WorldWideScience

Sample records for amd trial mira-1

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

    Directory of Open Access Journals (Sweden)

    Liubov Robman

    2017-06-01

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

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

    Science.gov (United States)

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

    2018-03-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  4. Blood Pressure Drugs and AMD

    Science.gov (United States)

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

  5. AMD study of unstable nuclei

    International Nuclear Information System (INIS)

    Horiuchi, Hisashi; Dote, Akinobu; Kimura, Masaaki

    2000-01-01

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

  6. AMD study of unstable nuclei

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-01-01

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

  7. Elusive drusen and changing terminology of AMD

    NARCIS (Netherlands)

    de Jong, P. T. V. M.

    2018-01-01

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

  8. AMD ja ATI kolivad kokku / Kalle Kose

    Index Scriptorium Estoniae

    Kose, Kalle

    2006-01-01

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

  9. AMD's 64-bit Opteron processor

    CERN Multimedia

    CERN. Geneva

    2003-01-01

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

  10. NLRP3 Inflammasome and Pathobiology in AMD

    Directory of Open Access Journals (Sweden)

    Lucia Celkova

    2015-01-01

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

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

    Science.gov (United States)

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

    1998-01-01

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

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

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    Caroline Brandl

    2015-01-01

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

  13. AMD genetics in India: The missing links

    Directory of Open Access Journals (Sweden)

    Akshay eAnand

    2016-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Semeraro F

    2013-08-01

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

  15. Vision Rehabilitation is Part of AMD Care

    Directory of Open Access Journals (Sweden)

    August Colenbrander

    2018-01-01

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

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

    Sparrow, Janet R

    2016-04-26

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

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

    Directory of Open Access Journals (Sweden)

    V. S. Akopyan

    2012-01-01

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

  19. Anker Energy battles AMD in West Virginia

    International Nuclear Information System (INIS)

    Frey, T.J.

    1998-01-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    2012-01-05

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

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

    Science.gov (United States)

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

    2009-03-15

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

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

    Directory of Open Access Journals (Sweden)

    Kristinn P Magnusson

    2006-01-01

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

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

    Science.gov (United States)

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

    2016-06-21

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

  5. Multifragmentation in Au + Au collisions studied with AMD-V

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Miltiadis K. Tsilimbaris

    2016-01-01

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

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

    Science.gov (United States)

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

    2018-03-01

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

  8. Removal of phosphorus using AMD-treated lignocellulosic material

    Science.gov (United States)

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

    2005-01-01

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

  9. Mitigating health problems associated with AMD in South Africa

    CSIR Research Space (South Africa)

    Schachtschneider, K

    2012-03-01

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

  10. Geophysical delineation of AMD in the Cradle of Humankind

    CSIR Research Space (South Africa)

    Van Schoor, Michael

    2016-08-01

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sara Domínguez

    2016-08-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Willich, Stefan N.

    2006-12-01

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

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

    OpenAIRE

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mark Fields

    2016-12-01

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

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

    Science.gov (United States)

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

    2016-12-08

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

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

    Science.gov (United States)

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

    2009-07-30

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

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

    Directory of Open Access Journals (Sweden)

    Luis Fernando Hernández-Zimbrón

    2018-01-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

  4. Overview of AMD (Automotive Metal Division)/USAMP projects

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-07-01

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

  5. Inherited Retinal Degenerative Clinical Trial Network. Addendum

    Science.gov (United States)

    2013-10-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Science.gov (United States)

    A.D. Karathanasis; C.D. Barton

    1999-01-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

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

    2018-03-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

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

    International Nuclear Information System (INIS)

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

    1993-01-01

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

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

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

    Index Scriptorium Estoniae

    Matsulevitsh, Lauri

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Min Li

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

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2018-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohammad Askari

    2015-10-01

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

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

    Science.gov (United States)

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

    2018-04-20

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-15

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

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

    Directory of Open Access Journals (Sweden)

    Shiro Kitano

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

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

    International Nuclear Information System (INIS)

    Kimura, Masaaki; Horiuchi, Hisashi

    2001-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Kaushal eSharma

    2014-07-01

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

  7. Avati teaduskeskus maakula ealise degeneratsiooniga (AMD-ga) võitlemiseks

    Index Scriptorium Estoniae

    2007-01-01

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

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

    Science.gov (United States)

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

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

  9. Secondary iron minerals present in AMD sediments from Smolník abandoned mine

    Czech Academy of Sciences Publication Activity Database

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2010-03-01

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

  11. AMD3465, a monomacrocyclic CXCR4 antagonist and potent HIV entry inhibitor

    DEFF Research Database (Denmark)

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

    2005-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Gardić Vojka

    2017-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

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

    1997-01-01

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

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

    Science.gov (United States)

    Paulose, Joby; Markose, Eldho

    2014-12-01

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

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

    International Nuclear Information System (INIS)

    Taddeo, F.J.

    1991-01-01

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

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

    OpenAIRE

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

    Singh, Rajendra

    1992-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Anna Wiktorowska-Owczarek

    2010-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Viren Kumar Govindaraju

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

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

    Science.gov (United States)

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Demetrios G. Vavvas

    2016-03-01

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

  4. [99mTc]O2-AMD3100 as a SPECT tracer for CXCR4 receptor imaging

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    OpenAIRE

    Mohammad Norouzifard; Ali Soleymani; Jamshid Shanbehzadeh

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rubina Tabassum

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2015-07-07

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-12-01

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

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

    International Nuclear Information System (INIS)

    Sugawa, Yoshio; Kimura, Masaaki; Horiuchi, Hisashi

    2001-01-01

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

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Raffaele Nuzzi

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2017-10-15

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

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

    Science.gov (United States)

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

    2011-02-01

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

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

    International Nuclear Information System (INIS)

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

    1996-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-12-01

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

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

    International Nuclear Information System (INIS)

    Kimura, Masaaki; Horiuchi, Hisashi

    2002-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    CSIR Research Space (South Africa)

    Oberholster, Paul J

    2014-09-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    Science.gov (United States)

    Tokarz, Paulina; Kaarniranta, Kai; Blasiak, Janusz

    2013-10-01

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

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

    NARCIS (Netherlands)

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

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

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

    Science.gov (United States)

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

    2018-03-01

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

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

    Science.gov (United States)

    Moschos, Marilita M; Nitoda, Eirini

    2018-01-01

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

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

    Science.gov (United States)

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

    2018-03-01

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

  12. Trials

    Directory of Open Access Journals (Sweden)

    Michele Fornaro

    2010-01-01

    Full Text Available Mental Retardation (MR is a developmental disability characterized by impairments in adaptive daily life skills and difficulties in social and interpersonal functioning. Since multiple causes may contribute to MR, associated clinical pictures may vary accordingly. Nevertheless, when psychiatric disorders as Treatment Resistant Depression (TRD and/or alcohol abuse co-exist, their proper detection and management is often troublesome, essentially due to a limited vocabulary MR people could use to describe their symptoms, feelings and concerns, and the lack of reliable screening tools. Furthermore, MR people are among the most medicated subjects, with (over prescription of antidepressants and/or typical antipsychotics being the rule rather than exception. Thus, treatment resistance or even worsening of depression, constitute frequent occurrences. This report describes the case of a person with MR who failed to respond to repetitive trials of antidepressant monotherapies, finally recovering using aripiprazole to fluvoxamine augmentation upon consideration of a putative bipolar diathesis for “agitated” TRD. Although further controlled investigations are needed to assess a putative bipolar diathesis in some cases of MR associated to TRD, prudence is advised in the long-term prescription of antidepressant monotherapies in such conditions.

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

    Science.gov (United States)

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

    2018-04-01

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

  14. Predictive Factors in OCT Analysis for Visual Outcome in Exudative AMD

    Directory of Open Access Journals (Sweden)

    Maria-Andreea Gamulescu

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-06-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohammad Norouzifard

    2011-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-12-01

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

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

    International Nuclear Information System (INIS)

    Kimura, Masaaki; Sugawa, Yoshio; Horiuchi, Hisashi

    2001-01-01

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

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

    International Nuclear Information System (INIS)

    Taniguchi, Yasutaka; Horiuchi, Hisashi; Kimura, Masaaki

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Venkata Ramana Murthy Chavali

    2015-02-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2013-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Wenxin Ma

    2009-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Nur Afiqah Mohamad

    2018-03-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yosuke Maeda

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

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

    Directory of Open Access Journals (Sweden)

    Gergely Losonczy

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

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

    Science.gov (United States)

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

    2018-04-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Directory of Open Access Journals (Sweden)

    John Paul SanGiovanni

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

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

    Science.gov (United States)

    McCullough, Clint D; Lund, Mark A

    2011-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Rui-Juan Guan

    2017-05-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

    Hatse, Sigrid; Princen, Katrien; Vermeire, Kurt

    2003-01-01

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

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

    Science.gov (United States)

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

    2012-07-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-04-01

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

  3. Radiotherapy of macular lesions in age-related macular degeneration (A.M.D.): preliminary results of a clinical study conducted in Lyon, France; Radiotherapie des degenerescences maculaires liees a l`age (DMLA): resultats preliminaires d`une etude lyonnaise

    Energy Technology Data Exchange (ETDEWEB)

    Martin, P. [Centre oncologie radiotherapie Saint-Jean, 69 - Lyon (France); Mauget, M. [Centre ophtalmologique d`imagerie, laser, 69 - Lyon (France); Gerard, J.P. [Service de radiotherapie-oncologie, CHU Lyon Sud, 69 - Pierre-Benite (France) (and others)

    1997-06-01

    To evaluate irradiation effects on functional signs and choroidal neo-vascular lesions in age-related macular degeneration (AMD) that does not respond to laser therapy. Since 1994, 250 consecutive AMD patients were treated by two radiotherapy teams for sub-foveal neo-vascular lesions. At the end of september 1996, 52 patients were evaluable with a 1-year follow-up. Group 1 (Department de Radiotherapie Oncologie, Centre Hospitalo-Universitaire Lyon Sud) included 26 patients who were treated with a lateral beam of 6 MV photons. The irradiation dose were 20 Gy in five fractions for small lesions and 28.8 Gy in eight fractions for larger lesions. Group 2 (Centre Oncologie Radiotherapie Saint-Jean) was composed of 26 patients treated with a mini-beam of 25 MV photons via lateral arc-therapy. Beam diameters (14 and 18 mm) were adapted to the lesion size. The total dose was 16 Gy in four fractions or 20 Gy in five fractions. Functional and anatomical results were assessed at 3, 6, 9 months and 1 year after radiation therapy. Stable visual acuity was observed in 44 % (23/52) of the patients and visual acuity was improved in 35 % (18/52) of the patients at 6 months. Good functional results reached 79 % (41/52) at 6 months and 74 % (17/23) at 12 months. There was no statistical difference between the two groups and dose levels. All severe complications (1 cataract, 3 dilated choroidal vessels, and 2 papillitis) occurred in group 1. Though it is too early to conclude on the best dose level, radiotherapy of sub-foveal neo-vascular lesions of AMD that cannot be treated via laser therapy provides encouraging results. The technique used must be very precise to adequately irradiate the fovea and spare surrounding sensitive areas. Further studies and trials involving patients` randomization are necessary to confirm these preliminary results. (author) 13 refs.

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

    Directory of Open Access Journals (Sweden)

    Dimitrios Brouzas

    2009-08-01

    Full Text Available Dimitrios Brouzas, Chryssanthi Koutsandrea, Marilita Moschos, Spiros Papadimitriou, Ioannis Ladas, Michael Apostolopoulos1st Eye Department , University of Athens, Athens, GreecePurpose: To report a severe ocular complication initiated ten days after intravitreal administration of bevacizumab (Avastin®, in a patient with exudative age-related macular degeneration (AMD.Patients and method: Case report.Results: Ten days after intravitreal injection of 1.25 mg Avastin®, the patient manifested acute loss of vision with excruciating pain. An extensive choroidal detachment was evident in close contact with the lens, which necessitated an emergency sclerotomy with reconstruction of the anterior chamber. Four months later, the eye proceeded to phthisis bulbi. Five months after the injection, the patient complained of mild pain, photophobia, and visual acuity deterioration from the fellow eye. The diagnosis of sympathetic ophthalmia was suggested and treated with intravitreal injections of triamcinolone acetonide every three months with good response, complicated by elevation of intraocular pressure which we managed with Ahmet valve implantation.Conclusion: Serious ocular complications after intravitreal of Avastin® can not be excluded, including massive choroidal hemorrhage and sympathetic ophthalmia of the fellow eye.Keywords: Avastin® complication, intravitreal injection, choroidal detachment, Phthisis bulbi, sympathetic ophthalmia

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

    Directory of Open Access Journals (Sweden)

    Varano M

    2016-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Patel PJ

    2017-11-01

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

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

    Science.gov (United States)

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

    2009-10-01

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

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

    Science.gov (United States)

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

    2014-09-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  10. A randomised, double-masked phase III/IV study of the efficacy and safety of Avastin® (Bevacizumab intravitreal injections compared to standard therapy in subjects with choroidal neovascularisation secondary to age-related macular degeneration: clinical trial design

    Directory of Open Access Journals (Sweden)

    Bunce Catey

    2008-10-01

    Full Text Available Abstract Background The management of neovascular age-related macular degeneration (nAMD has been transformed by the introduction of agents delivered by intravitreal injection which block the action of vascular endothelial growth factor-A (anti-VEGF agents. One such agent in widespread use is bevacizumab which was initially developed for use in oncology. Most of the evidence supporting the use of bevacizumab for nAMD has come from interventional case series and this clinical trial was initiated because of the increasing and widespread use of this agent in the treatment of nAMD (an off-label indication despite a lack of definitive unbiased safety and efficacy data. Methods and design The Avastin® (bevacizumab for choroidal neovascularisation (ABC trial is a double-masked randomised controlled trial comparing intravitreal bevacizumab injections to standard therapy in the treatment of nAMD. Patients are randomised to intravitreal bevacizumab or standard therapy available at the time of trial initiation (verteporfin photodynamic therapy, intravitreal pegaptanib or sham treatment. Ranibizumab treatment was not included in the control arm as it had not been licensed for use at the start of recruitment for this trial. The primary outcome is the proportion of patients gaining ≥ 15 letters of visual acuity at 1 year and secondary outcomes include the proportion of patients with stable vision and mean visual acuity change. Discussion The ABC Trial is the first double-masked randomised control trial to investigate the efficacy and safety of intravitreal bevacizumab in the treatment of nAMD. This trial fully recruited in November 2007 and results should be available in early 2009. Important design issues for this clinical trial include (a defining the control group (b use of gain in vision as primary efficacy end-point and (c use of pro re nata treatment using intravitreal bevacizumab rather than continuous therapy. Trial registration Current controlled

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

    Directory of Open Access Journals (Sweden)

    M. L. Perepechaeva

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    Science.gov (United States)

    Dumas, Stéphane; Coscas, Florence

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zuo-Hua Li

    2017-01-01

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

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

    International Nuclear Information System (INIS)

    Jackson, Laura M.; Parbhakar-Fox, Anita

    2016-01-01

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

  17. Clinical Trials

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    Full Text Available ... Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, or ... humans. What Are Clinical Trials? Clinical trials are research studies that explore whether a medical strategy, treatment, or ...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Science.gov (United States)

    Abboud, M; Benzerroug, M; Milazzo, S

    2017-02-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-15

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    John Timmons

    2010-03-01

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

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

    Science.gov (United States)

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

    2007-02-01

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

  5. Clinical Trials

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    Full Text Available ... questions and clinical trials. Optimizing our Clinical Trials Enterprise NHLBI has a strong tradition of supporting clinical ... multi-pronged approach to Optimize our Clinical Trials Enterprise that will make our clinical trials enterprise even ...

  6. Clinical Trials

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    Full Text Available ... to-kol). This plan explains how the trial will work. The trial is led by a principal ... for the clinical trial. The protocol outlines what will be done during the clinical trial and why. ...

  7. Clinical Trials

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    Full Text Available ... take part in a clinical trial. When researchers think that a trial's potential risks are greater than ... care costs for clinical trials. If you're thinking about taking part in a clinical trial, find ...

  8. Clinical Trials

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    Full Text Available ... of clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are ... earlier than they would be in general medical practice. This is because late-phase trials have large ...

  9. Clinical Trials

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    Full Text Available ... clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are a ... will be done during the clinical trial and why. Each medical center that does the study uses ...

  10. Clinical Trials

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    Full Text Available ... medical strategy, treatment, or device is safe and effective for humans. What Are Clinical Trials? Clinical trials ... and Centers sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include ...

  11. Clinical Trials

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    Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... kol). This plan explains how the trial will work. The trial is led by a principal investigator ( ...

  12. Clinical Trials

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    Full Text Available ... Trial Protocol Each clinical trial has a master plan called a protocol (PRO-to-kol). This plan explains how the trial will work. The trial ... clinical trial; and detailed information about the treatment plan. Eligibility Criteria A clinical trial's protocol describes what ...

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

    Science.gov (United States)

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

    2014-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Ariel Gustavo Zuquello

    2016-07-01

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

  15. Clinical Trials

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    Full Text Available ... need to travel or stay in hospitals to take part in clinical trials. For example, the National Institutes of Health Clinical Center in ... Maryland, runs clinical trials. Many other clinical trials take place in medical centers and ... trial can have many benefits. For example, you may gain access to new treatments before ...

  9. Clinical Trials

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    Full Text Available ... of clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are a key ... Enterprise NHLBI has a strong tradition of supporting clinical trials that have not only shaped medical practice around the world, but have improved the health ...

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    Full Text Available ... clinical trials. If you're thinking about taking part in a clinical trial, find out ahead of time about costs and coverage. You should learn about the risks and benefits of any clinical trial before you agree to take part in the trial. Talk with your doctor about ...

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    Full Text Available ... medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are a key research tool for ... other for moderate persistent asthma. The results provided important treatment information for doctors and patients. The results ...

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    Full Text Available ... groups, companies, and organizations also sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments ... sponsor trials that test principles or strategies. For example, one NHLBI study explored whether the benefits of ...

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    Full Text Available ... Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers (including ... our campus or trials NIH has sponsored at universities, medical centers, and hospitals. ClinicalTrials.gov View a ...

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    Full Text Available ... Entire Site NHLBI Entire Site Health Topics News & Resources Intramural Research ... or device is safe and effective for humans. What Are Clinical Trials? Clinical trials are research ...

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    Full Text Available ... sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include Government Agencies, ... and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers (including the NHLBI) usually ...

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    Full Text Available ... decisionmaking. The purpose of clinical trials is research, so the studies follow strict scientific standards. These standards ... otherwise. The purpose of clinical trials is research, so the studies follow strict scientific standards. These standards ...

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    Full Text Available ... identified earlier than they would be in general medical practice. This is because late-phase trials have large ... supporting clinical trials that have not only shaped medical practice around the world, but have improved the health ...

