvement of 2% in the efficiency has been noticed. During the tests standard CNG/LPG feeding systems have been used, what underlines utility value of the research. The stand tests results have been followed by combustion process simulation including exhaust forming and charge exchange.

Pro- and antiangiogenic VEGF and its receptor status for the severity of diabetic retinopathy

PubMed Central

Mondal, Lakshmi K.; Borah, Prasanta K.; Bhattacharya, Chandra K.; Mahanta, Jagadish

2017-01-01

Purpose Alteration of pro- and antiangiogenic homeostasis of vascular endothelial growth factor (VEGF) isoforms in patients with hyperglycemia seems crucial but substantially unexplored at least quantitatively for diabetic retinopathy (DR). Therefore, in the present study we aimed to estimate the difference between the pro- (VEGF165a) and antiangiogenic (VEGF165b) VEGF isoforms and its soluble receptors for severity of DR. Methods The study included 123 participants (diabetic retinopathy: 81, diabetic control: 20, non-diabetic control: 22) from the Regional Institute of Ophthalmology, Kolkata. The protein levels of VEGF165a (proangiogenic), VEGF165b (antiangiogenic), VEGF receptor 1 (VEGFR1), VEGFR2, and VEGFR3 in plasma were determined with enzyme-linked immunosorbent assay (ELISA). Results An imbalance in VEGF homeostasis, a statistically significant concomitant increase (p<0.0001) in the level of VEGF165a and a decrease in the level of VEGF165b, was observed with the severity of the disease. Increased differences between VEGF165a and VEGF165b i.e. VEGF165a-b concomitantly increased statistically significantly with the severity of the disease (p<0.0001), patients with diffuse diabetic macular edema (DME) with proliferative DR (PDR) had the highest imbalance. The plasma soluble form of VEGFR2 concentration consistently increased statistically significantly with the severity of the disease (p<0.0001). Conclusions The increased difference or imbalance between the pro- (VEGF165a) and antiangiogenic (VEGF165b) homeostasis of the VEGF isoforms, seems crucial for an adverse prognosis of DR and may be a better explanatory marker compared with either VEGF isoform. PMID:28680264

Development of a VOR/DME model for an advanced concepts simulator

NASA Technical Reports Server (NTRS)

Steinmetz, G. G.; Bowles, R. L.

1984-01-01

The report presents a definition of a VOR/DME, airborne and ground systems simulation model. This description was drafted in response to a need in the creation of an advanced concepts simulation in which flight station design for the 1980 era can be postulated and examined. The simulation model described herein provides a reasonable representation of VOR/DME station in the continental United States including area coverage by type and noise errors. The detail in which the model has been cast provides the interested researcher with a moderate fidelity level simulator tool for conducting research and evaluation of navigator algorithms. Assumptions made within the development are listed and place certain responsibilities (data bases, communication with other simulation modules, uniform round earth, etc.) upon the researcher.

Variable optical attenuator and dynamic mode group equalizer for few mode fibers.

PubMed

Blau, Miri; Weiss, Israel; Gerufi, Jonathan; Sinefeld, David; Bin-Nun, Moran; Lingle, Robert; Grüner-Nielsen, Lars; Marom, Dan M

2014-12-15

Variable optical attenuation (VOA) for three-mode fiber is experimentally presented, utilizing an amplitude spatial light modulator (SLM), achieving up to -28dB uniform attenuation for all modes. Using the ability to spatially vary the attenuation distribution with the SLM, we also achieve up to 10dB differential attenuation between the fiber's two supported mode group (LP₀₁ and LP₁₁). The spatially selective attenuation serves as the basis of a dynamic mode-group equalizer (DME), potentially gain-balancing mode dependent optical amplification. We extend the experimental three mode DME functionality with a performance analysis of a fiber supporting 6 spatial modes in four mode groups. The spatial modes' distribution and overlap limit the available dynamic range and performance of the DME in the higher mode count case.

Use of aluminum phosphate as the dehydration catalyst in single step dimethyl ether process

DOEpatents

Peng, Xiang-Dong; Parris, Gene E.; Toseland, Bernard A.; Battavio, Paula J.

1998-01-01

The present invention pertains to a process for the coproduction of methanol and dimethyl ether (DME) directly from a synthesis gas in a single step (hereafter, the "single step DME process"). In this process, the synthesis gas comprising hydrogen and carbon oxides is contacted with a dual catalyst system comprising a physical mixture of a methanol synthesis catalyst and a methanol dehydration catalyst. The present invention is an improvement to this process for providing an active and stable catalyst system. The improvement comprises the use of an aluminum phosphate based catalyst as the methanol dehydration catalyst. Due to its moderate acidity, such a catalyst avoids the coke formation and catalyst interaction problems associated with the conventional dual catalyst systems taught for the single step DME process.

Edema associated with quetiapine

PubMed Central

Koleva, Hristina K.; Erickson, Mark A.; Vanderlip, Erik R.; Tansey, Janeta; Mac, Joseph; Fiedorowicz, Jess G.

2010-01-01

Background Edema associated with quetiapine has been described in only one case report to date and represents a potentially serious adverse reaction. Methods We present a case series of three patients who developed bilateral leg edema following initiation of quetiapine. Results One of these patients had a recurrence of edema with subsequent rechallenge. Another patient developed quetiapine-induced edema following a prior episode of olanzapine-induced edema. All the cases present a compelling temporal relationship between the drug challenge and the adverse event. Conclusions Prompt recognition and intervention with discontinuation of the offending agent is important for this potentially serious, seemingly idiosyncratic, vascular complication. PMID:19439156

Prevalence and risk factors for diabetic retinopathy in Asian Indians with young onset type 1 and type 2 diabetes.

PubMed

Rajalakshmi, Ramachandran; Amutha, Anandakumar; Ranjani, Harish; Ali, Mohammed K; Unnikrishnan, Ranjit; Anjana, Ranjit Mohan; Narayan, K M Venkat; Mohan, Viswanathan

2014-01-01

To assess the prevalence and risk factors for diabetic retinopathy (DR) in people with young onset type 1 (T1DM-Y) and type 2 diabetes (T2DM-Y). T1DM-Y(n=150) and T2DM-Y(n=150) participants, age between 10 and 25 years at diagnosis, had a complete clinical evaluation, biochemical assessment, and four field digital retinal colour photography. The Early Treatment Diabetic Retinopathy Study grading system was used to grade DR. Proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) were considered as sight threatening DR. The prevalence of any DR was 53.3% [95% CI 45.3-61.3] in T1DM-Y (duration of diabetes: 12.4±7.4 years) and 52.7% [44.7-60.7] in T2DM-Y (11.8±8.3 years). The age and gender adjusted prevalence of DR, DME and PDR was 62.5%, 10% and 7.3% in T1DM-Y, whereas it was 65.8%,12.7% and 9.3% in T2DM-Y respectively. In multivariable logistic regression, diabetes duration [Odds ratio (OR) 1.99 per 5 years; CI 1.42-2.79], waist circumference [1.28 per 5 cm;1.05-1.56] and microalbuminuria [2.39 per 50 μg;1.07-5.31] were associated with DR in T1DM-Y, and diabetes duration [2.21 per 5 years; 1.61-3.02], diastolic blood pressure [1.54 per 5 mmHg;1.18-2.02], Glycated hemoglobin [1.37 per %;1.07-1.75] and lower stimulated C-peptide [1.54 per 0.5 pmol/ml;1.15-2.05;] were associated with DR in T2DM-Y. Over half of the people with young-onset diabetes, regardless of type, have retinopathy within 10-12 years of diabetes duration, emphasizing the need for regular eye screening and aggressive control of glucose and blood pressure to prevent DR. Copyright © 2014 Elsevier Inc. All rights reserved.

Glomerular Filtration Rate and/or Ratio of Urine Albumin to Creatinine as Markers for Diabetic Retinopathy: A Ten-Year Follow-Up Study.

PubMed

Romero-Aroca, Pedro; Baget-Bernaldiz, Marc; Navarro-Gil, Raul; Moreno-Ribas, Antonio; Valls-Mateu, Aida; Sagarra-Alamo, Ramon; Barrot-De La Puente, Joan F; Mundet-Tuduri, Xavier

2018-01-01

To determine the relationship between diabetic nephropathy and diabetic retinopathy on a population of type 2 diabetes mellitus patients. A prospective ten-year follow-up population-based study. We determined differences between estimated glomerular filtration rate (eGFR) using the chronic kidney disease epidemiology collaboration equation and urine albumin to creatinine ratio. Annual incidence of any-DR was 8.21 ± 0.60% (7.06%-8.92%), sight-threatening diabetic retinopathy (STDR) was 2.65 ± 0.14% (2.48%-2.88%), and diabetic macular edema (DME) was 2.21 ± 0.18% (2%-2.49%). Renal study results were as follows: UACR > 30 mg/g had an annual incidence of 7.02 ± 0.05% (6.97%-7.09%), eGFR < 60 ml/min/1.73 m 2 incidence was 5.89 ± 0.12% (5.70%-6.13%). Cox's proportional regression analysis of DR incidence shows that renal function studied by eGFR < 60 ml/min/1.73 m 2 was less significant ( p = 0.04, HR 1.223, 1.098-1.201) than UACR ≥ 300 mg/g ( p < 0.001, HR 1.485, 1.103-1.548). The study of STDR shows that eGFR < 60 ml/min/1.73 m 2 was significant ( p = 0.02, HR 1.890, 1.267-2.820), UACR ≥ 300 mg/g ( p < 0.001, HR 2.448, 1.595-3.757), and DME shows that eGFR < 60 ml/min/1.73 m 2 was significant ( p = 0.02, HR 1.920, 1.287-2.864) and UACR ≥ 300 mg/g ( p < 0.001, HR 2.432, 1.584-3.732). The UACR has a better association with diabetic retinopathy than the eGFR, although both are important risk factors for diabetic retinopathy.

An ab initio/Rice-Ramsperger-Kassel-Marcus study of the hydrogen-abstraction reactions of methyl ethers, H(3)COCH(3-x)(CH(3))(x), x = 0-2, by OH; mechanism and kinetics.

PubMed

Zhou, Chong-Wen; Simmie, John M; Curran, Henry J

2010-07-14

A theoretical study of the mechanism and kinetics of the H-abstraction reaction from dimethyl (DME), ethylmethyl (EME) and iso-propylmethyl (IPME) ethers by the OH radical has been carried out using the high-level methods CCSD(T)/CBS, G3 and G3MP2BH&H. The computationally less-expensive methods of G3 and G3MP2BH&H yield results for DME within 0.2-0.6 and 0.7-0.9 kcal mol(-1), respectively, of the coupled cluster, CCSD(T), values extrapolated to the basis set limit. So the G3 and G3MP2BH&H methods can be confidently used for the reactions of the higher ethers. A distinction is made between the two different kinds of H-atoms, classified as in/out-of the symmetry plane, and it is found that abstraction from the out-of-plane H-atoms proceeds through a stepwise mechanism involving the formation of a reactant complex in the entrance channel and product complex in the exit channel. The in-plane H-atom abstractions take place through a more direct mechanism and are less competitive. Rate constants of the three reactions have been calculated in the temperature range of 500-3000 K using the Variflex code, based on the weak collision, master equation/microcanonical variational RRKM theory including tunneling corrections. The computed total rate constants (cm(3) mol(-1) s(-1)) have been fitted as follows: k(DME) = 2.74 xT(3.94) exp (1534.2/T), k(EME) = 20.93 xT(3.61) exp (2060.1/T) and k(IPME) = 0.55 xT(3.93) exp (2826.1/T). Expressions of the group rate constants for the three different carbon sites are also provided.

Methyl Salicylate: A Reactive Chemical Warfare Agent Surrogate to Detect Reaction with Hypochlorite (POSTPRINT)

DTIC Science & Technology

2011-05-01

DMeS11,12 (tR = 14.83 min). The 3,5- DMeS crystallized spontaneously11 as colorless needles, melting point 143 146 C; 1HNMRdata: δ 7.785, 1Hd, J = 2.6 Hz, H...dichloro-phenol. Figure 2 shows two possible mecha- nisms, both promoted by the phenolic oxygen center— tautomerization to a β- keto acid and β

Conversion of Dimethyl Ether to Branched Hydrocarbons Over Cu/BEA: the Roles of Lewis Acidic and Metallic Sites in H2 Incorporation

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

Hensley, Jesse E.; Schaidle, Joshua A.; Ruddy, Daniel A.

2017-04-26

Conversion of biomass to fuels remains as one of the most promising approach to support our energy needs. It has been previously shown that the gasification of non-edible cellulosic biomass can be used to derive fuels like methanol and dimethyl ether (DME). However, the use of methanol and DME is limited due to the fact that they have low energy densities, poor lubricity and lower viscosity when compared to long-chain hydrocarbons. Increasing the blending percentage can also lead to undesired amounts of oxygenated molecules in the transportation fuel infrastructure, which restrict their applicability as jet or diesel fuels. Consequently, themore » petroleum-derived hydrocarbons remain as the main constituent of the middle-distillate based fuels. One way to increase the share of biofuels in middle-distillates is to use methanol/DME as building blocks for producing renewable, energy-dense hydrocarbons. One way to achieve this is by catalytically converting the DME and methanol to light olefins, followed by oligomerization to higher molecular weight premium alkanes, which can directly be used as kerosene/diesel fuels. Here, we report the catalytic dimerization of biomass-derived deoxygenated olefins into transportation fuel-range hydrocarbons under liquid-phase stirred-batch conditions. Specifically, the effect of operating conditions, such as reaction temperature, solvent-type, reaction duration and olefin-structure, on the conversion, selectivity and kinetics of dimerization of triptene (2,3,3-trimethyl-1-butene) were investigated. Triptene, as previously reported, is one of the major products of DME-homologation reaction over a BEA zeolite4. We show that triptene can be converted to high quality middle-distillates using a commercially available ion-exchange acid resin, Amberlyst-35 (dry) by the process of catalytic dimerization.« less

Evaluation of mercury biogeochemical cycling at the sediment-water interface in anthropogenically modified lagoon environments.

PubMed

Petranich, Elisa; Covelli, Stefano; Acquavita, Alessandro; Faganeli, Jadran; Horvat, Milena; Contin, Marco

2018-06-01

The Marano and Grado Lagoon is well known for being contaminated by mercury (Hg) from the Idrija mine (Slovenia) and the decommissioned chlor-alkali plant of Torviscosa (Italy). Experimental activities were conducted in a local fish farm to understand Hg cycling at the sediment-water interface. Both diffusive and benthic fluxes were estimated in terms of chemical and physical features. Mercury concentration in sediments (up to 6.81μg/g) showed a slight variability with depth, whereas the highest methylmercury (MeHg) values (up to 10ng/g) were detected in the first centimetres. MeHg seems to be produced and stored in the 2-3cm below the sediment-water interface, where sulphate reducing bacteria activity occurs and hypoxic-anoxic conditions become persistent for days. DMeHg in porewaters varied seasonally (from 0.1 and 17% of dissolved Hg (DHg)) with the highest concentrations in summer. DHg diffusive effluxes higher (up to 444ng/m 2 /day) than those reported in the open lagoon (~95ng/m 2 /day), whereas DMeHg showed influxes in the fish farm (up to -156ng/m 2 /day). The diurnal DHg and DMeHg benthic fluxes were found to be higher than the highest summer values previously reported for the natural lagoon environment. Bottom sediments, especially in anoxic conditions, seem to be a significant source of MeHg in the water column where it eventually accumulates. However, net fluxes considering the daily trend of DHg and DMeHg, indicated possible DMeHg degradation processes. Enhancing water dynamics in the fish farm could mitigate environmental conditions suitable for Hg methylation. Copyright © 2017. Published by Elsevier B.V.

Comparison of fecal culture and Danish Mix-ELISA for determination of Salmonella enterica subsp. enterica prevalence in growing swine.

PubMed

Funk, J A; Harris, I T; Davies, P R

2005-04-25

In the USA, control of food-borne salmonellosis associated with meat consumption has been predominantly focused at slaughter and processing. It is expected that standards at slaughter and processing will become more stringent, creating pressure to reduce prevalence of Salmonella-positive food animals through on-farm interventions. The aim of this study was to compare traditional fecal culture and the Danish Mix-ELISA (DME) for determination of Salmonella prevalence pre-harvest in swine. In Trial 1, five cohorts of individually identified pigs were longitudinally sampled during the growing period to compare the kinetics of prevalence as estimated by fecal culture and the DME. In Trial 2, the correlation between fecal prevalence and seroprevalence was estimated pre-marketing in 49 groups of pigs. In Trial 1, fecal prevalence and seroprevalence showed similar kinetics, with a tendency of a higher OD% cut-off to more closely approximate fecal prevalence. In Trial 2, correlations between fecal culture and the DME were 0.40, 0.36, 0.43, and 0.43 (p<0.001) for OD% cut-offs > or =10, 20, 30, and 40, respectively. Based on these results, a higher OD% cut-off would be recommended if more approximate estimation of fecal prevalence is desired and longitudinal sampling would be suggested for evaluating the impact of on-farm interventions for Salmonella reduction whether utilizing fecal culture or the DME. Further evaluation of the impact of Salmonella serovar present on farms on seroprevalence and the relationship of on-farm seroprevalence with food safety risk are needed prior to utilizing the DME for pre-harvest Salmonella diagnostics in the US swine herd.

Lung cancer risk in male workers occupationally exposed to diesel motor emissions in Germany.

PubMed

Brüske-Hohlfeld, I; Möhner, M; Ahrens, W; Pohlabeln, H; Heinrich, J; Kreuzer, M; Jöckel, K H; Wichmann, H E

1999-10-01

Although in several epidemiological studies exposure to diesel motor emissions (DME) shows an elevated lung cancer risk, it is still controversial whether DME is a human carcinogen. In a pooled analysis of two case-control studies on lung cancer in Germany a total of 3498 male cases with histologically or cytologically ascertained lung cancer and 3541 male population controls were included. Information about lifelong occupational and smoking history was obtained by questionnaire. Drivers of lorries, buses, taxies, diesel locomotives and forklift trucks, bulldozers, graders, excavators, and tractors, were considered as exposed to DME and their cumulative exposure was estimated. All odds ratios were adjusted for smoking and asbestos exposure. The evaluation of lung cancer risk for all jobs with DME-exposure combined showed an odds ratio of OR=1.43 (95%-CI: 1.23-1.67). Most pronounced was the increase in lung cancer risk in heavy equipment operators (OR=2. 31 95%-CI: 1.44-3.70). The risk of tractor drivers increased with length of employment and reached statistical significance for exposures longer than 30 years (OR=6.81, 95%-CI: 1.17-39.51). The group of professional drivers (e.g., trucks, buses, and taxies), showed an increased risk only in West Germany (OR=1.44, 95%-CI: 1. 18-1.76), but not in East Germany (OR=0.83, 95%-CI: 0.60-1.14). DME-exposure in other traffic related jobs (e.g., diesel engine locomotive drivers, switchmen, forklift operators) was associated with an odds ratio of OR=1.53 (95%-CI: 1.04-2.24). The study provides further evidence that occupational exposure to diesel motor emissions is associated with an increased lung cancer risk. Copyright 1999 Wiley-Liss, Inc.

78 FR 48995 - Medicare Program; Revisions to Payment Policies Under the Physician Fee Schedule, DME Face-to...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-12

...This document corrects technical errors that appeared in the final rule with comment period published in the Federal Register on November 16, 2012, entitled ``Medicare Program; Revisions to Payment Policies Under the Physician Fee Schedule, DME Face-to-Face Encounters, Elimination of the Requirement for Termination of Non-Random Prepayment Complex Medical Review and Other Revisions to Part B for CY 2013.''

Analysis of the Database of Theses and Dissertations from DME/UFSCAR about Astronomy Education

NASA Astrophysics Data System (ADS)

Rodrigues Ferreira, Orlando; Voelzke, Marcos Rincon

2013-11-01

The paper presents a brief analysis of the "Database of Theses and Dissertations about Astronomy Education" from the Department of Teaching Methodology (DME) of the Federal University of São Carlos(UFSCar). This kind of study made it possible to develop new analysis and statistical data, as well as to conduct a rating of Brazilian institutions that produce academic work in the area.

77 FR 33087 - Standard Instrument Approach Procedures, and Takeoff Minimums and Obstacle Departure Procedures...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-05

... Connersville, IN, Mettel Field, RNAV (GPS) RWY 36, Amdt 2 Hazard, KY, Wendell H Ford, LOC/DME RWY 14, Orig-A Hazard, KY, Wendell H Ford, RNAV (GPS) RWY 14, Amdt 1A Hazard, KY, Wendell H Ford, RNAV (GPS) RWY 32, Orig-A Hazard, KY, Wendell H Ford, VOR/DME RWY 14, Amdt 1B Lake Charles, LA, Lake Charles Rgnl, ILS OR...

Measurement of intestinal edema using an impedance analyzer circuit.

PubMed

Radhakrishnan, Ravi S; Shah, Kunal; Xue, Hasen; Moore-Olufemi, Stacey D; Moore, Frederick A; Weisbrodt, Norman W; Allen, Steven J; Gill, Brijesh; Cox, Charles S

2007-03-01

Acute intestinal edema adversely affects intestinal transit, permeability, and contractility. Current resuscitation modalities, while effective, are associated with development of acute intestinal edema. Knowledge of levels of tissue edema would allow clinicians to monitor intestinal tissue water and may help prevent the detrimental effects of edema. However, there is no simple method to measure intestinal tissue water without biopsy. We sought to develop a tissue impedance analyzer to measure tissue edema, without the need for invasive biopsy. Oscillating voltage input was applied to the analyzer circuit and an oscilloscope measured the voltage output across any load. Rats were randomized to three groups: sham, mild edema (80 mL/kg of NS resuscitation), and severe edema (80 mL/kg of NS resuscitation with intestinal venous hypertension). Intestinal edema was measured by wet-to-dry tissue weight ratio. Bowel impedance was measured and converted to capacitance using a standard curve. Acute intestinal edema causes a significant increase in bowel capacitance. This capacitance can be used to predict tissue water concentration. Using an impedance analyzer circuit, it is possible to measure intestinal edema reliably and quickly. This may prove to be a useful tool in the resuscitation of critically ill patients.

75 FR 63710 - Standard Instrument Approach Procedures, and Takeoff Minimums and Obstacle Departure Procedures...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-18

...: * * * Effective Upon Publication AIRAC date State City Airport FDC No. FDC date Subject 18-Nov-10 CQ SAIPAN ISLAND...... FRANCISCO C. ADA/ 0/1358 9/29/10 ILS OR LOC/DME RWY 7, AMDT 5B. SAIPAN INTL. 18-Nov-10 CQ SAIPAN ISLAND...... FRANCISCO C. ADA/ 0/1359 9/29/10 NDB/DME RWY 25, AMDT 2A SAIPAN INTL. 18-Nov-10 CQ SAIPAN ISLAND...

Development of a Polarizable Force Field for Molecular Dynamics Simulations of Poly (Ethylene Oxide) in Aqueous Solution.

PubMed

Starovoytov, Oleg N; Borodin, Oleg; Bedrov, Dmitry; Smith, Grant D

2011-06-14

We have developed a quantum chemistry-based polarizable potential for poly(ethylene oxide) (PEO) in aqueous solution based on the APPLE&P polarizable ether and the SWM4-DP polarizable water models. Ether-water interactions were parametrized to reproduce the binding energy of water with 1,2-dimethoxyethane (DME) determined from high-level quantum chemistry calculations. Simulations of DME-water and PEO-water solutions at room temperature using the new polarizable potentials yielded thermodynamic properties in good agreement with experimental results. The predicted miscibility of PEO and water as a function of the temperature was found to be strongly correlated with the predicted free energy of solvation of DME. The developed nonbonded force field parameters were found to be transferrable to poly(propylene oxide) (PPO), as confirmed by capturing, at least qualitatively, the miscibility of PPO in water as a function of the molecular weight.

Conceptual Design of Low-Temperature Hydrogen Production and High-Efficiency Nuclear Reactor Technology

NASA Astrophysics Data System (ADS)

Fukushima, Kimichika; Ogawa, Takashi

Hydrogen, a potential alternative energy source, is produced commercially by methane (or LPG) steam reforming, a process that requires high temperatures, which are produced by burning fossil fuels. However, as this process generates large amounts of CO2, replacement of the combustion heat source with a nuclear heat source for 773-1173K processes has been proposed in order to eliminate these CO2 emissions. In this paper, a novel method of nuclear hydrogen production by reforming dimethyl ether (DME) with steam at about 573K is proposed. From a thermodynamic equilibrium analysis of DME steam reforming, the authors identified conditions that provide high hydrogen production fraction at low pressure and temperatures of about 523-573K. By setting this low-temperature hydrogen production process upstream from a turbine and nuclear reactor at about 573K, the total energy utilization efficiency according to equilibrium mass and heat balance analysis is about 50%, and it is 75%for a fast breeder reactor (FBR), where turbine is upstream of the reformer.

Catalysts and methods for converting carbonaceous materials to fuels

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

Hensley, Jesse; Ruddy, Daniel A.; Schaidle, Joshua A.

Catalysts and processes designed to convert DME and/or methanol and hydrogen (H.sub.2) to desirable liquid fuels are described. These catalysts produce the fuels efficiently and with a high selectivity and yield, and reduce the formation of aromatic hydrocarbons by incorporating H.sub.2 into the products. Also described are process methods to further upgrade these fuels to higher molecular weight liquid fuel mixtures, which have physical properties comparable with current commercially used liquid fuels.

Chemical recycling of carbon dioxide to methanol and dimethyl ether: from greenhouse gas to renewable, environmentally carbon neutral fuels and synthetic hydrocarbons.

PubMed

Olah, George A; Goeppert, Alain; Prakash, G K Surya

2009-01-16

Nature's photosynthesis uses the sun's energy with chlorophyll in plants as a catalyst to recycle carbon dioxide and water into new plant life. Only given sufficient geological time can new fossil fuels be formed naturally. In contrast, chemical recycling of carbon dioxide from natural and industrial sources as well as varied human activities or even from the air itself to methanol or dimethyl ether (DME) and their varied products can be achieved via its capture and subsequent reductive hydrogenative conversion. The present Perspective reviews this new approach and our research in the field over the last 15 years. Carbon recycling represents a significant aspect of our proposed Methanol Economy. Any available energy source (alternative energies such as solar, wind, geothermal, and atomic energy) can be used for the production of needed hydrogen and chemical conversion of CO(2). Improved new methods for the efficient reductive conversion of CO(2) to methanol and/or DME that we have developed include bireforming with methane and ways of catalytic or electrochemical conversions. Liquid methanol is preferable to highly volatile and potentially explosive hydrogen for energy storage and transportation. Together with the derived DME, they are excellent transportation fuels for internal combustion engines (ICE) and fuel cells as well as convenient starting materials for synthetic hydrocarbons and their varied products. Carbon dioxide thus can be chemically transformed from a detrimental greenhouse gas causing global warming into a valuable, renewable and inexhaustible carbon source of the future allowing environmentally neutral use of carbon fuels and derived hydrocarbon products.

Photoacoustic diagnosis of edema in rat burned skin

NASA Astrophysics Data System (ADS)

Yoshida, Ken; Sato, Shunichi; Hatanaka, Kosuke; Saitoh, Daizoh; Ashida, Hiroshi; Sakamoto, Toshihisa; Obara, Minoru

2010-02-01

Diagnosis of edema, abnormal accumulation of water in tissue, is important for managing various traumatic injuries and diseases. However, there is no established method for real-time, noninvasive monitoring of edema. In severe extensive burn injuries, edema develops both topically and systemically due to the increased permeability of blood vessels. In this study, we examined photoacoustic (PA) monitoring of edema formed in rat burn models. Deep dermal burn with a 20% total body surface area was made in the dorsal skin of rats. Burn and its adjacent nonburn tissues were irradiated with 6-ns light pulses at 1430 nm, which is one of the absorption peak wavelengths of water in the near infrared. The PA signal amplitude increased until 12 - 24 hr postburn, and thereafter it gradually decreased to its initial level; the latter phase (after 24 hr postburn) coincided with a diuretic phase in the rats. There was a significant correlation between the PA signal amplitudes and water contents in the tissue measured by wet/dry weight method. These findings demonstrate the validity of PA measurement for real-time, noninvasive monitoring of edema.

Arsenic-Rich Polyarsenides Stabilized by Cp*Fe Fragments.

PubMed

Schmidt, Monika; Konieczny, David; Peresypkina, Eugenia V; Virovets, Alexander V; Balázs, Gabor; Bodensteiner, Michael; Riedlberger, Felix; Krauss, Hannes; Scheer, Manfred

2017-06-12

The redox chemistry of [Cp*Fe(η 5 -As 5 )] (1, Cp*=η 5 -C 5 Me 5 ) has been investigated by cyclic voltammetry, revealing a redox behavior similar to that of its lighter congener [Cp*Fe(η 5 -P 5 )]. However, the subsequent chemical reduction of 1 by KH led to the formation of a mixture of novel As n scaffolds with n up to 18 that are stabilized only by [Cp*Fe] fragments. These include the arsenic-poor triple-decker complex [K(dme) 2 ][{Cp*Fe(μ,η 2:2 -As 2 )} 2 ] (2) and the arsenic-rich complexes [K(dme) 3 ] 2 [(Cp*Fe) 2 (μ,η 4:4 -As 10 )] (3), [K(dme) 2 ] 2 [(Cp*Fe) 2 (μ,η 2:2:2:2 -As 14 )] (4), and [K(dme) 3 ] 2 [(Cp*Fe) 4 (μ 4 ,η 4:3:3:2:2:1:1 -As 18 )] (5). Compound 4 and the polyarsenide complex 5 are the largest anionic As n ligand complexes reported thus far. Complexes 2-5 were characterized by single-crystal X-ray diffraction, 1 H NMR spectroscopy, EPR spectroscopy (2), and mass spectrometry. Furthermore, DFT calculations showed that the intermediate [Cp*Fe(η 5 -As 5 )] - , which is presumably formed first, undergoes fast dimerization to the dianion [(Cp*Fe) 2 (μ,η 4:4 -As 10 )] 2- . © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Experimental Edema Disease of Swine (E. Coli ENTEROTOXEMIA) I. Detection and Preparation of an Active Principle

PubMed Central

Clugston, R. E.; Nielsen, N. O.

1974-01-01

Freeze-thaw lysates prepared from strains of Escherichia coli belonging to serogroups O138, O139, and O141 contained a principle (edema disease principle) which induced edema disease in swine. All freeze-thaw lysates contained endotoxic activity that tended to obscure the edema disease syndrome and methods were developed to reduce such activity. Freeze-thaw lysates prepared from E. coli O139 induced the most characteristic edema disease syndrome. Partially purified edema disease principle prepared from O139 freeze-thaw lysates by sequential precipitation with ammonium sulphate and streptomycin sulphate had increased specific activity with markedly reduced endotoxic activity. This material was insoluble at acidic pH but readily soluble at alkaline pH. The effective molecular weight of edema disease principle, based on retention and filtration properties of diaflo membranes, appeared to be greater than 50,000 and less than 100,000. The biological activity of edema disease principle was thermolabile. Sodium deoxycholate treatment of edema disease principle further reduced endotoxic activity. A thermolabile, ammonium sulphate precipitable material was prepared from E. coli O139 that induced a predictable syndrome which resembled edema disease clinically and pathologically following intravenous inoculation in pigs. PMID:4272954

Comparison of the Efficacy Between an Intravitreal and a Posterior Subtenon Injection of Triamcinolone Acetonide for the Treatment of Diffuse Diabetic Macular Edema

PubMed Central

Qamar, Rao Muhammad Rashad; Saleem, Muhammad Imran; Saleem, Muhammad Farhan

2013-01-01

Objective: To compare the efficacy of an intravitreal injection to a posterior subtenon injection of triamcinolone acetonide for the treatment of diffuse diabetic macular edema. Materials and Methods: Sixty patients with diabetes mellitus presenting with diffuse diabetic macular edema were recruited for the study. In each patient, one eye received a 4.0 mg (0.1 mL) intravitreal (IVT) injection of TA and the other eye was treated with a 40 mg (1.0 mL) posterior subtenon (PST) injection of triamcinolone acetonide (TA). We measured the visual acuity, the intraocular pressure (IOP) and the thickness of the macula using optical coherence tomography (OCT) before treatment and at one, three and six months after treatment. Results: Eyes treated with PST showed 1–3 lines of improvement in Snellen’s acuity from their pre-injection baseline visual status. The eyes in the IVT group showed 1–3 lines of improvement in Snellen’s acuity in 80% of the treated eyes, but 20% of the treated eyes did not display any benefit at the end of six months. The difference in acuity between an IVT injection and a PST injection at six months post-treatment was statistically significant (p<0.05). The macular thickness of the eyes treated with an IVT injection was significantly reduced after one (222.7±13.4 μm; p<0.001) and three months (228.1±10.6 μm; p<0.001) of treatment. The eyes treated with a PST injection displayed a slow response and a significant improvement in macular thickness that was observed only after three months (231.3±10.9 μm; p<0.001). The difference between the eyes treated with an IVT injection (385.2±11.3 μm) and those treated with a PST injection (235.4±8.7 μm) was significantly different six months after treatment (p<0.001). The IOP of the eyes treated with an IVT injection was significantly increased after one (17.7±1.1 mm/Hg; p<0.020), three (18.2±1.2 mm/Hg; p<0.003) and six months (18.1±1.320 mm/Hg; p<0.007) when compared to the baseline value (16.1±1.4 mm/Hg). The eyes treated with a PST injection displayed no significant increase in IOP after one (16.4±1.2 mm/Hg; p<0.450), three (16.3±1.1 mm/Hg; p<0.630) and six months (16.2±1.1 mm/Hg; p<0.720) when compared to the baseline value (16.2±1.3 mm/Hg). Conclusion: A PST injection is equally effective and safer than an IVT injection of TA for the management of diffuse DME. PMID:25610278

Catalysts and methods for converting carbonaceous materials to fuels

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

Hensley, Jesse; Ruddy, Daniel A.; Schaidle, Joshua A.

This disclosure relates to catalysts and processes designed to convert DME and/or methanol and hydrogen (H.sub.2) to desirable liquid fuels. These catalysts produce the fuels efficiently and with a high selectivity and yield, and reduce the formation of aromatic hydrocarbons by incorporating H.sub.2 into the products. This disclosure also describes process methods to further upgrade these fuels to higher molecular weight liquid fuel mixtures, which have physical properties comparable with current commercially used liquid fuels.

Comparison of microscopic and immunoassay examination in the diagnosis of intestinal protozoa of humans in Mansoura, Egypt.

PubMed

Elswaifi, Shaadi F; Palmieri, James R; El-Tantawy, Nora; El-Hussiny, Mona; Besheer, Tarek; Abohashem, Ekbal

2016-09-01

Protozoal diseases are prevalent globally and especially in developing countries that have relatively lower socioeconomic populations such as Egypt. Direct microscopic examination (DME) is used for the detection and identification of protozoa but lacks sufficient reliability, and thus may be detrimental in obtaining accurate diagnostic or epidemiological data. In this study, we determine the prevalence of infections by Giardia intestinalis, Cryptosporidium sp., and Entamoeba histolytica in humans in Egypt. Furthermore, we determine the reliability of DME in determining infections caused by these protozoa and compare the results to enzyme linked Immunosorbent assays (ELISA). Our results indicate that the prevalence of giardiasis, cryptosporidiosis, and entamoebiasis is 38, 22, and 16 %, respectively. The sensitivity and specificity of DME for detection of G. intestinalis is 45 and 99 %, for Cryptosporidium 66 and 99 %, and for Entamoeba 45 and 100 %, respectively. Our findings demonstrate that ELISA is more reliable for diagnostic and epidemiologic study purposes.

Reactivity of uranium(iii) with H2E (E = S, Se, Te): synthesis of a series of mononuclear and dinuclear uranium(iv) hydrochalcogenido complexes.

PubMed

Franke, Sebastian M; Rosenzweig, Michael W; Heinemann, Frank W; Meyer, Karsten

2015-01-01

We report the syntheses, electronic properties, and molecular structures of a series of mono- and dinuclear uranium(iv) hydrochalcogenido complexes supported by the sterically demanding but very flexible, single N-anchored tris(aryloxide) ligand ( Ad ArO) 3 N) 3- . The mononuclear complexes [(( Ad ArO) 3 N)U(DME)(EH)] (E = S, Se, Te) can be obtained from the reaction of the uranium(iii) starting material [(( Ad ArO) 3 N)U III (DME)] in DME via reduction of H 2 E and the elimination of 0.5 equivalents of H 2 . The dinuclear complexes [{(( Ad ArO) 3 N)U} 2 (μ-EH) 2 ] can be obtained by dissolving their mononuclear counterparts in non-coordinating solvents such as benzene. In order to facilitate the work with the highly toxic gases, we created concentrated THF solutions that can be handled using simple glovebox techniques and can be stored at -35 °C for several weeks.

Spatiotemporal correlation of optical coherence tomography in-vivo images of rabbit airway for the diagnosis of edema

NASA Astrophysics Data System (ADS)

Kang, DongYel; Wang, Alex; Volgger, Veronika; Chen, Zhongping; Wong, Brian J. F.

2015-07-01

Detection of an early stage of subglottic edema is vital for airway management and prevention of stenosis, a life-threatening condition in critically ill neonates. As an observer for the task of diagnosing edema in vivo, we investigated spatiotemporal correlation (STC) of full-range optical coherence tomography (OCT) images acquired in the rabbit airway with experimentally simulated edema. Operating the STC observer on OCT images generates STC coefficients as test statistics for the statistical decision task. Resulting from this, the receiver operating characteristic (ROC) curves for the diagnosis of airway edema with full-range OCT in-vivo images were extracted and areas under ROC curves were calculated. These statistically quantified results demonstrated the potential clinical feasibility of the STC method as a means to identify early airway edema.

Emission reduction potential of using gas-to-liquid and dimethyl ether fuels on a turbocharged diesel engine.

PubMed

Xinling, Li; Zhen, Huang

2009-03-15

A study of engine performance characteristics and both of regulated (CO, HC, NO(x), and smoke) and unregulated (ultrafine particle number, mass concentrations and size distribution) emissions for a turbocharged diesel engine fueled with conventional diesel, gas-to-liquid (GTL) and dimethyl ether (DME) fuels respectively at different engine loads and speeds have been carried out. The results indicated that fuel components significantly affected the engine performance and regulated/unregulated emissions. GTL exhibited almost the same power and torque output as diesel, while improved fuel economy. GTL significantly reduced regulated emissions with average reductions of 21.2% in CO, 15.7% in HC, 15.6% in NO(x) and 22.1% in smoke in comparison to diesel, as well as average reductions in unregulated emissions of total ultrafine particle number (N(tot)) and mass (M(tot)) emissions by 85.3% and 43.9%. DME can significantly increase torque and power, compared with the original diesel engine, as well as significantly reduced regulated emissions of 40.1% in HC, 48.2% in NO(x) and smoke free throughout all the engine conditions. However, N(tot) for DME is close to that for diesel. The reason is that the accumulation mode particle number emissions for DME are very low due to the characteristics of oxygen content and no C-C bond, which promotes the processes of nucleation and condensation of the semi-volatile compounds in the exhaust gas, as a result, a lot of nucleation mode particles produce.

Apatinib in refractory radiation-induced brain edema: A case report.

PubMed

Hu, Wei Guo; Weng, Yi Ming; Dong, Yi; Li, Xiang Pan; Song, Qi-Bin

2017-11-01

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has observed to be effective and safe in refractory radiation-induced brain edema, like Avastin did. Till now, there is no case report after apatinib came in the market. Two patients who received brain radiotherapy developed clinical manifestations of brain edema, including dizziness, headache, limb activity disorder, and so on. Two patients were both diagnosed as refractory radiation-induced brain edema. Two patients received apatinib (500 mg/day) for 2 and 4 weeks. Two patients got symptomatic improvements from apatinib in different degrees. Magnetic resonance imaging after apatinib treatments showed that compared with pre-treatment imaging, the perilesional edema reduced dramatically. However, the toxicity of apatinib was controllable and tolerable. Apatinib can obviously relieve the symptoms of refractory radiation-induced brain edema and improve the quality of life, which offers a new method for refractory radiation-induced brain edema in clinical practices. But that still warrants further investigation in the prospective study.

Evaluation of the vitreous microbial contamination rate in office-based three-port microincision vitrectomy surgery using Retrector technology.

PubMed

Rezende, Flavio A; Qian, Cynthia X; Sapieha, Przemyslaw

2014-05-01

To perform a microbiological contamination analysis of the vitreous during office-based micro-incision vitrectomy surgery (MIVS) assessing whether the bacteria detected correlated with patient's ocular conjunctival flora. This is a prospective, interventional, nonrandomized case series of patients undergoing office-based MIVS, anti-VEGF, and dexamethasone intravitreal injections (triple therapy) for the treatment of wet age-related macular degeneration (AMD) and diabetic macular edema (DME).All patients were operated at a small procedure room in an ambulatory clinic of the Department of Ophthalmology, University of Montreal, Quebec, Canada. Conjunctival samples were done before placing the sclerotomies. The MIVS was done with a 23-gauge retractable vitrector, a 27-gauge infusion line, and a 29-gauge chandelier. Undiluted and diluted vitreous were collected for aerobic, anaerobic and fungal cultures. Outcomes measured were bacterial species identification within samples collected from the conjunctiva and the vitreous. Thirty-seven patients (37 eyes) were recruited and completed over 17 months of follow-up. Twenty-eight had wet AMD and nine had DME. There were 13 men and 24 women, with a mean age of 78 years. Eighteen patients (46%) had culture positive conjunctival flora. Twenty-six bacterial colonies were tabulated in total from the conjunctival swabs. All bacteria detected were gram-positive bacteria (100%), most commonly: Staphylococcus epidermitis in 11 (42%) and Corynebacterium sp. in 6 (23%). Only 1/18 patients had more than 3 species isolated, 6/18 patients had 2 species and 11/18 patients had 1 species identified on the conjunctival swab. Only 1 of the 37 undiluted midvitreous samples was culture positive, equating to a contamination rate of 2.7%. None of the diluted vitreous samples were culture positive. All cultures were negative for fungus. No serious postoperative complications occurred, including bacterial endophthalmitis, choroidal detachment, and retinal detachment. This preliminary study of office-based MIVS gives us insights on the ocular surface microbial profile and vitreous contamination rate of performing such procedures outside the OR-controlled environment. Our initial results seem to indicate that there is little risk of bacterial translocation and contamination from the conjunctiva into the vitreous. Therefore, if endophthalmitis occurs post-operatively, the source may likely arise after the procedure. Larger studies are needed to confirm our data.

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

Hensley, Jesse; Ruddy, Daniel A.; Schaidle, Joshua A.

Catalysts and processes designed to convert DME and/or methanol and hydrogen (H.sub.2) to desirable liquid fuels are described. These catalysts produce the fuels efficiently and with a high selectivity and yield, and reduce the formation of aromatic hydrocarbons by incorporating H.sub.2 into the products. Also described are process methods to further upgrade these fuels to higher molecular weight liquid fuel mixtures, which have physical properties comparable with current commercially used liquid fuels.

Developing recombinant antibodies for biomarker detection

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

Baird, Cheryl L.; Fischer, Christopher J.; Pefaur, Noah B.

2010-10-01

Monoclonal antibodies (mAbs) have an essential role in biomarker validation and diagnostic assays. A barrier to pursuing these applications is the reliance on immunization and hybridomas to produce mAbs, which is time-consuming and may not yield the desired mAb. We recommend a process flow for affinity reagent production that utilizes combinatorial protein display systems (eg, yeast surface display or phage display) rather than hybridomas. These systems link a selectable phenotype-binding conferred by an antibody fragment-with a means for recovering the encoding gene. Recombinant libraries obtained from immunizations can produce high-affinity antibodies (<10 nM) more quickly than other methods. Non-immune librariesmore » provide an alternate route when immunizations are not possible, or when suitable mAbs are not recovered from an immune library. Directed molecular evolution (DME) is an integral part of optimizing mAbs obtained from combinatorial protein display, but can also be used on hybridoma-derived mAbs. Variants can easily be obtained and screened to increase the affinity of the parent mAb (affinity maturation). We discuss examples where DME has been used to tailor affinity reagents to specific applications. Combinatorial protein display also provides an accessible method for identifying antibody pairs, which are necessary for sandwich-type diagnostic assays.« less

Alkyl complexes of strontium and barium: synthesis and structural characterization of [(Me3Si)2(MeOMe2Si)C]2Sr(THF) and [(Me3Si)2(MeOMe2Si)C]2Ba(MeOCH2CH2OMe).

PubMed

Izod, Keith; Liddle, Stephen T; Clegg, William

2003-06-25

Metathesis between either SrI2 or BaI2 and 2 equiv of {(Me3Si)2(MeOMe2Si)C}K in THF yields the novel heavier alkali metal dialkyls {(Me3Si)2(MeOMe2Si)C}2M(L) [M(L) = Sr(THF) (2), Ba(DME) (3) (DME = 1,2-dimethoxyethane)] after recrystallization.

A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients.

PubMed

Kaidonis, Georgia; Gillies, Mark C; Abhary, Sotoodeh; Liu, Ebony; Essex, Rohan W; Chang, John H; Pal, Bishwanath; Sivaprasad, Sobha; Pefkianaki, Maria; Daniell, Mark; Lake, Stewart; Petrovsky, Nikolai; Hewitt, Alex W; Jenkins, Alicia; Lamoureux, Ecosse L; Gleadle, Jonathan M; Craig, Jamie E; Burdon, Kathryn P

2016-08-01

This study aimed to investigate whether the single-nucleotide polymorphism (SNP) rs2910164 residing within microRNA-146a (miR-146a) is associated with diabetic microvascular complications diabetic nephropathy (DN), proliferative diabetic retinopathy (PDR) or diabetic macular oedema (DME) in either Caucasian patients with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus. Caucasian patients with T1DM (n = 733) or T2DM (n = 2215) were recruited from ophthalmology, renal and endocrine clinics in Australia and the UK. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be on treatment with oral hypoglycaemic drugs or insulin. In total, 890 participants had DN (168 with T1DM and 722 with T2DM), 731 had PDR (251 with T1DM and 480 with T2DM) and 1026 had DME (170 with T1DM and 856 with T2DM). Participants were genotyped for SNP rs2910164 in miR-146a. Analyses investigating association were adjusted for relevant clinical covariates including age, sex, DM duration, HbA1c and hypertension. A significant association was found between the C allele of rs2910164 and DN in the T1DM group (OR 1.93; CI 1.23-3.03; P = 0.004), but no association found in the T2DM group (OR 1.05; CI 0.83-1.32; P = 0.691). In the subset of T2DM patients, the C allele was specifically associated with DME (OR 1.25; CI 1.03-1.53; P = 0.025). No association with DME was found in the T1DM group (OR 0.87; CI 0.54-1.42); P = 0.583), or with PDR for either type of DM. Rs2910164 is significantly associated with microvascular complications DN in patients with T1DM and DME in patients with T2DM.

Fourier Transform Microwave Spectrum of CO{_2} -(CH{_3}){_2} S

NASA Astrophysics Data System (ADS)

Kawashima, Yoshiyuki; Moritani, Takayuki; Hirota, Eizi

2012-06-01

In spite of the fact that the oxygen and sulfur atoms belong to the same group in the periodic table, oxygen-containing molecules and their corresponding sulfur analogues often exhibit characteristic differences in their chemical and physical properties. We have been interested in these differences and have investigated, in a systematic way using Fourier transform microwave (FTMW) spectroscopy combined with ab initio molecular orbital calculations, complexes consisting of dimethyl ether (DME)/dimethyl sulfide (DMS) and ethylene oxide (EO)/ ethylene sulfide (ES), each being attached to either one of rare gas atoms (Rg), CO, N{_2}, or CO{_2}. Among others the CO{_2}-DMS complex should be mentioned, which, in sharp contrast with its counterpart: CO{_2}-DME behaves anomalously, presumably because of low-frequency internal motions, and we have decided to explore it in detail by a FTMW spectrometer. We have generated the CO{_2}-DMS complex by supersonic expansion of a CO{_2} and DMS mixture diluted with Ar, and have scanned the frequency region from 5 to 24 GHz to record the rotational spectra of the complex. We have found it difficult to fit the observed transition frequencies to the ordinary rotational Hamiltonian, but have succeeded to assign 75 transitions by sum rules among the observed transition frequencies. We are suspecting the anomalous behavior of the complex to be caused by a low-frequency torsion of the moieties. In the case of the CO{_2}-DME, the internal rotations of the two methyl groups of the DME were shown to be locked to the CO{_2} by hydrogen bonding, whereas, for the CO{_2}-DMS, we have observed internal-rotation splittings of the two methyl groups of the DMS, indicating the structure of the CO{_2}-DMS complex being considerably different from that of the CO{_2}-DME. We will report the structure at the potential minima and the internal motion of the CO{_2}-DMS, in comparison with the results predicted by quantum chemical calculations. Y. Kawashima, A. Sato, Y. Orita, and E. Hirota J. Phys. Chem. A 116, 1224 2012. J. J. Newby, R. A. Peebles, and S. A. Peebles J. Phys. Chem. A 108, 11234 2004.

Medicare Financing of Graduate Medical Education

PubMed Central

Rich, Eugene C; Liebow, Mark; Srinivasan, Malathi; Parish, David; Wolliscroft, James O; Fein, Oliver; Blaser, Robert

2002-01-01

The past decade has seen ongoing debate regarding federal support of graduate medical education, with numerous proposals for reform. Several critical problems with the current mechanism are evident on reviewing graduate medical education (GME) funding issues from the perspectives of key stakeholders. These problems include the following: substantial interinstitutional and interspecialty variations in per-resident payment amounts; teaching costs that have not been recalibrated since 1983; no consistent control by physician educators over direct medical education (DME) funds; and institutional DME payments unrelated to actual expenditures for resident education or to program outcomes. None of the current GME reform proposals adequately address all of these issues. Accordingly, we recommend several fundamental changes in Medicare GME support. We propose a re-analysis of the true direct costs of resident training (with appropriate adjustment for local market factors) to rectify the myriad problems with per-resident payments. We propose that Medicare DME funds go to the physician organization providing resident instruction, keeping DME payments separate from the operating revenues of teaching hospitals. To ensure financial accountability, we propose that institutions must maintain budgets and report expenditures for each GME program. To establish educational accountability, Residency Review Committees should establish objective, annually measurable standards for GME program performance; programs that consistently fail to meet these minimum standards should lose discretion over GME funds. These reforms will solve several long-standing, vexing problems in Medicare GME funding, but will also uncover the extent of undersupport of GME by most other health care payers. Ultimately, successful reform of GME financing will require “all-payer” support. PMID:11972725

Operator procedure verification with a rapidly reconfigurable simulator

NASA Technical Reports Server (NTRS)

Iwasaki, Yumi; Engelmore, Robert; Fehr, Gary; Fikes, Richard

1994-01-01

Generating and testing procedures for controlling spacecraft subsystems composed of electro-mechanical and computationally realized elements has become a very difficult task. Before a spacecraft can be flown, mission controllers must envision a great variety of situations the flight crew may encounter during a mission and carefully construct procedures for operating the spacecraft in each possible situation. If, despite extensive pre-compilation of control procedures, an unforeseen situation arises during a mission, the mission controller must generate a new procedure for the flight crew in a limited amount of time. In such situations, the mission controller cannot systematically consider and test alternative procedures against models of the system being controlled, because the available simulator is too large and complex to reconfigure, run, and analyze quickly. A rapidly reconfigurable simulation environment that can execute a control procedure and show its effects on system behavior would greatly facilitate generation and testing of control procedures both before and during a mission. The How Things Work project at Stanford University has developed a system called DME (Device Modeling Environment) for modeling and simulating the behavior of electromechanical devices. DME was designed to facilitate model formulation and behavior simulation of device behavior including both continuous and discrete phenomena. We are currently extending DME for use in testing operator procedures, and we have built a knowledge base for modeling the Reaction Control System (RCS) of the space shuttle as a testbed. We believe that DME can facilitate design of operator procedures by providing mission controllers with a simulation environment that meets all these requirements.

Apatinib in refractory radiation-induced brain edema

PubMed Central

Hu, Wei Guo; Weng, Yi Ming; Dong, Yi; Li, Xiang Pan; Song, Qi-Bin

2017-01-01

Abstract Rationale: Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has observed to be effective and safe in refractory radiation-induced brain edema, like Avastin did. Till now, there is no case report after apatinib came in the market. Patient concerns: Two patients who received brain radiotherapy developed clinical manifestations of brain edema, including dizziness, headache, limb activity disorder, and so on. Diagnoses: Two patients were both diagnosed as refractory radiation-induced brain edema. Interventions: Two patients received apatinib (500 mg/day) for 2 and 4 weeks. Outcomes: Two patients got symptomatic improvements from apatinib in different degrees. Magnetic resonance imaging after apatinib treatments showed that compared with pre-treatment imaging, the perilesional edema reduced dramatically. However, the toxicity of apatinib was controllable and tolerable. Lessons: Apatinib can obviously relieve the symptoms of refractory radiation-induced brain edema and improve the quality of life, which offers a new method for refractory radiation-induced brain edema in clinical practices. But that still warrants further investigation in the prospective study. PMID:29145238

Study on systems based on coal and natural gas for producing dimethyl ether

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

Zhou, L.; Hu, S.Y.; Chen, D.J.

2009-04-15

China is a coal-dependent country and will remain so for a long time. Dimethyl ether (DME), a potential substitute for liquid fuel, is a kind of clean diesel motor fuel. The production of DME from coal is meaningful and is studied in this article. Considering the C/H ratios of coal and natural gas (NG), the cofeed (coal and NG) system (CFS), which does not contain the water gas shift process, is studied. It can reduce CO{sub 2} emission and increase the conversion rate of carbon, producing more DME. The CFS is simulated and compared with the coal-based and NG-based systemsmore » with different recycling ratios. The part of the exhaust gas that is not recycled is burned, producing electricity. On the basis of the simulation results, the thermal efficiency, economic index, and CO{sub 2} emission ratio are calculated separately. The CFS with a 100% recycling ratio has the best comprehensive evaluation index, while the energy, economy, and environment were considered at the same time.« less

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

Inhomogeneity induced and appropriately parameterized semilocal exchange and correlation energy functionals in two-dimensions.

PubMed

Patra, Abhilash; Jana, Subrata; Samal, Prasanjit

2018-04-07

The construction of meta generalized gradient approximations based on the density matrix expansion (DME) is considered as one of the most accurate techniques to design semilocal exchange energy functionals in two-dimensional density functional formalism. The exchange holes modeled using DME possess unique features that make it a superior entity. Parameterized semilocal exchange energy functionals based on the DME are proposed. The use of different forms of the momentum and flexible parameters is to subsume the non-uniform effects of the density in the newly constructed semilocal functionals. In addition to the exchange functionals, a suitable correlation functional is also constructed by working upon the local correlation functional developed for 2D homogeneous electron gas. The non-local effects are induced into the correlation functional by a parametric form of one of the newly constructed exchange energy functionals. The proposed functionals are applied to the parabolic quantum dots with a varying number of confined electrons and the confinement strength. The results obtained with the aforementioned functionals are quite satisfactory, which indicates why these are suitable for two-dimensional quantum systems.

Inhomogeneity induced and appropriately parameterized semilocal exchange and correlation energy functionals in two-dimensions

NASA Astrophysics Data System (ADS)

Patra, Abhilash; Jana, Subrata; Samal, Prasanjit

2018-04-01

The construction of meta generalized gradient approximations based on the density matrix expansion (DME) is considered as one of the most accurate techniques to design semilocal exchange energy functionals in two-dimensional density functional formalism. The exchange holes modeled using DME possess unique features that make it a superior entity. Parameterized semilocal exchange energy functionals based on the DME are proposed. The use of different forms of the momentum and flexible parameters is to subsume the non-uniform effects of the density in the newly constructed semilocal functionals. In addition to the exchange functionals, a suitable correlation functional is also constructed by working upon the local correlation functional developed for 2D homogeneous electron gas. The non-local effects are induced into the correlation functional by a parametric form of one of the newly constructed exchange energy functionals. The proposed functionals are applied to the parabolic quantum dots with a varying number of confined electrons and the confinement strength. The results obtained with the aforementioned functionals are quite satisfactory, which indicates why these are suitable for two-dimensional quantum systems.

Large-eddy simulation, atmospheric measurement and inverse modeling of greenhouse gas emissions at local spatial scales

NASA Astrophysics Data System (ADS)

Nottrott, Anders Andelman

Multiferroic materials and devices have attracted intensified interests due to the demonstrated strong magnetoelectric coupling in new multiferroic materials, artificial multiferroic heterostructures and devices with unique functionalities and superior performance characteristics. This offers great opportunities for achieving compact, fast, energy-efficient and voltage tunable spintronic devices. In traditional magnetic materials based magnetic random access memories (MRAM) devices, the binary information is stored as magnetization. The high coercivity of the ferromagnetic media requires large magnetic fields for switching the magnetic states thus consuming large amount of energy. In modern MRAM information writing process, spin-torque technique is utilized for minimizing the large energy for generating magnetic field by passing through a spin-polarized current directly to the magnets. However, both methods still need large current/current density to toggle the magnetic bits which consume large amount of energy. With the presence of multiferroic or magnetoelectric materials, spin is controlled by electric field which opens new opportunities for power-efficient voltage control of magnetization in spintronic devices leading to magnetoelectric random access memories (MERAM) with ultra-low energy consumption. However, state of the art multiferroic materials still have difficulty of realizing nonvolatile 180° magnetization reversal, which is desired in realizing MERAM. In a strain-mediated multiferroic system, the typical modification of the magnetism of ferromagnetic phase as a function of bipolar electric field shows a "butterfly" like behavior. This is due to the linear piezoelectricity of ferroelectric phase which has a "butterfly" like piezostrain as a function of electric field curve resulting from ferroelectric domain wall switching. In this case, the magnetization state is volatile because of the vanishing of the piezostrain at zero electric field. However, the non-volatile switching of magnetization would be more promising for information storage or MERAM devices with lower energy consumption and the magnetic state can be further controlled by voltage impulse. In this work, we first study the equivalent of direct and converse magnetoelectric effects. The resonant direct and converse magnetoelectric (ME) effects have been investigated experimentally and theoretically in FeGa/PZT/FeGa sandwich laminate composites. The frequency responses of direct and converse magnetoelectric effects were measured under the same electric and magnetic bias conditions. The resonant direct ME effect (DME) occurs at an antiresonance frequency, while resonant converse ME effect (CME) occurs at a resonance frequency. The antiresonance and resonance frequencies have close but different values under identical bias conditions. The magnitudes of resonant effective ME coefficients for direct and converse ME effects are also not equal. Based on different sets of constitutive equations of the materials for DME and CME, a new model was developed to describe the frequency response of DME and CME in laminate composite, which was in good agreement with the experimental results. Inequivalence of resonant ME effects is ascribed to the different mechanical and electrical boundary conditions for DME and CME. On the other hand, similar bias E and H field dependence was observed for both DME and CME resonance frequencies and resonant coefficients, indicating consistency between DME and CME effects. In the study of the frequency response of DME and CME, the linear piezoelectric effect is used. However, this linear piezoelectric effect in converse magnetoelectric coupling would lead to "butter-fly" like magnetization vs. electric field curve which leads to a "volatile" behavior in magnetic memory system. In the presented study, a unique ferroelastic switching pathway in ferroelectric substrates is utilized to produce two distinct, reversible and stable lattice strain states which leads to the establish of two stable magnetization states of the ferromagnetic thin film. In this process, instead of complete 180° ferromagnetic domain switching, 71°/109° ferroelastic domain wall switching is involved, where the electric polarization is switching between in-plane and out-of-plane direction. A voltage impulse induced reversible bistable magnetization switching in FeGaB/lead zirconate titanate (PZT) multiferroic heterostructures at room temperature is first demonstrated. Two reversible and stable voltage-impulse induced mechanical strain states were obtained in the PZT by applying an electric field impulse with its amplitude smaller than the electric coercive field, which led to reversible voltage impulse induced bistable magnetization switching. Direct and converse magnetoelectric effects are carefully quantified.

Functional Dependence between Septal Protein SepJ from Anabaena sp. Strain PCC 7120 and an Amino Acid ABC-Type Uptake Transporter.

PubMed

Escudero, Leticia; Mariscal, Vicente; Flores, Enrique

2015-08-01

In the diazotrophic filaments of heterocyst-forming cyanobacteria, two different cell types, the CO2-fixing vegetative cells and the N2-fixing heterocysts, exchange nutrients, including some amino acids. In the model organism Anabaena sp. strain PCC 7120, the SepJ protein, composed of periplasmic and integral membrane (permease) sections, is located at the intercellular septa joining adjacent cells in the filament. The unicellular cyanobacterium Synechococcus elongatus strain PCC 7942 bears a gene, Synpcc7942_1024 (here designated dmeA), encoding a permease homologous to the SepJ permease domain. Synechococcus strains lacking dmeA or lacking dmeA and expressing Anabaena sepJ were constructed. The Synechococcus dmeA mutant showed a significant 22 to 32% decrease in the uptake of aspartate, glutamate, and glutamine, a phenotype that could be partially complemented by Anabaena sepJ. Synechococcus mutants of an ATP-binding-cassette (ABC)-type transporter for polar amino acids showed >98% decreased uptake of glutamate irrespective of the presence of dmeA or Anabaena sepJ in the same strain. Thus, Synechococcus DmeA or Anabaena SepJ is needed to observe full (or close to full) activity of the ABC transporter. An Anabaena sepJ deletion mutant was significantly impaired in glutamate and aspartate uptake, which also in this cyanobacterium requires the activity of an ABC-type transporter for polar amino acids. SepJ appears therefore to generally stimulate the activity of cyanobacterial ABC-type transporters for polar amino acids. Conversely, an Anabaena mutant of three ABC-type transporters for amino acids was impaired in the intercellular transfer of 5-carboxyfluorescein, a SepJ-related property. Our results unravel possible functional interactions in transport elements important for diazotrophic growth. Membrane transporters are essential for many aspects of cellular life, from uptake and export of substances in unicellular organisms to intercellular molecular exchange in multicellular organisms. Heterocyst-forming cyanobacteria such as Anabaena represent a unique case of multicellularity, in which two cell types exchange nutrients and regulators. The SepJ protein located at the intercellular septa in the filaments of Anabaena contains a permease domain of the drug/metabolite transporter (DMT) superfamily that somehow contributes to intercellular molecular transfer. In this work, we have found that SepJ stimulates the activity of a polar amino acid uptake transporter of the ATP-binding-cassette (ABC) superfamily, which could itself affect an intercellular transfer activity related to SepJ, thus unraveling possible functional interactions between these different transporters. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Cystic Fibrosis Transmembrane Conductance Regulator Potentiation as a Therapeutic Strategy for Pulmonary Edema: A Proof-of-Concept Study in Pigs.

PubMed

Li, Xiaopeng; Vargas Buonfiglio, Luis G; Adam, Ryan J; Stoltz, David A; Zabner, Joseph; Comellas, Alejandro P

2017-12-01

To determine the feasibility of using a cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770/Kalydeco, Vertex Pharmaceuticals, Boston, MA), as a therapeutic strategy for treating pulmonary edema. Prospective laboratory animal investigation. Animal research laboratory. Newborn and 3 days to 1 week old pigs. Hydrostatic pulmonary edema was induced in pigs by acute volume overload. Ivacaftor was nebulized into the lung immediately after volume overload. Grams of water per grams of dry lung tissue were determined in the lungs harvested 1 hour after volume overload. Ivacaftor significantly improved alveolar liquid clearance in isolated pig lung lobes ex vivo and reduced edema in a volume overload in vivo pig model of hydrostatic pulmonary edema. To model hydrostatic pressure-induced edema in vitro, we developed a method of applied pressure to the basolateral surface of alveolar epithelia. Elevated hydrostatic pressure resulted in decreased cystic fibrosis transmembrane conductance regulator activity and liquid absorption, an effect which was partially reversed by cystic fibrosis transmembrane conductance regulator potentiation with ivacaftor. Cystic fibrosis transmembrane conductance regulator potentiation by ivacaftor is a novel therapeutic approach for pulmonary edema.