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    Full Text Available ... Working at the NHLBI Contact and FAQs Accessible Search Form Search the NHLBI, use the drop down list to ... to learn more about clinical research and to search for clinical trials: NHLBI Clinical Trials Browse a ...

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    Full Text Available ... people who fit the patient traits for that study (the eligibility criteria). Eligibility criteria differ from trial to trial. They include factors such as a patient's age and gender, the type and stage of disease, and whether ...

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    Full Text Available ... medical strategy, treatment, or device is safe and effective for humans. What Are Clinical Trials? Clinical trials ... medical strategy, treatment, or device is safe and effective for humans. These studies also may show which ...

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    Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... care providers might be part of your treatment team. They will monitor your health closely. You may ...

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    Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... Center for Health Information Email Alerts Jobs and Careers Site Index About NHLBI National Institute of Health ...

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    Full Text Available ... to main content U.S. Department of Health & Human ... of people. Clinical trials produce the best data available for health care decisionmaking. The purpose of clinical trials is research, ...

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    Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... include factors such as a patient's age and gender, the type and stage of disease, and whether ...

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    Full Text Available ... needed. For safety purposes, clinical trials start with small groups of patients to find out whether a ... phase I clinical trials test new treatments in small groups of people for safety and side effects. ...

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    Full Text Available ... trials are research studies that explore whether a medical strategy, treatment, or device is safe and effective ... trials are research studies that explore whether a medical strategy, treatment, or device is safe and effective ...

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    Full Text Available ... trials show what doesn't work or may cause harm. For example, the NHLBI Women's Health Initiative tested whether hormone therapy (HT) reduced the risk of heart disease in postmenopausal women. (When the trial began, HT ...

  8. Clinical Trials

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    Full Text Available ... organizations also sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments of Defense and ... to Expect During a clinical trial, doctors, nurses, social workers, and other health care providers might be ...

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    Full Text Available ... risks that outweigh any possible benefits. Clinical Trial Phases Clinical trials of new medicines or medical devices are done in phases. These phases have different purposes and help researchers ...

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    Full Text Available ... the past, clinical trial participants often were White men. Researchers assumed that trial results were valid for ... different ethnic groups sometimes respond differently than White men to the same medical approach. As a result, ...

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    Full Text Available ... clinical trials. An IRB is an independent committee created by the institution that sponsors a clinical trial. ... have not only shaped medical practice around the world, but have improved the health of millions of ...

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    Full Text Available ... or strategies work best for certain illnesses or groups of people. Some clinical trials show a positive result. For example, the National Heart, Lung, and Blood Institute (NHLBI) sponsored a trial of two different ...

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    Full Text Available ... and Centers sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include ... U.S. Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers ( ...

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    Full Text Available ... for trials with cutting-edge approaches, such as gene therapy or new biological treatments. Health insurance and ... trials that involve high-risk procedures (such as gene therapy) or vulnerable patients (such as children). A ...

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    Full Text Available ... comparison groups by chance, rather than choice. This method helps ensure that any differences observed during a ... to learn more about clinical research and to search for clinical trials: NHLBI Clinical Trials Browse a ...

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    Full Text Available ... healthy people to test new approaches to prevention, diagnosis, or screening. In the past, clinical trial participants ... DSMBs for large trials comparing alternative strategies for diagnosis or treatment. In addition, the NIH requires DSMBs ...

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    Full Text Available ... at the smallest dose and for the shortest time possible. Clinical trials, like the two described above, ... in a clinical trial, find out ahead of time about costs and coverage. You should learn about ...

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    Full Text Available ... Clinical trials produce the best data available for health care decisionmaking. The purpose of clinical trials is research, ... and advance medical care. They also can help health care decisionmakers direct resources to the strategies and treatments ...

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    Full Text Available ... whether a new approach causes any harm. In later phases of clinical trials, researchers learn more about ... other National Institutes of Health (NIH) Institutes and Centers sponsor clinical trials. Many other groups, companies, and ...

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    Full Text Available ... are research studies that explore whether a medical strategy, treatment, or device is safe and effective for ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ...

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    Full Text Available ... treatment, or device is safe and effective for humans. What Are Clinical Trials? Clinical trials are research ... are required to have an IRB. Office for Human Research Protections The U.S. Department of Health and ...

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    Full Text Available ... these results are important because they advance medical knowledge and help improve patient care. Sponsorship and Funding ... All types of clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical ...

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    Full Text Available ... well they work. The U.S. Food and Drug Administration (FDA) oversees these clinical trials. The NIH may partner with these companies or groups to help sponsor some trials. All ...

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    Full Text Available ... best data available for health care decisionmaking. The purpose of clinical trials is research, so the studies ... Thus, research in humans is needed. For safety purposes, clinical trials start with small groups of patients ...

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    Full Text Available ... trials produce the best data available for health care decisionmaking. The purpose of clinical trials is research, ... they advance medical knowledge and help improve patient care. Sponsorship and Funding The National Heart, Lung, and ...

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    Full Text Available ... Events About NHLBI About NHLBI Home Mission and Strategic Vision Leadership Scientific Divisions Operations and Administration Advisory ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ...

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    Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... Customer Service/Center for Health Information Email Alerts Jobs and Careers Site Index About NHLBI National Institute ...

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    Full Text Available ... Some companies and groups sponsor clinical trials that test the safety of products, such as medicines, and how well they work. The U.S. Food and Drug Administration (FDA) oversees these clinical trials. ...

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    Full Text Available ... What to Expect During a clinical trial, doctors, nurses, social workers, and other health care providers might ... enroll in a clinical trial, a doctor or nurse will give you an informed consent form that ...

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    Full Text Available ... and doctors' offices around the country. Benefits and Risks Possible Benefits Taking part in a clinical trial ... volunteer because they want to help others. Possible Risks Clinical trials do have risks and some downsides, ...

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    Full Text Available ... sponsored a trial of two different combinations of asthma treatments. The trial found that one of the ... much better than the other for moderate persistent asthma. The results provided important treatment information for doctors ...

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    Full Text Available ... Sponsors also may stop a trial, or part of a trial, early if the strategy or treatment is having harmful effects. Food and Drug Administration In the United States, the Food and Drug Administration (FDA) provides oversight ...

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    Full Text Available ... providers don't always cover all patient care costs for clinical trials. If you're thinking about ... clinical trial, find out ahead of time about costs and coverage. You should learn about the risks ...

  14. Clinical Trials

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    Full Text Available ... including the NHLBI) usually sponsor trials that test principles or strategies. For example, one NHLBI study explored ... risks. Other examples of clinical trials that test principles or strategies include studies that explore whether surgery ...

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    Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... Learn More Connect With Us Contact Us Directly Policies Privacy Policy Freedom of Information Act (FOIA) Accessibility ...

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    Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... your doctor about all of your treatment options. Together, you can make the best choice for you. ...

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    Full Text Available ... medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are a key research tool for ... and Usage No FEAR Act Grants and Funding Customer Service/Center for Health Information Email Alerts Jobs ...

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    Full Text Available ... resources to the strategies and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, you may get tests or treatments in a hospital, clinic, or doctor's office. In some ways, taking part in a clinical trial is different ...

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    Full Text Available ... Health Topics / About Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, ... tool for advancing medical knowledge and patient care. Clinical research is done only if doctors don't know ...

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    Full Text Available ... about your health or fill out forms about how you feel. Some people will need to travel or stay in hospitals to take part in clinical trials. For example, the National Institutes of Health Clinical Center in Bethesda, Maryland, runs clinical trials. Many other clinical trials take place ...

  2. Clinical Trials

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    Full Text Available ... more screening tests to see which test produces the best results. Some companies and groups sponsor clinical trials that test the ... and Drug Administration (FDA) oversees these clinical trials. The NIH may partner with these companies or groups to help sponsor some trials. All ...

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    Full Text Available ... child to enroll. Also, children aged 7 and older often must agree (assent) to take part in clinical trials. Clinical trials for children have the same scientific safeguards as clinical trials for adults. For more information, go to "How Do Clinical ...

  4. Clinical Trials

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    Full Text Available ... give permission for their child to enroll. Also, children aged 7 and older often must agree (assent) to take part in clinical trials. Find a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ...

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    Full Text Available ... part in a clinical trial is your decision. Talk with your doctor about all of your treatment options. Together, you can make the ... more about, or taking part in, clinical trials, talk with your doctor. He or she may know about ... clinical trials. NIH Clinical Research Studies ...

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

    Science.gov (United States)

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

    2017-11-01

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

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

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    John Timmons

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

  8. Clinical Trials

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    Full Text Available ... part. Randomization Most clinical trials that have comparison groups use randomization. This involves assigning patients to different comparison groups by chance, rather than choice. This ...

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    Full Text Available ... trial found that one of the combinations worked much better than the other for moderate persistent asthma. The results provided important treatment information for doctors and patients. The results from other clinical trials show what doesn't work or may cause harm. For example, the NHLBI ...

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    Full Text Available ... the clinical trial you take part in, the information gathered can help others and add to scientific knowledge. People who take part in clinical trials are vital to the process of improving medical care. Many people volunteer because ...

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    Full Text Available ... from other clinical trials show what doesn't work or may cause harm. For example, the NHLBI Women's Health Initiative ... safe a treatment is or how well it works. Children (aged 18 and younger) get ... legal consent for their child to take part in a clinical trial. When ...

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    Full Text Available ... other expenses (for example, travel and child care)? Who will be in charge of my care? What will happen after the trial? Taking part in a clinical trial is your decision. Talk with your doctor about all of your treatment ...

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    Full Text Available ... for trials with cutting-edge approaches, such as gene therapy or new biological treatments. Health insurance and health ... trials that involve high-risk procedures (such as gene therapy) or vulnerable patients (such as children). A DSMB's ...

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    Full Text Available ... to Expect During a clinical trial, doctors, nurses, social workers, and other health care providers might be part of your treatment ... clinical trials are vital to the process of improving medical care. Many people ... participants, it may not work for you. A new treatment may have side ...

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    Full Text Available ... Expect During a clinical trial, doctors, nurses, social workers, and other health care providers might be part of your treatment ... phase II clinical trials. The risk of side effects might be even greater for ... treatments. Health insurance and health care providers don't always ...

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    Full Text Available ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, talk with your doctor. He or she may know about studies going on in your area. You can visit the following website to learn more about ...

  17. Clinical Trials

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    Full Text Available ... benefits of lowering high blood pressure in the elderly outweighed the risks. Other examples of clinical trials ... child to enroll. Also, children aged 7 and older often must agree (assent) to ... as clinical trials for adults. For more information, go to "How Do Clinical ...

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    Full Text Available ... products, such as medicines, and how well they work. The U.S. Food and Drug Administration (FDA) oversees these clinical trials. ... cancer also increased. As a result, the U.S. Food and Drug Administration now recommends never using HT ... Clinical Trials Work If you take ...

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

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    Full Text Available ... include factors such as a patient's age and gender, the type and stage of disease, and whether ... How long will the trial last? Who will pay for the tests and treatments I receive? Will ...

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    Full Text Available ... medicines, and how well they work. The U.S. Food and Drug Administration (FDA) oversees these ... trials are a key research tool for advancing medical knowledge and patient care. ...

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    Full Text Available ... strict scientific standards. These standards protect patients and help produce reliable study results. Clinical trials are one ... are important because they advance medical knowledge and help improve patient care. Sponsorship and Funding The National ...

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    Full Text Available ... patients to find out whether a new approach causes any harm. In later phases of clinical trials, ... device improves patient outcomes; offers no benefit; or causes unexpected harm All of these results are important ...

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    Full Text Available ... and compare new treatments with other available treatments. Steps To Avoid Bias The researchers doing clinical trials take steps to avoid bias. "Bias" means that human choices ...

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    Full Text Available ... gathered can help others and add to scientific knowledge. People who take part in clinical trials are vital to the process of improving medical care. Many people volunteer because they want to help others. ...

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    Full Text Available ... materials, and offer advice on research-related issues. Data Safety Monitoring Board Every National Institutes of Health ( ... III clinical trial is required to have a Data and Safety Monitoring Board (DSMB). This board consists ...

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    ... of Personal Stories Peers Celebrating Art Peers Celebrating Music Be Vocal Support Locator DBSA In-Person Support ... by participating in a clinical trial is to science first and to the patient second. More About ...

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    Full Text Available ... to Expect During a clinical trial, doctors, nurses, social workers, and other health care providers might be ... the new approach. You also will have the support of a team of health care providers, who ...

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    Full Text Available ... final stages of a long and careful research process. The process often begins in a laboratory (lab), where scientists ... part in clinical trials are vital to the process of improving medical care. Many people volunteer because ...

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    Full Text Available ... as gene therapy) or vulnerable patients (such as children). A DSMB's role is to review data from a clinical trial for safety problems or differences in results among different groups. The DSMB also reviews research results ...

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    Full Text Available ... medical centers and doctors' offices around the country. Benefits and Risks Possible Benefits Taking part in a clinical trial can have many benefits. For example, you may gain access to new ...

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    Full Text Available ... or treatment is having harmful effects. Food and Drug Administration In the United States, the Food and Drug Administration (FDA) provides oversight for clinical trials that ...

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    Full Text Available ... Usually, a computer program makes the group assignments. Masking The term "masking" refers to not telling the clinical trial participants which treatment they're getting. Masking, or "blinding," helps avoid bias. For this reason, ...

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    Full Text Available ... you to explore NIH Clinical Center for patient recruitment and clinical trial information. For more information, please email the NIH Clinical Center Office of Patient Recruitment at cc-prpl@cc.nih.gov or call ...

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    Full Text Available ... organizations also sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments of Defense and ... how you feel. Some people will need to travel or stay in hospitals to take part in ...

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    Full Text Available ... clinical trials are required to have an IRB. Office for Human Research Protections The U.S. Department of Health and Human Services’ (HHS’) Office for Human Research Protections (OHRP) oversees all research ...

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    Full Text Available ... clinical trial. IRB members are doctors, statisticians, and community members. The IRB's purpose is to ensure that ... lung, and blood disorders. By engaging the research community and a broad group of stakeholders and advisory ...

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    Full Text Available ... successfully developed and evaluated to fill an important gap in information and education for parents, clinicians, researchers, ... gathered can help others and add to scientific knowledge. People who take part in clinical trials are ...

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-12-27

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

  12. Clinical Trials

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    Full Text Available ... an important gap in information and education for parents, clinicians, researchers, children, and the general public. What to Expect During a clinical trial, doctors, nurses, social workers, and other health care providers might be part of your treatment team. ...

  13. Clinical Trials

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    Full Text Available ... taking the same treatment the same way. These patients are closely watched by Data and Safety Monitoring Boards. Even if you don't directly ... risk procedures (such as gene therapy) or vulnerable patients (such as ... trial for safety problems or differences in results among different groups. ...

  14. The Trial

    Science.gov (United States)

    Bryant, Jen

    2004-01-01

    Growing up in Flemington, New Jersey, put Jen Bryant in the heart of the lore behind the Lindbergh baby kidnapping. Family stories of the events of the day and extensive research led to "The Trial," a novel in verse. The first several parts of this novel are included here.

  15. Clinical Trials

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    Full Text Available Skip to main content U.S. Department of Health & Human Services Health Topics Health Topics A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders and Blood Safety Sleep ...

  16. Clinical Trials

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    Full Text Available ... treatments produce better results for certain illnesses or groups of people; look at the best age and frequency for doing screening tests, such as mammography; and compare two or more screening tests to see which test ... Some companies and groups sponsor clinical trials that test the safety of ...

  17. Clinical Trials

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    Full Text Available ... patient has had certain treatments or has other health problems. Eligibility criteria ensure that new approaches are tested ... public. What to Expect During a clinical trial, doctors, nurses, social workers, and other health care providers might be part of your treatment ...

  18. Clinical Trials

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    Full Text Available ... This shows how the approach affects a living body and whether it's harmful. However, an approach that works well in the lab or animals doesn't always work well in people. Thus, research in humans is needed. For safety purposes, clinical trials start ...

  19. Clinical Trials

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    Full Text Available ... edge approaches, such as gene therapy or new biological treatments. Health insurance and health care providers don't ... of a trial, early if the strategy or treatment is having harmful effects. Food and Drug Administration In the United States, the Food and ...

  20. Clinical Trials

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    Full Text Available ... U.S. Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers (including the NHLBI) usually sponsor trials that test principles or strategies. For example, one NHLBI study explored whether the ...

  1. Clinical Trials

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    Full Text Available ... to main content U.S. Department of Health & Human Services Health Topics Health Topics A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders and Blood Safety Sleep Science and ...

  2. Clinical Trials

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    Full Text Available ... protect patients and help produce reliable study results. Clinical trials are one of the final stages of a long and careful research process. The process often begins in a laboratory (lab), where scientists first develop and test new ...

  3. Clinical Trials

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    Full Text Available ... benefits of lowering high blood pressure in the elderly outweighed the risks. Other examples of clinical trials ... child to enroll. Also, children aged 7 and older often must agree (assent) to take part ... about how you feel. Some people will need to travel or stay in hospitals ...

  4. Clinical Trials

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    Full Text Available ... Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders and Blood Safety Sleep ... Activity Population and Epidemiology Studies Women’s Health All Science A-Z Grants ... in the Press Research Features All Events Past Events Upcoming ...

  5. Clinical Trials

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    Full Text Available ... safe a treatment is or how well it works. Children (aged 18 and younger) get special protection as research subjects. Almost always, parents must give legal consent for their child to take part in a clinical trial. When ...

  6. Clinical Trials

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    Full Text Available ... As a result, the U.S. Food and Drug Administration now recommends never using HT to prevent heart disease. When HT is used for menopausal symptoms, it should be taken only at the smallest dose and for the shortest time possible. Clinical trials, like the two described above, ...

  7. Clinical Trials

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    Full Text Available ... Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies ... include factors such as a patient's age and gender, the type and stage of disease, ... helps ensure that any differences observed during a trial are due to the ...

  8. Clinical Trials

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    Full Text Available ... an important gap in information and education for parents, clinicians, researchers, children, and the general public. What to Expect During ... trial's potential risks are greater than minimal, both parents must give permission for their child to enroll. Also, children aged 7 and older ...

  9. Clinical Trials

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    Full Text Available ... Wide Range of Audiences The Children and Clinical Studies Program has been successfully developed and evaluated to fill an important gap in information and education for parents, clinicians, researchers, children, and the general public. What to Expect During a clinical trial, doctors, ...

  10. Clinical Trials

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    Full Text Available ... approach that works well in the lab or animals doesn't always work well in people. Thus, research in humans is needed. For safety purposes, clinical trials start with small groups of patients to find out whether a ...

  11. Textbook of clinical trials

    National Research Council Canada - National Science Library

    Day, Simon; Machin, David; Green, Sylvan B

    2006-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xix INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1 The Development of Clinical Trials Simon...