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

Tan, Eric C. D.; Talmadge, Michael; Dutta, Abhijit

This report was developed as part of the U.S. Department of Energy’s Bioenergy Technologies Office’s (BETO’s) efforts to enable the development of technologies for the production of infrastructure-compatible, cost-competitive liquid hydrocarbon fuels from lignocellulosic biomass feedstocks. The research funded by BETO is designed to advance the state of technology of biomass feedstock supply and logistics, conversion, and overall system sustainability. It is expected that these research improvements will be made within the 2022 timeframe. As part of their involvement in this research and development effort, the National Renewable Energy Laboratory and the Pacific Northwest National Laboratory investigate the economics ofmore » conversion pathways through the development of conceptual biorefinery process models and techno-economic analysis models. This report describes in detail one potential conversion process for the production of high-octane gasoline blendstock via indirect liquefaction of biomass. The processing steps of this pathway include the conversion of biomass to synthesis gas or syngas via indirect gasification, gas cleanup, catalytic conversion of syngas to methanol intermediate, methanol dehydration to dimethyl ether (DME), and catalytic conversion of DME to high-octane, gasoline-range hydrocarbon blendstock product. The conversion process configuration leverages technologies previously advanced by research funded by BETO and demonstrated in 2012 with the production of mixed alcohols from biomass. Biomass-derived syngas cleanup via reforming of tars and other hydrocarbons is one of the key technology advancements realized as part of this prior research and 2012 demonstrations. The process described in this report evaluates a new technology area for the downstream utilization of clean biomass-derived syngas for the production of high-octane hydrocarbon products through methanol and DME intermediates. In this process, methanol undergoes dehydration to DME, which is subsequently converted via homologation reactions to high-octane, gasoline-range hydrocarbon products.« less

Investigation of Ion-Solvent Interactions in Nonaqueous Electrolytes Using in Situ Liquid SIMS.

PubMed

Zhang, Yanyan; Su, Mao; Yu, Xiaofei; Zhou, Yufan; Wang, Jungang; Cao, Ruiguo; Xu, Wu; Wang, Chongmin; Baer, Donald R; Borodin, Oleg; Xu, Kang; Wang, Yanting; Wang, Xue-Lin; Xu, Zhijie; Wang, Fuyi; Zhu, Zihua

2018-03-06

Ion-solvent interactions in nonaqueous electrolytes are of fundamental interest and practical importance, yet debates regarding ion preferential solvation and coordination numbers persist. In this work, in situ liquid SIMS was used to examine ion-solvent interactions in three representative electrolytes, i.e., lithium hexafluorophosphate (LiPF 6 ) at 1.0 M in ethylene carbonate (EC)-dimethyl carbonate (DMC) and lithium bis(fluorosulfonyl)imide (LiFSI) at both low (1.0 M) and high (4.0 M) concentrations in 1,2-dimethoxyethane (DME). In the positive ion mode, solid molecular evidence strongly supports the preferential solvation of Li + by EC. Besides, from the negative spectra, we also found that PF 6 - forms association with EC, which has been neglected by previous studies due to the relatively weak interaction. In both LiFSI in DME electrolytes, however, no evidence shows that FSI - is associated with DME. Furthermore, strong salt ion cluster signals were observed in the 1.0 M LiPF 6 in EC-DMC electrolyte, suggesting that a significant amount of Li + ions stay in the vicinity of anions. In sharp comparison, weak ion cluster signals were detected in dilute LiFSI in DME electrolyte, suggesting most ions are well separated, in agreement with our molecular dynamics simulation results. These findings indicate that with virtues of little bias on detecting positive and negative ions and the capability of directly analyzing concentrated electrolytes, in situ liquid SIMS is a powerful tool that can provide key evidence for improved understanding on the ion-solvent interactions in nonaqueous electrolytes. Therefore, we anticipate wide applications of in situ liquid SIMS on investigations of various ion-solvent interactions in the near future.

Investigation of Ion-Solvent Interactions in Nonaqueous Electrolytes Using in Situ Liquid SIMS

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

Zhang, Yanyan; Su, Mao; Yu, Xiaofei

2018-02-06

Ion-solvent interactions in non-aqueous electrolytes are of fundamental interest and practical importance, yet debates regarding ion preferential solvation and coordination numbers persist. In this work, in situ liquid SIMS was used to examine ion-solvent interactions in three representative electrolytes, i.e., lithium hexafluorophosphate (LiPF6) at 1.0 M in ethylene carbonate (EC)-dimethyl carbonate (DMC), and lithium bis(fluorosulfonyl)imide (LiFSI) at both low (1.0 M) and high (4.0 M) concentrations in 1,2-dimethoxyethane (DME). In the positive ion mode, solid molecular evidence strongly supports the preferential solvation of Li+ by EC. Besides, from the negative spectra, we also found that PF6- forms association with EC,more » which has been neglected by previous studies due to the relatively weak interaction. While in both LiFSI in DME electrolytes, no evidence shows that FSI- is associated with DME. Furthermore, strong salt ion cluster signals were observed in the 1.0 M LiPF6 in EC-DMC electrolyte, suggesting that a significant amount of Li+ ions stay in vicinity of anions. In sharp comparison, weak ion cluster signals were detected in dilute LiFSI in DME electrolyte, suggesting most ions are well separated, in agreement with our molecular dynamics (MD) simulation results. These findings indicate that with virtues of little bias on detecting positive and negative ions and the capability of directly analyzing concentrated electrolytes, in situ liquid SIMS is a powerful tool that can provide key evidence for improved understanding on the ion-solvent interactions in non-aqueous electrolytes. Therefore, we anticipate wide applications of in situ liquid SIMS on investigations of various ion-solvent interactions in the near future.« less

Surgical resident education: what is the department's price for commitment?

PubMed

Meara, Michael P; Schlitzkus, Lisa L; Witherington, Mitzi; Haisch, Carl; Rotondo, Michael F; Schenarts, Paul J

2010-01-01

The current recession has impacted all aspects of our economy. Some residency programs have experienced faculty salary cuts, furlough days, and cessation of funding for travel to academic meetings. This milieu forced many residency programs to reevaluate their commitment to resident education, particularly for those expenses not provided for by Direct Medical Education (DME) and Indirect Medical Education (IME) funds. The purpose of this study was to determine what price a Department of Surgery pays to fulfill its commitment to resident education. A financial analysis of 1 academic year was performed for all expenses not covered by DME or IME funds and is paid for by the faculty practice plan. These expenses were categorized and further analyzed to determine the funds required for resident-related scholarly activity. A university-based general surgery residency program. Twenty-eight surgical residents and a program coordinator. The departmental faculty provided $153,141 during 1 academic year to support the educational mission of the residency. This amount is in addition to the $1.6 million in faculty time, $850,000 provided by the federal government in terms of DME funds, and $14 million of IME funds, which are distributed on an institutional basis. Resident presentations at scientific meetings accounted for $49,672, and program coordinator costs of $44,190 accounted for nearly two-thirds of this funding. The departmental faculty committed $6400 per categorical resident. In addition to DME and IME funds, a department of surgery must commit significant additional monies to meet the educational goals of surgical residency. Copyright © 2010 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Investigation of Ion–Solvent Interactions in Nonaqueous Electrolytes Using in Situ Liquid SIMS

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

Zhang, Yanyan; Su, Mao; Yu, Xiaofei

Ion-solvent interactions in non-aqueous electrolytes are of fundamental interest and practical importance, yet debates regarding ion preferential solvation and coordination numbers persist. In this work, in situ liquid SIMS was used to examine ion-solvent interactions in three representative electrolytes, i.e., lithium hexafluorophosphate (LiPF6) at 1.0 M in ethylene carbonate (EC)-dimethyl carbonate (DMC), and lithium bis(fluorosulfonyl)imide (LiFSI) at both low (1.0 M) and high (4.0 M) concentrations in 1,2-dimethoxyethane (DME). In the positive ion mode, solid molecular evidence strongly supports the preferential solvation of Li+ by EC. Besides, from the negative spectra, we also found that PF6- forms association with EC,more » which has been neglected by previous studies due to the relatively weak interaction. While in both LiFSI in DME electrolytes, no evidence shows that FSI- is associated with DME. Furthermore, strong salt ion cluster signals were observed in the 1.0 M LiPF6 in EC-DMC electrolyte, suggesting that a significant amount of Li+ ions stay in vicinity of anions. In sharp comparison, weak ion cluster signals were detected in dilute LiFSI in DME electrolyte, suggesting most ions are well separated, in agreement with our molecular dynamics (MD) simulation results. These findings indicate that with virtues of little bias on detecting positive and negative ions and the capability of directly analyzing concentrated electrolytes, in situ liquid SIMS is a powerful tool that can provide key evidence for improved understanding on the ion-solvent interactions in non-aqueous electrolytes. Therefore, we anticipate wide applications of in situ liquid SIMS on investigations of various ion-solvent interactions in the near future.« less

Objective assessment of leg edema using ultrasonography with a gel pad

PubMed Central

Iuchi, Terumi; Tsuchiya, Sayumi; Ohno, Naoki; Dai, Misako; Matsumoto, Masaru; Ogai, Kazuhiro; Sato, Aya; Sawazaki, Takuto; Miyati, Tosiaki; Tanaka, Shinobu; Sugama, Junko

2017-01-01

Ultrasonography (US) is useful for visual detection of edematous tissues to assess subcutaneous echogenicity. However, visualization of subcutaneous echogenicity is interpreted differently among operators because the evaluation is subjective and individual operators have unique knowledge. This study objectively assessed leg edema using US with a gel pad including fat for normalization of echogenicity in subcutaneous tissue. Five younger adults and four elderly people with leg edema were recruited. We compared assessments of US and limb circumference before and after the intervention of vibration to decrease edema in younger adults, and edema prior to going to sleep and reduced edema in the early morning in elderly people. These assessments were performed twice in elderly people by three operators and reliability, interrater differences, and bias were assessed. For US assessment, echogenicity in subcutaneous tissue was normalized to that of the gel pad by dividing the mean echogenicity of subcutaneous tissue by the mean echogenicity of the gel pad. In younger adults, the normalized subcutaneous echogenicity before the intervention was significantly higher than that after the intervention. In elderly people, echogenicity indicating edema was significantly higher than that after edema reduction. Edema was detected with accuracy rates of 76.9% in younger adults and 75.0% in elderly people. Meanwhile, limb circumference could be used to detect edema in 50.0% of healthy adults and 87.8% of elderly people. The intra-reliability was excellent (intraclass correlation coefficient > 0.9, p < 0.01), and the inter-reliability was good (intraclass correlation coefficient > 0.7, p < 0.01) for normalized subcutaneous echogenicity. Bland-Altman plots revealed that inter-rater differences and systematic bias were small. Normalized subcutaneous echogenicity with the pad can sensitively and objectively assess leg edema with high reliability. Therefore, this method has the potential to become a new gold standard for objective assessment of leg edema in clinical practice. PMID:28792959

Probing electronic wave functions of sodium-doped clusters: Dyson orbitals, anisotropy parameters, and ionization cross-sections

DOE PAGES

Gunina, Anastasia O.; Krylov, Anna I.

2016-11-14

We apply high-level ab initio methods to describe the electronic structure of small clusters of ammonia and dimethylether (DME) doped with sodium, which provide a model for solvated electrons. We investigate the effect of the solvent and cluster size on the electronic states. We consider both energies and properties, with a focus on the shape of the electronic wave function and the related experimental observables such as photoelectron angular distributions. The central quantity in modeling photoionization experiments is the Dyson orbital, which describes the difference between the initial N-electron and final (N-1)-electron states of a system. Dyson orbitals enter themore » expression of the photoelectron matrix element, which determines total and partial photoionization cross-sections. We compute Dyson orbitals for the Na(NH3)n and Na(DME)m clusters using correlated wave functions (obtained with equation-of-motion coupled-cluster model for electron attachment with single and double substitutions) and compare them with more approximate Hartree-Fock and Kohn-Sham orbitals. As a result, we also analyze the effect of correlation and basis sets on the shapes of Dyson orbitals and the experimental observables.« less

[Assessment of local and systemic inflammatory parameters of peripheral burn in an animal model].

PubMed

Torres, Wilmary; Mendoza, Liseth; Vicci, Hember; Eblen-Zajjur, Antonio; Navarro, María

2016-01-01

To evaluate the edema volume and leukocyte, platelet, and fibrinogen count of peripheral burn in an animal model. The back left leg of Rattus norvegicus (experimental group) was placed in water at 60 °C for 60 seconds or at room temperature (control group). An analysis was carried out before and after the induced burn (at 4, 8, 12, and 24 h). The edema volume was determined by an orthogonal photo, the leukocyte and platelet counts were determined using automated equipment, and the fibrinogen count was determined using the gravimetric method. The maximum value of the edema was recorded at 4 h and leukocytes at 24 h. The platelet count did not vary at different post-edema time intervals. The fibrinogen level increased at 4 h and 24 h. In this animal model we induced systemic inflammation characterized by leukocytosis and elevated fibrinogen levels, combined with edema located at the induction area.

Macular edema in underserved diabetic patients: Improving detection by enhancing the optical signature and data analysis techniques

NASA Astrophysics Data System (ADS)

Alhamami, Mastour Abdullah

Diabetic retinopathy and diabetic macular edema are chief causes of vision loss in working adults. Thus, retinal screening of patients with diabetes has become standard practice in some countries to prevent visual impairment and blindness from diabetic retinopathy. One goal is to improve techniques currently used to diagnose diabetic retinopathy. Another goal is to probe pathophysiological changes seen with imaging methods. Analysis was performed on a novel dataset from more than 2000 underserved adult diabetic patients, who were recruited for a screening study for diabetic eye disease. Data were collected from four county clinics at Alameda Health, Alameda County, CA. Over 90% of patients self-identified as a racial/ethnic identity other than non-Hispanic white. We investigated the prevalence and optical properties of macular edema. In the first study, a retrospective cohort study was performed to compare macular thickness in diabetic patients with and without macular edema to determine the presence of damage to the external limiting membrane or and the relation of damage to the ELM to damage to photoreceptors. In the second study, we investigated whether the information in red light better visualizes cysts in diabetic macular edema, as compared to green light. In the third study, we investigated whether the demographic and blood glucose information predict diabetic macular edema. Three logistic regression analyses were compared. In the fourth study, we examined how different outcome measures of retinal thickness vary with demographic and blood glucose measures, using a trichotomous variable for retinal thickness. The findings point strongly to large individual differences in the development of macular edema, which is difficult to diagnose with the most common methods in dark eyes. Further, while blood glucose was found to be important, there are additional differences in the potential for macular edema that are associated with ethnic group and gender.

Serial Sonographic Assessment of Pulmonary Edema in Patients With Hypertensive Acute Heart Failure.

PubMed

Martindale, Jennifer L; Secko, Michael; Kilpatrick, John F; deSouza, Ian S; Paladino, Lorenzo; Aherne, Andrew; Mehta, Ninfa; Conigiliaro, Alyssa; Sinert, Richard

2018-02-01

Objective measures of clinical improvement in patients with acute heart failure (AHF) are lacking. The aim of this study was to determine whether repeated lung sonography could semiquantitatively capture changes in pulmonary edema (B-lines) in patients with hypertensive AHF early in the course of treatment. We conducted a feasibility study in a cohort of adults with acute onset of dyspnea, severe hypertension in the field or at triage (systolic blood pressure ≥ 180 mm Hg), and a presumptive diagnosis of AHF. Patients underwent repeated dyspnea and lung sonographic assessments using a 10-cm visual analog scale (VAS) and an 8-zone scanning protocol. Lung sonographic assessments were performed at the time of triage, initial VAS improvement, and disposition from the emergency department. Sonographic pulmonary edema was independently scored offline in a randomized and blinded fashion by using a scoring method that accounted for both the sum of discrete B-lines and degree of B-line fusion. Sonographic pulmonary edema scores decreased significantly from initial to final sonographic assessments (P < .001). The median percentage decrease among the 20 included patient encounters was 81% (interquartile range, 55%-91%). Although sonographic pulmonary edema scores correlated with VAS scores (ρ = 0.64; P < .001), the magnitude of the change in these scores did not correlate with each other (ρ = -0.04; P = .89). Changes in sonographic pulmonary edema can be semiquantitatively measured by serial 8-zone lung sonography using a scoring method that accounts for B-line fusion. Sonographic pulmonary edema improves in patients with hypertensive AHF during the initial hours of treatment. © 2017 by the American Institute of Ultrasound in Medicine.

Cerebral edema induced in mice by a convulsive dose of soman. Evaluation through diffusion-weighted magnetic resonance imaging and histology

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

Testylier, Guy; Lahrech, Hana; Universite Joseph Fourier, Grenoble, F-38043

2007-04-15

Purpose: In the present study, diffusion-weighted magnetic resonance imaging (DW-MRI) and histology were used to assess cerebral edema and lesions in mice intoxicated by a convulsive dose of soman, an organophosphate compound acting as an irreversible cholinesterase inhibitor. Methods: Three hours and 24 h after the intoxication with soman (172 {mu}g/kg), the mice were anesthetized with an isoflurane/N{sub 2}O mixture and their brain examined with DW-MRI. After the imaging sessions, the mice were sacrificed for histological analysis of their brain. Results: A decrease in the apparent diffusion coefficient (ADC) was detected as soon as 3 h after the intoxication andmore » was found strongly enhanced at 24 h. A correlation was obtained between the ADC change and the severity of the overall brain damage (edema and cellular degeneration): the more severe the damage, the stronger the ADC drop. Anesthesia was shown to interrupt soman-induced seizures and to attenuate edema and cell change in certain sensitive brain areas. Finally, brain water content was assessed using the traditional dry/wet weight method. A significant increase of brain water was observed following the intoxication. Conclusions: The ADC decrease observed in the present study suggests that brain edema in soman poisoning is mainly intracellular and cytotoxic. Since entry of water into Brain was also evidenced, this type of edema is certainly mixed with others (vasogenic, hydrostatic, osmotic). The present study confirms the potential of DW-MRI as a non-invasive tool for monitoring the acute neuropathological consequences (edema and neurodegeneration) of soman-induced seizures.« less

Cold Aero Performance of a Two-Dimensional Mixer Ejector Nozzle

NASA Technical Reports Server (NTRS)

Balan, C.

2005-01-01

Since 1986, NASA and the U.S. aerospace industry have been assessing the economic viability and environmental acceptability of a second-generation supersonic civil transport, or High Speed Civil Transport (HSCT). Environmental acceptability in terms of airport community noise and economic viability are critical elements in this endeavor. Development of a propulsion system that satisfies strict airport noise regulations (FAR36 Stage III levels), at acceptable performance and weight, is critical to the success of any HSCT program. Two-dimensional mixer-ejector (2DME) exhaust systems are one approach in achieving this goal. In support of HSCT development, GEAE (GE Aircraft Engines), under contract to the NASA Glenn Research Center, conducted this test program at the NASA Langley 16 ft transonic wind tunnel to evaluate the cold aerodynamic performance aspects of the 2DME exhaust system concept. The effects of SAR (SAR, suppressor area ratio, = mixed-flow area/primary nozzle throat area), MAR (MAR = overall exhaust system exit/mixing-plane area), flap length, CER (suppressor chute expansion ratio), chute alignment, and free stream Mach number were investigated on a 1/11th cold aerodynamic scale model of a 2DME exhaust system.

Survey of the BY Draconis syndrome among dMe stars. [BVr photometry search for slow quasisinusoidal light variations

NASA Technical Reports Server (NTRS)

Bopp, B. W.; Espenak, F.

1977-01-01

Results are reported for a BVr photometric survey of 22 dK, dKe, dM, and dMe stars conducted to search for slow quasi-sinusoidal fluctuations in V (the BY Draconis syndrome). The (B-V) and (V-r) color indices are determined in an attempt to detect wavelength-dependent color changes produced by starspots and to infer starspot temperatures. It is found that nine of the stars exhibit variations in V of the order of 0.05 to 0.10 magnitude on a time scale of days or weeks, that at least three more display changes in mean light level over a period of years, that the stars generally tend to become redder at minimum light, and that some of the stars show no detectable color changes over their photometric cycle. The color data are taken to suggest a probable temperature difference of about 200 to 500 K between the stellar photospheres and starspots if the V variations are attributed to dark spots. It is concluded that the BY Draconis syndrome is clearly a very common occurrence among dMe stars.

Effects of sulfate-reducing bacteria on methylmercury at the sediment-water interface.

PubMed

Zeng, Lingxia; Luo, Guangjun; He, Tianrong; Guo, Yanna; Qian, Xiaoli

2016-08-01

Sediment cores (containing sediment and overlying water) from Baihua Reservoir (SW China) were cultured under different redox conditions with different microbial activities, to understand the effects of sulfate-reducing bacteria (SRB) on mercury (Hg) methylation at sediment-water interfaces. Concentrations of dissolved methyl mercury (DMeHg) in the overlying water of the control cores with bioactivity maintained (BAC) and cores with only sulfate-reducing bacteria inhibited (SRBI) and bacteria fully inhibited (BACI) were measured at the anaerobic stage followed by the aerobic stage. For the BAC and SRBI cores, DMeHg concentrations in waters were much higher at the anaerobic stage than those at the aerobic stage, and they were negatively correlated to the dissolved oxygen concentrations (r=-0.5311 and r=-0.4977 for BAC and SRBI, respectively). The water DMeHg concentrations of the SRBI cores were 50% lower than those of the BAC cores, indicating that the SRB is of great importance in Hg methylation in sediment-water systems, but there should be other microbes such as iron-reducing bacteria and those containing specific gene cluster (hgcAB), besides SRB, causing Hg methylation in the sediment-water system. Copyright © 2016. Published by Elsevier B.V.

Highly Active Electrolytes for Rechargeable Mg Batteries Based on [Mg2(μ-Cl)2]2+ Cation Complex in Dimethoxyethane

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

Cheng, Yingwen; Stolley, Ryan M.; Han, Kee Sung

2015-01-01

Highly active electrolytes based on a novel [Mg2(μ-Cl)2]2+ cation complex for reversible Mg deposition were developed and analyzed in this work. These electrolytes were formulated in dimethoxyethane through dehalodimerization of non-nucleophilic MgCl2 by reacting with either Mg salts (such as Mg(TFSI)2, TFSI= bis(trifluoromethane)sulfonylimide) or Lewis acid salts (such as AlEtCl2 or AlCl3). The cation complex was identified for the first time as [Mg2(μ-Cl)2(DME)4]2+ (DME=dimethoxyethane) and its molecular structure was characterized by single crystal X-ray diffraction, Raman spectroscopy and NMR. The electrolyte synthesis process was studied and rational approaches for formulating highly active electrolytes were proposed. Through control of the anions,more » electrolytes with efficiency close to 100%, wide electrochemical window (up to 3.5V) and high ionic conductivity (> 6 mS/cm) were obtained. The electrolyte synthesis and understandings developed in this work could bring significant opportunities for rational formulation of electrolytes with the general formula [Mg2(μ-Cl)2(DME)4][anion]x for practical Mg batteries.« less

A timeline for predicting durable medical equipment needs and interventions for amyotrophic lateral sclerosis patients.

PubMed

Bromberg, Mark B; Brownell, Alexander A; Forshew, Dallas A; Swenson, Michael

2010-01-01

ALS is progressive with increasing patient needs for durable medical equipment (DME) and interventions (gastric feeding tube - PEG, and non-invasive ventilation - NIV). We performed a chart review of deceased patients to determine the time-course of needs and their estimated costs. A timeline of needs was based on when clinic personnel felt an item was necessary. The point in time when an item or intervention was needed was expressed as a percentage of a patient's total disease duration. A wide range of DME and interventions was needed irrespective of site of ALS symptom onset (bulbar, upper, lower extremity), beginning at 10% of disease duration of lower extremity onset and increasing thereafter for all sites. The cumulative probability of costs of items and interventions began at 25%-50% of disease duration and increased to between $18,000 and $32,000 (USD), highest for lower extremity onset due to the cost of wheelchairs. We conclude that a high percentage of ALS patients will need a full spectrum of major DME items and interventions during the second half of disease duration. This results in a linear rise in costs over the second half of the disease duration.

TRICARE program; clarification of benefit coverage of durable equipment and ordering or prescribing durable equipment; clarification of benefit coverage of assistive technology devises under the Extended Care Health Option Program. Final rule.

PubMed

2014-12-31

This final rule modifies the TRICARE regulation to add a definition of assistive technology (AT) devices for purposes of benefit coverage under the TRICARE Extended Care Health Option (ECHO) Program and to amend the definitions of durable equipment (DE) and durable medical equipment (DME) to better conform the language in the regulation to the statute. The final rule amends the language that specifically limits ordering or prescribing of DME to only a physician under the Basic Program, as this amendment will allow certain other TRICARE authorized individual professional providers, acting within the scope of their licensure, to order or prescribe DME. This final rule also incorporates a policy clarification relating to luxury, deluxe, or immaterial features of equipment or devices. That is, TRICARE cannot reimburse for the luxury, deluxe, or immaterial features of equipment or devices, but can reimburse for the base or basic equipment or device that meet the beneficiary's needs. Beneficiaries may choose to pay the provider for the luxury, deluxe, or immaterial features if they desire their equipment or device to have these "extra features."

High Throughput Sequencing Identifies MicroRNAs Mediating α-Synuclein Toxicity by Targeting Neuroactive-Ligand Receptor Interaction Pathway in Early Stage of Drosophila Parkinson's Disease Model

PubMed Central

Kong, Yan; Liang, Xijun; Liu, Lin; Zhang, Dongdong; Wan, Chao; Gan, Zhenji; Yuan, Liudi

2015-01-01

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder with pathological features including death of dopaminergic neurons in the substantia nigra and intraneuronal accumulations of Lewy bodies. As the main component of Lewy bodies, α-synuclein is implicated in PD pathogenesis by aggregation into insoluble filaments. However, the detailed mechanisms underlying α-synuclein induced neurotoxicity in PD are still elusive. MicroRNAs are ~20nt small RNA molecules that fine-tune gene expression at posttranscriptional level. A plethora of miRNAs have been found to be dysregulated in the brain and blood cells of PD patients. Nevertheless, the detailed mechanisms and their in vivo functions in PD still need further investigation. By using Drosophila PD model expressing α-synuclein A30P, we examined brain miRNA expression with high-throughput small RNA sequencing technology. We found that five miRNAs (dme-miR-133-3p, dme-miR-137-3p, dme-miR-13b-3p, dme-miR-932-5p, dme-miR-1008-5p) were upregulated in PD flies. Among them, miR-13b, miR-133, miR-137 are brain enriched and highly conserved from Drosophila to humans. KEGG pathway analysis using DIANA miR-Path demonstrated that neuroactive-ligand receptor interaction pathway was most likely affected by these miRNAs. Interestingly, miR-137 was predicted to regulate most of the identified targets in this pathway, including dopamine receptor (DopR, D2R), γ-aminobutyric acid (GABA) receptor (GABA-B-R1, GABA-B-R3) and N-methyl-D-aspartate (NMDA) receptor (Nmdar2). The validation experiments showed that the expression of miR-137 and its targets was negatively correlated in PD flies. Further experiments using luciferase reporter assay confirmed that miR-137 could act on specific sites in 3’ UTR region of D2R, Nmdar2 and GABA-B-R3, which downregulated significantly in PD flies. Collectively, our findings indicate that α-synuclein could induce the dysregulation of miRNAs, which target neuroactive ligand-receptor interaction pathway in vivo. We believe it will help us further understand the contribution of miRNAs to α-synuclein neurotoxicity and provide new insights into the pathogenesis driving PD. PMID:26361355

High Throughput Sequencing Identifies MicroRNAs Mediating α-Synuclein Toxicity by Targeting Neuroactive-Ligand Receptor Interaction Pathway in Early Stage of Drosophila Parkinson's Disease Model.

PubMed

Kong, Yan; Liang, Xijun; Liu, Lin; Zhang, Dongdong; Wan, Chao; Gan, Zhenji; Yuan, Liudi

2015-01-01

Parkinson's disease (PD) is a prevalent neurodegenerative disorder with pathological features including death of dopaminergic neurons in the substantia nigra and intraneuronal accumulations of Lewy bodies. As the main component of Lewy bodies, α-synuclein is implicated in PD pathogenesis by aggregation into insoluble filaments. However, the detailed mechanisms underlying α-synuclein induced neurotoxicity in PD are still elusive. MicroRNAs are ~20nt small RNA molecules that fine-tune gene expression at posttranscriptional level. A plethora of miRNAs have been found to be dysregulated in the brain and blood cells of PD patients. Nevertheless, the detailed mechanisms and their in vivo functions in PD still need further investigation. By using Drosophila PD model expressing α-synuclein A30P, we examined brain miRNA expression with high-throughput small RNA sequencing technology. We found that five miRNAs (dme-miR-133-3p, dme-miR-137-3p, dme-miR-13b-3p, dme-miR-932-5p, dme-miR-1008-5p) were upregulated in PD flies. Among them, miR-13b, miR-133, miR-137 are brain enriched and highly conserved from Drosophila to humans. KEGG pathway analysis using DIANA miR-Path demonstrated that neuroactive-ligand receptor interaction pathway was most likely affected by these miRNAs. Interestingly, miR-137 was predicted to regulate most of the identified targets in this pathway, including dopamine receptor (DopR, D2R), γ-aminobutyric acid (GABA) receptor (GABA-B-R1, GABA-B-R3) and N-methyl-D-aspartate (NMDA) receptor (Nmdar2). The validation experiments showed that the expression of miR-137 and its targets was negatively correlated in PD flies. Further experiments using luciferase reporter assay confirmed that miR-137 could act on specific sites in 3' UTR region of D2R, Nmdar2 and GABA-B-R3, which downregulated significantly in PD flies. Collectively, our findings indicate that α-synuclein could induce the dysregulation of miRNAs, which target neuroactive ligand-receptor interaction pathway in vivo. We believe it will help us further understand the contribution of miRNAs to α-synuclein neurotoxicity and provide new insights into the pathogenesis driving PD.

Differentiation of fat, muscle, and edema in thigh MRIs using random forest classification

NASA Astrophysics Data System (ADS)

Kovacs, William; Liu, Chia-Ying; Summers, Ronald M.; Yao, Jianhua

2016-03-01

There are many diseases that affect the distribution of muscles, including Duchenne and fascioscapulohumeral dystrophy among other myopathies. In these disease cases, it is important to quantify both the muscle and fat volumes to track the disease progression. There has also been evidence that abnormal signal intensity on the MR images, which often is an indication of edema or inflammation can be a good predictor for muscle deterioration. We present a fully-automated method that examines magnetic resonance (MR) images of the thigh and identifies the fat, muscle, and edema using a random forest classifier. First the thigh regions are automatically segmented using the T1 sequence. Then, inhomogeneity artifacts were corrected using the N3 technique. The T1 and STIR (short tau inverse recovery) images are then aligned using landmark based registration with the bone marrow. The normalized T1 and STIR intensity values are used to train the random forest. Once trained, the random forest can accurately classify the aforementioned classes. This method was evaluated on MR images of 9 patients. The precision values are 0.91+/-0.06, 0.98+/-0.01 and 0.50+/-0.29 for muscle, fat, and edema, respectively. The recall values are 0.95+/-0.02, 0.96+/-0.03 and 0.43+/-0.09 for muscle, fat, and edema, respectively. This demonstrates the feasibility of utilizing information from multiple MR sequences for the accurate quantification of fat, muscle and edema.

Anti-inflammatory and cytotoxic activities of Bursera copallifera

PubMed Central

Columba-Palomares, M. F. María C.; Villareal, Dra. María L.; Acevedo Quiroz, M. C. Macdiel E.; Marquina Bahena, M. C. Silvia; Álvarez Berber, Dra. Laura P.; Rodríguez-López, Dra. Verónica

2015-01-01

Background: The plant species Bursera copallifera (DC) bullock is used in traditional medicine to treat inflammation. The leaves of this plant can be prepared as an infusion to treat migraines, bronchitis, and dental pain Objective: The purpose of this study was to determine the anti-inflammatory and cytotoxic activities of organic extracts from the stems, stem bark, and leaves of B. copallifera, which was selected based on the knowledge of its traditional use. Materials and Methods: We evaluated the ability of extracts to inhibit mouse ear inflammation in response to topical application of 12-O tetradecanoylphorbol-13-acetate. The extracts with anti-inflammatory activity were evaluated for their inhibition of pro-inflammatory enzymes. In addition, the in vitro cytotoxic activities of the organic extracts were evaluated using the sulforhodamine B assay. Results: The hydroalcoholic extract of the stems (HAS) exhibited an anti-inflammatory activity of 54.3% (0.5 mg/ear), whereas the anti-inflammatory activity of the dichloromethane-methanol extract from the leaves (DMeL) was 55.4% at a dose of 0.1 mg/ear. Methanol extract from the leaves (MeL) showed the highest anti-inflammatory activity (IC50 = 4.4 μg/mL), hydroalcoholic extract of leaves, and DMeL also reduce the enzyme activity, (IC50 = 6.5 μg/mL, IC50 = 5.7 μg/mL), respectively, from stems HAS exhibit activity at the evaluated concentrations (IC50 =6.4 μg/mL). The hydroalcoholic extract of the stems exhibited the highest cytotoxic activity against a breast adenocarcinoma cell line (MCF7, IC50 = 0.90 μg/mL), whereas DMeL exhibited an IC50 value of 19.9 μg/mL. Conclusion: In conclusion, extracts from leaves and stems inhibited cyclooxygenase-1, which is the target enzyme for nonsteroidal anti inflammatory drugs, and some of these extracts demonstrated substantial antiproliferative effects against the MCF7 cell line. These results validate the traditional use of B. copallifera. PMID:26664022

Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma.

PubMed

Lee, Yi-Ying; Chao, Tung-Bo; Sheu, Ming-Jen; Tian, Yu-Feng; Chen, Tzu-Ju; Lee, Sung-Wei; He, Hong-Lin; Chang, I-Wei; Hsing, Chung-Hsi; Lin, Ching-Yih; Li, Chien-Feng

2016-01-01

Background : Glutamate decarboxylase 1 (GAD1) which serves as a rate-limiting enzyme involving in the production of γ-aminobutyric acid (GABA), exists in the GABAergic neurons in the central nervous system (CNS). Little is known about the relevance of GAD1 to nasopharyngeal carcinoma (NPC). Through data mining on a data set derived from a published transcriptome database, this study first identified GAD1 as a differentially upregulated gene in NPC. We aimed to evaluate GAD1 expression and its prognostic effect on patients with early and locoregionally advanced NPC. Methods : We evaluated GAD1 immunohistochemistry and performed an H-score analysis on biopsy specimens from 124 patients with nonmetastasized NPC receiving treatment. GAD1 overexpression was defined as an H score higher than the median value. The findings of such an analysis are correlated with clinicopathological behaviors and survival rates, namely disease-specific survival (DSS), distant-metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) rates. Results : GAD1 overexpression was significantly associated with an increase in the primary tumor status ( p < 0.001) and American Joint Committee on Cancer (AJCC) stages III-IV ( p = 0.002) and was a univariate predictor of adverse outcomes of DSS ( p = 0.002), DMeFS ( p < 0.0001), and LRFS ( p = 0.001). In the multivariate comparison, in addition to advanced AJCC stages III-IV, GAD1 overexpression remained an independent prognosticator of short DSS ( p = 0.004, hazard ratio = 2.234), DMeFS ( p < 0.001, hazard ratio = 4.218), and LRFS ( p = 0.013, hazard ratio = 2.441) rates. Conclusions : Our data reveal that GAD1 overexpression was correlated with advanced disease status and may thus be a critical prognostic indicator of poor outcomes in NPC and a potential therapeutic target to facilitate the development of effective treatment modalities.

Variation at the NFATC2 Locus Increases the Risk of Thiazolidinedione-Induced Edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) Study

PubMed Central

Bailey, Swneke D.; Xie, Changchun; Do, Ron; Montpetit, Alexandre; Diaz, Rafael; Mohan, Viswanathan; Keavney, Bernard; Yusuf, Salim; Gerstein, Hertzel C.; Engert, James C.; Anand, Sonia

2010-01-01

OBJECTIVE Thiazolidinediones are used to treat type 2 diabetes. Their use has been associated with peripheral edema and congestive heart failure—outcomes that may have a genetic etiology. RESEARCH DESIGN AND METHODS We genotyped 4,197 participants of the multiethnic DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) trial with a 50k single nucleotide polymorphisms (SNP) array, which captures ∼2000 cardiovascular, inflammatory, and metabolic genes. We tested 32,088 SNPs for an association with edema among Europeans who received rosiglitazone (n = 965). RESULTS One SNP, rs6123045, in NFATC2 was significantly associated with edema (odds ratio 1.89 [95% CI 1.47–2.42]; P = 5.32 × 10−7, corrected P = 0.017). Homozygous individuals had the highest edema rate (hazard ratio 2.89, P = 4.22 × 10−4) when compared with individuals homozygous for the protective allele, with heterozygous individuals having an intermediate risk. The interaction between the SNP and rosiglitazone for edema was significant (P = 7.68 × 10−3). Six SNPs in NFATC2 were significant in both Europeans and Latin Americans (P < 0.05). CONCLUSIONS Genetic variation at the NFATC2 locus contributes to edema among individuals who receive rosiglitazone. PMID:20628086

A long-distance fluid transport pathway within fibrous connective tissues in patients with ankle edema.

PubMed

Li, Hongyi; Yang, Chongqing; Lu, Kuiyuan; Zhang, Liyang; Yang, Jiefu; Wang, Fang; Liu, Dongge; Cui, Di; Sun, Mingjun; Pang, Jianxin; Dai, Luru; Han, Dong; Liao, Fulong

2016-10-05

Although the microcirculatory dysfunctions of edema formation are well documented, the draining pattern of dermal edema lacks information. This study was to assess the potential drainage pathways of the interstitial fluid in patients with ankle edema using the anatomical and histological methods. Four amputees of lower leg participated in this study. Fluorescent imaging agent was injected into lateral ankle dermis in one volunteered patient before the amputation and three lower legs after the amputation. Physiologically in the volunteer or enhanced by cyclical compression on three amputated limbs, several fluorescent longitudinal pathways from ankle dermis to the broken end of the amputated legs were subsequently visualized and studied using histological methods, laser confocal microscopy and electron microscopy methods respectively. Interestingly, the fluorescent pathways confirmed to be fibrous connective tissues and the presence of two types: those of the cutaneous pathway (located in dermis or the interlobular septum among adipose tissues within the hypodermis) and those of the perivascular pathway (located in connective tissues surrounding the veins and the arteries). The intrinsic three-dimensional architecture of each fluorescent pathway was the longitudinally running and interconnected fibril bundles, upon which, an interfacial transport pathway within connective tissues was visualized by fluorescein. The current anatomical data suggested that a unique long-distance transport pathway composed of oriented fibrous connective tissues might play a pathophysiological role in draining dermal edema besides vascular circulations and provide novel understandings of general fibrous connective tissues in life science.

Semi-automated brain tumor and edema segmentation using MRI.

PubMed

Xie, Kai; Yang, Jie; Zhang, Z G; Zhu, Y M

2005-10-01

Manual segmentation of brain tumors from magnetic resonance images is a challenging and time-consuming task. A semi-automated method has been developed for brain tumor and edema segmentation that will provide objective, reproducible segmentations that are close to the manual results. Additionally, the method segments non-enhancing brain tumor and edema from healthy tissues in magnetic resonance images. In this study, a semi-automated method was developed for brain tumor and edema segmentation and volume measurement using magnetic resonance imaging (MRI). Some novel algorithms for tumor segmentation from MRI were integrated in this medical diagnosis system. We exploit a hybrid level set (HLS) segmentation method driven by region and boundary information simultaneously, region information serves as a propagation force which is robust and boundary information serves as a stopping functional which is accurate. Ten different patients with brain tumors of different size, shape and location were selected, a total of 246 axial tumor-containing slices obtained from 10 patients were used to evaluate the effectiveness of segmentation methods. This method was applied to 10 non-enhancing brain tumors and satisfactory results were achieved. Two quantitative measures for tumor segmentation quality estimation, namely, correspondence ratio (CR) and percent matching (PM), were performed. For the segmentation of brain tumor, the volume total PM varies from 79.12 to 93.25% with the mean of 85.67+/-4.38% while the volume total CR varies from 0.74 to 0.91 with the mean of 0.84+/-0.07. For the segmentation of edema, the volume total PM varies from 72.86 to 87.29% with the mean of 79.54+/-4.18% while the volume total CR varies from 0.69 to 0.85 with the mean of 0.79+/-0.08. The HLS segmentation method perform better than the classical level sets (LS) segmentation method in PM and CR. The results of this research may have potential applications, both as a staging procedure and a method of evaluating tumor response during treatment, this method can be used as a clinical image analysis tool for doctors or radiologists.

Toward automated selective retina treatment (SRT): an optical microbubble detection technique

NASA Astrophysics Data System (ADS)

Seifert, Eric; Park, Young-Gun; Theisen-Kunde, Dirk; Roh, Young-Jung; Brinkmann, Ralf

2018-02-01

Selective retina therapy (SRT) is an ophthalmological laser technique, targeting the retinal pigment epithelium (RPE) with repetitive microsecond laser pulses, while causing no thermal damage to the neural retina, the photoreceptors as well as the choroid. The RPE cells get damaged mechanically by microbubbles originating, at the intracellular melanosomes. Beneficial effects of SRT on Central Serous Retinopathy (CSR) and Diabetic Macula Edema (DME) have already been shown. Variations in the transmission of the anterior eye media and pigmentation variation of RPE yield in intra- and inter- individual thresholds of the pulse energy required for selective RPE damage. Those selective RPE lesions are not visible. Thus, dosimetry-systems, designed to detect microbubbles as an indicator for RPE cell damage, are demanded elements to facilitate SRT application. Therefore, a technique based on the evaluation of backscattered treatment light has been developed. Data of 127 spots, acquired during 10 clinical treatments of CSR patients, were assigned to a RPE cell damage class, validated by fluorescence angiography (FLA). An algorithm has been designed to match the FLA based information. A sensitivity of 0.9 with a specificity close to 1 is achieved. The data can be processed within microseconds. Thus, the process can be implemented in existing SRT lasers with an automatic pulse wise increasing energy and an automatic irradiation ceasing ability to enable automated treatment close above threshold to prevent adverse effects caused by too high pulse energy. Alternatively, a guidance procedure, informing the treating clinician about the adequacy of the actual settings, is possible.

Mechanistic differences between methanol and dimethyl ether carbonylation in side pockets and large channels of mordenite.

PubMed

Boronat, Mercedes; Martínez, Cristina; Corma, Avelino

2011-02-21

The activity and selectivity towards carbonylation presented by Brønsted acid sites located inside the 8MR pockets or in the main 12MR channels of mordenite is studied by means of quantum-chemical calculations, and the mechanistic differences between methanol and DME carbonylation are investigated. The selectivity towards carbonylation is higher inside the 8MR pockets, where the competitive formation of DME and hydrocarbons that finally leads to catalyst deactivation is sterically impeded. Moreover, inclusion of dispersion interactions in the calculations leads to agreement between the calculated activation barriers for the rate determining step and the experimentally observed higher reactivity of methoxy groups located inside the 8MR channels.

Diminished but Not Abolished Effect of Two His351 Mutants of Anthrax Edema Factor in a Murine Model

PubMed Central

Zhao, Taoran; Zhao, Xinghui; Liu, Ju; Meng, Yingying; Feng, Yingying; Fang, Ting; Zhang, Jinlong; Yang, Xiuxu; Li, Jianmin; Xu, Junjie; Chen, Wei

2016-01-01

Edema toxin (ET), which is composed of a potent adenylate cyclase (AC), edema factor (EF), and protective antigen (PA), is one of the major toxicity factors of Bacillus anthracis. In this study, we introduced mutations in full-length EF to generate alanine EF(H351A) and arginine EF(H351R) variants. In vitro activity analysis displayed that the adenylyl cyclase activity of both the mutants was significantly diminished compared with the wild-type EF. When the native and mutant toxins were administered subcutaneously in a mouse footpad edema model, severe acute swelling was evoked by wild-type ET, while the symptoms induced by mutant toxins were very minor. Systemic administration of these EF variants caused non-lethal hepatotoxicity. In addition, EF(H351R) exhibited slightly higher activity in causing more severe edema than EF(H351A). Our findings demonstrate that the toxicity of ET is not abolished by substitution of EF residue His351 by alanine or arginine. These results also indicate the potential of the mouse footpad edema model as a sensitive method for evaluating both ET toxicity and the efficacy of candidate therapeutic agents. PMID:26848687

ILM peeling in nontractional diabetic macular edema: review and metanalysis.

PubMed

Rinaldi, M; dell'Omo, R; Morescalchi, F; Semeraro, F; Gambicorti, E; Cacciatore, F; Chiosi, F; Costagliola, C

2017-10-31

To evaluate the effect of internal limiting membrane (ILM) peeling during vitrectomy for nontractional diabetic macular edema. PUBMED, MEDLINE and CENTRAL were reviewed using the following terms (or combination of terms): diabetic macular edema, nontractional diabetic macular edema, internal limiting membrane peeling, vitrectomy, Müller cells. Randomized and nonrandomized studies were included. The eligible studies compared anatomical and functional outcomes of vitrectomy with or without ILM peeling for tractional and nontractional diabetic macular edema. Postoperative best-corrected visual acuity and central macular thickness were considered, respectively, the primary and secondary outcomes. Meta-analysis on mean differences between vitrectomy with and without ILM peeling was performed using inverse variance method in random effects. Four studies with 672 patients were eligible for analysis. No significant difference was found between postoperative best-corrected visual acuity or best-corrected visual acuity change of ILM peeling group compared with nonpeeling group. There was no significant difference in postoperative central macular thickness and central macular thickness reduction between the two groups. The visual acuity outcomes in patients affected by nontractional diabetic macular edema using pars plana vitrectomy with ILM peeling versus no ILM peeling were not significantly different. A larger prospective and randomized study would be necessary.

Airborne field strength monitoring

NASA Astrophysics Data System (ADS)

Bredemeyer, J.; Kleine-Ostmann, T.; Schrader, T.; Münter, K.; Ritter, J.

2007-06-01

In civil and military aviation, ground based navigation aids (NAVAIDS) are still crucial for flight guidance even though the acceptance of satellite based systems (GNSS) increases. Part of the calibration process for NAVAIDS (ILS, DME, VOR) is to perform a flight inspection according to specified methods as stated in a document (DOC8071, 2000) by the International Civil Aviation Organization (ICAO). One major task is to determine the coverage, or, in other words, the true signal-in-space field strength of a ground transmitter. This has always been a challenge to flight inspection up to now, since, especially in the L-band (DME, 1GHz), the antenna installed performance was known with an uncertainty of 10 dB or even more. In order to meet ICAO's required accuracy of ±3 dB it is necessary to have a precise 3-D antenna factor of the receiving antenna operating on the airborne platform including all losses and impedance mismatching. Introducing precise, effective antenna factors to flight inspection to achieve the required accuracy is new and not published in relevant papers yet. The authors try to establish a new balanced procedure between simulation and validation by airborne and ground measurements. This involves the interpretation of measured scattering parameters gained both on the ground and airborne in comparison with numerical results obtained by the multilevel fast multipole algorithm (MLFMA) accelerated method of moments (MoM) using a complex geometric model of the aircraft. First results will be presented in this paper.

Correlation between subacute sensorimotor deficits and brain edema in two mouse models of intracerebral hemorrhage

PubMed Central

Krafft, Paul R.; McBride, Devin W.; Lekic, Tim; Rolland, William B.; Mansell, Charles E.; Ma, Qingyi; Tang, Jiping; Zhang, John H.

2014-01-01

Formation of brain edema after intracerebral hemorrhage (ICH) is highly associated with its poor outcome, thus it is clinically important to understand the effect brain edema has on outcome. However, the relationship between cerebral edema and behavioral deficits has not been thoroughly examined in the preclinical setting. Hence, this study aimed to evaluate the ability of common sensorimotor tests to predict the extent of brain edema in two mouse models of ICH. One hundred male CD-1 mice were subjected to sham surgery or ICH induction via intrastriatal injection of either autologous blood (30 μL) or bacterial collagenase (0.0375 U or 0.075 U). At 24 and 72 hours after surgery, animals underwent a battery of behavioral tests, including the modified Garcia neuroscore (Neuroscore), corner turn test (CTT), forelimb placing test (FPT), wire hang task (WHT) and beam walking (BW). Brain edema was evaluated via the wet weight/dry weight method. Intrastriatal injection of autologous blood or bacterial collagenase resulted in a significant increase in brain water content and associated sensorimotor deficits (p<0.05). A significant correlation between brain edema and sensorimotor deficits was observed for all behavioral tests except for WHT and BW. Based on these findings, we recommend implementing the Neuroscore, CTT and/or FPT in preclinical studies of unilateral ICH in mice. PMID:24518201

An investigation into the effects of different existing states of aluminum isopropoxide on copper-based catalysts for direct synthesis of dimethyl ether from syngas

NASA Astrophysics Data System (ADS)

Sun, Kai; Wang, Peng; Bian, Zhongkai; Huang, Wei

2018-01-01

Aluminum isopropoxide (AIP) is a vital raw material to produce high surface area alumina catalyst, which is used for catalytic applications, such as hydrocracking, Fischer-Tropsch and STD (syngas to dimethyl ether) reactions. However, the different existing states have an effect on hydrolysis and condensation in the process of precursor preparation. The Cu/Zn/Al slurry catalysts were prepared by aluminum isopropoxide, which were liquid state, crystalline state and solid state, utilizing a complete liquid phase preparation technology. In the dimethyl ether (DME) synthesis reaction, the aluminum resource of crystalline state was prepared for slurry catalyst, which presented high CO conversion and DME selectivity of 54.32% and 69.74%, respectively. Characterization results indicated that different forms of AIP have the variant coordination numbers of Al-O and polymerization degrees, and the catalyst prepared by crystalline state consists amount of tetra-coordinated Al and few hexa-coordinated Al, which can exert different hydrolysis and condensation process compared with other aluminum sources, and finally it contributes to the strong interaction between active site copper species and Zn/Al species, confirming more Cu+ is responsible for the synthesis of DME in the slurry reactor.

A Pulsed Plasma Thruster Using Dimethyl Ether as Propellant

NASA Astrophysics Data System (ADS)

Masui, Souichi; Okada, Terumasa; Kitatomi, Makoto; Kakami, Akira; Tachibana, Takeshi

The pulsed plasma thruster (PPT), has attracted attention again as a micro-thruster because of its compactness, light weight, and comparatively low power consumption. On the other hand, the propellant utilization efficiency of a conventinal Teflon PPT is relatively low among electric propulsion devices because a propellant that originates from late-time ablation produces negligible thrust. The liquid propellant PPT (LP-PPT), in which water or ethanol is fed with an injector, was proposed to overcome these difficulties. Thrust measurements show that a LP-PPT provides higher specific impulses than a conventional PPT. However, water requires temperature management for propellant storage due to its relatively high freezing point. Moreover, even if ethanol, which has a sufficiently low freezing point, is used as propellant, a pressurant is necessary, as well as water, because the vapor pressures are insufficient for self-pressurization. In this study, we propose to use dimethyl ether (DME) as the propellant. DME, which has a freezing point of 131 K at 1 atm and a vapor pressure of 6 atm at 298 K, can be stored in tanks as a liquid, and requires no feeding pressurant. We designed a DME pulsed plasma thruster to evaluate performance. Thrust measurement yielded a specific impulse of 430 s for a coaxial type at a capacitor-stored energy of 13 J.

Comparison of Oxygen Gauche Effects in Poly(Oxyethylene) and Poly(ethylene terephtylene) Based on Quantum Chemistry Calculations

NASA Technical Reports Server (NTRS)

Jaffe, Richard; Han, Jie; Yoon, Do; Langhoff, Stephen R. (Technical Monitor)

1997-01-01

The so-called oxygen gauche effect in poly(oxyethylene) (POE) and its model molecules such as 1,2-dimethoxyethane (DME) and diglyme (CH3OC2H4OC2H4OCH3) is manifested in the preference for gauche C-C bond conformations over trans. This has also been observed for poly(ethylene terephthalate) (PET). Our previous quantum chemistry calculations demonstrated that the large C-C gauche population in DME is due, in part, to a low-lying tg +/- g+ conformer that exhibits a substantial 1,5 CH ... O attraction. New calculations will be described that demonstrate the accuracy of the original quantum chemistry calculations. In addition, an extension of this work to model molecules for PET will be presented. It is seen that the C-C gauche preference is much stronger in 1,2 diacetoxyethane than in DME. In addition, there exist low-lying tg +/- g+/- and g+/-g+/-g+/- conformers that exhibit 1,5 CH ... O attractions involving the carbonyl oxygens. It is expected that the -O-C-C-O- torsional properties will be quite different in these two polymers. The quantum chemistry results are used to parameterize rotational isomeric states models (RIS) and force fields for molecular dynamics simulations of these polymers.

Hydrazino-methoxy-1,3,5-triazine Derivatives' Excellent Corrosion Organic Inhibitors of Steel in Acidic Chloride Solution.

PubMed

El-Faham, Ayman; Osman, Sameh M; Al-Lohedan, Hamad A; El-Mahdy, Gamal A

2016-06-01

The corrosion inhibition performance of 2-hydrazino-4,6-dimethoxy-1,3,5-tirazine (DMeHT), 2,4-dihydrazino-6-methoxy-1,3,5-triaizine (DHMeT), and 2,4,6-tridydrazino-1,3,5-triaizne (TH₃) on steel corrosion in acidic media was examined using electrochemical techniques. The results showed 2,4-Ddihydrazino-6-methoxy-1,3,5-triaizine (DHMeT) gave the best corrosion protection performance among the other hydrazino derivatives even at a low concentration of 25 ppm (95%). The number of hydrazino groups play an important role in the corrosion inhibition, where the two hydrazine groups increased the electrostatic interactions between the protonated tested compounds, the negatively charged steel surface resulted from the adsorption of the chloride anions, and the presence of the methoxy group made the compound more reliable for formation of film protection on the surface of steel through the lone pair of oxygen atoms. Electrochemical Impedance Spectroscopy (EIS) measurements suggested that the corrosion process of steel in presence of the hydrazino-s-triazine derivatives (TH₃, DMeHT and DHMeT) were being controlled by the charge transfer reaction. Polarization curves indicated that the examined TH₃, DMeHT and DHMeT behaved as mixed type inhibitors.

Time-resolved Spectroscopy of RS CVn Binaries and dMe Flare Stars

NASA Astrophysics Data System (ADS)

Brown, Alexander

One of the most striking feature of the first two years of EUVE spectroscopy is the frequent occurrence of largescale coronal variability, in the form of stellar flares and slower changes in activity level due to rotational modulation and evolution of active regions. We propose EUVE observations of a set of RS CVn and dMe star binaries, most with short (< 2 days) periods, to investigate the coronal conditions and physical processes associated with this variability. EUVE flare outbursts have mostly been long duration events lasting many satellite orbits and been readily studied using time-resolved spectroscopy. Our targets are the dMe binaries YY Gem, CC Eri and Gliese 2123, and the RS CVn systems EI Eri, AR Psc, and TY Pyx. YY Gem and TY Pyx are eclipsing systems and Deep Survey photometry will be used to investigate the size of the coronal emitting regions. Situated 73 arcmin from YY Gem is Castor (Alpha Gem) another X-ray source that can be observed (and spatially resolved) simultaneously. We shall use the DS lightcurve to guide our time resolved spectral analysis. Changes in the coronal emission measure as a function of temperature and possibly changes in coronal density will be used to constrain magnetic loop models.

The Redox-Active Chromium Phthalocyanine System: Isolation of Five Oxidation States from Pc4- CrI to Pc2- CrIII.

PubMed

Zhou, Wen; Thompson, John R; Leznoff, Clifford C; Leznoff, Daniel B

2017-02-16

The preparation and structural characterization of a series of chromium phthalocyanine complexes with multiple metal and ring oxidation states were achieved using PcCr II (1) (Pc=phthalocyanine) or PcCr II (THF) 2 (1⋅THF 2 ) as starting materials. The reaction of soluble 1⋅THF 2 with Br 2 or I 2 gave the PcCr III halide complexes PcCrX(THF) (X=I/I 3 , Br; 3, 4, respectively). Treatment of 1 with 0.5 equivalent of PhIO or air generated the dinuclear [PcCr(THF)] 2 (μ-O) (5), whereas the addition of one equivalent of AgSbF 6 to 1 resulted in oxidation to THF-solvated octahedral [PcCr III (THF) 2 ]SbF 6 (6). The reduction of 1 with three sequential equivalents of KEt 3 BH resulted in the isolation of [K(DME) 4 ][Pc 3- Cr II ] (7), [K(DME) 4 ] 2 [Pc 4- Cr II ] (8) and [K 6 (DME) 4 ][Pc 4- Cr I ] 2 (9), respectively. The reduced products are deep purple in colour, with visible absorption maxima between 500-580 nm. The ring-reduced complexes 7 and 8 are monomeric, whereas 9 is a 1D chain of dinuclear [PcCr] 2 units with intercalated K + cations and supported by Cr-Cr interactions of 2.988(2) Å. Addition of four equivalents of KC 8 resulted in the demetallated product PcK 2 (DME) 4 (10), which has a 1D chain structure. The isolation and structural characterization of new PcCr complexes spanning five oxidation states, including rare examples of crystalline reduced Pc-ring species emphasizes the broad redox activity and stability of phthalocyanine-based complexes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

First-Principles Mechanistic Analysis of Dimethyl Ether Electro-Oxidation on Monometallic Single-Crystal Surfaces

DOE PAGES

Herron, Jeffrey A.; Ferrin, Peter; Mavrikakis, Manos

2014-08-27

Dimethyl ether is an attractive alternative to petroleum fuels due to its physical properties, comparable energy density to methanol and ethanol, and minimal deleterious environmental/toxicological effects. For direct fuel cells, it has a number of advantages over other prominent fuels, including easier storage with respect to hydrogen, lower toxicity and crossover when compared to methanol, and more facile complete oxidation as compared to ethanol (which includes a relatively difficult to break C–C bond). However, the dimethyl ether electro-oxidation reaction is poorly understood, hindering the development of improved electrocatalysts. Using periodic, self-consistent (PW91-GGA) density functional theory calculations, we evaluate the thermochemistrymore » of dimethyl ether (DME) electro-oxidation, at the elementary step level, on 12 model, closed-packed facets of pure transition metals: Au, Ag, Cu, Pt, Pd, Ni, Ir, Rh, Co, Os, Ru, and Re. From the calculated thermochemistry, we determine the most probable reaction paths on each of these surfaces, focusing on Pt as a model system. Our results predict two key electro-oxidation peaks. At lower potentials, there is a peak corresponding to partial oxidation of DME to CO (and other surface poisoning species) or complete oxidation to CO 2 via formic acid as a key intermediate. A second, higher-potential peak is due to complete oxidation of adsorbed CO (and other surface poisoning species) to CO 2. Assuming the catalysts remain in their metallic state during the DME electro-oxidation process, our results suggest that the onset potential of the surfaces increases in the order Cu < Ni < Os < Rh < Ir < Co < Ru < Pt < Ag < Pd < Re < Au. Using our results, we construct a theoretical phase diagram showing predicted catalyst activity based on two key reactivity descriptors, the free energies of adsorbed CO and OH. Here, we compare all results to methanol electro-oxidation to understand key mechanistic differences and their impacts on optimal catalyst design for direct DME fuel cells.« less

Impact of baseline Diabetic Retinopathy Severity Scale scores on visual outcomes in the VIVID-DME and VISTA-DME studies.

PubMed

Staurenghi, Giovanni; Feltgen, Nicolas; Arnold, Jennifer J; Katz, Todd A; Metzig, Carola; Lu, Chengxing; Holz, Frank G

2017-10-19

To evaluate intravitreal aflibercept versus laser in subgroups of patients with baseline Diabetic Retinopathy Severity Scale (DRSS) scores ≤43, 47, and ≥53 in VIVID-DME and VISTA-DME. Patients with diabetic macular oedema were randomised to receive intravitreal aflibercept 2 mg every 4 weeks (2q4), intravitreal aflibercept 2 mg every 8 weeks after five initial monthly doses (2q8), or macular laser photocoagulation at baseline with sham injections at every visit. These post hoc analyses evaluate outcomes based on baseline DRSS scores in patients in the integrated dataset. The 2q4 and 2q8 treatment groups were also pooled. 748 patients had a baseline DRSS score based on fundus photographs (≤43, n=301; 47, n=153; ≥53, n=294). At week 100, the least squares mean difference between treatment groups (effect of intravitreal aflibercept above that of laser, adjusting for baseline best-corrected visual acuity) was 8.9 (95% CI 5.99 to 11.81), 9.7 (95% CI 5.54 to 13.91), and 11.0 (95% CI 7.96 to 14.1) letters in those with baseline DRSS scores ≤43, 47, and ≥53, respectively. The proportions of patients with ≥2 step DRSS score improvement were greater in the intravitreal aflibercept group versus laser, respectively, for those with baseline DRSS scores of ≤43 (13% vs 5.9%), 47 (25.8% vs 4.5%), and ≥53 (64.5% vs 28.4%). Regardless of baseline DRSS score, functional outcomes were superior in intravitreal aflibercept-treated patients, demonstrating consistent treatment benefit across various baseline levels of retinopathy. NCT01331681 and NCT01363440, Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cohesive taping and short-leg casting in acute low-type ankle sprains in physically active patients.

PubMed

Uslu, Mustafa; Inanmaz, Mustafa E; Ozsahin, Mustafa; Isık, Cengiz; Arıcan, Mehmet; Gecer, Yavuz

2015-07-01

Cohesive taping is commonly used for the prevention or treatment of ankle sprain injuries. Short-leg cast immobilization or splinting is another treatment option in such cases. To determine the clinical efficacy and antiedema effects of cohesive taping and short-leg cast immobilization in acute low-type ankle sprains of physically active patients, we performed a preliminary clinical study to assess objective evidence for edema and functional patient American Orthopaedic Foot and Ankle Society (AOFAS) scores with these alternative treatments. Fifty-nine physically active patients were included: 32 in the taping group and 27 in the short-leg cast group within a year. If a sprain was moderate (grade II) or mild (grade I), we used functional taping or short-leg cast immobilization for 10 days. We evaluated the edema and the functional scores of the injured ankle using the AOFAS Clinical Rating System on days 1, 10, and 100. In each group, edema significantly decreased and AOFAS scores increased indicating that both treatment methods were effective. With the numbers available, no statistically significant difference could be detected. Each treatment method was effective in decreasing the edema and increasing the functional scores of the ankle. At the beginning of treatment, not only the level of edema but also the initial functional scores of the ankle and examinations are important in making decisions regarding the optimal treatment option.

MRI Reveals Edema in Larynx (But Not in Brain) During Anaphylactic Hypotension in Anesthetized Rats

PubMed Central

Toyota, Ichiro; Tanida, Mamoru; Wang, Mofei; Kurata, Yasutaka; Tonami, Hisao

2013-01-01

Purpose Anaphylactic shock is sometimes accompanied by local interstitial edema due to increased vascular permeability. We performed magnetic resonance imaging (MRI) to compare edema in the larynx and brain of anesthetized rats during anaphylactic hypotension versus vasodilator-induced hypotension. Methods Male Sprague Dawley rats were subjected to hypotension induced by the ovalbumin antigen (n=7) or a vasodilator sodium nitroprusside (SNP; n=7). Apparent diffusion coefficient (ADC) and T2-relaxation time (T2RT) were quantified on MRI performed repeatedly for up to 68 min after the injection of either agent. The presence of laryngeal edema was also examined by histological examination. Separately, the occurrence of brain edema was assessed by measuring brain water content using the wet/dry method in rats with anaphylaxis (n=5) or SNP (n=5) and the non-hypotensive control rats (n=5). Mast cells in hypothalamus were morphologically examined. Results Mean arterial blood pressure similarly decreased to 35 mmHg after an injection of the antigen or SNP. Hyperintensity on T2-weighted images (as reflected by elevated T2RT) was found in the larynx as early as 13 min after an injection of the antigen, but not SNP. A postmortem histological examination revealed epiglottic edema in the rats with anaphylaxis, but not SNP. In contrast, no significant changes in T2RT or ADC were detectable in the brains of any rats studied. In separate experiments, the quantified brain water content did not increase in either anaphylaxis or SNP rats, as compared with the non-hypotensive control rats. The numbers of mast cells with metachromatic granules in the hypothalamus were not different between rats with anaphylaxis and SNP, suggesting the absence of anaphylactic reaction in hypothalamus. Conclusion Edema was detected using the MRI technique in the larynx during rat anaphylaxis, but not in the brain. PMID:24179686

Voice Quality and Gender Stereotypes: A Study of Lebanese Women with Reinke's Edema

ERIC Educational Resources Information Center

Matar, Nayla; Portes, Cristel; Lancia, Leonardo; Legou, Thierry; Baider, Fabienne

2016-01-01

Purpose Women with Reinke's edema (RW) report being mistaken for men during telephone conversations. For this reason, their masculine-sounding voices are interesting for the study of gender stereotypes. The study's objective is to verify their complaint and to understand the cues used in gender identification. Method Using a self-evaluation study,…

Effects of digital altimetry on pilot workload

NASA Technical Reports Server (NTRS)

Harris, R. L., Sr.; Glover, B. J.