  12. Types of Cancer Clinical Trials

    Science.gov (United States)

    Information about the several types of cancer clinical trials, including treatment trials, prevention trials, screening trials, supportive and palliative care trials. Each type of trial is designed to answer different research questions.

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

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

    2013-05-01

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

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

    Science.gov (United States)

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

    2016-04-01

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

  16. Understanding Clinical Trials

    Science.gov (United States)

    Watch these videos to learn about some basic aspects of cancer clinical trials such as the different phases of clinical trials, methods used to protect patient safety, and how the costs of clinical trials are covered.

  17. Hot Flashes amd Night Sweats (PDQ)

    Science.gov (United States)

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

  18. Neutralisation treatment of AMD at affordable cost

    African Journals Online (AJOL)

    2012-06-11

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

  19. Microprocesadores AMD: pasado, presente y futuro

    Directory of Open Access Journals (Sweden)

    Reynaldo Hernández Perdomo

    2005-01-01

    Full Text Available La evolución de la humanidad y en particular de la electrónica de los últimos años ha estado basada en los constantes avances en la fabricación de chips. Los circuitos integrados se han ido incorporando a todo los que nos rodea hasta el punto de que la vida sin ellos parece imposible. El microprocesador es uno de los logros más sobresalientes del siglo XX. Esas son palabras atrevidas, y hace un cuarto de siglo tal afirmación habría parecido absurda. Pero cada año, el microprocesador se acerca más al centro de nuestras vidas, forjándose un sitio en el núcleo de una máquina tras otra. Su presencia ha comenzado a cambiar la forma en que percibimos el mundo e incluso a nosotros mismos. Cada vez se hace más difícil pasar por alto el microprocesador como otro simple producto en una larga línea de innovaciones tecnológicas. No obstante que reconocemos la penetración del microprocesador en nuestras vidas, ya estamos creciendo indiferentes a la presencia de esos miles de máquinas diminutas que nos encontramos sin saberlo todos los días. Así que, antes de que se integre de manera demasiado imperceptible en nuestra diaria existencia, es el momento de celebrar al microprocesador y la revolución que ha originado, para apreciar el milagro que es en realidad cada uno de esos chips de silicio diminutos y meditar acerca de su significado para nuestras vidas y las de nuestros descendientes.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Maguire, Maureen G; Daniel, Ebenezer; Shah, Ankoor R; Grunwald, Juan E; Hagstrom, Stephanie A; Avery, Robert L; Huang, Jiayan; Martin, Revell W; Roth, Daniel B; Castellarin, Alessandro A; Bakri, Sophie J; Fine, Stuart L; Martin, Daniel F

    2013-10-01

    To assess the influence of drug; dosing regimen; and traditional, nontraditional, and genetic risk factors on the incidence of choroidal neovascularization (CNV) in the fellow eye of patients treated for CNV with ranibizumab or bevacizumab. Cohort study of patients enrolled in a multicenter, randomized clinical trial. Patients with no CNV in the fellow eye at the time of enrollment in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Eligibility criteria for the clinical trial required that study eyes have evidence on fluorescein angiography and optical coherence tomography of CNV secondary to age-related macular degeneration (AMD) and visual acuity between 20/25 and 20/320. Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different regimens for dosing over a 2-year period. The genotypes for 4 single nucleotide polymorphisms (SNPs) associated with risk of AMD were determined. Only patients without CNV in the fellow eye at baseline were considered at risk. The CATT ophthalmologists examined patients every 4 weeks through 2 years and recorded treatment for CNV in the fellow eye. Development of CNV in the fellow eye. Among 1185 CATT participants, 727 (61%) had no CNV in the fellow eye at enrollment. At 2 years, CNV had developed in 75 (20.6%) of 365 patients treated with ranibizumab and in 60 (16.6%) of 362 patients treated with bevacizumab (absolute difference, 4.0%; 95% confidence interval [CI], -1.7% to 9.6%; P = 0.17). The risk ratio for pro re nata dosing relative to monthly dosing was 1.1 (95% CI, 0.8-1.6). Greater elevation of the retinal pigment epithelium and fluid in the foveal center of the study eye were associated with increased incidence of CNV in the fellow eye. Incidence was not associated with genotype on rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3; P>0.35). Through 2 years, there was no statistically significant difference between ranibizumab and

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

    Directory of Open Access Journals (Sweden)

    Amelia O Clive

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

  3. Clinical trials of homoeopathy.

    Science.gov (United States)

    Kleijnen, J; Knipschild, P; ter Riet, G

    1991-01-01

    OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURES--Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS--In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS--At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials. PMID:1825800

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

    Science.gov (United States)

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

    2005-01-01

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

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

    Science.gov (United States)

    Ying, Gui-Shuang; Maguire, Maureen G

    2011-02-01

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

  6. Managing clinical trials

    Directory of Open Access Journals (Sweden)

    Kenyon Sara

    2010-07-01

    Full Text Available Abstract Managing clinical trials, of whatever size and complexity, requires efficient trial management. Trials fail because tried and tested systems handed down through apprenticeships have not been documented, evaluated or published to guide new trialists starting out in this important field. For the past three decades, trialists have invented and reinvented the trial management wheel. We suggest that to improve the successful, timely delivery of important clinical trials for patient benefit, it is time to produce standard trial management guidelines and develop robust methods of evaluation.

  7. Remune trial will stop; new trials planned.

    Science.gov (United States)

    James, J S

    1999-05-21

    A clinical trial using remune, the anti-HIV vaccine developed by the late Dr. Jonas Salk, has been ended. The study is a clinical-endpoint trial which looks for statistically significant differences in AIDS sickness or death between patients who add remune to their treatment regimens versus those who use a placebo. Agouron Pharmaceuticals and the Immune Response Corporation who were conducting the trial announced their decision to stop it after an analysis by the Data Safety Monitoring Board. No differences in clinical endpoints were found and it was projected that continuing the trial would likely not find any. The companies are now planning two new Phase III trials using viral load testing rather than clinical endpoints as study criteria.

  8. Inherited Retinal Degenerative Disease Clinical Trial Network

    Science.gov (United States)

    2012-10-01

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

  9. Research Areas - Clinical Trials

    Science.gov (United States)

    Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

  10. Clinical trial methodology

    National Research Council Canada - National Science Library

    Peace, Karl E; Chen, Ding-Geng

    2011-01-01

    "Now viewed as its own scientific discipline, clinical trial methodology encompasses the methods required for the protection of participants in a clinical trial and the methods necessary to provide...

  11. Hepatitis C: Clinical Trials

    Science.gov (United States)

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  12. [Early therapeutic trials for retinitis pigmentosa].

    Science.gov (United States)

    Dufier, Jean-Louis

    2003-01-01

    Non syndromic forms of Retinitis Pigmentosa (RP) constitute a collection of clinically and genetically heterogeneous inherited retinal degenerative diseases. They are characterized by a bilateral progressive visual loss susceptible to cause blindness. These diseases are transmitted through pedigrees according to all known modes of inheritance. They are bilateral and usually start during infancy. However, very early clinical presentations exist, such as those observed in children affected by Leber Congenital Amaurosis, as well as late onset autosomal dominant forms of retinitis pigmentosa. The characteristic clinical aspect of the rod-cone RP dystrophies is marked by alterations of the peripheral retina associated with a night blindness and a progressive narrowing of the visual field. The ophthalmoscopic examination of RP patients commonly reveals thin retinal arteries and scattered pigmentary accumulations. In contrast, there are cone rod retinal dystrophies whose onset is marked by a decreased visual acuity before the appearance of any visual field alteration. Some forms of RPs display an ocular fundus devoid of any pigmentary alteration. Syndromic forms of RPs are not uncommon. The association of deafness with RP is detected in nearly 30% of the patients. Other associations with RP can include mental deficiency, facial dysmorphy, microcephaly, obesity, kidney deficiency, immune deficiencies, metabolic disorders. The existence of such syndromic forms of RP localizes RPs at the crossroad of several medical specialties. A long lasting collaboration between our department of ophthalmology and the department of medical genetics of the Necker-Sick Children Hospital has allowed us to establish numerous genotype-phenotype correlations, especially in LCA and Stargardt's disease. ABCR gene mutations cause Stargardt disease. ABCR mutations may also cause some types of Ages Related Macular Degenerations (AMD). Nowadays, there is no known efficient therapy available for

  13. Understanding noninferiority trials

    Directory of Open Access Journals (Sweden)

    Seokyung Hahn

    2012-11-01

    Full Text Available Noninferiority trials test whether a new experimental treatment is not unacceptably less efficacious than an active control treatment already in use. With continuous improvements in health technologies, standard care, and clinical outcomes, the incremental benefits of newly developed treatments may be only marginal over existing treatments. Sometimes assigning patients to a placebo is unethical. In such circumstances, there has been increasing emphasis on the use of noninferiority trial designs. Noninferiority trials are more complex to design, conduct, and interpret than typical superiority trials. This paper reviews the concept of noninferiority trials and discusses some important issues related to them.

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

    Science.gov (United States)

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

    2014-01-22

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-03-01

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

  17. Clinical trial methodology

    National Research Council Canada - National Science Library

    Peace, Karl E; Chen, Ding-Geng

    2011-01-01

    ... in the pharmaceutical industry, Clinical trial methodology emphasizes the importance of statistical thinking in clinical research and presents the methodology as a key component of clinical research...

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

    Science.gov (United States)

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

    2017-04-01

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

  19. Preparation of 14c- amd 180-labeled 2-[2-methoxy-4-(methylsulfinyl)phenyl]-1H-imidazo[4,5-c]-pyridine hydrochloride (LY175326), a cardiotonic with inotropic and vasodilator activities

    International Nuclear Information System (INIS)

    Kau, Don; Krushinski, J.H.; Robertson, D.W.

    1985-01-01

    Two different forms of 14 C-labeled 2-methoxy-4-(methyl-thio)benzoic acid were prepared and employed in the synthesis of 14 C-labeled 2-:2-methoxy-4-(methylsulfinyl)phenyl:-1H-imidazo-[4,5-c]pyridine hydrochloride (LY175326), a cardiotonic with inotropic and vasodilator activities that is currently in clinical trials. The synthetic procedures described in this report allowed the introduction of the 14 C-label in the antepenultimate step. Additionally, an 18 0-labeled form of LY175326 was synthesized to facilitate kinetic analysis of the formation of its sulfide and sulfone metabolites. (author)

  20. Field trial of a pulsed limestone diversion well

    Science.gov (United States)

    Sibrell, Philip L.; Denholm, C.; Dunn, Margaret

    2013-01-01

    The use of limestone diversion wells to treat acid mine drainage (AMD) is well-known, but in many cases, acid neutralization is not as complete as would be desired. Reasons for this include channeling of the water through the limestone bed, and the slow reaction rate of the limestone gravel. A new approach to improve the performance of the diversion well was tested in the field at the Jennings Environmental Education Center, near Slippery Rock, PA. In this approach, a finer size distribution of limestone was used so as to allow fluidization of the limestone bed, thus eliminating channeling and increasing particle surface area for faster reaction rates. Also, water flow was regulated through the use of a dosing siphon, so that consistent fluidization of the limestone sand could be achieved. Testing began late in the summer of 2010, and continued through November of 2011. Initial system performance during the 2010 field season was good, with the production of net alkaline water, but hydraulic problems involving air release and limestone sand retention were observed. In the summer of 2011, a finer size of limestone sand was procured for use in the system. This material fluidized more readily, but acid neutralization tapered off after several days. Subsequent observations indicated that the hydraulics of the system was compromised by the formation of iron oxides in the pipe leading to the limestone bed, which affected water distribution and flow through the bed. Although results from the field trial were mixed, it is believed that without the formation of iron oxides and plugging of the pipe, better acid neutralization and treatment would have occurred. Further tests are being considered using a different hydraulic configuration for the limestone sand fluidized bed.

  1. Comparability of prostate trials

    DEFF Research Database (Denmark)

    Suciu, S; Sylvester, R; Iversen, P

    1993-01-01

    The present overview of advanced prostate cancer required the identification of randomized clinical trials studying the question of maximal androgen blockade versus the classic castration therapy. The heterogeneity of the trials concerned the type of castration (surgical or chemical) and the type...

  2. Conducting clinical trials in Singapore.

    Science.gov (United States)

    Woo, K T

    1999-04-01

    All clinical trials in Singapore will now have to conform to the Medicines (Clinical Trials) Amended Regulations 1998 and the Singapore Good Clinical Practice (GCP) Guidelines 1998. The Medical Clinical Research Committee (MCRC) has been established to oversee the conduct of clinical drug trials in Singapore and together with the legislations in place, these will ensure that clinical trials conducted in Singapore are properly controlled and the well-being of trial subjects are safe guarded. All clinical drug trials require a Clinical Trial Certificate from the MCRC before the trial can proceed. The hospital ethics committee (EC) vets the application for a trial certificate before it is sent to MCRC. The drug company sponsoring the trial has to indemnify the trial investigators and the hospital for negligence arising from the trial. The MCRC, apart from ensuring the safety of trial subjects, has to provide continuing review of the clinical trial and monitors adverse events in the course of the trial. The EC will conduct continuing review of clinical trials. When a non-drug clinical trial is carried out, the EC will ensure that the proposed protocol addresses ethical concerns and meets regulatory requirements for such trials. There is great potential for pharmaceutical Research & Development (R&D) in Singapore. We must develop our skills and infrastructure in clinical trials to enable Singapore to be a regional hub for R&D of drugs in Asia.

  3. Fundamentals of clinical trials

    CERN Document Server

    Friedman, Lawrence M; DeMets, David L; Reboussin, David M; Granger, Christopher B

    2015-01-01

    This is the fifth edition of a very successful textbook on clinical trials methodology, written by recognized leaders who have long and extensive experience in all areas of clinical trials. The three authors of the first four editions have been joined by two others who add great expertise.  Most chapters have been revised considerably from the fourth edition.  A chapter on regulatory issues has been included and the chapter on data monitoring has been split into two and expanded.  Many contemporary clinical trial examples have been added.  There is much new material on adverse events, adherence, issues in analysis, electronic data, data sharing, and international trials.  This book is intended for the clinical researcher who is interested in designing a clinical trial and developing a protocol. It is also of value to researchers and practitioners who must critically evaluate the literature of published clinical trials and assess the merits of each trial and the implications for the care and treatment of ...

  4. Update on TROG trials

    International Nuclear Information System (INIS)

    Joseph, D.

    2001-01-01

    Full text: Validation of treatment methodologies can only be achieved in the context of unambiguous, efficiently managed, randomised and controlled clinical trials. Since 1991, the Trans-Tasman Radiation Oncology Group (TROG) has coordinated over 29 protocols in radiation oncology, including several key randomised controlled trials. The impetus behind TROG is the establishment of an evidence base for particular approaches to radiotherapy and its adjunct use with alternative and complementary treatment methods. As the level of technology incorporated into radiotherapy continues to increase, as the need for improved accuracy in dose assessment increases and as the requirements of realistic quality assurance (QA) for clinical trials becomes more demanding it is imperative that all professionals involved in radiotherapy, including physicists, become actively involved in the QA of trials. This is particularly important for large scale multi-centre trials which intend to prove the benefits of particular treatment approaches on a national or international stage rather then in the context of a single clinic. This talk will: 1. Examine the outcomes of TROG trials to date in terms of the information obtained. 2. Briefly consider current and impending TROG trials and their requirements in terms of clinical and physics input. 3. Examine the results of international clinical trials in terms of the influence they have had on radiotherapy practice and health outcomes, and the advantages they have obtained by consistent co-operation between clinical and technological staff. 4. Consider the benefits of multi-centre clinical trials and the QA controls that are necessary to ensure accuracy of resulting recommendations. Copyright (2001) Australasian College of Physical Scientists and Engineers in Medicine

  5. ClinicalTrials.gov

    Data.gov (United States)

    U.S. Department of Health & Human Services — Provides patients, family members, health care professionals, and members of the public easy access to information on clinical trials for a wide range of diseases...

  6. OARSI Clinical Trials Recommendations

    DEFF Research Database (Denmark)

    Katz, J N; Losina, E; Lohmander, L S

    2015-01-01

    To highlight methodological challenges in the design and conduct of randomized trials of surgical interventions and to propose strategies for addressing these challenges. This paper focuses on three broad areas: enrollment; intervention; and assessment including implications for analysis. For eac...

  7. Cancer clinical trials

    International Nuclear Information System (INIS)

    Scheurlen, A.; Kay, R.; Baum, M.

    1988-01-01

    This book contains the proceedings on Cancer clinical trials: A critical appraisal. Topics covered include: Scientific fundamentals; Heterogeneous treatment effects; On combining information: Historical controls, overviews, and comprehensive cohort studies; and assessment of quality of life

  8. Comparability of prostate trials

    DEFF Research Database (Denmark)

    Suciu, S; Sylvester, R; Iversen, P

    1993-01-01

    The present overview of advanced prostate cancer required the identification of randomized clinical trials studying the question of maximal androgen blockade versus the classic castration therapy. The heterogeneity of the trials concerned the type of castration (surgical or chemical) and the type...... of antiandrogen (flutamide, Anandron, or cyproterone acetate) added to castration. This paper reviews the different types of heterogeneity that might exist among trials that are involved in the overview: study design, randomization procedure, treatment evaluation, statistical evaluation, and data maturity....... In order to overcome these various types of heterogeneity and to compare like with like, the treatment comparison should be stratified a posteriori by question (i.e., type of castration or type of anti-androgen studied) and by study. In this way, one may draw valid conclusions. Of course, those trials...

  9. Falsificationism and clinical trials.

    Science.gov (United States)

    Senn, S J

    1991-11-01

    The relevance of the philosophy of Sir Karl Popper to the planning, conduct and analysis of clinical trials is examined. It is shown that blinding and randomization can only be regarded as valuable for the purpose of refuting universal hypotheses. The purpose of inclusion criteria is also examined. It is concluded that a misplaced belief in induction is responsible for many false notions regarding clinical trials.

  10. The OA Trial Bank

    DEFF Research Database (Denmark)

    van Middelkoop, Marienke; Arden, N K; Atchia, I.

    2016-01-01

    Objective: To evaluate the efficacy of intra-articular (IA) glucocorticoids for knee or hip osteoarthritis (OA) in specific subgroups of patients with severe pain and inflammatory signs using individual patient data (IPD) from existing trials. Design: Randomized trials evaluating one or more IA...... glucocorticoid preparation in patients with knee or hip OA, published from 1995 up to June 2012 were selected from the literature. IPD obtained from original trials included patient and disease characteristics and outcomes measured. The primary outcome was pain severity at short-term follow-up (up to 4 weeks...... Interval 1.50-26.31) when receiving IA glucocorticoid injection compared to placebo. No statistical significant interaction effects were found between inflammatory signs and IA glucocorticoid injections compared to placebo and to tidal irrigation at all follow-up points. Conclusions: This IPD meta...