1985-01-01

A series of VOR-DME instrument landing approaches was flown in the DC-9 full-workload simulator to compare pilot performance, scan behavior, and workload when using a computer-drum-pointer altimeter (CDPA) and a digital altimeter (DA). Six pilots executed two sets of instrument landing approaches, with a CDPA on one set and a DA on the other set. Pilot scanning parameters, flight performance, and subjective opinion data were evaluated. It is found that the processes of gathering information from the CDPA and the DA are different. The DA requires a higher mental workload than the CDPA for a VOR-DME type landing approach. Mental processing of altitude information after transitioning back to the attitude indicator is more evident with the DA than with the CDPA.

Correlation between subacute sensorimotor deficits and brain edema in two mouse models of intracerebral hemorrhage.

PubMed

Krafft, Paul R; McBride, Devin W; Lekic, Tim; Rolland, William B; Mansell, Charles E; Ma, Qingyi; Tang, Jiping; Zhang, John H

2014-05-01

Formation of brain edema after intracerebral hemorrhage (ICH) is highly associated with its poor outcome. However, the relationship between cerebral edema and behavioral deficits has not been thoroughly examined in the preclinical setting. Hence, this study aimed to evaluate the ability of common sensorimotor tests to predict the extent of brain edema in two mouse models of ICH. One hundred male CD-1 mice were subjected to sham surgery or ICH induction via intrastriatal injection of either autologous blood (30 μL) or bacterial collagenase (0.0375U or 0.075U). At 24 and 72 h after surgery, animals underwent a battery of behavioral tests, including the modified Garcia neuroscore (Neuroscore), corner turn test (CTT), forelimb placing test (FPT), wire hang task (WHT) and beam walking (BW). Brain edema was evaluated via the wet weight/dry weight method. Intrastriatal injection of autologous blood or bacterial collagenase resulted in a significant increase in brain water content and associated sensorimotor deficits (p<0.05). A significant correlation between brain edema and sensorimotor deficits was observed for all behavioral tests except for WHT and BW. Based on these findings, we recommend implementing the Neuroscore, CTT and/or FPT in preclinical studies of unilateral ICH in mice. Copyright © 2014 Elsevier B.V. All rights reserved.

Partial results after treatment of diabetic macular edema with Bevacizumab

PubMed Central

Marius, Giurgică; Dorin, Chiseliță; Doina, Dimofte

2015-01-01

Purpose: To present the morphological and functional results after treating diabetic macular edema with Bevacizumab. Patient and method: It is a prospective trial which includes 15 patients with diabetic macular edema (proved by OCT and fluorescein angiography examination). The inclusion criteria are: central retinal thickness over 250 µm, visual acuity of the studied eye between 0.1 and 0.5, absence of a previous treatment. We excluded patients with macular edema caused by other ethiology or with any other macular disease. Every patient was treated with 3 intravitreal injections with Bevacizumab at every 6 weeks; we analyzed the results after 4 months. Results: The mean visual acuity improved from 0.33 ± 0.06 at baseline to 0.49 ± 0.13 at 4 months (or from 31±3.9 ETDRS letters to 39±5.67 letters). The central retinal thickness decreased from 457 ± 174 µm to 338 ± 139 µm. There was also an improvement of retinal sensibility on the microperimetry map. Conclusions: The treatment of diabetic macular edema produced an increase of visual acuity and a decrease of macular thickness after the first 3 injections with Avastin, but it is necessary to monitor the patients to detect the rebound of the edema and to initiate retreatment. PMID:29450315

Partial results after treatment of diabetic macular edema with Bevacizumab.

PubMed

Marius, Giurgică; Dorin, Chiseliță; Doina, Dimofte

2015-01-01

Purpose: To present the morphological and functional results after treating diabetic macular edema with Bevacizumab. Patient and method: It is a prospective trial which includes 15 patients with diabetic macular edema (proved by OCT and fluorescein angiography examination). The inclusion criteria are: central retinal thickness over 250 µm, visual acuity of the studied eye between 0.1 and 0.5, absence of a previous treatment. We excluded patients with macular edema caused by other ethiology or with any other macular disease. Every patient was treated with 3 intravitreal injections with Bevacizumab at every 6 weeks; we analyzed the results after 4 months. Results: The mean visual acuity improved from 0.33 ± 0.06 at baseline to 0.49 ± 0.13 at 4 months (or from 31±3.9 ETDRS letters to 39±5.67 letters). The central retinal thickness decreased from 457 ± 174 µm to 338 ± 139 µm. There was also an improvement of retinal sensibility on the microperimetry map. Conclusions: The treatment of diabetic macular edema produced an increase of visual acuity and a decrease of macular thickness after the first 3 injections with Avastin, but it is necessary to monitor the patients to detect the rebound of the edema and to initiate retreatment.

Evaluation of kinesthetic sense and hand function in women with breast cancer-related lymphedema.

PubMed

Karadibak, Didem; Yavuzsen, Tugba

2015-06-01

[Purpose] This study evaluated the functional ability and kinesthetic sense of the hands of women with breast cancer-related lymphedema. [Subjects and Methods] Fifty-seven women experiencing lymphedema after breast surgery and adjuvant radiotherapy were included. The patients were divided into two groups: women with hand edema (HE+, n = 29) and without hand edema (HE-, n = 28) after breast cancer treatment. Arm edema severity, hand size, functional mobility and kinesthetic sense of the hand, and daily living skills were evaluated. [Results] The mean age of the patients was 55.8 years. In both groups, functional mobility, kinesthetic sense, and daily living skills decreased significantly with increasing edema severity. However, there was no significant difference between groups with respect to functional mobility or daily living skills. The kinesthetic sense of the hand was better in the HE- group than the HE+ group. There was a significant negative relationship between the severity of edema and hand function. [Conclusion] Breast cancer-related lymphedema can negatively impact women's functional mobility and kinesthetic sense of the hands as well as daily living skills.

Evaluation of kinesthetic sense and hand function in women with breast cancer-related lymphedema

PubMed Central

Karadibak, Didem; Yavuzsen, Tugba

2015-01-01

[Purpose] This study evaluated the functional ability and kinesthetic sense of the hands of women with breast cancer-related lymphedema. [Subjects and Methods] Fifty-seven women experiencing lymphedema after breast surgery and adjuvant radiotherapy were included. The patients were divided into two groups: women with hand edema (HE+, n = 29) and without hand edema (HE−, n = 28) after breast cancer treatment. Arm edema severity, hand size, functional mobility and kinesthetic sense of the hand, and daily living skills were evaluated. [Results] The mean age of the patients was 55.8 years. In both groups, functional mobility, kinesthetic sense, and daily living skills decreased significantly with increasing edema severity. However, there was no significant difference between groups with respect to functional mobility or daily living skills. The kinesthetic sense of the hand was better in the HE− group than the HE+ group. There was a significant negative relationship between the severity of edema and hand function. [Conclusion] Breast cancer-related lymphedema can negatively impact women’s functional mobility and kinesthetic sense of the hands as well as daily living skills. PMID:26180295

Comparison of reduction of edema after rest and after muscle exercises in treatment of chronic venous insufficiency

PubMed Central

Quilici, Belczak Cleusa Ema; Gildo, Cavalheri; de Godoy, Jose Maria Pereira; Quilici, Belczak Sergio; Augusto, Caffaro Roberto

2009-01-01

Aim The aim of this work was to compare the reduction in edema obtained in the conservative treatment of phlebopathies after resting and after performing a muscle exercise program in the Trendelenburg position. Methods Twenty-eight limbs of 24 patients with venous edema of distinct etiologies and classified as between C3 and C5 using CEAP classification. Volumetric evaluation by water displacement was carried out before and after resting in the Trendelenburg position and after performing programmed muscle exercises 24 hours later under identical conditions of time, position and temperature. For the statistical analysis the paired t-test was used with an alpha error of 5% being considered acceptable. Results The average total volume of the lower limbs was 3,967.46 mL. The mean reduction in edema obtained after resting was 92.9 mL, and after exercises it was 135.4 mL, giving a statistically significant difference (p-value = 0.0007). Conclusion In conclusion, exercises are more efficient to reduce the edema of lower limbs than resting in the Trendelenburg position. PMID:19602249

Validity of a New Quantitative Evaluation Method that Uses the Depth of the Surface Imprint as an Indicator for Pitting Edema.

PubMed

Kogo, Haruki; Murata, Jun; Murata, Shin; Higashi, Toshio

2017-01-01

This study examined the validity of a practical evaluation method for pitting edema by comparing it to other methods, including circumference measurements and ultrasound image measurements. Fifty-one patients (102 legs) from a convalescent ward in Maruyama Hospital were recruited for study 1, and 47 patients (94 legs) from a convalescent ward in Morinaga Hospital were recruited for study 2. The relationship between the depth of the surface imprint and circumferential measurements, as well as the relationship between the depth of the surface imprint and the thickness of the subcutaneous soft tissue on an ultrasonogram, were analyzed using a Spearman correlation coefficient by rank. There was no significant relationship between the surface imprint depth and circumferential measurements. However, there was a significant relationship between the depth of the surface imprint and the thickness of the subcutaneous soft tissue as measured on an ultrasonogram (correlation coefficient 0.736). Our findings suggest that our novel evaluation method for pitting edema, based on a measurement of the surface imprint depth, is both valid and useful.

Poloxamer-188 reduces muscular edema after tourniquet-induced ischemia-reperfusion injury in rats.

PubMed

Walters, Thomas J; Mase, Vincent J; Roe, Janet L; Dubick, Michael A; Christy, Robert J

2011-05-01

Skeletal muscle injury can result in significant edema, which can in turn lead to the development of acute extremity compartment syndrome (CS). Poloxamer-188 (P-188), a multiblock copolymer surfactant, has been shown to decrease edema by sealing damaged membranes in a number of tissues after a variety of injury modalities. The objective is to determine whether the administration of P-188 significantly reduces skeletal muscle edema associated with ischemia/reperfusion injury (I-R). Male Sprague-Dawley rats underwent 180 minutes of tourniquet-induced ischemia. Five minutes before tourniquet release, rats received either a bolus of (1) P-188 (150 mg/kg; P-188 group) or (2) vehicle (Vehicle group) via a jugular catheter (n=10 per group). After 240 minutes reperfusion, both groups received a second bolus of either P-188 (P-188) or vehicle (Vehicle) via a tail vein catheter. Sixteen hours later, rats were killed; muscle weights were determined, infarct size (2,3,5-triphenyltetrazolium chloride method), and blinded histologic analysis (hematoxylin and eosin) were performed on the gastrocnemius and tibialis anterior muscles, as well as indices of antioxidant status. P-188 resulted in significantly less edema (wet weight) and reduced an index of lipid peroxidation compared with Vehicle (p<0.05). Wet:dry weight ratios were less in the P-188 group (indicating less edema). Muscle viability as indicated by 2,3,5-triphenyltetrazolium chloride staining or routine histology did not reveal statistically significant differences between groups. P-188 significantly reduced ischemia-reperfusion-related muscle edema and lipid peroxidation but did not impact muscle viability. Excess edema can lead to acute extremity CS, which is associated with significant morbidity and mortality. P-188 may provide a potential adjunctive treatment for the reduction of CS.

Accuracy of transpulmonary thermodilution versus gravimetric measurement of extravascular lung water.

PubMed

Katzenelson, Rita; Perel, Azriel; Berkenstadt, Haiim; Preisman, Sergei; Kogan, Samuel; Sternik, Leonid; Segal, Eran

2004-07-01

Pulmonary edema is a severe and often life-threatening condition. The diagnosis of pulmonary edema and its quantification have great clinical significance and yet can be difficult. A new technique based on thermodilution measurement using a single indicator has recently been developed (PiCCO, Pulsion Medical Systems, AG Germany). This method allows the measurement of extravascular lung water and thus can quantify degree of pulmonary edema. The technique has not been compared with a gold standard, gravimetric measurement of extravascular lung water. Therefore, the objective of this study was to determine the ability of extravascular lung water measurement with the PiCCO to reflect the extravascular lung water as measured with a gravimetric technique in a dog model of pulmonary edema. Prospective, randomized animal study. A university animal research laboratory. Fifteen mongrel dogs (n = 5/group) weighing 20-30 kg. The dogs were anesthetized and mechanically ventilated. Five dogs served as controls; in five dogs hydrostatic pulmonary edema was induced using inflation of a left atrial balloon combined with fluid administration to maintain a high pulmonary artery occlusion pressure; and in five dogs pulmonary edema was induced by intravenous injection of oleic acid. After a period of stabilization in a state of pulmonary edema, extravascular lung water was measured with the PiCCO monitor. The animals were then killed, and extravascular lung water was measured using a gravimetric technique. There was a very close (r =.967, p <.001) relationship between transpulmonary thermodilution and gravimetric measurements. The measurement with the PiCCO was consistently higher, by 3.01 +/- 1.34 mL/kg, than the gravimetric measurement. Measurement of extravascular lung water using transpulmonary thermodilution with a single indicator is very closely correlated with gravimetric measurement of lung water in both increased permeability and hydrostatic pulmonary edema.

Mathematical model in post-mortem estimation of brain edema using morphometric parameters.

PubMed

Radojevic, Nemanja; Radnic, Bojana; Vucinic, Jelena; Cukic, Dragana; Lazovic, Ranko; Asanin, Bogdan; Savic, Slobodan

2017-01-01

Current autopsy principles for evaluating the existence of brain edema are based on a macroscopic subjective assessment performed by pathologists. The gold standard is a time-consuming histological verification of the presence of the edema. By measuring the diameters of the cranial cavity, as individually determined morphometric parameters, a mathematical model for rapid evaluation of brain edema was created, based on the brain weight measured during the autopsy. A cohort study was performed on 110 subjects, divided into two groups according to the histological presence or absence of (the - deleted from the text) brain edema. In all subjects, the following measures were determined: the volume and the diameters of the cranial cavity (longitudinal and transverse distance and height), the brain volume, and the brain weight. The complex mathematical algorithm revealed a formula for the coefficient ε, which is useful to conclude whether a brain edema is present or not. The average density of non-edematous brain is 0.967 g/ml, while the average density of edematous brain is 1.148 g/ml. The resulting formula for the coefficient ε is (5.79 x longitudinal distance x transverse distance)/brain weight. Coefficient ε can be calculated using measurements of the diameters of the cranial cavity and the brain weight, performed during the autopsy. If the resulting ε is less than 0.9484, it could be stated that there is cerebral edema with a reliability of 98.5%. The method discussed in this paper aims to eliminate the burden of relying on subjective assessments when determining the presence of a brain edema. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Bone stress injury of the ankle in professional ballet dancers seen on MRI

PubMed Central

Elias, Ilan; Zoga, Adam C; Raikin, Steven M; Peterson, Judith R; Besser, Marcus P; Morrison, William B; Schweitzer, Mark E

2008-01-01

Background Ballet Dancers have been shown to have a relatively high incidence of stress fractures of the foot and ankle. It was our objective to examine MR imaging patterns of bone marrow edema (BME) in the ankles of high performance professional ballet dancers, to evaluate clinical relevance. Methods MR Imaging was performed on 12 ankles of 11 active professional ballet dancers (6 female, 5 male; mean age 24 years, range 19 to 32). Individuals were imaged on a 0.2 T or 1.5 T MRI units. Images were evaluated by two musculoskeletal radiologists and one orthopaedic surgeon in consensus for location and pattern of bone marrow edema. In order to control for recognized sources of bone marrow edema, images were also reviewed for presence of osseous, ligamentous, tendinous and cartilage injuries. Statistical analysis was performed to assess the strength of the correlation between bone marrow edema and ankle pain. Results Bone marrow edema was seen only in the talus, and was a common finding, observed in nine of the twelve ankles imaged (75%) and was associated with pain in all cases. On fluid-sensitive sequences, bone marrow edema was ill-defined and centered in the talar neck or body, although in three cases it extended to the talar dome. No apparent gender predilection was noted. No occult stress fracture could be diagnosed. A moderately strong correlation (phi = 0.77, p= 0.0054) was found between edema and pain in the study population. Conclusion Bone marrow edema seems to be a specific MRI finding in the talus of professional ballet dancers, likely related to biomechanical stress reactions, due to their frequently performed unique maneuvers. Clinically, this condition may indicate a sign of a bone stress injury of the ankle. PMID:18371230

Non-contrast T1-mapping detects acute myocardial edema with high diagnostic accuracy: a comparison to T2-weighted cardiovascular magnetic resonance

PubMed Central

2012-01-01

Background T2w-CMR is used widely to assess myocardial edema. Quantitative T1-mapping is also sensitive to changes in free water content. We hypothesized that T1-mapping would have a higher diagnostic performance in detecting acute edema than dark-blood and bright-blood T2w-CMR. Methods We investigated 21 controls (55 ± 13 years) and 21 patients (61 ± 10 years) with Takotsubo cardiomyopathy or acute regional myocardial edema without infarction. CMR performed within 7 days included cine, T1-mapping using ShMOLLI, dark-blood T2-STIR, bright-blood ACUT2E and LGE imaging. We analyzed wall motion, myocardial T1 values and T2 signal intensity (SI) ratio relative to both skeletal muscle and remote myocardium. Results All patients had acute cardiac symptoms, increased Troponin I (0.15-36.80 ug/L) and acute wall motion abnormalities but no LGE. T1 was increased in patient segments with abnormal and normal wall motion compared to controls (1113 ± 94 ms, 1029 ± 59 ms and 944 ± 17 ms, respectively; p < 0.001). T2 SI ratio using STIR and ACUT2E was also increased in patient segments with abnormal and normal wall motion compared to controls (all p < 0.02). Receiver operator characteristics analysis showed that T1-mapping had a significantly larger area-under-the-curve (AUC = 0.94) compared to T2-weighted methods, whether the reference ROI was skeletal muscle or remote myocardium (AUC = 0.58-0.89; p < 0.03). A T1 value of greater than 990 ms most optimally differentiated segments affected by edema from normal segments at 1.5 T, with a sensitivity and specificity of 92 %. Conclusions Non-contrast T1-mapping using ShMOLLI is a novel method for objectively detecting myocardial edema with a high diagnostic performance. T1-mapping may serve as a complementary technique to T2-weighted imaging for assessing myocardial edema in ischemic and non-ischemic heart disease, such as quantifying area-at-risk and diagnosing myocarditis. PMID:22720998

Conversion of (η(5)-C2B9H10R)TaX3 (X = Me, NMe2) to (η(6)-C2B9H10R)TaX' (X' = NMe2, azaallyl) in the absence of a reducing agent: synthesis and structure of tantallacarboranes incorporating an arachno-η(6)-C2B9(4-) ligand.

PubMed

Xiang, Li; Xie, Zuowei

2014-08-04

Heating a benzene solution of [η(5)-(Me2NCH2CH2)C2B9H10] Ta(NMe2)3 (1) in the presence of pyridine gave an unprecedented complex [η(1):η(6)-(Me2NCH2CH2)C2B9H10]Ta (NMe2)(NC5H5) (2). On the other hand, reaction of (η(5)-C2B9H11)TaMe3 with adamantly isonitrile (AdNC) in dimethoxyethane (DME) at room temperature afforded another unexpected complex (η(6)-C2B9H11)Ta[η(3)-C,C,N-CH2C(CH3)NAd](DME) (4). These results show that pyridine and DME are essential for the formation of 2 and 4, respectively. It is suggested that the nido-η(5)-C2B9H10R(2−) ligand in tantallacarboranes takes up two electrons released by reductive elimination to form an arachno-η(6)-C2B9H10R(4−) fragment via the cage C–C bond cleavage.

78 FR 72155 - Medicare Program; End-Stage Renal Disease Prospective Payment System, Quality Incentive Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-02

...This rule updates and makes revisions to the End-Stage Renal Disease (ESRD) prospective payment system (PPS) for calendar year (CY) 2014. This rule also sets forth requirements for the ESRD quality incentive program (QIP), including for payment year (PY) 2016 and beyond. In addition, this rule clarifies the grandfathering provision related to the 3-year minimum lifetime requirement (MLR) for Durable Medical Equipment (DME), and provides clarification of the definition of routinely purchased DME. This rule also implements budget-neutral fee schedules for splints and casts, and intraocular lenses (IOLs) inserted in a physician's office. Finally, this rule makes a few technical amendments and corrections to existing regulations related to payment for durable medical equipment, prosthetics, orthotics, and supplies (DMEPOS) items and services.

Solvation of the fluorine containing anions and their lithium salts in propylene carbonate and dimethoxyethane.

PubMed

Chaban, Vitaly

2015-07-01

Electrolyte solutions based on the propylene carbonate (PC)-dimethoxyethane (DME) mixtures are of significant importance and urgency due to emergence of lithium-ion batteries. Solvation and coordination of the lithium cation in these systems have been recently attended in detail. However, analogous information concerning anions (tetrafluoroborate, hexafluorophosphate) is still missed. This work reports PM7-MD simulations (electronic-structure level of description) to include finite-temperature effects on the anion solvation regularities in the PC-DME mixture. The reported result evidences that the anions appear weakly solvated. This observation is linked to the absence of suitable coordination sites in the solvent molecules. In the concentrated electrolyte solutions, both BF4(-) and PF6(-) prefer to exist as neutral ion pairs (LiBF4, LiPF6).

Effect of Lavender (Lavandula angustifolia) Essential Oil on Acute Inflammatory Response

PubMed Central

Cardia, Gabriel Fernando Esteves; Cavalcante, Heitor Augusto Otaviano; Cassarotti, Larissa Laila; Salvadego, Valter Eduardo Cocco; Spironello, Ricardo Alexandre; Bersani-Amado, Ciomar Aparecida

2018-01-01

Lavandula angustifolia is a plant of Lamiaceae family, with many therapeutic properties and biological activities, such as anticonvulsant, anxiolytic, antioxidant, anti-inflammatory, and antimicrobial activities. The aim of this study was to evaluate the effect of Lavandula angustifolia Mill. essential oil (LEO) on acute inflammatory response. LEO was analyzed using gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) methods and showed predominance of 1,8-cineole (39.83%), borneol (22.63%), and camphor (22.12%). LEO at concentrations of 0.5, 1, 3, and 10 μg/ml did not present in vitro cytotoxicity. Additionally, LEO did not stimulate the leukocyte chemotaxis in vitro. The LEO topical application at concentrations of 0.25, 0.5, and 1 mg/ear reduced edema formation, myeloperoxidase (MPO) activity, and nitric oxide (NO) production in croton oil-induced ear edema model. In carrageenan-induced paw edema model, LEO treatment at doses of 75, 100, and 250 mg/kg reduced edema formation, MPO activity, and NO production. In dextran-induced paw edema model, LEO at doses of 75 and 100 mg/kg reduced paw edema and MPO activity. In conclusion, LEO presented anti-inflammatory activity, and the mechanism proposed of LEO seems to be, at least in part, involving the participation of prostanoids, NO, proinflammatory cytokines, and histamine. PMID:29743918

Glyburide is associated with attenuated vasogenic edema in stroke patients

PubMed Central

Kimberly, W. Taylor; Battey, Thomas W. K.; Pham, Ly; Wu, Ona; Yoo, Albert J.; Furie, Karen L.; Singhal, Aneesh B.; Elm, Jordan J.; Stern, Barney J.; Sheth, Kevin N.

2016-01-01

Background and Purpose Brain edema is a serious complication of ischemic stroke that can lead to secondary neurological deterioration and death. Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 (SUR1) and transient receptor potential cation channel subfamily M member 4 (TRPM4). However, the relevance of this pathway to the development of cerebral edema in stroke patients is not known. Methods Using a case control design, we retrospectively assessed neuroimaging and blood markers of cytotoxic and vasogenic edema in subjects who were enrolled in the Glyburide Advantage in Malignant Edema and Stroke-Pilot (GAMES-Pilot) trial. We compared serial brain magnetic resonance images (MRIs) to a cohort with similar large volume infarctions. We also compared matrix metalloproteinase-9 plasma level in large hemispheric stroke. Results We report that IV glyburide was associated with attenuated T2 fluid attenuated inversion recovery (FLAIR) signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood matrix metalloproteinase-9 (MMP-9) level. Conclusions Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. Verification of these potential imaging and blood biomarkers is warranted in the context of a randomized, placebo-controlled trial. PMID:24072459

Effect of Adding Oral Calcium Dobesilate to Laser Photocoagulation on the Macular Thickness in Patients with Diabetic Macular Edema: A Randomized Clinical Trial

PubMed Central

Feghhi, Mostafa; Farrahi, Fereydoun; Abbaspour, Mohammadreza; Takhtaeian, Akbar

2014-01-01

Purpose: To evaluate the effect of oral calcium dobesilate (Doxium) on macular thickness in clinically significant macular edema (CSME). Methods: Overall, 71 eyes of 40 patients with non-proliferative diabetic retinopathy and clinically significant macular edema were included. All patients were received laser treatment for macular edema. Coherence optical tomography was used to determine the retinal thickness. Patients were randomized into two groups: group A received three Doxium capsule daily and group B received three placebo capsule daily for six months. Results: The mean macular thickness before and after treatment in the group A was 340 and 257 micrometers respectively (24.5% reduced), and in the group B was 336 micrometers and 263 micrometers respectively (21.5% reduced). Macular thickness significantly decreased after treatment in both groups and the reduction in group A is higher but the difference of reduction between the two groups was not statistically significant (P>0.05). Conclusion: In respect to the effect of adding oral Doxium to Laser Photocoagulation on the macular thickness in patients with diabetic macular edema, this study showed no statistically significant difference between Doxium and placebo. PMID:25436194

Chemical Compositions and Abundance Anomalies in Stellar Coronae ADP 99

NASA Technical Reports Server (NTRS)

Drake, Jeremy; Oliversen, Ronald J. (Technical Monitor)

2003-01-01

Progress has been made using both EUVE (Extreme Ultraviolet Explorer) and ASCA (Advanced Satellite for Cosmology and Astrophysics) data and a new postdoctoral scientist has now been hired. Stars studied to date include YY Gem (dMe binary), xi Boo A (intermediate activity G8 V), xi UMa (more active G quadruple system) HR1099 (K1 IV + G5 V) RS CVn-like, AU Mic (dMe). In addition to a paper that concentrated on abundancies in HR1099, a paper was recently submitted on the coronal abundances of AR(tilde)Lac that revealed an interesting pattern of overabundances of very low FIP elements (Al and Ca) compared to the low FIP elements Si, Mg and Fe. Two papers are nearing completion on methods of analysis and on the abundances in the corona of AU(tilde)Mic. Additionally, two invited conference proceedings papers are being published on this work. The main conclusion of the study to date is that our existing ideas of coronal abundance anomalies need complete revision. The solar-like FIP effect is replaced by a pattern than appears to enhance high FIP elements rather than low FIP elements in very active stars. The archival studies we are undertaking now are revealing some key details of these patterns, and are beginning to map out the anomalies as a function of spectral type, a key goal of this study.

Short communication: Feed utilization and its associations with fertility and productive life in 11 commercial Pennsylvania tie-stall herds.

PubMed

Vallimont, J E; Dechow, C D; Daubert, J M; Dekleva, M W; Blum, J W; Liu, W; Varga, G A; Heinrichs, A J; Baumrucker, C R

2013-02-01

The objectives of this study were to quantify the relationships of various definitions of feed utilization with both fertility and productive life. Intake and body measurement data were collected monthly on 970 cows in 11 tie-stall herds for 6 consecutive months. Measures of feed utilization for this study were dry matter intake (DMI), dry matter intake efficiency (DME, defined as 305-d fat-corrected milk/305-d DMI), DME with intake adjusted for maintenance requirements (DMEM), crude protein efficiency (defined as 305-d protein yield/305-d crude protein intake), and 2 definitions of residual feed intake (RFI). The first, RFI(reg), was calculated by regressing daily DMI on daily milk, fat, and protein yields, body weight (BW), daily body condition score (BCS) gain or loss, the interaction between BW and BCS gain or loss, and days in milk. The second, RFI(NRC), was estimated by subtracting 305-d DMI predicted according to their fat-corrected milk and BW from actual 305-d DMI. Data were analyzed with 8-trait animal models and included one measure of feed utilization and milk, fat, and protein yields, BW, BCS, days open (DO), and productive life (PL). The genetic correlation between DME and DO was 0.53 (± 0.19) and that between DME and PL was 0.66 (± 0.10). These results show that cows who had higher feed efficiency had greater DO (undesirable) and greater PL (desirable). Results were similar for the genetic correlation between DO and crude protein efficiency (0.42). Productive life had genetic correlations of -0.22 with BW and -0.48 with BCS, suggesting that larger, fatter cows in this study had shorter PL. Correlations between estimated breeding values for feed utilization and official sire genetic evaluations for fertility were in agreement with the results from the multiple-trait models. Selection programs intended to enhance feed efficiency should factor relationships with functional traits to avoid unfavorable effects on cow fertility. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Assessment of the inhibitory effects of pyrethroids against human carboxylesterases

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

Lei, Wei

Pyrethroids are broad-spectrum insecticides that widely used in many countries, while humans may be exposed to these toxins by drinking or eating pesticide-contaminated foods. This study aimed to investigate the inhibitory effects of six commonly used pyrethroids against two major human carboxylesterases (CES) including CES1 and CES2. Three optical probe substrates for CES1 (DME, BMBT and DMCB) and a fluorescent probe substrate for CES2 (DDAB) were used to characterize the inhibitory effects of these pyrethroids. The results demonstrated that most of the tested pyrethroids showed moderate to weak inhibitory effects against both CES1 and CES2, but deltamethrin displayed strong inhibitionmore » towards CES1. The IC{sub 50} values of deltamethrin against CES1-mediated BMBT, DME, and DMCB hydrolysis were determined as 1.58 μM, 2.39 μM, and 3.3 μM, respectively. Moreover, deltamethrin was cell membrane permeable and capable of inhibition endogenous CES1 in living cells. Further investigation revealed that deltamethrin inhibited CES1-mediated BMBT hydrolysis via competitive manner but noncompetitively inhibited DME or DMCB hydrolysis. The inhibition behaviors of deltamethrin against CES1 were also studied by molecular docking simulation. The results demonstrated that CES1 had at least two different ligand-binding sites, one was the DME site and another was the BMBT site which was identical to the binding site of deltamethrin. In summary, deltamethrin was a strong reversible inhibitor against CES1 and it could tightly bind on CES1 at the same ligand-binding site as BMBT. These findings are helpful for the deep understanding of the interactions between xenobiotics and CES1. - Highlights: • The inhibitory effects of six commonly used pyrethroids on human carboxylesterases were investigated. • Deltamethrin displayed strong inhibitory effects against human carboxylesterase 1 (CES1). • Deltamethrin was cell membrane permeable and could inhibit intracellular CES1 in living cells. • Both experimental and docking studies demonstrated that CES1 had at least two different ligand-binding sites.« less

Zinc(II) complexes with heterocyclic ether, acid and amide. Crystal structure, spectral, thermal and antibacterial activity studies

NASA Astrophysics Data System (ADS)

Jabłońska-Wawrzycka, Agnieszka; Rogala, Patrycja; Czerwonka, Grzegorz; Hodorowicz, Maciej; Stadnicka, Katarzyna

2016-02-01

The reaction of zinc salts with heterocyclic ether (1-ethoxymethyl-2-methylimidazole (1-ExMe-2-MeIm)), acid (pyridine-2,3-dicarboxylic acid (2,3-pydcH2)) and amide (3,5-dimethylpyrazole-1-carboxamide (3,5-DMePzCONH2)) yielded three new zinc complexes formulated as [Zn(1-ExMe-2-MeIm)2Cl2] 1, fac-[Zn(H2O)6][Zn(2,3-pydcH)3]22 and [Zn(3,5-DMePz)2(NCO)2] 3. Complexes of 1 and 3 are four-coordinated with a tetrahedron as coordination polyhedron. However, compound 2 forms an octahedral cation-anion complex. The complex 3 was prepared by eliminating of the carboxamide group from the ligand and then the 3,5-dimethylpyrazole (3,5-DMePz) and isocyanates formed were employed as new ligands. The IR and X-ray studies have confirmed a bidentate fashion of coordination of the 2,3-pydcH and monodentate fashion of coordination of the 1-ExMe-2-MeIm and 3,5-DMePz to the Zn(II) ions. The crystal packing of Zn(II) complexes are stabilized by intermolecular classical hydrogen bonds of O-H⋯O and N-H⋯O types. The most interesting feature of the supramolecular architecture of complexes is the existence of C-H⋯O, C-H⋯Cl and C-H⋯π interactions and π⋯π stacking, which also contributes to structural stabilisation. The correlation between crystal structure and thermal stability of zinc complexes is observed. In all compounds the fragments of ligands donor-atom containing go in the last steps. Additionally, antimicrobial activities of compounds were carried out against certain Gram-positive and Gram-negative bacteria and counts of CFU (colony forming units) were also determined. The achieved results confirmed a significant antibacterial activity of some tested zinc complexes. On the basis of the Δ log CFU values the antibacterial activity of zinc complexes follows the order: 3 > 2 > 1. Influence a number of N-donor atoms in zinc environment on antibacterial activity is also observed.