  11. The CYTONOX trial

    DEFF Research Database (Denmark)

    Gade, Christina; Mikus, Gerd; Christensen, Hanne Rolighed

    2016-01-01

    INTRODUCTION: In Denmark, it is estimated that 3-5% of children are obese. Obesity is associated with pathophysiological alterations that may lead to alterations in the pharmacokinetics of drugs. In adults, obesity was found to influence important drug-metabolising enzyme pathways. The impact...... of obesity-related alterations on drug metabolism and its consequences for drug dosing remains largely unknown in both children and adults. An altered drug metabolism may contribute significantly to therapeutic failure or toxicity. The aim of this trial is to investigate the in vivo activity of CYP3A4, CYP2E......1 and CYP1A2 substrates in obese versus non-obese children. METHODS: The CYTONOX trial is an open-label explorative pharmacokinetic trial. We intend to include 50 obese and 50 non-obese children. The primary end points are: in vivo clearance of CYP3A4, CYP2E1 and CYP1A2 substrates, which...

  12. The FOCUS trial

    DEFF Research Database (Denmark)

    Glenthøj, Louise B; Fagerlund, Birgitte; Randers, Lasse

    2015-01-01

    BACKGROUND: Cognitive deficits are a distinct feature among people at ultra-high risk (UHR) for psychosis and pose a barrier to functional recovery. Insufficient evidence exists on how to ameliorate these cognitive deficits in patients at UHR for psychosis and hence improve daily living and quality...... of life. The aim of the trial is to investigate whether cognitive remediation can improve cognitive and psychosocial function in patients at UHR for psychosis. METHODS: The FOCUS trial (Function and Overall Cognition in Ultra-high risk States) is a randomised, parallel group, observer-blinded clinical...... trial enrolling 126 patients meeting the standardised criteria of being at UHR for psychosis. Patients are recruited from psychiatric in- and outpatient facilities in the Copenhagen catchment area. Patients are randomised to one of the two treatment arms: cognitive remediation plus standard treatment...

  13. Randomised clinical trial

    DEFF Research Database (Denmark)

    Reimer, C; Lødrup, A; Smith, G

    2016-01-01

    of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. MethodsThis was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using...

  14. OARSI Clinical Trials Recommendations

    DEFF Research Database (Denmark)

    Kraus, V B; Blanco, F J; Englund, M

    2015-01-01

    The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from...

  15. OARSI Clinical Trials Recommendations

    DEFF Research Database (Denmark)

    McAlindon, T. E.; Driban, J. B.; Henrotin, Y.

    2015-01-01

    The goal of this document is to update the original OARSI recommendations specifically for the design, conduct, and reporting of clinical trials that target symptom or structure modification among individuals with knee osteoarthritis (OA). To develop recommendations for the design, conduct...

  16. [Clinical trials in nursing journals].

    Science.gov (United States)

    Di Giulio, Paola; Campagna, Sara; Dimonte, Valerio

    2014-01-01

    Clinical trials are pivotal for the development of nursing knowledge. To describe the clinical trials published in nursing journals in the last two years and propose some general reflections on nursing research. A search with the key-word trial was done on PubMed (2009-2013) on Cancer Nursing, European Journal of Oncology Nursing, International Journal of Nursing Studies, Journal of Advanced Nursing, Journal of Clinical Nursing and Nursing Research. Of 228 trials identified, 104 (45.8%) were published in the last 2 years. Nurses from Asian countries published the larger number of trials. Educational and supportive interventions were the most studied (61/104 trials), followed by clinical interventions (33/104). Samples were limited and most trials are monocentric. A growing number of trials is published, on issues relevant for the nursing profession, however larger samples and multicentric studies would be necessary.

  17. The COLOFOL trial

    DEFF Research Database (Denmark)

    Hansdotter Andersson, Pernilla; Wille-Jørgensen, Peer; Horváth-Puhó, Erzsébet

    2016-01-01

    population. To be eligible, patients had to be 75 years or younger and curatively resected for stage II or III colorectal cancer. Exclusion criteria were hereditary colorectal cancer, no signed consent, other malignancy, and life expectancy less than 2 years due to concomitant disease. In four of the 24......INTRODUCTION: The COLOFOL trial, a prospective randomized multicenter trial comparing two follow-up regimes after curative surgical treatment for colorectal cancer, focuses on detection of asymptomatic recurrences. This paper aims to describe the design and recruitment procedure in the COLOFOL...... participating centers, we scrutinized hospital inpatient data to identify all colorectal cancer patients who underwent surgery, in order to ascertain all eligible patients who were not included in the study and to compare them with enrolled patients. RESULTS: Of a total of 4,445 eligible patients, 2...

  18. Ethics of clinical trials.

    Science.gov (United States)

    Palter, S F

    1996-05-01

    The modern clinical trial is a form of human experimentation. There is a long history of disregard for individual rights of the patient in this context, and special attention must be paid to ethical guidelines for these studies. Clinical trials differ in basic ways from clinical practice. Foremost is the introduction of outside interests, beyond those of the patient's health, into the doctor-patient therapeutic alliance. Steps must be taken to protect the interests of the patient when such outside influence exists. Kantian moral theory and the Hippocratic oath dictate that the physician must respect the individual patient's rights and hold such interests paramount. These principles are the basis for informed consent. Randomization of patients is justified when a condition of equipoise exists. The changing nature of health care delivery in the United States introduces new outside interests into the doctor-patient relationship.

  19. Complement pathway biomarkers and age-related macular degeneration

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2016-01-01

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

  20. Gateways to clinical trials.

    Science.gov (United States)

    Bayés, M; Rabasseda, X; Prous, J R

    2007-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide

  1. Gateways to clinical trials.

    Science.gov (United States)

    Bayés, M; Rabasseda, X; Prous, J R

    2005-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort

  2. Clinical trials in India.

    Science.gov (United States)

    Maiti, Rituparna; M, Raghavendra

    2007-07-01

    The concept of outsourcing for the development and global studies on new drugs has become widely accepted in the pharmaceutical industry due to its cost and uncertainty. India is going to be the most preferred location for contract pharma research and development due to its huge treatment naïve population, human resources, technical skills, adoption/amendment/implementation of rules/laws by regulatory authorities, and changing economic environment. But still 'miles to go' to fulfill the pre-requisites to ensure India's success. In spite of all the pitfalls, the country is ambitious and optimist to attract multinational pharmaceutical companies to conduct their clinical trials in India.

  3. Quality Evaluation of Yoghurt from Cowmilk, Soymilk amd Cow ...

    African Journals Online (AJOL)

    Proximate analyses carried out on samples of cow milk, soymilk and cow/soymilk Yoghurts showed significant difference (P<0.05) in the % crude protein, crude fat and carbohydrate contents. For crude protein they were 3.49 ± 0.04, 2.78 ± 0.13 and 2.02 ± 0.4 for cow yoghurt, cow/soy yoghurt and soy yoghurt respectively.

  4. Clustering aspects of sd shell nuclei studied by AMD

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Masaaki [Yukawa Institute for Theoretical Physics, Kyoto University, Kyoto 606-8502 (Japan); Taniguchi, Yasutaka [Department of Physics, Kyoto University, Kitashirakawa, Kyoto 606-8502 (Japan); En' yo, Yoshiko [Yukawa Institute for Theoretical Physics, Kyoto University, Kyoto 606-8502 (Japan); Horiuchi, Hisashi [Department of Physics, Kyoto University, Kitashirakawa, Kyoto 606-8502 (Japan)

    2006-10-10

    The new clustering aspects of sd-shell nuclei found by the recent application of the antisymmetrized molecular dynamics are reported. In this paper we present two topics, 'superdeformed band of {sup 32}S and {sup 16}O + {sup 16}O clustering' and 'molecular-orbital and di-nuclei states in {sup 22}Ne'. In the first topic, it will be shown that the superdeformed band of 32S has a considerable amount of {sup 16}O + {sup 16}O cluster component, and can be regarded as to belong to a family of the {sup 16}O + {sup 16}O molecular bands. In the second topic, the presence of the molecularorbital band which has an {alpha} + {sup 16}O cluster core surrounded by two covalently neutrons is suggested together with an {alpha} + {sup 18}O di-nuclei band.

  5. Clustering aspects of sd shell nuclei studied by AMD

    International Nuclear Information System (INIS)

    Kimura, Masaaki; Taniguchi, Yasutaka; En'yo, Yoshiko; Horiuchi, Hisashi

    2006-01-01

    The new clustering aspects of sd-shell nuclei found by the recent application of the antisymmetrized molecular dynamics are reported. In this paper we present two topics, 'superdeformed band of 32 S and 16 O + 16 O clustering' and 'molecular-orbital and di-nuclei states in 22 Ne'. In the first topic, it will be shown that the superdeformed band of 32S has a considerable amount of 16 O + 16 O cluster component, and can be regarded as to belong to a family of the 16 O + 16 O molecular bands. In the second topic, the presence of the molecularorbital band which has an α + 16 O cluster core surrounded by two covalently neutrons is suggested together with an α + 18 O di-nuclei band

  6. Decentral amd renewable power generation; Dezentrale und erneuerbare Stromerzeugung

    Energy Technology Data Exchange (ETDEWEB)

    Arndt, Ulli [EWE AG, Oldenburg (Germany). Abt. Forschung und Entwicklung

    2011-07-01

    The inspiration for the design of an energy system of the future constitutes the necessary change of the power generation structure deriving from renewable energy sources such as wind power and solar energy. In Germany, the captured feeding volume of renewable energy amounts 89.1 TWh per annum in 2009. The high demands on a stable and efficient network operation require an intelligent networking of information and communication technology. This network enables the production facilities and consumption components to communicate with renewable energies. EWE AG (Oldenburg, Federal Republic of Germany) develops and implements an active smart grid as a distribution network with a virtual power plants and energy marketplaces, with network services and management algorithms and a new tariff system feedback sysem for the involvement of domestic consumers.

  7. Total Phenol amd Flavonoid contents of Crude Extract and Fractions ...

    African Journals Online (AJOL)

    Phenolic compounds are numerous in plants and are essential part of human diet. Picralima nitida has been extensively used in African folk medicine especially in West Africa. The present study evaluated the total phenolic and flavonoid contents of the extract and fractions of Picralima nitida. The methanol extracts of P.

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

    Science.gov (United States)

    Gowri, S; Kannan, Sridharan

    2017-01-01

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

  9. Japan nuclear ship sea trial

    International Nuclear Information System (INIS)

    Yamazaki, Hiroshi; Kitamura, Toshikatus; Mizushima, Toshihiko

    1992-01-01

    The sea trial of the first Japan nuclear Ship 'MUTSU' was conducted from the end of October to December in 1990. The purpose of the sea trial was to verify the nuclear propulsive performances and maneuverabilities. The present report describes the results of the sea trial. These results are classified into four items: 1. Speed test and engineering performance tests 2. Maneuvering performance tests 3. Vibration tests 4. Other tests. Acceptable performances were demonstrated, as expected in the original design. The experience of the use of the Global Positioning System (GPS), which were newly adopted for the sea trial, is also reported. (author)

  10. [Maraviroc: clinical trials results].

    Science.gov (United States)

    Chidiac, C; Katlama, C; Yeni, P

    2008-03-01

    Just over a decade after identification of chemokine receptors CCR5 and CXCR4 as coreceptors for HIV, maraviroc (Celsentri), the first CCR5 antagonist, has recently obtained its Marketing Authorization in the United States and Europe, for treatment of treatment-experienced adult patients infected with only CCR5-tropic HIV-1 detectable. CCR5 antagonists, after fusion inhibitor enfuvirtide available since 2003, also belong to entry inhibitors. These molecules, unlike previous antiretrovirals, do not target the virus but its target cell by blocking viral penetration. Maraviroc has shown its clinical efficacy in patients failing other antiretroviral classes. Its safety profile was similar to placebo in two large phase III trials. However, careful assessment of both hepatic and immunologic safety of this new therapeutic class is needed. Viral tropism testing has to be investigated before using maraviroc in the clinic, because CCR5 antagonists are not active against CXCR4 viruses. For the moment indicated for the treatment-experienced patient population, maraviroc could in the future benefit to other types of patients, depending on ongoing trials results.

  11. Gateways to clinical trials.

    Science.gov (United States)

    Bayés, M; Rabasseda, X; Prous, J R

    2006-10-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (-)-gossypol, 2-deoxyglucose, 3,4-DAP, 7-monohydroxyethylrutoside; Ad5CMV-p53, adalimumab, adefovir dipivoxil, ADH-1, alemtuzumab, aliskiren fumarate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, amrubicin hydrochloride, AN-152, anakinra, anecortave acetate, antiasthma herbal medicine intervention, AP-12009, AP-23573, apaziquone, aprinocarsen sodium, AR-C126532, AR-H065522, aripiprazole, armodafinil, arzoxifene hydrochloride, atazanavir sulfate, atilmotin, atomoxetine hydrochloride, atorvastatin, avanafil, azimilide hydrochloride; Bevacizumab, biphasic insulin aspart, BMS-214662, BN-83495, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, cetuximab, chrysin, ciclesonide, clevudine, clofarabine, clopidogrel, CNF-1010, CNTO-328, CP-751871, CX-717, Cypher; Dapoxetine hydrochloride, darifenacin hydrobromide, dasatinib, deferasirox, dextofisopam, dextromethorphan/quinidine sulfate, diclofenac, dronedarone hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Edaravone, efaproxiral sodium, emtricitabine, entecavir, eplerenone, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, ezetimibe, ezetimibe/simvastatin; Finrozole, fipamezole hydrochloride, fondaparinux sodium, fulvestrant; Gabapentin enacarbil, gaboxadol, gefitinib, gestodene, ghrelin (human); Human insulin, human papillomavirus vaccine; Imatinib mesylate, immunoglobulin intravenous (human), indiplon, insulin detemir, insulin glargine, insulin glulisine, intranasal insulin, istradefylline, i.v. gamma

  12. Treatment of geographic atrophy by the topical administration of OT-551: results of a phase II clinical trial.

    Science.gov (United States)

    Wong, Wai T; Kam, Waynekid; Cunningham, Denise; Harrington, Molly; Hammel, Keri; Meyerle, Catherine B; Cukras, Catherine; Chew, Emily Y; Sadda, Srinivas R; Ferris, Frederick L

    2010-12-01

    To investigate the safety and preliminary efficacy of OT-551, a disubstituted hydroxylamine with antioxidant properties, for the treatment of geographic atrophy (GA), the advanced atrophic form of age-related macular degeneration (AMD). The study was a single-center, open-label phase II trial, enrolling 10 participants with bilateral GA. Topical 0.45% OT-551 was administered in one randomly assigned eye three times daily for 2 years. Safety measures were assessed by complete ophthalmic examination, fundus photography, and review of symptoms. The primary efficacy outcome measure was the change in best corrected visual acuity at 24 months. Secondary efficacy measures included changes in area of GA, contrast sensitivity, microperimetry measurements, and total drusen area from baseline. Study drug was well tolerated and was associated with few adverse events. The mean change in BCVA at 2 years was +0.2 ± 13.3 letters in the study eyes and -11.3 ± 7.6 letters in fellow eyes (P = 0.0259). However, no statistically significant differences were found between the study and fellow eyes for all other secondary outcome measures. OT-551 was well tolerated by study participants and was not associated with any serious adverse effects. Efficacy measurements in this small study indicate a possible effect in maintaining visual acuity. However, the absence of significant effects on other outcomes measures in this study suggests that OT-551, in the current concentration and mode of delivery, may have limited or no benefit as a treatment for GA (ClinicalTrials.gov number, NCT00306488).

  13. Market trials of irradiated chicken

    International Nuclear Information System (INIS)

    Fox, John A.; Olson, Dennis G.

    1998-01-01

    The potential market for irradiated chicken breasts was investigated using a mail survey and a retail trial. Results from the mail survey suggested a significantly higher level of acceptability of irradiated chicken than did the retail trial. A subsequent market experiment involving actual purchases showed levels of acceptability similar to that of the mail survey when similar information about food irradiation was provided

  14. Defendants' Rights in Criminal Trials.

    Science.gov (United States)

    Martin, Ralph C., II; Keeley, Elizabeth

    1997-01-01

    Reviews the protections afforded by the Constitution for defendants in criminal trials. These include the right to a jury trial (in cases of possible incarceration), an impartial jury, and the requirement of a unanimous verdict. Defends the use of plea bargaining as essential to an efficient criminal justice system. (MJP)

  15. Cross-Over Clinical Trials?

    Directory of Open Access Journals (Sweden)

    Latif Gachkar

    2017-01-01

    Full Text Available Abstract Cross-Over Clinical Trials in comparison with Parallel groups clinical trials have some advantages such as control of confounding variables, small sample size, and short time to implement the research project. But this type of research has few essential limitations that discusses in this monogram.

  16. OARSI Clinical Trials Recommendations

    DEFF Research Database (Denmark)

    Emery, C. A.; Roos, Ewa M.; Verhagen, E.

    2015-01-01

    The risk of post-traumatic osteoarthritis (PTOA) substantially increases following joint injury. Research efforts should focus on investigating the efficacy of preventative strategies in high quality randomized controlled trials (RCT). The objective of these OARSI RCT recommendations is to inform...... the design, conduct and analytical approaches to RCTs evaluating the preventative effect of joint injury prevention strategies. Recommendations regarding the design, conduct, and reporting of RCTs evaluating injury prevention interventions were established based on the consensus of nine researchers...... internationally with expertise in epidemiology, injury prevention and/or osteoarthritis (OA). Input and resultant consensus was established through teleconference, face to face and email correspondence over a 1 year period. Recommendations for injury prevention RCTs include context specific considerations...

  17. Industrial demonstration trials

    International Nuclear Information System (INIS)

    Gelee, M.; Fabre, C.; Villepoix, R. de; Fra, J.; Le Foulgoc, L.; Morel, Y.; Querite, P.; Roques, R.