Fatty acid composition and preclinical resarches on Anthemis wiedemanniana Fisch. & Mey.: Discovery of a new anti-inflammatory agent

PubMed Central

Gönenç, Tuba Mert; Akkol, Esra Küpeli; Süntar, Ipek; Erdoğan, Tuğçe Fafal; Kıvçak, Bijen

2014-01-01

Background: Anthemis species have been used for the treatment of gastrointestinal disorders, hemorrhoid, stomachache and inflammatory diseases in Turkish folk medicine. Anthemis wiedemanniana Fisch. And Mey. is an endemic plant used as painkiller, antispasmodic, sedative and for the treatment of urinary inflammations. Objective: The objective of the present study is to evaluate the anti-inflamatory activity of the extracts of A. wiedemanniana by using in vivo methods. Materials and Methods: Carrageenan-, PGE2- and serotonin-induced hind paw edema, 12-O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema and acetic acid-induced increase in capillary permeability models were used for the anti-inflammatory activity assessment. Moreover, the fatty acid composition of A. wiedemanniana was investigated by gas chromatography (GC). Results: n-Hexane, diethyl ether and total sesquiterpene lactone extracts exhibited significant inhibition in carrageenan-induced hind paw edema and acetic acid-induced increase in capillary permeability model. n-Hexane and total sesquiterperne lactone extracts showed anti-inflammatory activity in PGE2- and serotonin-induced hind paw edema model. However none of the extracts displayed significant activity in TPA-induced ear edema model in mice. C4:0 (Buthyric acid), C20:0 (Arachidic acid) and C16:1 (Palmitoleik acid) were found to be the major fatty acids in these species. Saturated fatty acids (SFA) were found in higher amounts than monounsaturated fatty acids and polyunsaturated fatty acids. SFAs were determined as 63.17%, UFAs as 20.89% and PuFAs as 15.95%. Conclusion: This study confirms the traditional usage of A. wiedemanniana for inflammatory diseases. PMID:24696546

Computed microtomography visualization and quantification of mouse ischemic brain lesion by nonionic radio contrast agents

PubMed Central

Dobrivojević, Marina; Bohaček, Ivan; Erjavec, Igor; Gorup, Dunja; Gajović, Srećko

2013-01-01

Aim To explore the possibility of brain imaging by microcomputed tomography (microCT) using x-ray contrasting methods to visualize mouse brain ischemic lesions after middle cerebral artery occlusion (MCAO). Methods Isolated brains were immersed in ionic or nonionic radio contrast agent (RCA) for 5 days and subsequently scanned using microCT scanner. To verify whether ex-vivo microCT brain images can be used to characterize ischemic lesions, they were compared to Nissl stained serial histological sections of the same brains. To verify if brains immersed in RCA may be used afterwards for other methods, subsequent immunofluorescent labeling with anti-NeuN was performed. Results Nonionic RCA showed better gray to white matter contrast in the brain, and therefore was selected for further studies. MicroCT measurement of ischemic lesion size and cerebral edema significantly correlated with the values determined by Nissl staining (ischemic lesion size: P=0.0005; cerebral edema: P=0.0002). Brain immersion in nonionic RCA did not affect subsequent immunofluorescent analysis and NeuN immunoreactivity. Conclusion MicroCT method was proven to be suitable for delineation of the ischemic lesion from the non-infarcted tissue, and quantification of lesion volume and cerebral edema. PMID:23444240

47 CFR 87.171 - Class of station symbols.

Code of Federal Regulations, 2013 CFR

2013-10-01

...—VHF omni-range RLS—Surveillance radar RLT—Radionavigation land test RLW—Microwave landing system RNV—Radio Navigation Land/DME RPC—Ramp Control TJ—Aircraft earth station in the Aeronautical Mobile...

47 CFR 87.171 - Class of station symbols.

Code of Federal Regulations, 2011 CFR

2011-10-01

...—VHF omni-range RLS—Surveillance radar RLT—Radionavigation land test RLW—Microwave landing system RNV—Radio Navigation Land/DME RPC—Ramp Control TJ—Aircraft earth station in the Aeronautical Mobile...

47 CFR 87.171 - Class of station symbols.

Code of Federal Regulations, 2012 CFR

2012-10-01

...—VHF omni-range RLS—Surveillance radar RLT—Radionavigation land test RLW—Microwave landing system RNV—Radio Navigation Land/DME RPC—Ramp Control TJ—Aircraft earth station in the Aeronautical Mobile...

Alpha-Tocopherol Reduces Brain Edema and Protects Blood-Brain Barrier Integrity following Focal Cerebral Ischemia in Rats.

PubMed

Haghnejad Azar, Adel; Oryan, Shahrbanoo; Bohlooli, Shahab; Panahpour, Hamdollah

2017-01-01

This study was conducted to examine the neuroprotective effects of α-tocopherol against edema formation and disruption of the blood-brain barrier (BBB) following transient focal cerebral ischemia in rats. Ninety-six male Sprague-Dawley rats were divided into 3 major groups (n = 32 in each), namely the sham, and control and α-tocopherol-treated (30 mg/kg) ischemic groups. Transient focal cerebral ischemia (90 min) was induced by occlusion of the left middle cerebral artery. At the end of the 24-hour reperfusion period, the animals were randomly selected and used for 4 investigations (n = 8) in each of the 3 main groups: (a) assessment of neurological score and measurement of infarct size, (b) detection of brain edema formation by the wet/dry method, (c) evaluation of BBB permeability using the Evans blue (EB) extravasation technique, and (d) assessment of the malondialdehyde (MDA) and reduced glutathione (GSH) concentrations using high-performance liquid chromatography methods. Induction of cerebral ischemia in the control group produced extensive brain edema (brain water content 83.8 ± 0.11%) and EB leakage into brain parenchyma (14.58 ± 1.29 µg/g) in conjunction with reduced GSH and elevated MDA levels (5.86 ± 0.31 mmol/mg and 63.57 ± 5.42 nmol/mg, respectively). Treatment with α-tocopherol significantly lowered brain edema formation and reduced EB leakage compared with the control group (p < 0.001, 80.1 ± 0.32% and 6.66 ± 0.87 µg/g, respectively). Meanwhile, treatment with α-tocopherol retained tissue GSH levels and led to a lower MDA level (p < 0.01, 10.17 ± 0.83 mmol/mg, and p < 0.001, 26.84 ± 4.79 nmol/mg, respectively). Treatment with α-tocopherol reduced ischemic edema formation and produced protective effects on BBB function following ischemic stroke occurrence. This effect could be through increasing antioxidant activity. © 2016 S. Karger AG, Basel.

Pathogenesis of Brain Edema and Investigation into Anti-Edema Drugs

PubMed Central

Michinaga, Shotaro; Koyama, Yutaka

2015-01-01

Brain edema is a potentially fatal pathological state that occurs after brain injuries such as stroke and head trauma. In the edematous brain, excess accumulation of extracellular fluid results in elevation of intracranial pressure, leading to impaired nerve function. Despite the seriousness of brain edema, only symptomatic treatments to remove edema fluid are currently available. Thus, the development of novel anti-edema drugs is required. The pathogenesis of brain edema is classified as vasogenic or cytotoxic edema. Vasogenic edema is defined as extracellular accumulation of fluid resulting from disruption of the blood-brain barrier (BBB) and extravasations of serum proteins, while cytotoxic edema is characterized by cell swelling caused by intracellular accumulation of fluid. Various experimental animal models are often used to investigate mechanisms underlying brain edema. Many soluble factors and functional molecules have been confirmed to induce BBB disruption or cell swelling and drugs targeted to these factors are expected to have anti-edema effects. In this review, we discuss the mechanisms and involvement of factors that induce brain edema formation, and the possibility of anti-edema drugs targeting them. PMID:25941935

The MR appearance of volume overload in the lower extremities

NASA Technical Reports Server (NTRS)

Meler, J. D.; Solomon, M. A.; Steele, J. R.; Yancy, C. W. Jr; Parkey, R. W.; Fleckenstein, J. L.; Blomqvist, C. G. (Principal Investigator)

1997-01-01

PURPOSE: Our goal was to describe the MR findings of volume overload (VO) in the lower extremities. METHOD: Fifteen individuals were studied, including eight healthy controls and seven patients with VO (four cardiac, three renal). MR evaluation included various SE techniques. Edema detection, localization, and symmetry were assessed subjectively. Relaxation time estimates were also made of the subcutaneous tissue, marrow, and three muscles. RESULTS: Subcutaneous tissue was markedly edematous in seven of seven patients and asymmetric in four of seven, whereas marrow was normal in all patients. Muscle edema was mild and asymmetric in six and two of seven patients, respectively. Perifascial fluid collections were identified in six of seven patients. CONCLUSION: Subcutaneous tissue edema is the dominant feature of VO in the lower extremities. Perifascial fluid is common but does not necessarily distribute symmetrically. Muscle edema is relatively mild. These findings should aid in identifying VO as the potential cause of swelling in patients with swollen legs.

High altitude pulmonary edema-clinical features, pathophysiology, prevention and treatment

PubMed Central

Paralikar, Swapnil J.

2012-01-01

High altitude pulmonary edema (HAPE) is a noncardiogenic pulmonary edema which typically occurs in lowlanders who ascend rapidly to altitudes greater than 2500-3000 m. Early symptoms of HAPE include a nonproductive cough, dyspnoea on exertion and reduced exercise performance. Later, dyspnoea occurs at rest. Clinical features are cyanosis, tachycardia, tachypnoea and elevated body temperature generally not exceeding 38.5°C. Rales are discrete initially and located over the middle lung fields. HAPE mainly occurs due to exaggerated hypoxic pulmonary vasoconstriction and elevated pulmonary artery pressure. It has been observed that HAPE is a high permeability type of edema occurring also due to leaks in the capillary wall (‘stress failure’). Slow descent is the most effective method for prevention; in addition, graded ascent and time for acclimatization, low sleeping altitudes, avoidance of alcohol and sleeping pills, and avoidance of exercise are the key to preventing HAPE. Treatment of HAPE consists of immediate improvement of oxygenation either by supplemental oxygen, hyperbaric treatment, or by rapid descent. PMID:23580834

IN VIVO ANTI-INFLAMMATORY EFFECTS OF TARAXASTEROL AGAINST ANIMAL MODELS

PubMed Central

Wang, Ying; Li, Guan-Hao; Liu, Xin-Yu; Xu, Lu; Wang, Sha-Sha; Zhang, Xue-Mei

2017-01-01

Background: Traditional Chinese medicine Taraxacum officinale has been widely used to treat various inflammatory diseases. Taraxasterol is one of the main active components isolated from Taraxacum officinale. Recently, we have demonstrated that taraxasterol has the in vitro anti-inflammatory effects. This study aims to determine the in vivo anti-inflammatory effects of taraxasterol against animal models. Materials and Methods: Anti-inflammatory effects were assessed in four animal models by using dimethylbenzene-induced mouse ear edema, carrageenan-induced rat paw edema, acetic acid-induced mouse vascular permeability and cotton pellet-induced rat granuloma tests. Results: Our results demonstrated that taraxasterol dose-dependently attenuated dimethylbenzene-induced mouse ear edema and carrageenan-induced rat paw edema, decreased acetic acid-induced mouse vascular permeability and inhibited cotton pellet-induced rat granuloma formation. Conclusion: Our finding indicates that taraxasterol has obvious in vivo anti-inflammatory effects against animal models. It will provide experimental evidences for the traditional use of Taraxacum officinale and taraxasterol in inflammatory diseases. PMID:28480383

Fluorescein angiography vs. optical coherence tomography for diagnosis of uveitic macular edema

PubMed Central

Kempen, John H.; Sugar, Elizabeth A.; Jaffe, Glenn J.; Acharya, Nisha R.; Dunn, James P.; Elner, Susan G.; Lightman, Susan L.; Thorne, Jennifer E.; Vitale, Albert T.; Altaweel, Michael M.

2013-01-01

Objective To evaluate agreement between fluorescein angiography (FA) and optical coherence tomography (OCT) for diagnosis of macular edema in patients with uveitis. Design Multicenter cross-sectional study Participants Four hundred seventy-nine eyes with uveitis of 255 patients Methods The macular status of dilated eyes with intermediate, posterior or panuveitis was assessed via Stratus-3 OCT and FA. Kappa statistics evaluated agreement between the diagnostic approaches. Main Outcome Measures Macular thickening (center point thickness ≥240 μm per reading center grading of OCT images-“MT”) and macular leakage (central subfield fluorescein leakage ≥0.44 disk areas per reading center grading of FA images-“ML”); agreement amongst these outcomes in diagnosing “macular edema.” Results OCT (90.4%) more frequently returned usable information regarding macular edema than FA (77%) and biomicroscopy (76%). Agreement in diagnosis of MT and ML (κ=0.44) was moderate. ML was present in 40% of cases free of MT, whereas MT was present in 34% of cases without ML. Biomicroscopic evaluation for macular edema failed to detect 40% and 45% of cases of MT and ML respectively and diagnosed 17% and 17% of cases with macular edema which did not have MT or ML respectively; these results may underestimate biomicroscopic errors (ophthalmologists were not explicitly masked to OCT and FA results). Among eyes free of ML, phakic eyes without cataract rarely (4%) had MT. No factors were found that effectively ruled out ML when MT was absent. Conclusion OCT and FA offered only moderate agreement regarding macular edema status in uveitis cases, probably because what they measure (MT and ML) are related but non-identical macular pathologies. Given its lower cost, greater safety, and greater likelihood of obtaining usable information, OCT may be the best initial test for evaluation of suspected macular edema. However, given that ML cannot be ruled out if MT is absent and vice versa, obtaining the second test after a negative result on the first seems justified when detection of ML or MT would alter management. Given that biomicroscopic evaluation for macular edema frequently erred, ancillary testing for macular edema seems indicated when knowledge of ML or MT status would affect management. PMID:23706700

Palliative Care Edema: Patient Population, Causal Factors, and Types of Edema Referred to a Specialist Palliative Care Edema Service.

PubMed

Real, Shirley; Cobbe, Sinead; Slattery, Sinead

2016-07-01

Edema in palliative care patients is a common symptom, however, the research base for all aspects of its care is extremely poor. To evaluate a specialist palliative care edema service in order to report on the patient population referred, the types of edema encountered, and the causes of edema. Prior to study, three different edema types were described for evaluation: lymphedema, nonlymphatic edema, and a combination of the two. Retrospective chart evaluation was completed from August 2013 through January 2014. Patients with edema assessed by the specialist palliative care physiotherapy edema service. Sixty-three cases were included, comprising 10.5% of all new palliative care referrals during the study period. Ninety-two percent (n = 58) had a diagnosis of cancer and 57% (n = 36) were female. Age ranged from 45-97 years. The most common edema type was a mixed edema (46%, n = 29), followed by lymphedema (27%, n = 18) and nonlymphatic edema (16%, n = 10). Lymphorrhea occurred in 9.5% of cases. The most common reasons for edema, based on clinical opinion, were blocked lymphatics (33%) and dependency from immobility (27%). The most common site for edema was in the lower limbs (89%, n = 56). The time lapse from the last treatment to death ranged from 1-225 days. Having a mixed edema type or lymphorrhea was a relatively poor prognostic sign. This is the first study to describe in detail the occurrence of edema in palliative care patients. Edema may be present for many months prior to death making the search for effective treatments imperative.

Characterization of symptoms and edema distribution in premenstrual syndrome

PubMed Central

Tacani, Pascale Mutti; Ribeiro, Danielle de Oliveira; Barros Guimarães, Barbara Evelyn; Machado, Aline Fernanda Perez; Tacani, Rogério Eduardo

2015-01-01

Background Premenstrual syndrome is a group of symptoms linked to the menstrual cycle, and edema is among these symptoms. Physiotherapy is often sought by many patients for the treatment of edema; however, for an adequate prescription of physiotherapeutic procedures, the distribution of edema throughout the body has yet to be characterized. Objective To determine the most frequent symptoms and body regions that present with edema in women during the premenstrual period. Subjects and methods Sixty women with a mean age of 24.6±4.7 years were evaluated during their premenstrual (between days 21 and 28) and menstrual period (between days 1 and 3), and the collected data included body mass, height, biotype (body-fat distribution), face, breast, limb-circumference measurements, and limb-volume estimate, and an adapted version of the Premenstrual Symptoms Screening Tool was used. Statistical analysis was performed using Student’s t-test and the test for equality of two proportions (P≤0.05). Results Premenstrual syndrome was identified in 91.7% of the women, and the most frequent symptoms were irritability (73.33%) and physical symptoms, including swelling (65%), and anxiety (58.3%). Edema was detected in the following areas: facial, epigastric, mammary, umbilical, and pubic, the mid-third of the arms, distal forearm, in both thighs and in the mid-third of the legs determined by circumference measurements, and in both upper and lower limbs, according to the estimated volume. Conclusion In this study population, the most frequent symptoms were irritability, physical symptoms, and anxiety, with distribution of edema in the face, breast, abdomen, pubic area, distal upper limb, and proximal lower limb. PMID:25792857

Position Measurement Standard Evaluation

DOT National Transportation Integrated Search

1975-02-01

The objectives of the Position Measurement Standard Program were to collect navigation data from three DME receivers and a low-frequency GLOBAL Navigation system, and evaluate their relative performance against a reference radar. Flight test data dur...

Challenges in the Greener Production of Formates/Formic Acid, Methanol, and DME by Heterogeneously Catalyzed CO2 Hydrogenation Processes

PubMed Central

2017-01-01

The recent advances in the development of heterogeneous catalysts and processes for the direct hydrogenation of CO2 to formate/formic acid, methanol, and dimethyl ether are thoroughly reviewed, with special emphasis on thermodynamics and catalyst design considerations. After introducing the main motivation for the development of such processes, we first summarize the most important aspects of CO2 capture and green routes to produce H2. Once the scene in terms of feedstocks is introduced, we carefully summarize the state of the art in the development of heterogeneous catalysts for these important hydrogenation reactions. Finally, in an attempt to give an order of magnitude regarding CO2 valorization, we critically assess economical aspects of the production of methanol and DME and outline future research and development directions. PMID:28656757

Medicare program; end-stage renal disease prospective payment system, quality incentive program, and durable medical equipment, prosthetics, orthotics, and supplies.

PubMed

2013-12-02

This rule updates and makes revisions to the End-Stage Renal Disease (ESRD) prospective payment system (PPS) for calendar year (CY) 2014. This rule also sets forth requirements for the ESRD quality incentive program (QIP), including for payment year (PY) 2016 and beyond. In addition, this rule clarifies the grandfathering provision related to the 3-year minimum lifetime requirement (MLR) for Durable Medical Equipment (DME), and provides clarification of the definition of routinely purchased DME. This rule also implements budget-neutral fee schedules for splints and casts, and intraocular lenses (IOLs) inserted in a physician's office. Finally, this rule makes a few technical amendments and corrections to existing regulations related to payment for durable medical equipment, prosthetics, orthotics, and supplies (DMEPOS) items and services.

New Catalyst Reduces Wasted Carbon in Biofuel Process, Lowers Cost

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

Researchers at NREL recently developed a catalyst formulation that incorporates more hydrogen into the DME-to-high-octane gasoline process, resulting in a higher yield to gasoline-range products. Further, the researchers developed a secondary process that efficiently couples a portion of the gasoline-range product to yield jet/diesel fuels. The modified catalyst doubles the conversion rate of DME, which can be produced from biomass, to the high-octane gasoline product and significantly decreases the formation of wasted byproducts. For the distillate-range product, 80% of the mixture is in line with ASTM standards for use as a jet fuel blendstock. The increased productivity of high-octane gasolinemore » and the development of a value-added distillate blendstock process further improve the economic viability toward commercially implementing this renewable fuels process.« less

2,5-Dimethoxy-1,4-Benzoquinone (DMBQ) as Organic Cathode for Rechargeable Magnesium-Ion Batteries

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

Pan, Baofei; Zhou, Dehua; Huang, Jinhua

2016-01-01

2,5-Dimethoxy-1,4-benzoquinone (DMBQ) was reinvestigated as a cathode material with magnesium electrolytes that are capable of plating/stripping magnesium for rechargeable magnesium-ion batteries. Two electrolytes, the magnesium bis(trifluoromethylsulfonyl)imide mixed with MgCl2 in dimethoxyethane (Mg(TFSI)(2)-2MgCl(2) in DME) electrolyte, and the Mg(TFSI)(2) in diglyme were selected. The Mg(TFSI)(2)-2MgCl(2) in DME enabled Mg-DMBQ batteries with a discharge potentials above 2.0 V vs Mg/Mg2+, which is superior to the previous reported potential in Mg-DMBQ batteries with conventional magnesium salt-based electrolytes (1.1 V, vs Mg/Mg2+), and also excels the well-known Chevrel phase Mo6S8 in magnesium-ion batteries (1.2 V, vs Mg/Mg2+).

78 FR 40835 - Medicare Program; End-Stage Renal Disease Prospective Payment System, Quality Incentive Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-08

...This rule proposes to update and make revisions to the End- Stage Renal Disease (ESRD) prospective payment system (PPS) for calendar year (CY) 2014. This rule also proposes to set forth requirements for the ESRD quality incentive program (QIP), including for payment year (PY) 2016 and beyond. In addition, this rule proposes to clarify the grandfathering provision related to the 3-year minimum lifetime requirement (MLR) for Durable Medical Equipment (DME). In addition, it provides clarification of the definition of routinely purchased DME. This rule also proposes the implementation of budget- neutral fee schedules for splints and casts, and intraocular lenses (IOLs) inserted in a physician's office. Finally, this rule would make a few technical amendments and corrections to existing regulations related to payment for DMEPOS items and services.

Simulation of an automatically-controlled STOL aircraft in a microwave landing system multipath environment

NASA Technical Reports Server (NTRS)

Toda, M.; Brown, S. C.; Burrous, C. N.

1976-01-01

The simulated response is described of a STOL aircraft to Microwave Landing System (MLS) multipath errors during final approach and touchdown. The MLS azimuth, elevation, and DME multipath errors were computed for a relatively severe multipath environment at Crissy Field California, utilizing an MLS multipath simulation at MIT Lincoln Laboratory. A NASA/Ames six-degree-of-freedom simulation of an automatically-controlled deHavilland C-8A STOL aircraft was used to determine the response to these errors. The results show that the aircraft response to all of the Crissy Field MLS multipath errors was small. The small MLS azimuth and elevation multipath errors did not result in any discernible aircraft motion, and the aircraft response to the relatively large (200-ft (61-m) peak) DME multipath was noticeable but small.

Flow field and scalar measurements in a series of turbulent partially-premixed dimethyl ether/air jet flames

DOE PAGES

Coriton, Bruno; Im, Seong -Kyun; Gamba, Mirko; ...

2017-03-12

Here, we present a series of benchmark flames consisting of six partially-premixed piloted dimethyl ether (DME)/air jet flames. These flames provide an opportunity to understand turbulence-flame interactions for oxygenated fuels and to develop predictive models for these interactions using a canonical burner geometry. The development of accurate models for DME/air flames would establish a foundation for studies of more complex oxygenated fuels. The flames are stabilized on a piloted jet burner similar to that of the partially-premixed methane/air jet flames that have been studied extensively within the context of the TNF Workshop. This series of six jet flames spans jetmore » exit Reynolds numbers, ReD, from 29,300 to 73,300 and stoichiometric mixture fractions, ξ st, from 0.35 to 0.60. Flame conditions range from very low probability of localized extinction to a high probability of localized extinction and subsequent re-ignition. Measurements in the flames are compared at downstream locations from 5 to 25 diameters above the nozzle exit. Mean and fluctuating velocity components are measured using stereo particle image velocimetry (SPIV). Simultaneous laser-induced fluorescence (LIF) imaging of OH and CH 2O provides insights into the distribution of these intermediate species in partially-premixed DME/air flames. OH LIF imaging is also combined with SPIV to investigate the strain rate field across the reaction zone.« less

Effect of oral mineral and energy supplementation on blood mineral concentrations, energetic and inflammatory profile, and milk yield in dairy cows affected with dystocia.

PubMed

Benzaquen, M; Galvão, K N; Coleman, A E; Santos, J E P; Goff, J P; Risco, C A

2015-05-01

The objectives of this study were to determine the effect of mineral/energy supplementation of dairy cows with dystocia on blood mineral concentrations, energetic and inflammatory profiles, and milk yield. Multiparous Holstein cows with dystocia were randomly assigned into two groups, (1) treated with a mineral/energy supplement (DME, n= 18) and (2) not treated (DNT, n= 22). A group of cows with normal parturition were randomly selected and were left untreated (NNT, n= 25). Cows in DME received an oral drench of 110 g of calcium and 400 g of propionate as calcium propionate plus 110 g potassium chloride and 150 g of magnesium sulfate administered within 6 h of calving and again 3 days post-partum. Compared to cows with a normal parturition, dystocic cows had decreased plasma calcium concentrations, increased plasma haptoglobin, decreased milk yield at 1 day post-partum, and tended to have increased rectal temperatures from 1 to 12 days post-partum. Compared with cows in DNT, those in DME had decreased plasma calcium concentrations and increased plasma magnesium concentrations 2 and 3 days post-partum, and a tendency for an increase in rectal temperature from 1 to 12 days post-partum. Dystocia is detrimental to calcium homeostasis post-partum, but mineral/energy supplementation as undertaken in this study is not recommended for use in cows with dystocia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ranibizumab for the Treatment of Diabetic Macular Oedema in the Real-World Clinical Setting in Portugal: A Multicentre Study.

PubMed

Farinha, Cláudia; Martins, Amélia; Neves, Arminda; Soares, Raquel; Ruão, Miguel; Ornelas, Mário; Neves, Pedro; Gomes Rodrigues, Filipa; Coelho, Constança; Silva, Rufino

2018-06-08

The purpose of this study was to evaluate the 2-year outcome of ranibizumab for diabetic macular oedema (DME) in the real-life clinical practice of five ophthalmology departments of the National Health Service (NHS) in Portugal. This is a retrospective multicentre study. The clinical records on consecutive patients with DME from clinical practice treated with 0.5 mg intravitreal ranibizumab and followed up for 24 months were reviewed. Efficacy outcomes comprised the change in best corrected visual acuity (BCVA) and central macular thickness (CMT) evaluated by SD-OCT. Multivariate regression analysis was performed to explore predictors of BCVA. A total of 122 eyes of 93 patients were included. The median BCVA change by 24 months was +5.0 letters (IQR 12.0) (p < 0.001) and the CMT change was -89.0 µm (IQR 165.0) (p < 0.001). By 24 months, 21.4% of the eyes had gained ≥15 letters and 8.6% had lost ≥15 letters. The median number of injections given during follow-up was 5.0 (IQR 4.0). A greater baseline CMT and a more disrupted status of the external limiting membrane were predictive of worse BCVA at 24 months (p ≤ 0.015). DME treatment with ranibizumab in the Portuguese NHS is associated with anatomic and functional improvement by 2 years; however, our results are below those reported in major clinical trials, and undertreatment is probably the cause. © 2018 S. Karger AG, Basel.

Flow field and scalar measurements in a series of turbulent partially-premixed dimethyl ether/air jet flames

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

Coriton, Bruno; Im, Seong -Kyun; Gamba, Mirko

Here, we present a series of benchmark flames consisting of six partially-premixed piloted dimethyl ether (DME)/air jet flames. These flames provide an opportunity to understand turbulence-flame interactions for oxygenated fuels and to develop predictive models for these interactions using a canonical burner geometry. The development of accurate models for DME/air flames would establish a foundation for studies of more complex oxygenated fuels. The flames are stabilized on a piloted jet burner similar to that of the partially-premixed methane/air jet flames that have been studied extensively within the context of the TNF Workshop. This series of six jet flames spans jetmore » exit Reynolds numbers, ReD, from 29,300 to 73,300 and stoichiometric mixture fractions, ξ st, from 0.35 to 0.60. Flame conditions range from very low probability of localized extinction to a high probability of localized extinction and subsequent re-ignition. Measurements in the flames are compared at downstream locations from 5 to 25 diameters above the nozzle exit. Mean and fluctuating velocity components are measured using stereo particle image velocimetry (SPIV). Simultaneous laser-induced fluorescence (LIF) imaging of OH and CH 2O provides insights into the distribution of these intermediate species in partially-premixed DME/air flames. OH LIF imaging is also combined with SPIV to investigate the strain rate field across the reaction zone.« less

Evaluation of anti-inflammatory potential of leaf extracts of Skimmia anquetilia

PubMed Central

Kumar, Vijender; Bhat, Zulfiqar Ali; Kumar, Dinesh; Khan, NA; Chashoo, IA

2012-01-01

Objective To evaluate anti-inflammatory potential of leaf extract of Skimmia anquetilia by in-vitro and in-vivo anti-inflammatory models. Methods Acute toxicity study was carried out to determine the toxicity level of different extract using acute toxic class method as described in Organization of Economic Co-operation and Development Guidelines No.423. Carrageenan (1% w/w) was administered and inflammation was induced in rat paw. The leaf extracts of Skimmia anquetilia were evaluated for anti-inflammatory activity by in-vitro human red blood cell (HRBC) membrane stabilization method and in-vivo carrangeenan-induced rat paw edema method. Results The in-vitro membrane stabilizing test showed petroleum ether (PE), chloroform (CE), ethyl acetate (EE), methanol (ME) and aqueous extracts (AE) showed 49.44%, 59.39%, 60.15%, 68.40% and 52.18 % protection, respectively as compared to control groups. The in-vivo results of CE, EE and ME showed 58.20%, 60.17% and 67.53% inhibition of inflammation after 6h administration of test drugs in albino rats. The potency of the leaf extracts of Skimmia anquetilia were compared with standard diclofenac (10 mg/kg) which showed 74.18% protection in in-vitro HRBC membrane stabilization test and 71.64% inhibition in in-vivo carrangeenan-induced rat paw edema model. The ME showed a dose dependent significant (P< 0.01) anti-inflammatory activity in human red blood cell membrane stabilization test and reduction of edema in carrageenan induced rat paw edema. Conclusions The present investigation has confirmed the anti-inflammatory activity of Skimmia anquetilia due to presence of bioactive phytoconstitutes for the first time and provide the pharmacological evidence in favor of traditional claim of Skimmia anquetilia as an anti- inflammatory agent. PMID:23569983

Noninvasive quantitative documentation of cutaneous inflammation in vivo using spectral imaging

NASA Astrophysics Data System (ADS)

Stamatas, Georgios N.; Kollias, Nikiforos

2006-02-01

Skin inflammation is often accompanied by edema and erythema. While erythema is the result of capillary dilation and subsequent local increase of oxygenated hemoglobin (oxy-Hb) concentration, edema is characterized by an increase in extracellular fluid in the dermis leading to local tissue swelling. Edema and erythema are typically graded visually. In this work we tested the potential of spectral imaging as a non-invasive method for quantitative documentation of both the erythema and the edema reactions. As examples of dermatological conditions that exhibit skin inflammation we imaged patients suffering from acne, herpes zoster, and poison ivy rashes using a hyperspectral-imaging camera. Spectral images were acquired in the visible and near infrared part of the spectrum, where oxy-Hb and water demonstrate absorption bands. The values of apparent concentrations of oxy-Hb and water were calculated based on an algorithm that takes into account spectral contributions of deoxy-hemoglobin, melanin, and scattering. In each case examined concentration maps of oxy-Hb and water can be constructed that represent quantitative visualizations of the intensity and extent of erythema and edema correspondingly. In summary, we demonstrate that spectral imaging can be used in dermatology to quantitatively document parameters relating to skin inflammation. Applications may include monitoring of disease progression as well as efficacy of treatments.