    1975-01-01

    Prototypes of the plant components, meeting the specifications set by the process and built by industrial firms in collaboration with the supervisor and the C.E.A., are subjected to trial runs on the UF 6 test bench of the Pierrelatte testing zone. These items of equipment (diffuser, compressor, exchanger) are placed in an industrial operation context very similar to that of an enrichment plant. Their performance is measured within a broad region around the working point and their reliability observed over periods up to several tens of thousands of hours. Between 1969 and 1973 six industrial demonstration test benches have been built, marking the stages in the technical preparation of the 1973 file on the basis of which the decision of building was taken by Eurodif [fr

  18. LTDNA Evidence on Trial

    Science.gov (United States)

    Roberts, Paul

    2016-01-01

    Adopting the interpretative/hermeneutical method typical of much legal scholarship, this article considers two sets of issues pertaining to LTDNA profiles as evidence in criminal proceedings. The section titled Expert Evidence as Forensic Epistemic Warrant addresses some rather large questions about the epistemic status and probative value of expert testimony in general. It sketches a theoretical model of expert evidence, highlighting five essential criteria: (1) expert competence; (2) disciplinary domain; (3) methodological validity; (4) materiality; and (5) legal admissibility. This generic model of expert authority, highlighting law's fundamentally normative character, applies to all modern forms of criminal adjudication, across Europe and farther afield. The section titled LTDNA Evidence in UK Criminal Trials then examines English and Northern Irish courts' attempts to get to grips with LTDNA evidence in recent cases. Better appreciating the ways in which UK courts have addressed the challenges of LTDNA evidence may offer some insights into parallel developments in other legal systems. Appellate court rulings follow a predictable judicial logic, which might usefully be studied and reflected upon by any forensic scientist or statistician seeking to operate effectively in criminal proceedings. Whilst each legal jurisdiction has its own unique blend of jurisprudence, institutions, cultures and historical traditions, there is considerable scope for comparative analysis and cross-jurisdictional borrowing and instruction. In the spirit of promoting more nuanced and sophisticated international interdisciplinary dialogue, this article examines UK judicial approaches to LTDNA evidence and begins to elucidate their underlying institutional logic. Legal argument and broader policy debates are not confined to considerations of scientific validity, contamination risks and evidential integrity, or associated judgments of legal admissibility or exclusion. They also crucially

  19. ANFO truck burn trials

    Energy Technology Data Exchange (ETDEWEB)

    Rosen von, B.; Contestabile, E. [Natural Resources Canada, CANMET Canadian Explosives Research Laboratory, Ottawa, ON (Canada)

    2003-10-01

    This report describes the investigation of a tractor-trailer explosion. A truck loaded with 18,000 kg of commercial explosives, of which 13,000 kg was ammonium nitrate with fuel oil (ANFO), caught fire when it struck a rockcut near Walden, Ontario on August 5, 1998. The fire resulted in the detonation of the load. The Canadian Explosives Research Laboratory (CERL) conducted a test program to examine the suitability of existing explosive transportation regulations. Unconfined burns of ANFO were performed. The accident was recreated in two burn trials in an attempt to identify the mechanism that led from fire to detonation. Two full-scale tests were conducted using complete tractor-trailers, each in a jack-knifed position with most of the explosives placed on the ground in front of the trailer. ANFO was used in the first test to determine its response to thermal stimulus and the likelihood of detonation or explosion. The second test involved ANFO, a slurry and an emulsion. Thermocouples and video cameras were used to observe the burning characteristics of the explosives, the truck and its components. The explosives burned steadily for 80 minutes in each test. Many truck components, such as tires, spring brake chambers and the fuel tank ruptured violently due to the heat. Although no detonation occurred in the test trials, it was concluded that under favourable conditions, many truck components, might produce fragments with enough energy to initiate heat-sensitized explosives. It was suggested that a fragment impact caused the detonation at Walden. 4 refs., 7 tabs., 8 figs.

  20. LTDNA Evidence on Trial.

    Science.gov (United States)

    Roberts, Paul

    2016-01-01

    Adopting the interpretative/hermeneutical method typical of much legal scholarship, this article considers two sets of issues pertaining to LTDNA profiles as evidence in criminal proceedings. The section titled Expert Evidence as Forensic Epistemic Warrant addresses some rather large questions about the epistemic status and probative value of expert testimony in general. It sketches a theoretical model of expert evidence, highlighting five essential criteria: (1) expert competence; (2) disciplinary domain; (3) methodological validity; (4) materiality; and (5) legal admissibility. This generic model of expert authority, highlighting law's fundamentally normative character, applies to all modern forms of criminal adjudication, across Europe and farther afield. The section titled LTDNA Evidence in UK Criminal Trials then examines English and Northern Irish courts' attempts to get to grips with LTDNA evidence in recent cases. Better appreciating the ways in which UK courts have addressed the challenges of LTDNA evidence may offer some insights into parallel developments in other legal systems. Appellate court rulings follow a predictable judicial logic, which might usefully be studied and reflected upon by any forensic scientist or statistician seeking to operate effectively in criminal proceedings. Whilst each legal jurisdiction has its own unique blend of jurisprudence, institutions, cultures and historical traditions, there is considerable scope for comparative analysis and cross-jurisdictional borrowing and instruction. In the spirit of promoting more nuanced and sophisticated international interdisciplinary dialogue, this article examines UK judicial approaches to LTDNA evidence and begins to elucidate their underlying institutional logic. Legal argument and broader policy debates are not confined to considerations of scientific validity, contamination risks and evidential integrity, or associated judgments of legal admissibility or exclusion. They also crucially

  1. Using simulation to aid trial design: Ring-vaccination trials.

    Directory of Open Access Journals (Sweden)

    Matt David Thomas Hitchings

    2017-03-01

    Full Text Available The 2014-6 West African Ebola epidemic highlights the need for rigorous, rapid clinical trial methods for vaccines. A challenge for trial design is making sample size calculations based on incidence within the trial, total vaccine effect, and intracluster correlation, when these parameters are uncertain in the presence of indirect effects of vaccination.We present a stochastic, compartmental model for a ring vaccination trial. After identification of an index case, a ring of contacts is recruited and either vaccinated immediately or after 21 days. The primary outcome of the trial is total vaccine effect, counting cases only from a pre-specified window in which the immediate arm is assumed to be fully protected and the delayed arm is not protected. Simulation results are used to calculate necessary sample size and estimated vaccine effect. Under baseline assumptions about vaccine properties, monthly incidence in unvaccinated rings and trial design, a standard sample-size calculation neglecting dynamic effects estimated that 7,100 participants would be needed to achieve 80% power to detect a difference in attack rate between arms, while incorporating dynamic considerations in the model increased the estimate to 8,900. This approach replaces assumptions about parameters at the ring level with assumptions about disease dynamics and vaccine characteristics at the individual level, so within this framework we were able to describe the sensitivity of the trial power and estimated effect to various parameters. We found that both of these quantities are sensitive to properties of the vaccine, to setting-specific parameters over which investigators have little control, and to parameters that are determined by the study design.Incorporating simulation into the trial design process can improve robustness of sample size calculations. For this specific trial design, vaccine effectiveness depends on properties of the ring vaccination design and on the

  2. Social media in clinical trials.

    Science.gov (United States)

    Thompson, Michael A

    2014-01-01

    Social media has potential in clinical trials for pointing out trial issues, addressing barriers, educating, and engaging multiple groups involved in cancer clinical research. Social media is being used in clinical trials to highlight issues such as poor accrual and barriers; educate potential participants and physicians about clinical trial options; and is a potential indirect or direct method to improve accrual. We are moving from a passive "push" of information to patients to a "pull" of patients requesting information. Patients and advocates are often driving an otherwise reluctant health care system into communication. Online patient communities are creating new information repositories. Potential clinical trial participants are using the Twittersphere and other sources to learn about potential clinical trial options. We are seeing more organized patient-centric and patient-engaged forums with the potential to crowd source to improve clinical trial accrual and design. This is an evolving process that will meet many individual, institutional, and regulatory obstacles as we move forward in a changed research landscape.

  3. Quality Assurance for Clinical Trials

    Science.gov (United States)

    Ibbott, Geoffrey S.; Haworth, Annette; Followill, David S.

    2013-01-01

    Cooperative groups, of which the Radiation Therapy Oncology Group is one example, conduct national clinical trials that often involve the use of radiation therapy. In preparation for such a trial, the cooperative group prepares a protocol to define the goals of the trial, the rationale for its design, and the details of the treatment procedure to be followed. The Radiological Physics Center (RPC) is one of several quality assurance (QA) offices that is charged with assuring that participating institutions deliver doses that are clinically consistent and comparable. The RPC does this by conducting a variety of independent audits and credentialing processes. The RPC has compiled data showing that credentialing can help institutions comply with the requirements of a cooperative group clinical protocol. Phantom irradiations have been demonstrated to exercise an institution’s procedures for planning and delivering advanced external beam techniques (1–3). Similarly, RPC data indicate that a rapid review of patient treatment records or planning procedures can improve compliance with clinical trials (4). The experiences of the RPC are presented as examples of the contributions that a national clinical trials QA center can make to cooperative group trials. These experiences illustrate the critical need for comprehensive QA to assure that clinical trials are successful and cost-effective. The RPC is supported by grants CA 10953 and CA 81647 from the National Cancer Institute, NIH, DHHS. PMID:24392352

  4. Frailty Intervention Trial (FIT

    Directory of Open Access Journals (Sweden)

    Lockwood Keri

    2008-10-01

    Full Text Available Abstract Background Frailty is a term commonly used to describe the condition of an older person who has chronic health problems, has lost functional abilities and is likely to deteriorate further. However, despite its common use, only a small number of studies have attempted to define the syndrome of frailty and measure its prevalence. The criteria Fried and colleagues used to define the frailty syndrome will be used in this study (i.e. weight loss, fatigue, decreased grip strength, slow gait speed, and low physical activity. Previous studies have shown that clinical outcomes for frail older people can be improved using multi-factorial interventions such as comprehensive geriatric assessment, and single interventions such as exercise programs or nutritional supplementation, but no interventions have been developed to specifically reverse the syndrome of frailty. We have developed a multidisciplinary intervention that specifically targets frailty as defined by Fried et al. We aim to establish the effects of this intervention on frailty, mobility, hospitalisation and institutionalisation in frail older people. Methods and Design A single centre randomised controlled trial comparing a multidisciplinary intervention with usual care. The intervention will target identified characteristics of frailty, functional limitations, nutritional status, falls risk, psychological issues and management of chronic health conditions. Two hundred and thirty people aged 70 and over who meet the Fried definition of frailty will be recruited from clients of the aged care service of a metropolitan hospital. Participants will be followed for a 12-month period. Discussion This research is an important step in the examination of specifically targeted frailty interventions. This project will assess whether an intervention specifically targeting frailty can be implemented, and whether it is effective when compared to usual care. If successful, the study will establish a

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

    Directory of Open Access Journals (Sweden)

    Wen-Sheng Cheng

    2017-01-01

    Full Text Available The overall goal of treating age-related macular degeneration (AMD is to target the underlying cause of the disease and prevent, or at least slow down, the loss of vision, which requires the preservation of the choroid, retinal pigment epithelium (RPE, and photoreceptors. At present, there is no proven drug treatment for dry AMD; however, the cessation of smoking and treatments based on the age-related eye diseases study vitamin formula combined with a healthy diet are considered the only options for slowing disease progression. A number of pharmaceutical agents are currently under evaluation for the treatment of dry AMD using strategies such as reduction RPE and photoreceptor loss, neuroprotection, visual cycle modulators, suppression of inflammation, prevention of oxidative damage, and choroidal perfusion enhancers. The hope is that some of these therapies will achieve significant improvement to current management and prevent future loss of vision in this devastating eye condition.

  6. clinical trials of Sutherlandia frutescens

    African Journals Online (AJOL)

    economic and political imperatives surrounding randomised controlled trials and the ambiguous, or even ..... the medicinal properties of the plant, as reported both in the book, and also in the .... London, UK: Harvard University Press. Latour, B.

  7. Lung Cancer Precision Medicine Trials

    Science.gov (United States)

    Patients with lung cancer are benefiting from the boom in targeted and immune-based therapies. With a series of precision medicine trials, NCI is keeping pace with the rapidly changing treatment landscape for lung cancer.

  8. a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    MS Yıldırım

    2016-02-01

    Full Text Available The aim of this study was to compare the effects of static stretching, proprioceptive neuromuscular facilitation (PNF stretching and Mulligan technique on hip flexion range of motion (ROM in subjects with bilateral hamstring tightness. A total of 40 students (mean age: 21.5±1.3 years, mean body height: 172.8±8.2 cm, mean body mass index: 21.9±3.0 kg • m-2 with bilateral hamstring tightness were enrolled in this randomized trial, of whom 26 completed the study. Subjects were divided into 4 groups performing (I typical static stretching, (II PNF stretching, (III Mulligan traction straight leg raise (TSLR technique, (IV no intervention. Hip flexion ROM was measured using a digital goniometer with the passive straight leg raise test before and after 4 weeks by two physiotherapists blinded to the groups. 52 extremities of 26 subjects were analyzed. Hip flexion ROM increased in all three intervention groups (p<0.05 but not in the no-intervention group after 4 weeks. A statistically significant change in initial–final assessment differences of hip flexion ROM was found between groups (p<0.001 in favour of PNF stretching and Mulligan TSLR technique in comparison to typical static stretching (p=0.016 and p=0.02, respectively. No significant difference was found between Mulligan TSLR technique and PNF stretching (p=0.920. The initial–final assessment difference of hip flexion ROM was similar in typical static stretching and no intervention (p=0.491. A 4-week stretching intervention is beneficial for increasing hip flexion ROM in bilateral hamstring tightness. However, PNF stretching and Mulligan TSLR technique are superior to typical static stretching. These two interventions can be alternatively used for stretching in hamstring tightness.

  9. Global warming on trial

    International Nuclear Information System (INIS)

    Broeker, W.S.

    1992-01-01

    Jim Hansen, a climatologist at NASA's Goddard Space Institute, is convinced that the earth's temperature is rising and places the blame on the buildup of greenhouse gases in the atmosphere. Unconvinced, John Sununu, former White House chief of staff, doubts that the warming will be great enough to produce serious threat and fears that measures to reduce the emissions would throw a wrench into the gears that drive the Unites States' troubled economy. During his three years at the White House, Sununu's view prevailed, and although his role in the debate has diminished, others continue to cast doubt on the reality of global warming. A new lobbying group called the Climate Council has been created to do just this. Burning fossil fuels is not the only problem; a fifth of emissions of carbon dioxide now come from clearing and burning forests. Scientists are also tracking a host of other greenhouse gases that emanate from a variety of human activities; the warming effect of methane, chlorofluorocarbons and nitrous oxide combined equals that of carbon dioxide. Although the current warming from these gases may be difficult to detect against the background noise of natural climate variation, most climatologists are certain that as the gases continue to accumulate, increases in the earth's temperature will become evident even to skeptics. If the reality of global warming were put on trial, each side would have trouble making its case. Jim Hansen's side could not prove beyond a reasonable doubt that carbon dioxide and other greenhouse gases have warmed the planet. But neither could John Sununu's side prove beyond a reasonable doubt that the warming expected from greenhouse gases has not occurred. To see why each side would have difficulty proving its case, this article reviews the arguments that might be presented in such a hearing

  10. Trial Watch: Anticancer radioimmunotherapy.

    Science.gov (United States)

    Vacchelli, Erika; Vitale, Ilio; Tartour, Eric; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-09-01

    Radiotherapy has extensively been employed as a curative or palliative intervention against cancer throughout the last century, with a varying degree of success. For a long time, the antineoplastic activity of X- and γ-rays was entirely ascribed to their capacity of damaging macromolecules, in particular DNA, and hence triggering the (apoptotic) demise of malignant cells. However, accumulating evidence indicates that (at least part of) the clinical potential of radiotherapy stems from cancer cell-extrinsic mechanisms, including the normalization of tumor vasculature as well as short- and long-range bystander effects. Local bystander effects involve either the direct transmission of lethal signals between cells connected by gap junctions or the production of diffusible cytotoxic mediators, including reactive oxygen species, nitric oxide and cytokines. Conversely, long-range bystander effects, also known as out-of-field or abscopal effects, presumably reflect the elicitation of tumor-specific adaptive immune responses. Ionizing rays have indeed been shown to promote the immunogenic demise of malignant cells, a process that relies on the spatiotemporally defined emanation of specific damage-associated molecular patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of other treatment modalities such as surgery (both in neo-adjuvant and adjuvant settings) or chemotherapy. Moreover, at least under some circumstances, radiotherapy may potentiate anticancer immune responses as elicited by various immunotherapeutic agents, including (but presumably not limited to) immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell-based interventions and Toll-like receptor agonists. Here, we review the rationale of using radiotherapy, alone or combined with immunomodulatory agents, as a means to elicit or boost anticancer immune responses, and present recent clinical trials investigating the therapeutic potential of this approach in

  11. LTDNA Evidence on Trial

    Directory of Open Access Journals (Sweden)

    Paul Roberts

    2016-10-01

    factfinders in criminal trials.

  12. Successful recruitment to trials: findings from the SCIMITAR+ Trial.

    Science.gov (United States)

    Peckham, Emily; Arundel, Catherine; Bailey, Della; Callen, Tracy; Cusack, Christina; Crosland, Suzanne; Foster, Penny; Herlihy, Hannah; Hope, James; Ker, Suzy; McCloud, Tayla; Romain-Hooper, Crystal-Bella; Stribling, Alison; Phiri, Peter; Tait, Ellen; Gilbody, Simon

    2018-01-19

    Randomised controlled trials (RCT) can struggle to recruit to target on time. This is especially the case with hard to reach populations such as those with severe mental ill health. The SCIMITAR+ trial, a trial of a bespoke smoking cessation intervention for people with severe mental ill health achieved their recruitment ahead of time and target. This article reports strategies that helped us to achieve this with the aim of aiding others recruiting from similar populations. SCIMITAR+ is a multi-centre pragmatic two-arm parallel-group RCT, which aimed to recruit 400 participants with severe mental ill health who smoke and would like to cut down or quit. The study recruited primarily in secondary care through community mental health teams and psychiatrists with a smaller number of participants recruited through primary care. Recruitment opened in October 2015 and closed in December 2016, by which point 526 participants had been recruited. We gathered information from recruiting sites on strategies which led to the successful recruitment in SCIMITAR+ and in this article present our approach to trial management along with the strategies employed by the recruiting sites. Alongside having a dedicated trial manager and trial management team, we identified three main themes that led to successful recruitment. These were: clinicians with a positive attitude to research; researchers and clinicians working together; and the use of NHS targets. The overriding theme was the importance of relationships between both the researchers and the recruiting clinicians and the recruiting clinicians and the participants. This study makes a significant contribution to the limited evidence base of real-world cases of successful recruitment to RCTs and offers practical guidance to those planning and conducting trials. Building positive relationships between clinicians, researchers and participants is crucial to successful recruitment.

  13. Clinical trials. A pending subject.

    Science.gov (United States)

    Gil-Extremera, B; Jiménez-López, P; Mediavilla-García, J D

    2018-04-01

    Clinical trials are essential tools for the progress of clinical medicine in its diagnostic and therapeutic aspects. Since the first trial in 1948, which related tobacco use with lung cancer, there have been more than 150,000 clinical trials to date in various areas (paediatrics, cardiology, oncology, endocrinology, etc.). This article highlights the importance for all physicians to participate, over the course of their professional career, in a clinical trial, due to the inherent benefits for patients, the progress of medicine and for curricular prestige. The authors have created a synthesis of their experience with clinical trials on hypertension, diabetes, dyslipidaemia and ischaemic heart disease over the course of almost 3 decades. Furthermore, a brief reference has been made to the characteristics of a phase I unit, as well as to a number of research studies currently underway. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  14. Pragmatic trial design elements showed a different impact on trial interpretation and feasibility than explanatory elements

    NARCIS (Netherlands)

    Nieuwenhuis, Joost B.; Irving, Elaine; Oude Rengerink, Katrien; Lloyd, Emily; Goetz, Iris; Grobbee, Diederick E.; Stolk, Pieter; Groenwold, Rolf H H; Zuidgeest, Mira G P

    2016-01-01

    OBJECTIVE: To illustrate how pragmatic trial design elements, or inserting explanatory trial elements in pragmatic trials affect validity, generalizability, precision and operational feasibility. STUDY DESIGN AND SETTING: From illustrative examples identified through the IMI Get Real Consortium, we

  15. Practical trials in medical education

    DEFF Research Database (Denmark)

    Tolsgaard, Martin G; Kulasegaram, Kulamakan M; Ringsted, Charlotte

    2017-01-01

    participants across several settings and (iii) multiple outcome measures with long-term follow-up to evaluate both benefits and risks. Questions posed by practical trials may be proactive in applying theory in the development of educational innovations or reactive to educational reforms and innovations. Non......CONTEXT: Concerns have been raised over the gap between education theory and practice and how research can contribute to inform decision makers on their choices and priorities. Little is known about how educational theories and research outcomes produced under optimal conditions in highly...... controlled settings generalise to the real-life education context. One way of bridging this gap is applying the concept of practical trials in medical education. In this paper we elaborate on characteristics of practical trials and based on examples from medical education we discuss the challenges...

  16. Adaptive designs in clinical trials

    Directory of Open Access Journals (Sweden)

    Suresh Bowalekar

    2011-01-01

    Full Text Available In addition to the expensive and lengthy process of developing a new medicine, the attrition rate in clinical research was on the rise, resulting in stagnation in the development of new compounds. As a consequence to this, the US Food and Drug Administration released a critical path initiative document in 2004, highlighting the need for developing innovative trial designs. One of the innovations suggested the use of adaptive designs for clinical trials. Thus, post critical path initiative, there is a growing interest in using adaptive designs for the development of pharmaceutical products. Adaptive designs are expected to have great potential to reduce the number of patients and duration of trial and to have relatively less exposure to new drug. Adaptive designs are not new in the sense that the task of interim analysis (IA/review of the accumulated data used in adaptive designs existed in the past too. However, such reviews/analyses of accumulated data were not necessarily planned at the stage of planning clinical trial and the methods used were not necessarily compliant with clinical trial process. The Bayesian approach commonly used in adaptive designs was developed by Thomas Bayes in the 18th century, about hundred years prior to the development of modern statistical methods by the father of modern statistics, Sir Ronald A. Fisher, but the complexity involved in Bayesian approach prevented its use in real life practice. The advances in the field of computer and information technology over the last three to four decades has changed the scenario and the Bayesian techniques are being used in adaptive designs in addition to other sequential methods used in IA. This paper attempts to describe the various adaptive designs in clinical trial and views of stakeholders about feasibility of using them, without going into mathematical complexities.

  17. Adaptive designs in clinical trials.

    Science.gov (United States)

    Bowalekar, Suresh

    2011-01-01

    In addition to the expensive and lengthy process of developing a new medicine, the attrition rate in clinical research was on the rise, resulting in stagnation in the development of new compounds. As a consequence to this, the US Food and Drug Administration released a critical path initiative document in 2004, highlighting the need for developing innovative trial designs. One of the innovations suggested the use of adaptive designs for clinical trials. Thus, post critical path initiative, there is a growing interest in using adaptive designs for the development of pharmaceutical products. Adaptive designs are expected to have great potential to reduce the number of patients and duration of trial and to have relatively less exposure to new drug. Adaptive designs are not new in the sense that the task of interim analysis (IA)/review of the accumulated data used in adaptive designs existed in the past too. However, such reviews/analyses of accumulated data were not necessarily planned at the stage of planning clinical trial and the methods used were not necessarily compliant with clinical trial process. The Bayesian approach commonly used in adaptive designs was developed by Thomas Bayes in the 18th century, about hundred years prior to the development of modern statistical methods by the father of modern statistics, Sir Ronald A. Fisher, but the complexity involved in Bayesian approach prevented its use in real life practice. The advances in the field of computer and information technology over the last three to four decades has changed the scenario and the Bayesian techniques are being used in adaptive designs in addition to other sequential methods used in IA. This paper attempts to describe the various adaptive designs in clinical trial and views of stakeholders about feasibility of using them, without going into mathematical complexities.

  18. The DiaS trial

    DEFF Research Database (Denmark)

    Andreasson, Kate; Krogh, Jesper; Rosenbaum, Bent

    2014-01-01

    BACKGROUND: In Denmark 8,000 to 10,000 people will attempt suicide each year. The Centre of Excellence in Suicide Prevention in the Capital Region of Denmark is treating patients with suicidal behavior, and a recent survey has shown that 30% of the patients are suffering from borderline personali...... measured at week 28. Other exploratory outcomes are included such as severity of symptoms, suicide intention and ideation, depression, hopelessness, self-esteem, impulsivity, anger, and duration of respective treatments. TRIAL REGISTRATION: Clinical Trial.gov: NCT01512602....

  19. Problematic trial detection in ClinicalTrials.gov

    NARCIS (Netherlands)

    Hartgerink, C.H.J.; George, Stephen

    2015-01-01

    Clinical trials are crucial in determining the effectiveness of treatments and directly affect clinical and policy decisions. These decisions are undermined if the data are problematic due to data fabrication or other errors. Researchers have worked on developing statistical methods to detect

  20. Trials by Juries: Suggested Practices for Database Trials

    Science.gov (United States)

    Ritterbush, Jon

    2012-01-01

    Librarians frequently utilize product trials to assess the content and usability of a database prior to committing funds to a new subscription or purchase. At the 2012 Electronic Resources and Libraries Conference in Austin, Texas, three librarians presented a panel discussion on their institutions' policies and practices regarding database…

  1. Evaluation Using Sequential Trials Methods.

    Science.gov (United States)

    Cohen, Mark E.; Ralls, Stephen A.

    1986-01-01

    Although dental school faculty as well as practitioners are interested in evaluating products and procedures used in clinical practice, research design and statistical analysis can sometimes pose problems. Sequential trials methods provide an analytical structure that is both easy to use and statistically valid. (Author/MLW)

  2. SARCOPENIA: DESIGNING PHASE IIB TRIALS

    Science.gov (United States)

    CHUMLEA, WM.C.; CESARI, M.; EVANS, W.J.; FERRUCCI, L.; FIELDING, R.A.; PAHOR, M.; STUDENSKI, S.; VELLAS, B.

    2012-01-01

    Sarcopenia is the age-related involuntary loss of skeletal muscle mass and functionality that can lead to the development of disability, frailty and increased health care costs. The development of interventions aimed at preventing and/or treating sarcopenia is complex, requiring the adoption of assumptions and standards that are not well established scientifically or clinically. A number of investigators and clinicians (both from academia and industry) met in Rome (Italy) in 2009 to develop a consensus definition of sarcopenia. Subsequently, in Albuquerque (New Mexico, USA) in 2010, the same group met again to consider the complex issues necessary for designing Phase II clinical trials for sarcopenia. Current clinical trial data indicate that fat-free mass (FFM) parameters are responsive to physical activity/nutritional treatment modalities over short time periods, but pharmacological trials of sarcopenia have yet to show significant efficacy. In order to conduct a clinical trial within a reasonable time frame, groups that model or display accelerated aging and loss of FFM are necessary. Few studies have used acceptable designs for testing treatment effects, sample sizes or primary outcomes that could provide interpretable findings or effects across studies. Dual energy x ray absorptiometry (DXA) is the measure of choice for assessing FFM, but sufficient time is needed for changes to be detected accurately and reliably. A tool set that would allow clinical, basic and epidemiological research on sarcopenia to advance rapidly toward diagnosis and treatment phases should be those reflecting function and strength. PMID:21623466

  3. The Best Bypass Surgery Trial

    DEFF Research Database (Denmark)

    Møller, Christian H; Jensen, Birte Østergaard; Gluud, Christian

    2007-01-01

    Recent trials suggest that off-pump coronary artery bypass grafting (OPCAB) reduces the risk of mortality and morbidity compared with conventional coronary artery bypass grafting (CCAB) using cardiopulmonary bypass. Patients with a moderate- to high-risk of complications after CCAB may have...

  4. Medical Editors Trial Amnesty (META)

    African Journals Online (AJOL)

    may change jobs, with the result that important work remains unfinished; or investigators may discover a recently published trial on the same topic and conclude that their own results are now redundant. Editors must also take some responsibility. There is a limit to the number of reports we can publish and sometimes we are ...

  5. [Lower Uterine Segment Trial: A pragmatic open multicenter randomized trial].

    Science.gov (United States)

    Rozenberg, P; Deruelle, P; Sénat, M-V; Desbrière, R; Winer, N; Simon, E; Ville, Y; Kayem, G; Boutron, I

    2018-04-01

    The data from literature show that trial of labor and elective repeat cesarean delivery after a prior cesarean delivery both present significant risks and benefits, and these risks and benefits differ for the woman and her fetus. The benefits to the woman can be at the expense of her fetus and vice-versa. This uncertainty is compounded by the scarcity of high-level evidence that preclude accurate quantification of the risks and benefits that could help provide a fair counseling about a trial of labor and elective repeat cesarean delivery. An interesting way of research is to evaluate the potential benefits of a decision rule associated to the ultrasound measurement of the lower uterine segment (LUS). Indeed, ultrasonography may be helpful in determining a specific risk for a given patient by measuring the thickness of the LUS, i,e, the thickness of the cesarean delivery scar area. Although only small and often methodologically biased data have been published, they look promising as their results are concordant: ultrasonographic measurements of the LUS thickness is highly correlated with the intraoperative findings at cesarean delivery. Furthermore, the thinner the LUS becomes on ultrasound, the higher the likelihood of a defect in the LUS. Finally, ultrasound assessment of LUS has an excellent negative predictive value for the risk of uterine defect. Therefore, this exam associated with a rule of decision could help to reduce the rate of elective repeat cesarean delivery and especially to reduce the fetal and maternal mortality and morbidity related to trial of labor after a prior cesarean delivery. This is a pragmatic open multicenter randomized trial with two parallel arms. Randomization will be centralized and computerized. Since blindness is impossible, an adjudication committee will evaluate the components of the primary composite outcome in order to avoid evaluation bias. An interim analysis will be planned mid-strength of the trial. Ultrasound will be

  6. [Principles of controlled clinical trials].

    Science.gov (United States)

    Martini, P

    1962-01-01

    The recovery of the patient should be facilitated as the result of therapeutic research. The basic rule for every therapeutic-clinical trial mist involve a comparison of therapeutic approaches. In acute conditions, such as acute infectious diseases, infarcts, etc., comparisons should be made between two or more groups: the collective therapeutic comparison = the between patients trial. The formation of groups, to be compared one with the other can be justified only if one is reasonably sure that a pathogenic condition indeed exists. In chronic diseases, which extend essentially unchanged over a lengthy period but are nevertheless reversible, therapeutic comparisons may be made between two or more time intervals within the course of the disease in the same individual. This type of therapeutic trial rests primarily upon a (refined!) type of specious reasoning and secondarily, upon modified statistics: the individual therapeutic comparison = the within patient trial. The collective therapeutic comparison, on the one hand, and the individual therapeutic comparison on the other, overlap somewhat in scope. The immediate therapeutic effect is not always an indication of its true value, which may become evident only upon long-term treatment. The short-term trials of therapeutic regimens in an individual must, therefore, be frequently supplemented by long-term trials which can only be carried out by comparing two groups. For many clinical investigations, therefore, the joint efforts of numerous hospitals are absolutely necessary. The second basic rule of therapeutic research is the elimination of secondary causes. The difficulties introduced by these secondary considerations are far greater in therapeutic trials carried out on ambulatory patients than has been hitherto realized. In order to remove subjective secondary causes, the author demanded, in 1931, the use of hidden or illusory media (placebos, dummies) that is, unconscious causative agents. The double blind

  7. HIV/AIDS Clinical Trials Fact Sheet

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Overview Home Understanding HIV/AIDS Fact Sheets HIV/ ... 4 p.m. ET) Send us an email HIV/AIDS Clinical Trials Last Reviewed: August 25, 2017 ...

  8. NCI National Clinical Trials Network Structure

    Science.gov (United States)

    Learn about how the National Clinical Trials Network (NCTN) is structured. The NCTN is a program of the National Cancer Institute that gives funds and other support to cancer research organizations to conduct cancer clinical trials.

  9. Clinical trials in neurology: design, conduct, analysis

    National Research Council Canada - National Science Library

    Ravina, Bernard

    2012-01-01

    .... Clinical Trials in Neurology aims to improve the efficiency of clinical trials and the development of interventions in order to enhance the development of new treatments for neurologic diseases...

  10. PUPTH Prehospital Air Medical Plasma (PAMP) Trial

    Science.gov (United States)

    2014-07-01

    for ability to continue. If unable to improve, they may be replaced . Two formal interim analyses of efficacy will be performed when 33% and 67% of...will be entered and maintained on a password protected SSL website designed for this trial. The data entered for the PAMPer trial will be...testing procedure for clinical trials. Biometrics , 1979. 35(3): p. 549‐56. 96. Murray, D.M., ed. The Design and Analysis of Group Randomized Trials

  11. Trial-to-Trial Fluctuations in Attentional State and Their Relation to Intelligence

    Science.gov (United States)

    Unsworth, Nash; McMillan, Brittany D.

    2014-01-01

    Trial-to-trial fluctuations in attentional state while performing measures of intelligence were examined in the current study. Participants performed various measures of fluid and crystallized intelligence while also providing attentional state ratings prior to each trial. It was found that pre-trial attentional state ratings strongly predicted…

  12. Interpreting clinical trial results by deductive reasoning: In search of improved trial design.

    Science.gov (United States)

    Kurbel, Sven; Mihaljević, Slobodan

    2017-10-01

    Clinical trial results are often interpreted by inductive reasoning, in a trial design-limited manner, directed toward modifications of the current clinical practice. Deductive reasoning is an alternative in which results of relevant trials are combined in indisputable premises that lead to a conclusion easily testable in future trials. © 2017 WILEY Periodicals, Inc.

  13. Trial Courts in the Judicial Process.

    Science.gov (United States)

    McKnight, R. Neal

    1981-01-01

    Describes a college course which examines the organizational and behavioral characteristics of trial courts in the American judicial process. A major course objective is to help students understand the trial court process as a political process by showing how trial court organizations are involved in the allocation of social values. (RM)

  14. Terrorists on Trial: A Performative Perspective

    NARCIS (Netherlands)

    de Graaf, B.A.

    On 30 March 2011, ICCT – The Hague organised an Expert Meeting entitled ‘Terrorism Trials as Theatre: A Performative Perspective’. The Expert Meeting applied a performative perspective to three well known and recent trials in different parts of the world: the trials against the Dutch Hofstad Group,

  15. Maximizing scientific knowledge from randomized clinical trials

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Atar, Dan; Pitt, Bertram

    2010-01-01

    Trialists have an ethical and financial responsibility to plan and conduct clinical trials in a manner that will maximize the scientific knowledge gained from the trial. However, the amount of scientific information generated by randomized clinical trials in cardiovascular medicine is highly vari...

  16. Spine device clinical trials: design and sponsorship.

    Science.gov (United States)

    Cher, Daniel J; Capobianco, Robyn A

    2015-05-01

    Multicenter prospective randomized clinical trials represent the best evidence to support the safety and effectiveness of medical devices. Industry sponsorship of multicenter clinical trials is purported to lead to bias. To determine what proportion of spine device-related trials are industry-sponsored and the effect of industry sponsorship on trial design. Analysis of data from a publicly available clinical trials database. Clinical trials of spine devices registered on ClinicalTrials.gov, a publicly accessible trial database, were evaluated in terms of design, number and location of study centers, and sample size. The relationship between trial design characteristics and study sponsorship was evaluated using logistic regression and general linear models. One thousand six hundred thrity-eight studies were retrieved from ClinicalTrials.gov using the search term "spine." Of the 367 trials that focused on spine surgery, 200 (54.5%) specifically studied devices for spine surgery and 167 (45.5%) focused on other issues related to spine surgery. Compared with nondevice trials, device trials were far more likely to be sponsored by the industry (74% vs. 22.2%, odds ratio (OR) 9.9 [95% confidence interval 6.1-16.3]). Industry-sponsored device trials were more likely multicenter (80% vs. 29%, OR 9.8 [4.8-21.1]) and had approximately four times as many participating study centers (pdevices not sponsored by the industry. Most device-related spine research is industry-sponsored. Multicenter trials are more likely to be industry-sponsored. These findings suggest that previously published studies showing larger effect sizes in industry-sponsored vs. nonindustry-sponsored studies may be biased as a result of failure to take into account the marked differences in design and purpose. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Elizabeth Waters

    2017-08-01

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

  18. Pediatric Obstructive Uropathy: Clinical Trials

    International Nuclear Information System (INIS)

    Chan, C. M. C.; Scheinman, J. I.; Roth, K. S.

    2005-01-01

    As the powerful tools of molecular biology continue to delineate new concepts of pathogenesis of diseases, new molecular-level therapeutic modalities are certain to emerge. In order to design and execute clinical trials to evaluate outcomes of these new treatment modalities, we will soon need a new supply of investigators with training and experience in clinical research. The slowly-progressive nature of chronic pediatric kidney disease often results in diagnosis being made at a time remote from initial result, and the inherently slow rate of progression makes changes difficult to measure. Thus, development of molecular markers for both diagnosis and rate of progression will be critical to studies of new therapeutic modalities. We will review general aspects of clinical trials and will use current and past studies as examples to illustrate specific points, especially as these apply to chronic kidney disease associated with obstructive uropathy in children. (author)

  19. GPON FTTH trial: lessons learned

    Science.gov (United States)

    Weis, Erik; Hölzl, Rainer; Breuer, Dirk; Lange, Christoph

    2009-11-01

    This paper reports on a FTTH field trial with GPON (Gigabit-capable passive optical network) technology in the network of Deutsche Telekom in the region of the cities of Berlin and Potsdam. Focus of this trial was to gain practical experience regarding GPON technology, fibre installation in existing ducts with micro duct technology, fibre cabling in customer buildings and impact on operational processes. Furthermore it is reported on an initial Deutsche Telekom FTTB deployment based on GPON technology in the city of Dresden with the main targets to obtain practical deployment and operation experiences with fibre-based access networks and to provide broadband access to a part of the city formerly not servable by DSL (digital subscriber line) technology.