Efficacy of adhesive strips to reduce postoperative periorbital edema and ecchymosis following rhinoplasty

PubMed

Tatar, Sedat; Bulam, Mehmet Hakan; Özmen, Selahattin

2018-02-23

Background/aim: Periorbital edema and ecchymosis may develop following rhinoplasty. The aim of this study was to assess the efficacy of adhesive strip application on the upper and lower eyelids to reduce postoperative edema and ecchymosis following rhinoplasty. Materials and methods: The eyelids of one side were randomly selected, and an adhesive strip of standard size and number was applied at the end of the operation. The strips were removed at postoperative day 3; photos of the eyes were taken at days 3 and 7. Edema and ecchymosis were graded on a scale from 1 to 4. The ecchymosis areas on the lower and upper eyelids were measured and compared in square centimeters. Results: The mean ecchymosis area of the lower eyelid on the side of the adhesive strip and on the side without the strip was 1.63 cm2 and 3.32 cm2 in the early period, respectively. It was 1.15 cm2 on the upper eyelid on the side of the adhesive strip, and 1.87 cm2 on the side without the strip. It was 0.224 cm2 on the side of the adhesive strip, and 0.498 cm2 on the side without the adhesive strip in the late period. Conclusion: Applying adhesive strips reduces periorbital edema and ecchymosis.

Strategy for the Management of Macular Edema in Retinal Vein Occlusion: The European VitreoRetinal Society Macular Edema Study

PubMed Central

Adelman, Ron A.; Parnes, Aaron J.; Bopp, Silvia; Saad Othman, Ihab; Ducournau, Didier

2015-01-01

Objective. To compare the efficacy of different therapies in the treatment of macular edema associated with retinal vein occlusion (RVO). Design. This is a nonrandomized, multicenter collaborative study. Participants. 86 retina specialists from 29 countries provided clinical information, including choice of treatment and outcome, on 2,603 patients with macular edema including 738 cases of RVO. Methods. Reported data included the type and number of treatments performed, visual acuities, and other clinical and diagnostic findings. Main Outcome Measures. The mean increase in visual acuity and mean number of treatments performed. Results. 358 cases of central retinal vein occlusion (CRVO) and 380 cases of branch retinal vein occlusion (BRVO) were included in this investigation. Taking all RVO cases together, pars plana vitrectomy with internal limiting membrane (ILM) peeling alone resulted in an improvement in vision greater than other therapies. Those treated with intravitreal antivascular endothelial growth factor (anti-VEGF) injection alone showed the second greatest improvement in vision. Dexamethasone intravitreal implant alone and intravitreal triamcinolone alone both resulted in modest visual gains. Conclusions. In the treatment of macular edema in RVO, vitrectomy with ILM peeling may achieve visual improvement and may be a good option for certain cases. Anti-VEGF injection is the most effective of the nonsurgical treatments. PMID:25705695

A novel method of edema fluid drainage in obstructive lymphedema of limbs by implantation of hydrophobic silicone tubes.

PubMed

Olszewski, Waldemar L; Zaleska, Marzanna

2015-10-01

Lymphedema of limbs is caused by partial or total obstruction of lymphatic collectors as a consequence of skin and deep soft tissue inflammation, trauma of soft tissues and bones, lymphadenectomy, and irradiation in cancer therapy. According to the statistics of the World Health Organization, around 300 million people are affected by pathologic edema of limbs. Effective treatment of such large cohorts has been a challenge for centuries. However, none of the conservative and surgical methods applied so far proved to restore the shape and function of limbs to normal conditions. Actually, physiotherapy is the therapy of choice as a main modality or supplementary to surgical procedures divided into two groups: the bridging drainage and excisional techniques. The microsurgical operations can be performed if some parts of the peripheral collecting lymphatics remain patent and partially drain edematous regions. However, in advanced cases of lymphedema, all main lymphatics are obstructed and tissue fluid accumulates in the interstitial spaces, spontaneously forming "blind channels" or "lakes." The only solution would be to create artificial pathways for edema fluid flow away to the nonobstructed regions where absorption of fluid can take place. The aim of this study was to form artificial pathways for edema fluid flow by subcutaneous implantation of silicone tubes placed along the limb from the lower leg to the lumbar or hypogastric region. In a group of 20 patients with obstructive lymphedema of the lower limbs that developed after lymphadenectomy and irradiation of the pelvis because of uterine cancer with unsuccessful conservative therapy, implantation was done, followed by external compression as intermittent pneumatic compression and elastic support of tissues. Postoperative circumference measurements, lymphoscintigraphy, and ultrasonography of tissues were carried out during 2 years of follow-up. There was a fast decrease of calf circumference since the day of implantation during weeks by a mean 3% with stabilization afterward. Patency of tubes and accumulation of fluid around them were seen on ultrasonography and lymphoscintigraphy in all cases. No tissue cellular reaction to silicone tubes was noted. The simplicity of the surgical procedure, decrease of limb edema, and lack of tissue reaction to the implant make the method worth applying in advanced stages of lymphedema with large volumes of accumulated tissue edema fluid. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Modulation of VEGF-Induced Retinal Vascular Permeability by Peroxisome Proliferator-Activated Receptor-β/δ

PubMed Central

Suarez, Sandra; McCollum, Gary W.; Bretz, Colin A.; Yang, Rong; Capozzi, Megan E.; Penn, John S.

2014-01-01

Purpose. Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability contributes to diabetic macular edema (DME), a serious vision-threatening condition. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) antagonist/reverse agonist, GSK0660, inhibits VEGF-induced human retinal microvascular endothelial cell (HRMEC) proliferation, tubulogenesis, and oxygen-induced retinal vasculopathy in newborn rats. These VEGF-induced HRMEC behaviors and VEGF-induced disruption of endothelial cell junctional complexes may well share molecular signaling events. Thus, we sought to examine the role of PPARβ/δ in VEGF-induced retinal hyperpermeability. Methods. Transendothelial electrical resistance (TEER) measurements were performed on HRMEC monolayers to assess permeability. Claudin-1/Claudin-5 localization in HRMEC monolayers was determined by immunocytochemistry. Extracellular signal-regulated protein kinases 1 and 2 (Erk 1/2) phosphorylation, VEGF receptor 1 (VEGFR1) and R2 were assayed by Western blot analysis. Expression of VEGFR1 and R2 was measured by quantitative RT-PCR. Last, retinal vascular permeability was assayed in vivo by Evans blue extravasation. Results. Human retinal microvascular endothelial cell monolayers treated with VEGF for 24 hours showed decreased TEER values that were completely reversed by the highest concentration of GSK0660 (10 μM) and PPARβ/δ-directed siRNA (20 μM). In HRMEC treated with VEGF, GSK0660 stabilized tight-junctions as evidenced by Claudin-1 staining, reduced phosphorylation of Erk1/2, and reduced VEGFR1/2 expression. Peroxisome proliferator-activated receptor β/δ siRNA had a similar effect on VEGFR expression and Claudin-1, supporting the specificity of GSK0660 in our experiments. Last, GSK0660 significantly inhibited VEGF-induced retinal vascular permeability and reduced retinal VEGFR1and R2 levels in C57BL/6 mice. Conclusions. These data suggest a protective effect for PPARβ/δ antagonism against VEGF-induced vascular permeability, possibly through reduced VEGFR expression. Therefore, antagonism/reverse agonism of PPARβ/δ siRNA may represent a novel therapeutic methodology against retinal hyperpermeability and is worthy of future investigation. PMID:25406289

3D multimodal MRI brain glioma tumor and edema segmentation: a graph cut distribution matching approach.

PubMed

Njeh, Ines; Sallemi, Lamia; Ayed, Ismail Ben; Chtourou, Khalil; Lehericy, Stephane; Galanaud, Damien; Hamida, Ahmed Ben

2015-03-01

This study investigates a fast distribution-matching, data-driven algorithm for 3D multimodal MRI brain glioma tumor and edema segmentation in different modalities. We learn non-parametric model distributions which characterize the normal regions in the current data. Then, we state our segmentation problems as the optimization of several cost functions of the same form, each containing two terms: (i) a distribution matching prior, which evaluates a global similarity between distributions, and (ii) a smoothness prior to avoid the occurrence of small, isolated regions in the solution. Obtained following recent bound-relaxation results, the optima of the cost functions yield the complement of the tumor region or edema region in nearly real-time. Based on global rather than pixel wise information, the proposed algorithm does not require an external learning from a large, manually-segmented training set, as is the case of the existing methods. Therefore, the ensuing results are independent of the choice of a training set. Quantitative evaluations over the publicly available training and testing data set from the MICCAI multimodal brain tumor segmentation challenge (BraTS 2012) demonstrated that our algorithm yields a highly competitive performance for complete edema and tumor segmentation, among nine existing competing methods, with an interesting computing execution time (less than 0.5s per image). Copyright © 2014 Elsevier Ltd. All rights reserved.

77 FR 68065 - Amendment of Class D and Class E Airspace; Lewiston, ID

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-15

... Measuring Equipment (VOR/ DME), and the Lewiston-Nez Perce Instrument Landing System (ILS) Localizer... feet or more above the surface of the earth. * * * * * ANM ID E5 Lewiston, ID [Modified] Lewiston-Nez...

75 FR 67210 - IFR Altitudes; Miscellaneous Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-02

......... 10000 Sec. 95.6345 VOR Federal Airway V345 is Amended To Read in Part HAYWARD, WI VOR/DME..... *GRASS, WI FIX **10000 *6000--MRA *10000--MCA GRASS, WI FIX, SW BND. **3000--MOCA **4000--GNSS MEA HAYWARD...

Edema

MedlinePlus

Edema Overview Edema is swelling caused by excess fluid trapped in your body's tissues. Although edema can affect any part of your body, you ... in your hands, arms, feet, ankles and legs. Edema can be the result of medication, pregnancy or ...

Volume measurement of the leg with the depth camera for quantitative evaluation of edema

NASA Astrophysics Data System (ADS)

Kiyomitsu, Kaoru; Kakinuma, Akihiro; Takahashi, Hiroshi; Kamijo, Naohiro; Ogawa, Keiko; Tsumura, Norimichi

2017-02-01

Volume measurement of the leg is important in the evaluation of leg edema. Recently, method for measurement by using a depth camera is proposed. However, many depth cameras are expensive. Therefore, we propose a method using Microsoft Kinect. We obtain a point cloud of the leg by Kinect Fusion technique and calculate the volume. We measured the volume of leg for three healthy students during three days. In each measurement, the increase of volume was confirmed from morning to evening. It is known that the volume of leg is increased in doing office work. Our experimental results meet this expectation.

Computed microtomography visualization and quantification of mouse ischemic brain lesion by nonionic radio contrast agents.

PubMed

Dobrivojević, Marina; Bohaček, Ivan; Erjavec, Igor; Gorup, Dunja; Gajović, Srećko

2013-02-01

To explore the possibility of brain imaging by microcomputed tomography (microCT) using x-ray contrasting methods to visualize mouse brain ischemic lesions after middle cerebral artery occlusion (MCAO). Isolated brains were immersed in ionic or nonionic radio contrast agent (RCA) for 5 days and subsequently scanned using microCT scanner. To verify whether ex-vivo microCT brain images can be used to characterize ischemic lesions, they were compared to Nissl stained serial histological sections of the same brains. To verify if brains immersed in RCA may be used afterwards for other methods, subsequent immunofluorescent labeling with anti-NeuN was performed. Nonionic RCA showed better gray to white matter contrast in the brain, and therefore was selected for further studies. MicroCT measurement of ischemic lesion size and cerebral edema significantly correlated with the values determined by Nissl staining (ischemic lesion size: P=0.0005; cerebral edema: P=0.0002). Brain immersion in nonionic RCA did not affect subsequent immunofluorescent analysis and NeuN immunoreactivity. MicroCT method was proven to be suitable for delineation of the ischemic lesion from the non-infarcted tissue, and quantification of lesion volume and cerebral edema.

21 CFR 172.860 - Fatty acids.

Code of Federal Regulations, 2013 CFR

2013-04-01

... the gas chromatographic-electron capture method prescribed in paragraph (c)(3) of this section. If..._locations.html. (3) The gas chromatographic-electron capture method for testing fatty acids for chick-edema...

21 CFR 172.860 - Fatty acids.

Code of Federal Regulations, 2012 CFR

2012-04-01

... the gas chromatographic-electron capture method prescribed in paragraph (c)(3) of this section. If..._locations.html. (3) The gas chromatographic-electron capture method for testing fatty acids for chick-edema...

Identifying a Clinically Meaningful Threshold for Change in Uveitic Macular Edema Evaluated by Optical Coherence Tomography

PubMed Central

Sugar, Elizabeth A.; Jabs, Douglas A.; Altaweel, Michael M.; Lightman, Sue; Acharya, Nisha; Vitale, Albert T.; Thorne, Jennifer E.

2011-01-01

Purpose To identify a clinically meaningful threshold for change in retinal thickness measured by optical coherence tomography (OCT) for patients with uveitic macular edema, using correlation with change in visual acuity. Design Cross-sectional and longitudinal study. Methods 128 eyes (101 individuals) with macular edema enrolled in the Multicenter Uveitis Steroid Treatment (MUST) trial. At enrollment and after six months of follow-up, retinal thickness was measured at the central subfield with time domain OCT and visual acuity was measured with logarithmic (ETDRS) visual acuity charts. Participants were classified as having macular edema if the retinal thickness was ≥260μm. Results A threshold for change in retinal center subfield thickness of 20% balanced the percentage of false positives and negatives for predicting greater than 10-letter change in visual acuity with sensitivity of 77% and a specificity of 75%. The results were similar for greater than 5 or 15 or greater letter changes. Those with a 20% or greater reduction in retinal thickness had a mean 11.0 letter improvement (95% CI: 7.7 to 14.3) as compared to a -0.4 letter change (95% CI: -4.1 to 3.3) in visual acuity for those without a 20% reduction (p < 0.01). Conclusions In addition to being above the level of measurement uncertainty, a 20% change in retinal thickness in patients with macular edema appears to be optimal for clinically important changes in visual acuity and may be considered as an outcome for clinical trials of treatments for uveitic macular edema. PMID:21861971

Prone position in balloon kyphoplasty leads to no secondary vertebral compression fractures in osteoporotic spine – a MRI study

PubMed Central

Spalteholz, Matthias; Strasser, Evald; Hantel, Torsten; Gahr, Ralf Herbert

2014-01-01

Purpose: Vertebral compression fractures are the most common fractures in the elderly. Long lasting pain and deformity is responsible for consecutive impairment with markedly reduced life quality, increased morbidity and mortality. The beneficial effects of balloon kyphoplasty are verified in many studies. Subsequent fracture risk is not finally clarified, cement related risks and deformity related risks are discussed. There is less knowledge about the risk of bone marrow edema and new fractures during balloon kyphoplasty procedure. The goal of this study is to examine, if prone position during kyphoplasty is an independent risk factor for new fractures in the osteoporotic spine. Methods: Consecutive MRI study of 20 patients with fresh, non-traumatic thoracolumbar vertebral compression fractures and balloon kyphoplasty treatment. MRI Scans of the thoracolumbar spine were obtained after surgery, before patients have been mobilized. Specific MRI changes like new bone marrow edema, signal intensity changes in adjacent and remote segments and new fractures were assessed by specialized neuro-radiologist. Results: 20 MR images were examined within 48 hours after balloon kyphoplasty procedure. 85% did not show bone marrow edema extent changes after kyphoplasty. We found minor increase of bone marrow edema within the augmented vertebral body in 3 cases. We did not find any new bone marrow edema and no new fractures in adjacent and remote segments after balloon kyphoplasty treatment. Conclusion: Prone position leads to no new bone marrow edema and no new fractures in the osteoporotic spine. Accordingly, prone position has no risk for adjacent level fractures in osteoporotic spines. PMID:26504728

CMR imaging of edema in myocardial infarction using cine balanced steady-state free precession.

PubMed

Kumar, Andreas; Beohar, Nirat; Arumana, Jain Mangalathu; Larose, Eric; Li, Debiao; Friedrich, Matthias G; Dharmakumar, Rohan

2011-12-01

The aim of this study was to investigate the capabilities of balanced steady-state free precession (bSSFP) cardiac magnetic resonance imaging as a novel cine imaging approach for characterizing myocardial edema in animals and patients after reperfused myocardial infarction. Current cardiac magnetic resonance methods require 2 separate scans for assessment of myocardial edema and cardiac function. Mini-pigs (n = 13) with experimentally induced reperfused myocardial infarction and patients with reperfused ST-segment elevation myocardial infarction (n = 26) underwent cardiac magnetic resonance scans on days 2 to 4 post-reperfusion. Cine bSSFP, T2-weighted short TI inversion recovery (T2-STIR), and late gadolinium enhancement were performed at 1.5-T. Cine bSSFP and T2-STIR images were acquired with a body coil to mitigate surface coil bias. Signal, contrast, and the area of edema were compared. Additional patients (n = 10) were analyzed for the effect of microvascular obstruction on bSSFP. A receiver-operator characteristic analysis was performed to assess the accuracy of edema detection. An area of hyperintense bSSFP signal consistent with edema was observed in the infarction zone (contrast-to-noise ratio: 37 ± 13) in all animals and correlated well with the area of late gadolinium enhancement (R = 0.83, p < 0.01). In all patients, T2-STIR and bSSFP images showed regional hyperintensity in the infarction zone. Normalized contrast-to-noise ratios were not different between T2-STIR and bSSFP. On a slice basis, the volumes of hyperintensity on T2-STIR and bSSFP images correlated well (R = 0.86, p < 0.001), and their means were not different. When compared with T2-STIR, bSSFP was positive for edema in 25 of 26 patients (96% sensitivity) and was negative in all controls (100% specificity). All patients with microvascular obstruction showed a significant reduction of signal in the subendocardial infarction zone compared with infarcted epicardial tissue without microvascular obstruction (p < 0.05). Myocardial edema from ST-segment elevation myocardial infarction can be detected using cine bSSFP imaging with image contrast similar to T2-STIR. This new imaging approach allows evaluation of cardiac function and edema simultaneously, thereby reducing patient scan time and increasing efficiency. Further work is necessary to optimize edema contrast in bSSFP images. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The Role of Constitutive Androstane Receptor in Oxazaphosphorine-mediated Induction of Drug-metabolizing Enzymes in Human Hepatocytes

PubMed Central

Wang, Duan; Li, Linhao; Fuhrman, Jennifer; Ferguson, Stephen; Wang, Hongbing

2013-01-01

Purpose The objective of this study was to investigate the roles of the constitutive androstane receptor (CAR) in cyclophosphamide (CPA)- and ifosfamide (IFO)-mediated induction of hepatic drug-metabolizing enzymes (DME). Methods Induction of DMEs was evaluated using real-time RT-PCR and Western blotting analysis in human primary hepatocyte (HPH) cultures. Activation of CAR, pregnane X receptor (PXR), and aryl hydrocarbon receptor by CPA and IFO was assessed in cell-based reporter assays in HepG2 cells and/or nuclear translocation assays in HPHs. Results CYP2B6 reporter activity was significantly enhanced by CPA and IFO in HepG2 cells co-transfected with CYP2B6 reporter plasmid and a chemical-responsive human CAR variant (CAR1+A) construct. Real-time RT-PCR and Western blotting analysis in HPHs showed that both CPA and IFO induced the expressions of CYP2B6 and CYP3A4. Notably, treatment of HPHs with CPA but not IFO resulted in significant nuclear accumulation of CAR, which represents the initial step of CAR activation. Further studies in HPHs demonstrated that selective inhibition of PXR by sulforaphane preferentially repressed IFO- over CPA-mediated induction of CYP2B6. Conclusion These results provide novel insights into the differential roles of CAR in the regulation of CPA- and IFO-induced DME expression and potential drug-drug interactions. PMID:21487929

Synthesis of δ- and α-Carbolines via Nickel-Catalyzed [2 + 2 + 2] Cycloaddition of Functionalized Alkyne-Nitriles with Alkynes.

PubMed

Wang, Gaonan; You, Xu; Gan, Yi; Liu, Yuanhong

2017-01-06

A new method for the synthesis of δ- and α-carbolines through Ni-catalyzed [2 + 2 + 2] cycloaddition of ynamide-nitriles or alkyne-cyanamides with alkynes has been developed. The catalytic system of NiCl 2 (DME)/dppp/Zn with a low-cost Ni(II)-precursor was first utilized in Ni-catalyzed [2 + 2 + 2] cycloaddition reactions, and the in situ generated Lewis acid may play an important role for the successful transformation. Not only internal alkynes but also terminal alkynes undergo the desired cycloaddition reactions efficiently to furnish the carboline derivatives with wide diversity and functional group tolerance.

Edema and elasticity of a fronto-temporal decompressive craniectomy

PubMed Central

Takada, Daikei; Nagai, Hidemasa; Moritake, Kouzo; Akiyama, Yasuhiko

2012-01-01

Background: Decompressive craniectomy is undertaken for relief of brain herniation caused by acute brain swelling. Brain stiffness can be estimated by palpating the decompressive cranial defect and can provide some relatively subjective information to the neurosurgeon to help guide care. The goal of the present study was to objectively evaluate transcutaneous stiffness of the cranial defect using a tactile resonance sensor and to describe the values in patients with a decompressive window in order to characterize the clinical association between brain edema and stiffness. Methods: Data were prospectively collected from 13 of 37 patients who underwent a decompressive craniectomy in our hospital during a 5-year period. Transcutaneous stiffness was measured as change in frequency and as elastic modulus. Results: Stiffness variables of the decompressive site were measured without any adverse effect and subsequent calculations revealed change in frequency = 101.71 ± 36.42 Hz, and shear elastic modulus = 1.99 ± 1.11 kPa. Conclusions: The elasticity of stiffness of a decompressive site correlated with brain edema, cisternal cerebrospinal fluid pressure, and brain shift, all of which are related to acute brain edema. PMID:22347679

DNS of a turbulent lifted DME jet flame

DOE PAGES

Minamoto, Yuki; Chen, Jacqueline H.

2016-05-07

A three-dimensional direct numerical simulation (DNS) of a turbulent lifted dimethyl ether (DME) slot jet flame was performed at elevated pressure to study interactions between chemical reactions with low-temperature heat release (LTHR), negative temperature coefficient (NTC) reactions and shear generated turbulence in a jet in a heated coflow. By conditioning on mixture fraction, local reaction zones and local heat release rate, the turbulent flame is revealed to exhibit a “pentabrachial” structure that was observed for a laminar DME lifted flame [Krisman et al., (2015)]. The propagation characteristics of the stabilization and triple points are also investigated. Potential stabilization points, spatialmore » locations characterized by preferred temperature and mixture fraction conditions, exhibit autoignition characteristics with large reaction rate and negligible molecular diffusion. The actual stabilization point which coincides with the most upstream samples from the pool of potential stabilization points fovr each spanwise location shows passive flame structure with large diffusion. The propagation speed along the stoichiometric surface near the triple point is compared with the asymptotic value obtained from theory [Ruetsch et al., (1995)]. At stoichiometric conditions, the asymptotic and averaged DNS values of flame displacement speed deviate by a factor of 1.7. However, accounting for the effect of low-temperature species on the local flame speed increase, these two values become comparable. In conclusion, this suggests that the two-stage ignition influences the triple point propagation speed through enhancement of the laminar flame speed in a configuration where abundant low-temperature products from the first stage, low-temperature ignition are transported to the lifted flame by the high-velocity jet.« less

Dioxo-Fluoroalkoxide Tungsten(VI) Complexes for Growth of WOx Thin Films by Aerosol-Assisted Chemical Vapor Deposition.

PubMed

Bonsu, Richard O; Kim, Hankook; O'Donohue, Christopher; Korotkov, Roman Y; Abboud, Khalil A; Anderson, Timothy J; McElwee-White, Lisa

2015-08-03

The soluble bis(fluoroalkoxide) dioxo tungsten(VI) complexes WO2(OR)2(DME) [1, R = C(CF3)2CH3; 2, R = C(CF3)3] have been synthesized by alkoxide-chloride metathesis and evaluated as precursors for aerosol-assisted chemical vapor deposition (AACVD) of WOx. The (1)H NMR and (19)F NMR spectra of 1 and 2 are consistent with an equilibrium between the dimethoxyethane (DME) complexes 1 and 2 and the solvato complexes WO2(OR)2(CD3CN)2 [1b, R = C(CF3)2CH3; 2b, R = C(CF3)3] in acetonitrile-d3 solution. Studies of the fragmentation of 1 and 2 by mass spectrometry and thermolysis resulted in observation of DME and the corresponding alcohols, with hexafluoroisobutylene also generated from 1. DFT calculations on possible decomposition mechanisms for 1 located pathways for hydrogen abstraction by a terminal oxo to form hexafluoroisobutylene, followed by dimerization of the resulting terminal hydroxide complex and dissociation of the alcohol. AACVD using 1 occurred between 100 and 550 °C and produced both substoichiometric amorphous WOx and a polycrystalline W18O49 monoclinic phase, which exhibits 1-D preferred growth in the [010] direction. The work function (4.9-5.6 eV), mean optical transmittance (39.1-91.1%), conductivity (0.4-2.3 S/cm), and surface roughness (3.4-7.9 nm) of the WOx films are suitable for charge injection layers in organic electronics.

mobilityRERC state of the science: How science influences public policy in seating and mobility.

PubMed

Hostak, Rita S; Edwards, Doran; Sprigle, Stephen

2013-11-01

In the United States (US), wheeled mobility and seating equipment is classified as Durable Medical Equipment (DME). DME includes a wide array of devices including canes, walkers, home oxygen equipment, hospital beds, and wheelchairs. Seating and mobility devices reflect a wide range of DME, from relatively simple standard manual wheelchairs and cushions to highly complex manual and power wheelchairs and custom seating systems. This wide range of complexity results in a wide range of policies that govern the provision of seating and mobility equipment. This article results from a presentation during the Wheeled Mobility Rehabilitation Engineering Research Center's (RERC's) State of the Science Conference in 2012. The presentation was designed to proffer key concepts related to coverage policies and policy decision-making. Topics covered include an introduction to key policy issues impacting seating and mobility equipment, a description of the barriers that prevent or hinder research being used to inform coverage policy decisions, discussion of the challenges surrounding evidence-based policy decisions regarding seating and mobility, and suggestions of strategies for including policy makers and other stakeholders in setting research priorities and in reporting research findings. In the United States, wheeled mobility and seating equipment are classified as Durable Medical Equipments which are governed by a wide range of policies. Researchers should be encouraged to supplement research articles with articles that explicitly address clinical and policy implications of the work. Policy-makers should be encouraged to engage researchers to insure the breadth of knowledge and evidence is represented and understood.

Quantitative evaluation of benign meningioma and hemangiopericytoma with peritumoral brain edema by 64-slice CT perfusion imaging.

PubMed

Ren, Guang; Chen, Shuang; Wang, Yin; Zhu, Rui-jiang; Geng, Dao-ying; Feng, Xiao-yuan

2010-08-05

Hemangiopericytomas (HPCs) have a relentless tendency for local recurrence and metastases, differentiating between benign meningiomas and HPCs before surgery is important for both treatment planning and the prognosis appraisal. The purpose of this study was to evaluate the correlations between CT perfusion parameters and microvessel density (MVD) in extra-axial tumors and the possible role of CT perfusion imaging in preoperatively differentiating benign meningiomas and HPCs. Seventeen patients with benign meningiomas and peritumoral edema, 12 patients with HPCs and peritumoral edema underwent 64-slice CT perfusion imaging pre-operation. Perfusion was calculated using the Patlak method. The quantitative parameters, include cerebral blood volume (CBV), permeability surface (PS) of parenchyma, peritumoral edema among benign meningiomas and HPCs were compared respectively. CBV and PS in parenchyma, peritumoral edema of benign meningiomas and HPCs were also compared to that of the contrallateral normal white matter respectively. The correlations between CBV, PS of tumoral parenchyma and MVD were examined. The value of CBV and PS in parenchyma of HPCs were significantly higher than that of benign meningiomas (P < 0.05), while the values of CBV and PS in peritumoral edema of benign meningiomas and HPCs were not significantly different (P > 0.05). MVD in parenchyma of HPCs were significantly higher than that of benign meningiomas (P < 0.05). There were positive correlations between CBV and MVD (r = 0.648, P < 0.05), PS and MVD (r = 0.541, P < 0.05) respectively. Furthermore, the value of CBV and PS in parenchyma of benign meningiomas and HPCs were significantly higher than that of contrallateral normal white matter (P < 0.05), the value of CBV in peritumoral edema of benign meningiomas and HPCs were significantly lower than that of contrallateral normal white matter (P < 0.05), while the value of PS in peritumoral edema of benign meningiomas and HPCs were not significantly different with that of contrallateral normal white matter (P > 0.05). CT perfusion imaging can provide critical information on the vascularity of HPC and benign meningiomas. Determination of maximal CBV and corresponding PS values in the parenchyma may be useful in the preoperative differentiating HPC from benign meningiomas.

78 FR 68699 - IFR Altitudes; Miscellaneous Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-15

... MAROC, IL FIX *3000 *2400--MOCA MAROC, IL FIX PONTIAC, IL VOR/DME..... 2500 Sec. 95.6066 VOR Federal... NASHVILLE, TN VORTAC *LENON, TN FIX **3000 *6500--MRA **2400--MOCA *LENON, TN FIX HARME, TN FIX **3000 [[Page 68701

[Study on the heterogeneity of edema in severe preeclampsia].

PubMed

Shi, Junmei; Yang, Zi; Chen, Lei

2014-05-06

The aim of this study was to analysis the clinical edema forms and explore the heterogeneity of edema in severe preeclampsia (PE) . From February 2002 to February 2009, Peking University Third Hospital admitted with severe preeclampsia 228 cases who were enrolled in this study. The form is divided into no edema (A-type), pure interstitial edema (B-type), a simple cavity gap edema (C-type) and mixed interstitial edema that coexist with lacunar edema (D-type). Analysis and comparison of various types of edema in patients with different clinical manifestations of prenatal care models, laboratory parameters, the incidence of gestational age, complications and obstetric and perinatal outcomes, and analyze the relationship between different types of edema and albumins and the peak value of proteinuria. Edema was seen in 86% (197/228) of all of cases. Compared the cases who have regular prenatal care with those who have irregular care, differences were statistically significant in edema type composition ratio (P < 0.01) and the incidence of serious complications (P < 0.01), and serum albumin levels (P < 0.01), but not in the peak value of proteinuria (P > 0.05); Compared early-onset PE and late-onset PE patients, differences were statistically significant in edema type composition ratio (P < 0.01) and peak value of proteinuria (P < 0.01), but not in serum albumin levels and the incidence of serious complications (P > 0.05). Comparison between the various types of edema, differences were statistically significant in serum albumin levels and peak value of proteinuria and incidence of serious complications and the gestational week at PE onset and the incidence of treatment preterm labor (P < 0.05).Occurrence of placental abruption, heart failure and HELLP syndrome had statistical significance in different types of edema(P < 0.05). The varying degrees of interstitial edema were correlated with serum albumin levels (r = -0.19, P < 0.05) and serious complication occurrence (r = -0.232, P < 0.05), but no correlation displayed with the peak value of urinary protein (P > 0.05). The manifestations of edema were diverse in severe preeclampsia. The forms of edema were related to the PE onset of gestational age and serious complication involving in different organs.Strengthen prenatal care and early detection of edema may improve adverse obstetric outcomes.

NTCP Modeling of Subacute/Late Laryngeal Edema Scored by Fiberoptic Examination

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

Rancati, Tiziana; Fiorino, Claudio, E-mail: fiorino.claudio@hsr.i; Sanguineti, Giuseppe

2009-11-01

Purpose: Finding best-fit parameters of normal tissue complication probability (NTCP) models for laryngeal edema after radiotherapy for head and neck cancer. Methods and Materials: Forty-eight patients were considered for this study who met the following criteria: (1) grossly uninvolved larynx, (2) no prior major surgery except for neck dissection and tonsillectomy, (3) at least one fiberoptic examination of the larynx within 2 years from radiotherapy, (4) minimum follow-up of 15 months. Larynx dose-volume histograms (DVHs) were corrected into a linear quadratic equivalent one at 2 Gy/fr with alpha/beta = 3 Gy. Subacute/late edema was prospectively scored at each follow-up examinationmore » according to the Radiation Therapy Oncology Group scale. G2-G3 edema within 15 months from RT was considered as our endpoint. Two NTCP models were considered: (1) the Lyman model with DVH reduced to the equivalent uniform dose (EUD; LEUD) and (2) the Logit model with DVH reduced to the EUD (LOGEUD). The parameters for the models were fit to patient data using a maximum likelihood analysis. Results: All patients had a minimum of 15 months follow-up (only 8/48 received concurrent chemotherapy): 25/48 (52.1%) experienced G2-G3 edema. Both NTCP models fit well the clinical data: with LOGEUD the relationship between EUD and NTCP can be described with TD50 = 46.7 +- 2.1 Gy, n = 1.41 +- 0.8 and a steepness parameter k = 7.2 +- 2.5 Gy. Best fit parameters for LEUD are n = 1.17 +- 0.6, m = 0.23 +- 0.07 and TD50 = 47.3 +- 2.1 Gy. Conclusions: A clear volume effect was found for edema, consistent with a parallel architecture of the larynx for this endpoint. On the basis of our findings, an EUD <30-35 Gy should drastically reduce the risk of G2-G3 edema.« less

[The role of laryngopharyngeal reflux in the pathogenesis of Reinke's edema].

PubMed

Wang, J S; Li, J R

2016-12-01

Objective: To determine the significance of laryngopharyngeal reflux(LPR) in Reinke's edema. Method: Sixteen patients who have been diagnosed as Reinke's edema between February 2014 to June 2016 were included in this study. The control group included fifty vocal cord leukoplakia and early glottic cancer patients for the corresponding period. RSI,RFS,numbers of laryngopharyngeal acid reflux events,and time of laryngopharyngeal acid exposure were evaluated between two groups. Result: The mean RSI of the Reinke's edema was 11.2±3.8,the mean RFS was 8.2±1.5,the median numbers of laryngopharyngeal acid reflux events was 4.0［0.0；9.0］,the time of laryngopharyngeal acid exposure was 5.6［0.0；16.7］min.The rate of LPR positive in Reinke's edema patients was 100.0%（16/16）by RSI and RFS,56.2%（9/16）by 24 hour MII-pH monitoring.The mean RSI of the control group was 8.6±3.2,the mean RFS was 6.8±2.1,the median numbers of laryngopharyngeal acid reflux events was 0.0［0.0；3.0］,the time of laryngopharyngeal acid exposure was 0.0［0.0；4.3］min.The rate of LPR positive in control group was 58.0%（29/50）by RSI and RFS,28.0%（14/50）by 24 hour MII-pH monitoring.There were statistically significance in RSI,RFS,numbers of laryngopharyngeal acid reflux events,and time of laryngopharyngeal acid exposure between two groups( P <0.01 or P <0.05). Conclusion: Laryngopharyngeal reflux might play a role as an etiologic factor in Reinke's edema,awareness should increase about acid suppression therapy in Reinke's edema. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Perioperative Corticosteroids Reduce Short-Term Edema and Ecchymosis in Rhinoplasty: A Meta-Analysis

PubMed Central

Coroneos, Christopher J; Voineskos, Sophocles H; Cook, Deborah J; Farrokhyar, Forough; Thoma, Achilleas

2016-01-01

Abstract Background A number of randomized controlled trials (RCTs) have investigated the role of perioperative corticosteroids in rhinoplasty. Each of these trials however has an insufficient sample sizes to reach definitive conclusions and detect harms. Three recent reviews have analyzed edema and ecchymosis outcomes following rhinoplasty; each arrived at a different conclusion and recommendation. Objective To estimate the effectiveness of systemic perioperative corticosteroid treatment compared to placebo for clinical outcomes in rhinoplasty using a methodologically rigorous meta-analysis. Methods Electronic databases were searched without language restriction. Included trials were randomized controlled trials of systemic perioperative corticosteroid treatment vs placebo in rhinoplasty evaluating at least one of: edema, ecchymosis, bleeding, cosmetic outcome, and patient satisfaction. The Cochrane risk of bias tool was applied to included trials, and the quality of evidence for each outcome was assessed using the GRADE approach. Results Analyses included 336 patients from eight trials. Perioperative corticosteroids reduced the worst edema (SMD: −1.03, 95%CI −1.30 to −0.76, P < .001) and ecchymosis (SMD: −0.78, 95%CI −1.09 to 0.47, P < .001) after rhinoplasty. At one day postoperative, a single dose of perioperative corticosteroid reduced edema (SMD −1.15, 95%CI −1.42 to −0.87, P < .001) and ecchymosis (SMD −0.79, 95%CI −1.05 to −0.52, P < .001). No clinical benefit in edema or ecchymosis was found seven days postoperatively, nor did intraoperative bleeding increase. Conclusions There is high quality evidence to support perioperative systemic corticosteroid treatment in rhinoplasty to reduce short-term edema and ecchymosis without increased intraoperative bleeding. These findings are not present at seven days. For future trials, we suggest evaluation of patient satisfaction, and correlation with long-term cosmetic outcome. Level of Evidence: 2 PMID:26773090

MRI reveals edema in larynx (but not in brain) during anaphylactic hypotension in anesthetized rats.

PubMed

Toyota, Ichiro; Tanida, Mamoru; Shibamoto, Toshishige; Wang, Mofei; Kurata, Yasutaka; Tonami, Hisao

2013-11-01

Anaphylactic shock is sometimes accompanied by local interstitial edema due to increased vascular permeability. We performed magnetic resonance imaging (MRI) to compare edema in the larynx and brain of anesthetized rats during anaphylactic hypotension versus vasodilator-induced hypotension. Male Sprague Dawley rats were subjected to hypotension induced by the ovalbumin antigen (n=7) or a vasodilator sodium nitroprusside (SNP; n=7). Apparent diffusion coefficient (ADC) and T2-relaxation time (T2RT) were quantified on MRI performed repeatedly for up to 68 min after the injection of either agent. The presence of laryngeal edema was also examined by histological examination. Separately, the occurrence of brain edema was assessed by measuring brain water content using the wet/dry method in rats with anaphylaxis (n=5) or SNP (n=5) and the non-hypotensive control rats (n=5). Mast cells in hypothalamus were morphologically examined. Mean arterial blood pressure similarly decreased to 35 mmHg after an injection of the antigen or SNP. Hyperintensity on T2-weighted images (as reflected by elevated T2RT) was found in the larynx as early as 13 min after an injection of the antigen, but not SNP. A postmortem histological examination revealed epiglottic edema in the rats with anaphylaxis, but not SNP. In contrast, no significant changes in T2RT or ADC were detectable in the brains of any rats studied. In separate experiments, the quantified brain water content did not increase in either anaphylaxis or SNP rats, as compared with the non-hypotensive control rats. The numbers of mast cells with metachromatic granules in the hypothalamus were not different between rats with anaphylaxis and SNP, suggesting the absence of anaphylactic reaction in hypothalamus. Edema was detected using the MRI technique in the larynx during rat anaphylaxis, but not in the brain.

Pathophysiology and the Monitoring Methods for Cardiac Arrest Associated Brain Injury.

PubMed

Reis, Cesar; Akyol, Onat; Araujo, Camila; Huang, Lei; Enkhjargal, Budbazar; Malaguit, Jay; Gospodarev, Vadim; Zhang, John H

2017-01-11

Cardiac arrest (CA) is a well-known cause of global brain ischemia. After CA and subsequent loss of consciousness, oxygen tension starts to decline and leads to a series of cellular changes that will lead to cellular death, if not reversed immediately, with brain edema as a result. The electroencephalographic activity starts to change as well. Although increased intracranial pressure (ICP) is not a direct result of cardiac arrest, it can still occur due to hypoxic-ischemic encephalopathy induced changes in brain tissue, and is a measure of brain edema after CA and ischemic brain injury. In this review, we will discuss the pathophysiology of brain edema after CA, some available techniques, and methods to monitor brain oxygen, electroencephalography (EEG), ICP (intracranial pressure), and microdialysis on its measurement of cerebral metabolism and its usefulness both in clinical practice and possible basic science research in development. With this review, we hope to gain knowledge of the more personalized information about patient status and specifics of their brain injury, and thus facilitating the physicians' decision making in terms of which treatments to pursue.

Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study.

PubMed

Schmidt-Erfurth, Ursula; Lang, Gabriele E; Holz, Frank G; Schlingemann, Reinier O; Lanzetta, Paolo; Massin, Pascale; Gerstner, Ortrud; Bouazza, Abdelkader Si; Shen, Haige; Osborne, Aaron; Mitchell, Paul

2014-05-01

To evaluate long-term efficacy and safety profiles during 3 years of individualized ranibizumab treatment in patients with visual impairment due to diabetic macular edema (DME). Phase IIIb, multicenter, 12-month, randomized core study and 24-month open-label extension study. Of the 303 patients who completed the randomized RESTORE 12-month core study, 240 entered the extension study. In the extension study, patients were eligible to receive individualized ranibizumab treatment as of month 12 guided by best-corrected visual acuity (BCVA) and disease progression criteria at the investigators' discretion. Concomitant laser treatment was allowed according to the Early Treatment Diabetic Retinopathy Study guidelines. Based on the treatments received in the core study, the extension study groups were referred to as prior ranibizumab, prior ranibizumab + laser, and laser. Change in BCVA and incidence of ocular and nonocular adverse events (AEs) over 3 years. Overall, 208 patients (86.7%) completed the extension study. In patients treated with ranibizumab during the core study, consecutive individualized ranibizumab treatment during the extension study led to an overall maintenance of BCVA and central retinal subfield thickness (CRST) observed at month 12 over the 2-year extension study (+8.0 letters, -142.1 μm [prior ranibizumab] and +6.7 letters, -145.9 μm [prior ranibizumab + laser] from baseline at month 36) with a median of 6.0 injections (mean, 6.8 injections; prior ranibizumab) and 4.0 (mean, 6.0 injections; prior ranibizumab + laser). In the prior laser group, a progressive BCVA improvement (+6.0 letters) and CRST reduction (-142.7 μm) at month 36 were observed after allowing ranibizumab during the extension study, with a median of 4.0 injections (mean, 6.5 injections) from months 12 to 35. Patients in all 3 treatment groups received a mean of <3 injections in the final year. No cases of endophthalmitis, retinal tear, or retinal detachment were reported. The most frequently reported ocular and nonocular adverse effects over 3 years were cataract (16.3%) and nasopharyngitis (23.3%). Eight deaths were reported during the extension study, but none were suspected to be related to the study drug/procedure. Ranibizumab was effective in improving and maintaining BCVA and CRST outcomes with a progressively declining number of injections over 3 years of individualized dosing. Ranibizumab was generally well tolerated with no new safety concerns over 3 years. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

48 CFR 1034.201 - Policy.

Code of Federal Regulations, 2014 CFR

2014-10-01

... CONTRACTING MAJOR SYSTEM ACQUISITION Earned Value Management System 1034.201 Policy. (a) (1) An Earned Value Management System (EVMS) is required for major acquisitions for development/modernization/enhancement (DME..., Earned Value Management System; and, as appropriate, 1052.234-4, Earned Value Management System Alternate...

48 CFR 1034.201 - Policy.

Code of Federal Regulations, 2013 CFR

2013-10-01

... CONTRACTING MAJOR SYSTEM ACQUISITION Earned Value Management System 1034.201 Policy. (a) (1) An Earned Value Management System (EVMS) is required for major acquisitions for development/modernization/enhancement (DME..., Earned Value Management System; and, as appropriate, 1052.234-4, Earned Value Management System Alternate...

48 CFR 1034.201 - Policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

... CONTRACTING MAJOR SYSTEM ACQUISITION Earned Value Management System 1034.201 Policy. (a) (1) An Earned Value Management System (EVMS) is required for major acquisitions for development/modernization/enhancement (DME..., Earned Value Management System; and, as appropriate, 1052.234-4, Earned Value Management System Alternate...

76 FR 25232 - Standard Instrument Approach Procedures, and Takeoff Minimums and Obstacle Departure Procedures...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

... Patterson, LA, Harry P Williams Memorial, NDB RWY 6, Amdt 11 Slidell, LA, Slidell, Takeoff Minimums and... Harrisonville, MO, Lawrence Smith Memorial, VOR/DME RWY 35, Orig-A, CANCELLED Lincoln Park, NJ, Lincoln Park...

Control of Lower Extremity Edema in Patients with Diabetes: Double Blind Randomized Controlled Trial Assessing the Efficacy of Mild Compression Diabetic Socks

PubMed Central

Wu, Stephanie C.; Crews, Ryan T.; Skratsky, Melissa; Overstreet, Julia; Yalla, Sai V.; Winder, Michelle; Ortiz, Jacquelyn; Andersen, Charles A.

2017-01-01

Aims Persons with diabetes frequently present with lower extremity (LE) edema; however, compression therapy is generally avoided for fear of compromising arterial circulation in a population with a high prevalence of peripheral arterial disease. This double blind randomized controlled trial (RCT) assessed whether diabetic socks with mild compression could reduce LE edema in patients with diabetes without negatively impacting vascularity. Methods Eighty subjects with LE edema and diabetes were randomized to receive either mild-compression knee high diabetic socks (18–25mmHg) or non-compression knee high diabetic socks. Subjects were instructed to wear the socks during all waking hours. Follow-up visits occurred weekly for four consecutive weeks. Edema was quantified through midfoot, ankle, and calf circumferences and cutaneous fluid measurements. Vascular status was tracked via ankle brachial index (ABI), toe brachial index (TBI), and skin perfusion pressure (SPP). Results Seventy-seven subjects (39 controls and 38 mild-compression subjects) successfully completed the study. No statistical differences between the two groups in terms of age, body mass index, gender, and ethnicity. Repeated measures analysis of variance and Sidak corrections for multiple comparisons were used for data analyses. Subjects randomized to mild-compression diabetic socks demonstrated significant decreases in calf and ankle circumferences at the end of treatment as compared to baseline. LE circulation did not diminish throughout the study with no significant decreases in ABI, TBI or SPP for either group. Conclusions Results of this RCT suggest that mild compression diabetic sock may be effectively and safely used in patients with diabetes and LE edema. PMID:28315576

Effective therapy to reduce edema after total knee arthroplasty Multi-layer compression therapy or standard therapy with cool pack - a randomized controlled pilot trial

PubMed

Stocker, Brigitta; Babendererde, Christine; Rohner-Spengler, Manuela; Müller, Urs W; Meichtry, André; Luomajoki, Hannu

2018-02-01

Background: After total knee arthroplasty (TKA) efficient control and reduction of postoperative edema is of great importance. Aim: The aim of this pilot study (EKNZ 2014 – 225 DRKS00006271) was to investigate the effectiveness of multi-layer compression therapy (MLCT) to reduce edema in the early period after surgery compared to the standard treatment with Cool Pack. Methods: In this randomized controlled pilot trial, sixteen patients after TKA were randomized into an intervention group (IG) or a control group (CG). Circumferential measurements were used to assess edema. Secondary outcomes were range of motion (ROM), pain (numeric rating scale, NRS) and function as measured with the fast Self Paced Walking Test (fSPWT). Results: Clinically relevant differences in edema reduction between the two groups were found in the early postoperative period and at the six weeks follow up. Six days postoperatively the group time interaction (IE) in favor of the IG were −3.8 cm (95 % CI: −5.1; −2.4) when measured 10 cm proximal to the joint space and −2.7 cm (CI: −4.1; −1.3) when measured 5 cm proximally. We further observed differences in secondary outcomes in favor of the CG. Six days postoperatively the IE for knee flexion was –8.3 ° (CI: −22.0; 5.4) and for the fSPWT it was 12.8 seconds (CI: −16.4; 41.3). Six weeks postoperatively these differences diminished. Conclusions: The findings suggest that MLCT could be an alternative treatment to reduce postoperative edema in patients after total knee arthroplasty. Eventually possible negative effects on early knee flexion and function must be considered.

Influence of Prostatic Edema on {sup 131}CS Permanent Prostate Seed Implants: A Dosimetric and Radiobiological Study

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

Kehwar, Than S., E-mail: kehwarts@upmc.ed; Jones, Heather A.; Huq, M. Saiful

2011-06-01

Purpose: To study the influence of prostatic edema on postimplant physical and radiobiological parameters using {sup 131}Cs permanent prostate seed implants. Methods and Materials: Thirty-one patients with early prostate cancer who underwent {sup 131}Cs permanent seed implantation were evaluated. Dose-volume histograms were generated for each set of prostate volumes obtained at preimplantation and postimplantion days 0, 14, and 28 to compute quality indices (QIs) and fractional doses at level x (FD{sub x}). A set of equations for QI, FD{sub x}, and biologically effective doses at dose level D{sub x} (BED{sub x}) were defined to account for edema changes with timemore » after implant. Results: There were statistically significant differences found between QIs of pre- and postimplant plans at day 0, except for the overdose index (ODI). QIs correlated with postimplant time, and FD{sub x} was found to increase with increasing postimplant time. With the effect of edema, BED at different dose levels showed less improvement due to the short half-life of {sup 131}Cs, which delivers about 85% of the prescribed dose before the prostate reaches its original volume due to dissipation of edema. Conclusions: Results of the study show that QIs, FD{sub x}, and BEDs at the level of D{sub x} changed from preneedle plans to postimplant plans and have statistically significant differences (p < 0.05), except for the ODI (p = 0.106), which suggests that at the time of {sup 131}C seed implantation, the effect of edema must be accounted for when defining the seed positions, to avoid the possibility of poor dosimetric and radiobiologic results for {sup 131}Cs seed implants.« less

Risk Factors Related to Lower Limb Edema, Compression, and Physical Activity During Pregnancy: A Retrospective Study.

PubMed

Ochalek, Katarzyna; Pacyga, Katarzyna; Curyło, Marta; Frydrych-Szymonik, Aleksandra; Szygula, Zbigniew

2017-06-01

The aim of the article was to assess risk factors and to analyze methods applied in the prevention and treatment of lower limb edema in pregnant women with a particular focus on compression therapy and exercise. Fifty-four women during the early 24-hour period following delivery were assigned to two groups-either to a group with swellings of lower limbs during pregnancy, located mostly in the region of feet and lower legs (Group A, n = 42), or to a group without edema (Group B, n = 12). Two subgroups, namely A1 and A2, were additionally distinguished in Group A. Compression therapy that consisted in wearing circular-knit compression garments, usually at compression level 1 (ccl1), with three cases of compression level 2 (ccl2) was applied only in Group A1 (n = 18 women). The analysis has led to a conclusion that there is a link between the occurrence of edema during pregnancy on the one hand and the pregravidity episodes of venous conditions (vascular insufficiency and thrombosis, p < 0.05) and the lack of physical exercise during pregnancy (p = 0.01) on the other hand. However, interdependence between the occurrence of edema and the number of times a female had been pregnant, physical activity before gravidity, or body mass index before gravidity has not been identified. Only 33% of the analyzed women applied compression therapy during pregnancy; a half of them continued to apply compression during the postpartum period. Compression therapy in combination with proper physical exercises appears to be an effective means to prevent and treat venous thrombosis and lower limb edema in pregnant women, yet further research in line with the principles of evidence-based medicine is required.

The Effects of Shilajit on Brain Edema, Intracranial Pressure and Neurologic Outcomes following the Traumatic Brain Injury in Rat

PubMed Central

Khaksari, Mohammad; Mahmmodi, Reza; Shahrokhi, Nader; Shabani, Mohammad; Joukar, Siavash; Aqapour, Mobin

2013-01-01

Objective(s): Brain edema is one of the most serious causes of death within the first few days after trauma brain injury (TBI). In this study we have investigated the role of Shilajit on brain edema, blood-brain barrier (BBB) permeability, intracranial pressure (ICP) and neurologic outcomes following brain trauma. Materials and Methods: Diffuse traumatic brain trauma was induced in rats by drop of a 250 g weight from a 2 m high (Marmarou’s methods). Animals were randomly divided into 5 groups including sham, TBI, TBI-vehicle, TBI-Shi150 group and TBI-Shi250 group. Rats were undergone intraperitoneal injection of Shilajit and vehicle at 1, 24, 48 and 72 hr after trauma. Brain water content, BBB permeability, ICP and neurologic outcomes were finally measured. Results: Brain water and Evans blue dye contents showed significant decrease in Shilajit-treated groups compared to the TBI-vehicle and TBI groups. Intracranial pressure at 24, 48 and 72 hr after trauma had significant reduction in Shilajit-treated groups as compared to TBI-vehicle and TBI groups (P<0.001). The rate of neurologic outcomes improvement at 4, 24, 48 and 72 hr after trauma showed significant increase in Shilajit-treated groups in comparison to theTBI- vehicle and TBI groups (P <0.001). Conclusion: The present results indicated that Shilajit may cause in improvement of neurologic outcomes through decreasing brain edema, disrupting of BBB, and ICP after the TBI. PMID:23997917

Bilateral periorbital edema in systemic lupus erythematosus.

PubMed

Norden, D; Weinberg, J; Schumacher, H R; Keenan, G; Freundlich, B

1993-12-01

Periorbital edema is a rare manifestation of systemic lupus erythematosus (SLE). We describe a patient with SLE who developed bilateral periorbital edema during her lupus flares. Conjunctival biopsy confirmed the presence of inflammation. Resolution occurred only after high doses of corticosteroids. The differential diagnosis of periorbital edema and possible etiologies of the edema are briefly discussed.

76 FR 11978 - Proposed Amendment of Federal Airways; Alaska

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-04

... Federal airways in Alaska. Due to construction of wind turbines on Fire Island, AK, the Anchorage VOR is... NDB/DME (Lat. 56[deg]57'15'' N., long. 158[deg]38'51'' W.) BATTY Fix (Lat. 59[deg]03'57'' N., long...

75 FR 72942 - Standard Instrument Approach Procedures, and Takeoff Minimums and Obstacle Departure Procedures...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-29

..., Takeoff Minimums and Obstacle DP, Amdt 3 Harvard, NE, Harvard State, RNAV (GPS) RWY 35, Orig Harvard, NE, Harvard State, Takeoff Minimums and Obstacle DP, Orig Harvard, NE, Harvard State, VOR/DME RNAV OR GPS RWY...

Thermodynamic Investigation of the Interaction between Polymer and Gases

NASA Astrophysics Data System (ADS)

Mahmood, Syed Hassan

This thesis investigates the interaction between blowing agents and polymer matrix. Existing theoretical model was further developed to accommodate the polymer and blowing agent under study. The obtained results are not only useful for the optimization of the plastic foam fabrication process but also provides a different approach to usage of blowing agents. A magnetic suspension balance and an in-house visualizing dilatometer were used to obtain the sorption of blowing agents in polymer melts under elevated temperature and pressure. The proposed theoretical approach based on the thermodynamic model of SS-EOS is applied to understand the interaction of blowing agents with the polymer melt and one another (in the case of blend blowing agent). An in-depth study of the interaction of a blend of CO2 and DME with PS was conducted. Experimental volume swelling of the blend/PS mixture was measured and compared to the theoretical volume swelling obtained via ternary based SS-EOS, insuring the models validity. The effect of plasticization due to dissolution of DME on the solubility of CO2 in PS was then investigated by utilizing the aforementioned model. It was noted that the dissolution of DME increased the concentration of CO2 in PS and lowering the saturation pressure needed to dissolved a certain amount of CO2 in PS melt. The phenomenon of retrograde vitrification in PMMA induced due dissolution of CO2 was investigated in light of the thermodynamic properties resulting from the interaction of polymer and blowing agent. Solubility and volume swelling were measured in the pressure and temperature ranges promoting vitrification phenomenon, with relation being established between the thermodynamic properties and the vitrification process. Foaming of PMMA was conducted at various temperature values to investigate the application of this phenomenon.

Stabilized three-stage oxidation of DME/air mixture in a micro flow reactor with a controlled temperature profile

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

Oshibe, Hiroshi; Nakamura, Hisashi; Tezuka, Takuya

Ignition and combustion characteristics of a stoichiometric dimethyl ether (DME)/air mixture in a micro flow reactor with a controlled temperature profile which was smoothly ramped from room temperature to ignition temperature were investigated. Special attention was paid to the multi-stage oxidation in low temperature condition. Normal stable flames in a mixture flow in the high velocity region, and non-stationary pulsating flames and/or repetitive extinction and ignition (FREI) in the medium velocity region were experimentally confirmed as expected from our previous study on a methane/air mixture. In addition, stable double weak flames were observed in the low velocity region for themore » present DME/air mixture case. It is the first observation of stable double flames by the present methodology. Gas sampling was conducted to obtain major species distributions in the flow reactor. The results indicated that existence of low-temperature oxidation was conjectured by the production of CH{sub 2}O occured in the upstream side of the experimental first luminous flame, while no chemiluminescence from it was seen. One-dimensional computation with detailed chemistry and transport was conducted. At low mixture velocities, three-stage oxidation was confirmed from profiles of the heat release rate and major chemical species, which was broadly in agreement with the experimental results. Since the present micro flow reactor with a controlled temperature profile successfully presented the multi-stage oxidations as spatially separated flames, it is shown that this flow reactor can be utilized as a methodology to separate sets of reactions, even for other practical fuels, at different temperature. (author)« less

Implications of Dynamic Loading and Changing Climate on Mercury Bioaccumulation in a Planktivorous Fish (Orthodon microlepidotus)

NASA Astrophysics Data System (ADS)

Carroll, R. W. H.; Flickinger, A.; Warwick, J. J.; Schumer, R.

2015-12-01

A bioenergetic and mercury (Hg) mass balance (BioHg) model is developed for the Sacramento blackfish (Orthodon microlepidotus), a filter feeding cyprinid found in northern California and Nevada. Attention focuses on the Lahontan Reservoir in northern Nevada, which receives a strong temporally varying load of dissolved methylmercury (DMeHg) from the Carson River. Hg loads are the result of contaminated bank erosion during high flows and diffusion from bottom sediments during low flows. Coupling of dynamic reservoir loading with periods of maximum plankton growth and maximum fish consumption rates are required to explain the largest body burdens observed in the planktivore. In contrast, the large body burdens cannot be achieved using average water column concentrations. The United States Bureau of Reclamation has produced future streamflow estimates for 2000-2099 using 112 CMIP3 climate projections and the Variable Infiltration Capacity (VIC) model. These are used to drive a fully dynamic Hg transport model to assess changes in contaminant loading to the reservoir and implications on planktivorous bioaccumulation. Model results suggest the future loads of DMeHg entering the Lahontan Reservoir will decrease most significantly in the spring and summer due to channel width increases and depth decreases in the Carson River which reduce bank erosion over the century. The modeled concentrations of DMeHg in the reservoir are expected to increase during the summer due to a decrease in reservoir volume affecting the concentrations more than the decrease in loads, and the model results show that bioaccumulation levels may increase in the upstream sections of the reservoir while maintaining contamination levels above the federal action limit for human consumption in the lower reservoir.

Vitex negundo inhibits cyclooxygenase-2 inflammatory cytokine-mediated inflammation on carrageenan-induced rat hind paw edema

PubMed Central

Chattopadhyay, Pronobesh; Hazarika, Soilyadhar; Dhiman, Sunil; Upadhyay, Aadesh; Pandey, Anurag; Karmakar, Sanjeev; Singh, Lokendra

2012-01-01

Background: Vitex negundo L. (Verbenaceae) is a hardy plant widely distributed in the Indian subcontinent and used for treatment of a wide spectrum of health disorders in traditional and folk medicine, some of which have been experimentally validated. In present study, we aimed to investigate the anti-inflammatory effects of V. negundo in carrageenan-induced paw edema in rats, and to investigate the probable mechanism of anti-inflammatory action. Materials and Methods: Paw edema was produced by injecting 1% solution of carrageenan, and the paw volume was measured before and after carrageenan injection up to 5 h. V. negundo leaf oil was extracted using a Clevenger apparatus and administered by a trans-dermal route to Wistar rats and the percentage of inhibition of inflammation was observed using a Plethysmometer by comparing a compound aerosol-based formulation with 1 mg diclofinac diethylamine BP and 7 mg methyl salicylate IP/kg body weight served as a standard drug whereas paraffin oil served as the placebo group. After withdrawing of blood, serum was separated and cyclooxygenase (COX)-1 and COX-2 inhibitory activities were measured by the enzyme immuno assay (EIA) method by using a COX inhibitor screening assay kit. Results and Discussion: V. negundo leaf oil significantly (P < 0.05) reduced the carrageenan-induced paw edema as compared to the placebo group (paraffin oil) and 1 mg diclofinac diethylamine BP and 7 mg methyl salicylate IP showed the maximum inhibition of paw edema as compared to the V. negundo leaf oil treated group and the control group. Also in the present study V. negundo leaf oil showed significantly (P < 0.05) inhibits COX-1 pathways rather than COX-2 pathways as compared to the V. negundo leaf oil treated group. Conclusion: It is suggested that the V. negundo leaf oil is a potent anti-inflammatory agent and acts via inhibition of COX-2 without much interfering COX-1 pathways. PMID:22923950

Edema: a silent but important factor.

PubMed

Villeco, June P

2012-01-01

Edema is a normal response to injury. Even the smallest injury is associated with some inflammation, and initial edema is part of the normal inflammatory process. However, edema becomes a concern when it persists beyond the inflammatory phase. Once we have progressed into the rebuilding, or fibroplastic phase of healing, edema will delay healing and contribute to complications such as pain and stiffness. Early prevention and management to prevent this progression are therefore critical. This article discusses edema in relation to stages of healing and presents the research behind techniques available to the clinician to manage localized extracellular upper extremity edema in the patient with an intact lymphatic system. Copyright © 2012 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

The effect of relaxation techniques on edema, anxiety and depression in post-mastectomy lymphedema patients undergoing comprehensive decongestive therapy: A clinical trial.

PubMed

Abbasi, Bahareh; Mirzakhany, Navid; Angooti Oshnari, Leila; Irani, Ashkan; Hosseinzadeh, Samaneh; Tabatabaei, Seyed Mehdi; Haghighat, Shahpar

2018-01-01

Lymphedema is sometimes accompanied by high degrees of anxiety and depression. This study aimed to assess the effects of relaxation techniques on the level of edema, anxiety and depression in women undergoing Comprehensive Decongestive Therapy (CDT). This clinical trial compared two treatment methods in 31 women with post-mastectomy lymphedema, including 15 cases who received CDT and 16 who received RCDT (Relaxation plus CDT). The edema volume, anxiety and depression scores were compared at the first and last sessions of the first phase of the treatment and six weeks afterwards. The edema, anxiety and depression scores were 63.6%, 54.1% and 65.5% in the RCDT group and 60.7%, 31.4% and 35.2% in the CDT group. There were significant differences between the two groups in terms of the reduction in depression (p = 0.024) and anxiety (p = 0.011) scores throughout the study. This significant relationship was due to the differences in the depression score in the 3rd and 9th weeks of the study between the two groups. Similarly, anxiety levels differed significantly between the two groups at the 9th week of the study (P = 0.013). Relaxation techniques reduced the anxiety and depression scores and the volume of edema in the patients with lymphedema. The addition of this intervention to the therapeutic package for lymphedema patients requires further studies in terms of cost-effectiveness.

77 FR 64444 - VOR Federal Airway V-595; Oregon

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-22

... Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking (NPRM). SUMMARY: This action... this action to redescribe the route due to the scheduled decommissioning of the Portland, OR, VOR/DME... suggestions presented are particularly helpful in developing reasoned regulatory decisions on the proposal...