  20. Accrual to Cancer Clinical Trials

    LENUS (Irish Health Repository)

    Kelly, C

    2016-07-01

    Accrual to cancer clinical trials (CCT) is imperative to safeguard continued improvement in cancer outcomes. A retrospective chart review was performed of patients (n=140) starting a new anti-cancer agent in a north Dublin cancer centre. This review was performed over a four-month period, beginning in November 2015. Only 29% (n=41) had a CCT option. The overall accrual rate to CCT was 5% (n=7), which is comparable to internationally reported figures. The main reasons for failure to recruit to CCT included the lack of a CCT option for cancer type (n=30, 23%), stage (n=25, 19%), and line of treatment (n=23, 17%). Over the last decade, the rate of accrual to CCTs has in fact doubled and the number of trials open to recruitment has tripled. Ongoing governmental and philanthropic support is necessary to continue this trend to further expand CCT patient options with a target accrual rate of 10%.

  1. Methodology series module 4: Clinical trials

    Directory of Open Access Journals (Sweden)

    Maninder Singh Setia

    2016-01-01

    Full Text Available In a clinical trial, study participants are (usually divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care. We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1 parallel study design, (2 cross-over design, (3 factorial design, and (4 withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials. Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an "open trial." However, many of the trials are not open - they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India.

  2. Methodology Series Module 4: Clinical Trials.

    Science.gov (United States)

    Setia, Maninder Singh

    2016-01-01

    In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an "open trial." However, many of the trials are not open - they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India.

  3. Credentialing for participation in clinical trials

    International Nuclear Information System (INIS)

    Followill, David S.; Urie, Marcia; Galvin, James M.; Ulin, Kenneth; Xiao, Ying; FitzGerald, Thomas J.

    2012-01-01

    The National Cancer Institute (NCI) clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence-based clinical trial processes for improvements in patient care. The cooperative groups are undergoing a transformation process to launch, conduct, and publish clinical trials more rapidly. Institutional participation in clinical trials can be made more efficient and include the expansion of relationships with international partners. This paper reviews the current processes that are in use in radiation therapy trials and the importance of maintaining effective credentialing strategies to assure the quality of the outcomes of clinical trials. The paper offers strategies to streamline and harmonize credentialing tools and processes moving forward as the NCI undergoes transformative change in the conduct of clinical trials.

  4. Credentialing for participation in clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Followill, David S. [Radiological Physics Center, Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Urie, Marcia [Quality Assurance Review Center, Department of Radiation Oncology, University of Massachusetts Medical School, Lincoln, RI (United States); Galvin, James M. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Radiation Therapy Oncology Group, Philadelphia, PA (United States); Ulin, Kenneth [Quality Assurance Review Center, Department of Radiation Oncology, University of Massachusetts Medical School, Lincoln, RI (United States); Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, MA (United States); Xiao, Ying [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Radiation Therapy Oncology Group, Philadelphia, PA (United States); FitzGerald, Thomas J., E-mail: dfollowi@mdanderson.org [Quality Assurance Review Center, Department of Radiation Oncology, University of Massachusetts Medical School, Lincoln, RI (United States); Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, MA (United States)

    2012-12-26

    The National Cancer Institute (NCI) clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence-based clinical trial processes for improvements in patient care. The cooperative groups are undergoing a transformation process to launch, conduct, and publish clinical trials more rapidly. Institutional participation in clinical trials can be made more efficient and include the expansion of relationships with international partners. This paper reviews the current processes that are in use in radiation therapy trials and the importance of maintaining effective credentialing strategies to assure the quality of the outcomes of clinical trials. The paper offers strategies to streamline and harmonize credentialing tools and processes moving forward as the NCI undergoes transformative change in the conduct of clinical trials.

  5. Clinical Trials in Noninfectious Uveitis

    Science.gov (United States)

    Kim, Jane S.; Knickelbein, Jared E.; Nussenblatt, Robert B.; Sen, H. Nida

    2015-01-01

    The treatment of noninfectious uveitis continues to remain a challenge for many ophthalmologists. Historically, clinical trials in uveitis have been sparse, and thus, most treatment decisions have largely been based on clinical experience and consensus guidelines. The current treatment paradigm favors initiation then tapering of corticosteroids with addition of steroid-sparing immunosuppressive agents for persistence or recurrence of disease. Unfortunately, in spite of a multitude of highly unfavorable systemic effects, corticosteroids are still regarded as the mainstay of treatment for many patients with chronic and refractory noninfectious uveitis. However, with the success of other conventional and biologic immunomodulatory agents in treating systemic inflammatory and autoimmune conditions, interest in targeted treatment strategies for uveitis has been renewed. Multiple clinical trials on steroid-sparing immunosuppressive agents, biologic agents, intraocular corticosteroid implants, and topical ophthalmic solutions have already been completed, and many more are ongoing. This review discusses the results and implications of these clinical trials investigating both alternative and novel treatment options for noninfectious uveitis. PMID:26035763

  6. Market Trials of Irradiated Spices

    International Nuclear Information System (INIS)

    Charoen, Saovapong; Eemsiri, Jaruratana; Sajjabut, Surasak

    2009-07-01

    Full text: The objectives of the experiment were to disseminate irradiated retail foods to the domestic publics and to test consumer acceptance on irradiated ground chilli and ground pepper. Market trials of irradiated ground chilli and ground pepper were carried out at 2 local markets and 4 in Bangkok and Nontaburi in 2005-2007. Before the start of the experiment, processing room, gamma irradiation room and labels of the products were approved by Food and Drug Administration, Thailand. 50 grams of irradiated products were packaged in plastic bags for the market trials. 688 and 738 bags of ground chilli and ground pepper were sold, respectively. Questionnaires distributed with the products were commented by 59 consumers and statistically analyzed by experimental data pass program. 88.1 and 91.4 percents of the consumers were satisfied with the quality and the price, respectively. 79.7% of the consumers chose to buy irradiated ground chilli and ground pepper because they believed that the quality of irradiated products were better than that of non-irradiated ones. 91.5% of the consumers would certainly buy irradiated chilli and pepper again. Through these market trials, it was found that all of the products were sold out and the majority of the consumers who returned the questionnaires was satisfied with the irradiated ground chilli and ground pepper and also had good attitude toward irradiated foods

  7. Clinical trials and gender medicine.

    Science.gov (United States)

    Cassese, Mariarita; Zuber, Veronica

    2011-01-01

    Women use more medicines than men because they fall ill more often and suffer more from chronic diseases, but also because women pay more attention to their health and have more consciousness and care about themselves. Although medicines can have different effects on women and men, women still represent a small percentage in the first phases of trials (22%) which are essential to verify drugs dosage, side effects, and safety. Even though women are more present in trials, studies results are not presented with a gender approach. This situation is due to educational, social, ethical and economical factors. The scientific research must increase feminine presence in clinical trials in order to be equal and correct, and all the key stakeholder should be involved in this process. We still have a long way to cover and it doesn't concern only women but also children and old people. The aim is to have a medicine not only illness-focused but patient-focused: a medicine able to take into consideration all the patient characteristics and so to produce a really personalized therapy. What above described is part of the reasons why in 2005 was founded the National Observatory for Women's Health (Osservatorio Nazionale sulla Salute della Donna, ONDa) which promotes a gender health awareness and culture in Italy, at all the levels of the civil and scientific society.

  8. Clinical trials and gender medicine

    Directory of Open Access Journals (Sweden)

    Mariarita Cassese

    2011-01-01

    Full Text Available Women use more medicines than men because they fall ill more often and suffer more from chronic diseases, but also because women pay more attention to their health and have more consciousness and care about themselves. Although medicines can have different effects on women and men, women still represent a small percentage in the first phases of trials (22% which are essential to verify drugs dosage, side effects, and safety. Even though women are more present in trials, studies results are not presented with a gender approach. This situation is due to educational, social, ethical and economical factors. The scientific research must increase feminine presence in clinical trials in order to be equal and correct, and all the key stakeholder should be involved in this process. We still have a long way to cover and it doesn't concern only women but also children and old people. The aim is to have a medicine not only illness-focused but patient-focused: a medicine able to take into consideration all the patient characteristics and so to produce a really personalized therapy. What above described is part of the reasons why in 2005 was founded the National Observatory for Women's Health (Osservatorio Nazionale sulla Salute della Donna, ONDa which promotes a gender health awareness and culture in Italy, at all the levels of the civil and scientific society.

  9. Informed consent in surgical trials.

    Science.gov (United States)

    Etchells, E

    1999-12-01

    All participants must provide a valid consent to surgical clinical trials. A valid consent requires patient capacity, adequate disclosure of information, and voluntariness. Capacity is the ability to understand information relevant to making a decision and to appreciate the reasonably foreseeable consequences of a decision or lack of decision. To protect vulnerable persons, an incapable person should not be enrolled in most clinical trials. The only exception is if the study can only be conducted on incapable persons. If the willing research participant is incapable, consent must be obtained from others through a process called substitute (or proxy) consent. Disclosure refers to the provision of relevant information to the patient and its comprehension by the patient. Most surgical trials carry more than minimal risks, so the requirement for careful disclosure of these risks to potential participants is generally stringent. Voluntariness refers to the freedom of a person to make a treatment decision. In specific circumstances related to emergency research, the requirement for consent may be waived. Waiver can be justified only if the delay required to obtain consent would prevent the research from occurring and only after prior consultation with from the "community" of potential research participants.

  10. Impact of a cancer clinical trials web site on discussions about trial participation: a cluster randomized trial.

    Science.gov (United States)

    Dear, R F; Barratt, A L; Askie, L M; Butow, P N; McGeechan, K; Crossing, S; Currow, D C; Tattersall, M H N

    2012-07-01

    Cancer patients want access to reliable information about currently recruiting clinical trials. Oncologists and their patients were randomly assigned to access a consumer-friendly cancer clinical trials web site [Australian Cancer Trials (ACT), www.australiancancertrials.gov.au] or to usual care in a cluster randomized controlled trial. The primary outcome, measured from audio recordings of oncologist-patient consultations, was the proportion of patients with whom participation in any clinical trial was discussed. Analysis was by intention-to-treat accounting for clustering and stratification. Thirty medical oncologists and 493 patients were recruited. Overall, 46% of consultations in the intervention group compared with 34% in the control group contained a discussion about clinical trials (P=0.08). The mean consultation length in both groups was 29 min (P=0.69). The proportion consenting to a trial was 10% in both groups (P=0.65). Patients' knowledge about randomized trials was lower in the intervention than the control group (mean score 3.0 versus 3.3, P=0.03) but decisional conflict scores were similar (mean score 42 versus 43, P=0.83). Good communication between patients and physicians is essential. Within this context, a web site such as Australian Cancer Trials may be an important tool to encourage discussion about clinical trial participation.

  11. Macular Morphology and Visual Acuity in the Second Year of the Comparison of Age-Related Macular Degeneration Treatments Trials.

    Science.gov (United States)

    Sharma, Sumit; Toth, Cynthia A; Daniel, Ebenezer; Grunwald, Juan E; Maguire, Maureen G; Ying, Gui-Shuang; Huang, Jiayan; Martin, Daniel F; Jaffe, Glenn J

    2016-04-01

    To describe the association between morphologic features on fundus photography (FP), fluorescein angiography (FA), and optical coherence tomography (OCT) and visual acuity (VA) in the second year of the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Prospective cohort study within a randomized clinical trial. Participants in the CATT. Study eye eligibility required angiographic and OCT evidence of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and VA between 20/25 and 20/320. Treatment was assigned randomly to ranibizumab or bevacizumab with 3 different dosing regimens over a 2-year period. Fluid type, location, and thickness; retina and subretinal tissue complex thickness on OCT; size and lesion composition on FP and FA; and VA. Among 1185 CATT participants, 993 (84%) had fluid on OCT at baseline and completed 2 years of follow-up. At 2 years, intraretinal fluid (IRF), subretinal fluid (SRF), sub-retinal pigment epithelium (RPE) fluid, and subretinal tissue complex thickness decreased in all treatment groups. Ranibizumab monthly was best able to resolve each type of fluid. Eyes with SRF in the foveal center on OCT had better mean VA than eyes with no SRF (72.8 vs. 66.6 letters; P = 0.006). Eyes with IRF in the foveal center had worse mean VA than eyes without IRF (59.9 vs. 70.9 letters; P 212 μm (59.4 vs. 71.3 vs. 70.3 letters; P < 0.0001). At 2 years, the mean VA (letters) of eyes varied substantially by the type of subfoveal pathology on FP and FA: 70.6 for no pathology; 74.1 for fluid only; 73.3 for CNV or pigment epithelial (RPE) detachment; 68.4 for nongeographic atrophy; and 62.9 for geographic atrophy, hemorrhage, RPE tear, or scar (P < 0.0001). The associations between VA and morphologic features identified through year 1 were maintained or strengthened during year 2. Eyes with foveal IRF, abnormally thin retina, greater thickness of the subretinal tissue complex on OCT, and subfoveal

  12. Physical activity and trial-by-trial adjustments of response conflict.

    Science.gov (United States)

    Kamijo, Keita; Takeda, Yuji

    2013-08-01

    The relationship of physical activity to trial-by-trial adjustments of response conflict was assessed using behavioral task performance, the N2 event-related brain potential component, and phase-locking values (PLVs) in a lower gamma band during a perceptual conflict task. Nineteen physically active and 19 inactive young adults (mean age = 21.3 years) performed a Navon task, using a global letter made up of local letters of either the same kind (congruent trials) or a different kind (incongruent trials). Findings revealed that active individuals exhibited smaller N2 amplitudes and greater PLVs on incongruent trials that were preceded by incongruent trials compared with those preceded by congruent trials. Such phenomena were not observed for inactive individuals. These results suggest that greater physical activity is associated with larger trial-by-trial adjustments of response conflict, which we attribute to upregulation of top-down cognitive control and reductions in response conflict.

  13. Microbicide clinical trial adherence: insights for introduction.

    Science.gov (United States)

    Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabether; McCormack, Sheena

    2013-04-08

    After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs.

  14. Critical concepts in adaptive clinical trials

    Directory of Open Access Journals (Sweden)

    Park JJH

    2018-03-01

    Full Text Available Jay JH Park,1 Kristian Thorlund,2,3 Edward J Mills2,3 1Department of Medicine, University of British Columbia, Vancouver, BC, Canada; 2Department of Health Research Methods, Evidence, and Impact (HEI, McMaster University, Hamilton, ON, Canada; 3The Bill and Melinda Gates Foundation, Seattle, WA, USA Abstract: Adaptive clinical trials are an innovative trial design aimed at reducing resources, decreasing time to completion and number of patients exposed to inferior interventions, and improving the likelihood of detecting treatment effects. The last decade has seen an increasing use of adaptive designs, particularly in drug development. They frequently differ importantly from conventional clinical trials as they allow modifications to key trial design components during the trial, as data is being collected, using preplanned decision rules. Adaptive designs have increased likelihood of complexity and also potential bias, so it is important to understand the common types of adaptive designs. Many clinicians and investigators may be unfamiliar with the design considerations for adaptive designs. Given their complexities, adaptive trials require an understanding of design features and sources of bias. Herein, we introduce some common adaptive design elements and biases and specifically address response adaptive randomization, sample size reassessment, Bayesian methods for adaptive trials, seamless trials, and adaptive enrichment using real examples. Keywords: adaptive designs, response adaptive randomization, sample size reassessment, Bayesian adaptive trials, seamless trials, adaptive enrichment

  15. Where are clinical trials going? Society and clinical trials.

    Science.gov (United States)

    Sleight, P

    2004-02-01

    Clinical trials now increasingly impinge on society at large. First there is growing emphasis from health organizations on the need for unbiased evidence about the effectiveness of promoted remedies. Second, as most novel treatments accrue increased costs to society, these need to be evaluated in terms of value for money. Third, there has been confusion and concern about the resolution of conflicting evidence, especially the role of advertising and commercial pressures from a powerful pharmaceutical industry motivated by profit. Fourth, there is concern about research fraud and the ethics of clinical trials. Fifth, there is increasing suspicion of political advice, which sometimes has sought to reassure an anxious public on the basis of complex and possibly inadequate scientific information. Some of these issues are addressed by truly independent and properly constituted data and safety monitoring committees, which are of particular importance when academic investigators or universities have a large financial conflict of interest. This is now more problematic with the current encouragement of investigator-led spin-off companies. These issues are best resolved by independent financial support (from government or other institutions) rather than relying on the commercial sponsor.

  16. Predictive value of diminutive colonic adenoma trial: the PREDICT trial.

    Science.gov (United States)

    Schoenfeld, Philip; Shad, Javaid; Ormseth, Eric; Coyle, Walter; Cash, Brooks; Butler, James; Schindler, William; Kikendall, Walter J; Furlong, Christopher; Sobin, Leslie H; Hobbs, Christine M; Cruess, David; Rex, Douglas

    2003-05-01

    Diminutive adenomas (1-9 mm in diameter) are frequently found during colon cancer screening with flexible sigmoidoscopy (FS). This trial assessed the predictive value of these diminutive adenomas for advanced adenomas in the proximal colon. In a multicenter, prospective cohort trial, we matched 200 patients with normal FS and 200 patients with diminutive adenomas on FS for age and gender. All patients underwent colonoscopy. The presence of advanced adenomas (adenoma >or= 10 mm in diameter, villous adenoma, adenoma with high grade dysplasia, and colon cancer) and adenomas (any size) was recorded. Before colonoscopy, patients completed questionnaires about risk factors for adenomas. The prevalence of advanced adenomas in the proximal colon was similar in patients with diminutive adenomas and patients with normal FS (6% vs. 5.5%, respectively) (relative risk, 1.1; 95% confidence interval [CI], 0.5-2.6). Diminutive adenomas on FS did not accurately predict advanced adenomas in the proximal colon: sensitivity, 52% (95% CI, 32%-72%); specificity, 50% (95% CI, 49%-51%); positive predictive value, 6% (95% CI, 4%-8%); and negative predictive value, 95% (95% CI, 92%-97%). Male gender (odds ratio, 1.63; 95% CI, 1.01-2.61) was associated with an increased risk of proximal colon adenomas. Diminutive adenomas on sigmoidoscopy may not accurately predict advanced adenomas in the proximal colon.

  17. Gatekeepers for pragmatic clinical trials.

    Science.gov (United States)

    Whicher, Danielle M; Miller, Jennifer E; Dunham, Kelly M; Joffe, Steven

    2015-10-01

    To successfully implement a pragmatic clinical trial, investigators need access to numerous resources, including financial support, institutional infrastructure (e.g. clinics, facilities, staff), eligible patients, and patient data. Gatekeepers are people or entities who have the ability to allow or deny access to the resources required to support the conduct of clinical research. Based on this definition, gatekeepers relevant to the US clinical research enterprise include research sponsors, regulatory agencies, payers, health system and other organizational leadership, research team leadership, human research protections programs, advocacy and community groups, and clinicians. This article provides a framework to help guide gatekeepers' decision-making related to the use of resources for pragmatic clinical trials. Relevant ethical considerations for gatekeepers include (1) concern for the interests of individuals, groups, and communities affected by the gatekeepers' decisions, including protection from harm and maximization of benefits; (2) advancement of organizational mission and values; and (3) stewardship of financial, human, and other organizational resources. Separate from these ethical considerations, gatekeepers' actions will be guided by relevant federal, state, and local regulations. This framework also suggests that to further enhance the legitimacy of their decision-making, gatekeepers should adopt transparent processes that engage relevant stakeholders when feasible and appropriate. We apply this framework to the set of gatekeepers responsible for making decisions about resources necessary for pragmatic clinical trials in the United States, describing the relevance of the criteria in different situations and pointing out where conflicts among the criteria and relevant regulations may affect decision-making. Recognition of the complex set of considerations that should inform decision-making will guide gatekeepers in making justifiable choices regarding

  18. Center-Within-Trial Versus Trial-Level Evaluation of Surrogate Endpoints

    Science.gov (United States)

    Renfro, Lindsay A.; Shi, Qian; Xue, Yuan; Li, Junlong; Shang, Hongwei; Sargent, Daniel J.

    2014-01-01

    Evaluation of candidate surrogate endpoints using individual patient data from multiple clinical trials is considered the gold standard approach to validate surrogates at both patient and trial levels. However, this approach assumes the availability of patient-level data from a relatively large collection of similar trials, which may not be possible to achieve for a given disease application. One common solution to the problem of too few similar trials involves performing trial-level surrogacy analyses on trial sub-units (e.g., centers within trials), thereby artificially increasing the trial-level sample size for feasibility of the multi-trial analysis. To date, the practical impact of treating trial sub-units (centers) identically to trials in multi-trial surrogacy analyses remains unexplored, and conditions under which this ad hoc solution may in fact be reasonable have not been identified. We perform a simulation study to identify such conditions, and demonstrate practical implications using a multi-trial dataset of patients with early stage colon cancer. PMID:25061255

  19. OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of rehabilitation interventions for osteoarthritis.

    Science.gov (United States)

    Fitzgerald, G K; Hinman, R S; Zeni, J; Risberg, M A; Snyder-Mackler, L; Bennell, K L

    2015-05-01

    A Task Force of the Osteoarthritis Research Society International (OARSI) has previously published a set of guidelines for the conduct of clinical trials in osteoarthritis (OA) of the hip and knee. Limited material available on clinical trials of rehabilitation in people with OA has prompted OARSI to establish a separate Task Force to elaborate guidelines encompassing special issues relating to rehabilitation of OA. The Task Force identified three main categories of rehabilitation clinical trials. The categories included non-operative rehabilitation trials, post-operative rehabilitation trials, and trials examining the effectiveness of devices (e.g., assistive devices, bracing, physical agents, electrical stimulation, etc.) that are used in rehabilitation of people with OA. In addition, the Task Force identified two main categories of outcomes in rehabilitation clinical trials, which include outcomes related to symptoms and function, and outcomes related to disease modification. The guidelines for rehabilitation clinical trials provided in this report encompass these main categories. The report provides guidelines for conducting and reporting on randomized clinical trials. The topics include considerations for entering patients into trials, issues related to conducting trials, considerations for selecting outcome measures, and recommendations for statistical analyses and reporting of results. The focus of the report is on rehabilitation trials for hip, knee and hand OA, however, we believe the content is broad enough that it could be applied to rehabilitation trials for other regions as well. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  20. Trial publication after registration in ClinicalTrials.Gov: a cross-sectional analysis.

    Directory of Open Access Journals (Sweden)

    Joseph S Ross

    2009-09-01

    Full Text Available ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication.We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515, nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46% of trials were published, among which 96 (31% provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357 were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001, but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22. Among trials that reported an end date, 75 of 123 (61% completed prior to 2004, 50 of 96 (52% completed during 2004, and 62 of 149 (42% completed during 2005 were published (p = 0.006.Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low. Without greater attention to reporting of all data

  1. Strategies to improve retention in randomised trials

    Science.gov (United States)

    Brueton, Valerie C; Tierney, Jayne; Stenning, Sally; Harding, Seeromanie; Meredith, Sarah; Nazareth, Irwin; Rait, Greta

    2013-01-01

    Background Loss to follow-up from randomised trials can introduce bias and reduce study power, affecting the generalisability, validity and reliability of results. Many strategies are used to reduce loss to follow-up and improve retention but few have been formally evaluated. Objectives To quantify the effect of strategies to improve retention on the proportion of participants retained in randomised trials and to investigate if the effect varied by trial strategy and trial setting. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PreMEDLINE, EMBASE, PsycINFO, DARE, CINAHL, Campbell Collaboration's Social, Psychological, Educational and Criminological Trials Register, and ERIC. We handsearched conference proceedings and publication reference lists for eligible retention trials. We also surveyed all UK Clinical Trials Units to identify further studies. Selection criteria We included eligible retention trials of randomised or quasi-randomised evaluations of strategies to increase retention that were embedded in 'host' randomised trials from all disease areas and healthcare settings. We excluded studies aiming to increase treatment compliance. Data collection and analysis We contacted authors to supplement or confirm data that we had extracted. For retention trials, we recorded data on the method of randomisation, type of strategy evaluated, comparator, primary outcome, planned sample size, numbers randomised and numbers retained. We used risk ratios (RR) to evaluate the effectiveness of the addition of strategies to improve retention. We assessed heterogeneity between trials using the Chi2 and I2 statistics. For main trials that hosted retention trials, we extracted data on disease area, intervention, population, healthcare setting, sequence generation and allocation concealment. Main results We identified 38 eligible retention trials. Included trials evaluated six broad types of strategies to improve retention. These

  2. Single-Trial Inference on Visual Attention

    DEFF Research Database (Denmark)

    Dyrholm, Mads; Kyllingsbæk, Søren; Vangkilde, Signe Allerup

    2011-01-01

    In this paper we take a step towards single-trial behavioral modeling within a Theory of Visual Attention (TVA). In selective attention tasks, such as the Partial Report paradigm, the subject is asked to ignore distractors and only report stimuli that belong to the target class. Nothing about...... Report trial. This result retrodicts a latent attentional state of the subject using the observed response from that particular trial and thus differs from other predictions made with TVA which are based on expected values of observed variables. We show an example of the result in single-trial analysis...

  3. Power analysis of trials with multilevel data

    CERN Document Server

    Moerbeek, Mirjam

    2015-01-01

    Power Analysis of Trials with Multilevel Data covers using power and sample size calculations to design trials that involve nested data structures. The book gives a thorough overview of power analysis that details terminology and notation, outlines key concepts of statistical power and power analysis, and explains why they are necessary in trial design. It guides you in performing power calculations with hierarchical data, which enables more effective trial design.The authors are leading experts in the field who recognize that power analysis has attracted attention from applied statisticians i

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

    Science.gov (United States)

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

    2017-08-03

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

  5. Inactive trials of transport systems

    International Nuclear Information System (INIS)

    Haberlin, M.M.; Hardy, A.R.

    1985-06-01

    The design and manufacture of a mock-up of a crate handling and size reduction (CHSR) facility, an experimental programme on the evaluation of a commercial air-transporter, and the selection, manufacture and commissioning trials of an integrated conveyor system for transporting crated waste into and within the mock-up facility, are considered. The mock-up facility was used for the test programme on the air-transporter and conveyor system. The air-transporter was considered suitable for transporting waste on the metal floor in the main dismantling area of the CHSR facility because it can tolerate asymmetric loading, the exhaust air flow liberated from the air-pads is low and it has excellent manoeuvrability. Commissioning trials were carried out on a commercial conveyor system consisting of unpowered rollers in the reception area, a powered slatted conveyor in the air-lock and an unpowered roller table placed on the air-transporter in the working area. It was demonstrated that a large asymmetrically loaded wooden crate can be transported into and within the facility by this method. Further design and experimental work necessary before the system can be used for remote operation is discussed. (author)

  6. The L'Aquila trial

    Science.gov (United States)

    Amato, Alessandro; Cocco, Massimo; Cultrera, Giovanna; Galadini, Fabrizio; Margheriti, Lucia; Nostro, Concetta; Pantosti, Daniela

    2013-04-01

    The first step of the trial in L'Aquila (Italy) ended with a conviction of a group of seven experts to 6 years of jail and several million euros refund for the families of the people who died during the Mw 6.3 earthquake on April 6, 2009. This verdict has a tremendous impact on the scientific community as well as on the way in which scientists deliver their expert opinions to decision makers and society. In this presentation, we describe the role of scientists in charge of releasing authoritative information concerning earthquakes and seismic hazard and the conditions that led to the verdict, in order to discuss whether this trial represented a prosecution to science, and if errors were made in communicating the risk. Documents, articles and comments about the trial are collected in the web site http://processoaquila.wordpress.com/. We will first summarize what was the knowledge about the seismic hazard of the region and the vulnerability of L'Aquila before the meeting of the National Commission for Forecasting and Predicting Great Risks (CGR) held 6 days before the main shock. The basic point of the accusation is that the CGR suggested that no strong earthquake would have occurred (which of course was never mentioned by any seismologist participating to the meeting). This message would have convinced the victims to stay at home, instead of moving out after the M3.9 and M3.5 earthquakes few hours before the mainshock. We will describe how the available scientific information was passed to the national and local authorities, and in general how the Italian scientific Institution in charge of seismic monitoring and research (INGV), the Civil Protection Department (DPC) and the CGR should interact according to the law. As far as the communication and outreach to the public, the scientific Institutions as INGV have the duty to communicate scientific information. Instead, the risk management and the definition of actions for risk reduction is in charge of Civil

  7. Comparison of reporting phase I trial results in ClinicalTrials.gov and matched publications.

    Science.gov (United States)

    Shepshelovich, D; Goldvaser, H; Wang, L; Abdul Razak, A R; Bedard, P L

    2017-12-01

    Background Data on completeness of reporting of phase I cancer clinical trials in publications are lacking. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching primary publications published prior to November 1, 2016. Reporting in primary publications was compared with the ClinicalTrials.gov database using a 28-point score (2=complete; 1=partial; 0=no reporting) for 14 items related to study design, outcome measures and safety profile. Inconsistencies between primary publications and ClinicalTrials.gov were recorded. Linear regression was used to identify factors associated with incomplete reporting. Results After a review of 583 trials in ClinicalTrials.gov , 163 matching primary publications were identified. Publications reported outcomes that did not appear in ClinicalTrials.gov in 25% of trials. Outcomes were upgraded, downgraded or omitted in publications in 47% of trials. The overall median reporting score was 23/28 (interquartile range 21-25). Incompletely reported items in >25% publications were: inclusion criteria (29%), primary outcome definition (26%), secondary outcome definitions (53%), adverse events (71%), serious adverse events (80%) and dates of study start and database lock (91%). Higher reporting scores were associated with phase I (vs phase I/II) trials (ppublication in journals with lower impact factor (p=0.004). Conclusions Reported results in primary publications for early phase cancer trials are frequently inconsistent or incomplete compared with ClinicalTrials.gov entries. ClinicalTrials.gov may provide more comprehensive data from new cancer drug trials.

  8. Trial Sequential Methods for Meta-Analysis

    Science.gov (United States)

    Kulinskaya, Elena; Wood, John

    2014-01-01

    Statistical methods for sequential meta-analysis have applications also for the design of new trials. Existing methods are based on group sequential methods developed for single trials and start with the calculation of a required information size. This works satisfactorily within the framework of fixed effects meta-analysis, but conceptual…

  9. Challenges in conducting clinical trials in nephrology

    DEFF Research Database (Denmark)

    Baigent, Colin; Herrington, William G; Coresh, Josef

    2017-01-01

    Despite the high costs of treatment of people with kidney disease and associated comorbid conditions, the amount of reliable information available to guide the care of such patients is very limited. Some treatments have been assessed in randomized trials, but most such trials have been too small ...

  10. Blinded trials taken to the test

    DEFF Research Database (Denmark)

    Hróbjartsson, A; Forfang, E; Haahr, M T

    2007-01-01

    Blinding can reduce bias in randomized clinical trials, but blinding procedures may be unsuccessful. Our aim was to assess how often randomized clinical trials test the success of blinding, the methods involved and how often blinding is reported as being successful....

  11. RTOG: Updated results of randomized trials

    International Nuclear Information System (INIS)

    Curran, Walter J.

    1997-01-01

    Objective: To review the background, rationale and available results for recently completed randomized comparative clinical trials of the Radiation Therapy Oncology Group (RTOG), including inter group trials in which the RTOG has been the managing group or a major participant. When available, laboratory studies will be correlated with clinical results

  12. Clinical Trials Management | Division of Cancer Prevention

    Science.gov (United States)

    Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials. Protocol Information Office The central clearinghouse for clinical trials management within the Division of Cancer Prevention.Read more about the Protocol Information Office. | Information for researchers about developing, reporting, and managing NCI-funded

  13. Controversy, Trials, and Crime--Oh My!

    Science.gov (United States)

    Rott, Kim

    2006-01-01

    Teenagers' innate interest with the justice system is one of the reasons that so many high school literary classics teem with criminals, controversial issues, and trials. Novels such as "To Kill a Mockingbird," "A Separate Peace," "The Crucible," and "Twelve Angry Men" feature high-impact trials. In the author's desire to tap into this interest,…

  14. Alien wavelength modeling tool and field trial

    DEFF Research Database (Denmark)

    Sambo, N.; Sgambelluri, A.; Secondini, M.

    2015-01-01

    A modeling tool is presented for pre-FEC BER estimation of PM-QPSK alien wavelength signals. A field trial is demonstrated and used as validation of the tool's correctness. A very close correspondence between the performance of the field trial and the one predicted by the modeling tool has been...

  15. Maximizing scientific knowledge from randomized clinical trials

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Atar, Dan; Pitt, Bertram

    2010-01-01

    , in particular with respect to collaboration with the trial sponsor and to analytic pitfalls. The advantages of creating screening databases in conjunction with a given clinical trial are described; and finally, the potential for posttrial database studies to become a platform for training young scientists...

  16. The Eichmann Trial on East German Television

    NARCIS (Netherlands)

    Keilbach, Judith

    2014-01-01

    abstractThe trial against Adolf Eichmann was one of the first transnational media events on television. Its world-wide coverage required transnational cooperation. Using East German television reports about the trial this article argues that although the event transcended national borders it

  17. The Eichmann Trial on East German Television

    Directory of Open Access Journals (Sweden)

    Judith Keilbach

    2014-06-01

    Full Text Available The trial against Adolf Eichmann was one of the first transnational media events on television. Its world-wide coverage required transnational cooperation. Using East German television reports about the trial this article argues that although the event transcended national borders it maintained at the same time ideological boundaries.

  18. Internet trials: participant experiences and perspectives.

    Science.gov (United States)

    Mathieu, Erin; Barratt, Alexandra; Carter, Stacy M; Jamtvedt, Gro

    2012-10-23

    Use of the Internet to conduct randomised controlled trials is increasing, and provides potential to increase equity of access to medical research, increase the generalisability of trial results and decrease the costs involved in conducting large scale trials. Several studies have compared response rates, completeness of data, and reliability of surveys using the Internet and traditional methods, but very little is known about participants' attitudes towards Internet-based randomised trials or their experience of participating in an Internet-based trial. To obtain insights into the experiences and perspectives of participants in an Internet-based randomised controlled trial, their attitudes to the use of the Internet to conduct medical research, and their intentions regarding future participation in Internet research. All English speaking participants in a recently completed Internet randomised controlled trial were invited to participate in an online survey. 1246 invitations were emailed. 416 participants completed the survey between May and October 2009 (33% response rate). Reasons given for participating in the Internet RCT fell into 4 main areas: personal interest in the research question and outcome, ease of participation, an appreciation of the importance of research and altruistic reasons. Participants' comments and reflections on their experience of participating in a fully online trial were positive and less than half of participants would have participated in the trial had it been conducted using other means of data collection. However participants identified trade-offs between the benefits and downsides of participating in Internet-based trials. The main trade-off was between flexibility and convenience - a perceived benefit - and a lack connectedness and understanding - a perceived disadvantage. The other tradeoffs were in the areas of: ease or difficulty in use of the Internet; security, privacy and confidentiality issues; perceived benefits and

  19. Terrorists on Trial: A Performative Perspective

    Directory of Open Access Journals (Sweden)

    Beatrice de Graaf

    2011-03-01

    Full Text Available On 30 March 2011, ICCT organised an Expert Meeting entitled “Terrorism Trials as Theatre: A Performative Perspective”. The Expert Meeting applied a performative perspective to three well known and recent trials in different parts of the world: the trials against the Dutch Hofstad Group, the Mumbai 2008 Terrorist Attack Trial and the Guantanamo Military Tribunals. As such, the Expert Meeting did not concentrate solely on the immediate judicial performance of the magistrates and/or the defence; instead, the trials were put in their wider sociological context, adopting notions of social drama and communication sciences. This Expert Meeting Paper is a further adaptation of the Discussion Paper that was used as basis for debate during the Meeting.

  20. Strategies to improve recruitment to randomised trials.

    Science.gov (United States)

    Treweek, Shaun; Pitkethly, Marie; Cook, Jonathan; Fraser, Cynthia; Mitchell, Elizabeth; Sullivan, Frank; Jackson, Catherine; Taskila, Tyna K; Gardner, Heidi

    2018-02-22

    Recruiting participants to trials can be extremely difficult. Identifying strategies that improve trial recruitment would benefit both trialists and health research. To quantify the effects of strategies for improving recruitment of participants to randomised trials. A secondary objective is to assess the evidence for the effect of the research setting (e.g. primary care versus secondary care) on recruitment. We searched the Cochrane Methodology Review Group Specialised Register (CMR) in the Cochrane Library (July 2012, searched 11 February 2015); MEDLINE and MEDLINE In Process (OVID) (1946 to 10 February 2015); Embase (OVID) (1996 to 2015 Week 06); Science Citation Index & Social Science Citation Index (ISI) (2009 to 11 February 2015) and ERIC (EBSCO) (2009 to 11 February 2015). Randomised and quasi-randomised trials of methods to increase recruitment to randomised trials. This includes non-healthcare studies and studies recruiting to hypothetical trials. We excluded studies aiming to increase response rates to questionnaires or trial retention and those evaluating incentives and disincentives for clinicians to recruit participants. We extracted data on: the method evaluated; country in which the study was carried out; nature of the population; nature of the study setting; nature of the study to be recruited into; randomisation or quasi-randomisation method; and numbers and proportions in each intervention group. We used a risk difference to estimate the absolute improvement and the 95% confidence interval (CI) to describe the effect in individual trials. We assessed heterogeneity between trial results. We used GRADE to judge the certainty we had in the evidence coming from each comparison. We identified 68 eligible trials (24 new to this update) with more than 74,000 participants. There were 63 studies involving interventions aimed directly at trial participants, while five evaluated interventions aimed at people recruiting participants. All studies were in