11 results on '"iAMD"'
Search Results
2. Biomarkers for the Progression of Intermediate Age-Related Macular Degeneration
- Author
-
Eleonora M. Lad, Robert P. Finger, and Robyn Guymer
- Subjects
Age-related macular degeneration ,Biomarkers ,iAMD ,Geographic atrophy ,Neovascular AMD ,Ophthalmology ,RE1-994 - Abstract
Abstract Age-related macular degeneration (AMD) is a leading cause of severe vision loss worldwide, with a global prevalence that is predicted to substantially increase. Identifying early biomarkers indicative of progression risk will improve our ability to assess which patients are at greatest risk of progressing from intermediate AMD (iAMD) to vision-threatening late-stage AMD. This is key to ensuring individualized management and timely intervention before substantial structural damage. Some structural biomarkers suggestive of AMD progression risk are well established, such as changes seen on color fundus photography and more recently optical coherence tomography (drusen volume, pigmentary abnormalities). Emerging biomarkers identified through multimodal imaging, including reticular pseudodrusen, hyperreflective foci, and drusen sub-phenotypes, are being intensively explored as risk factors for progression towards late-stage disease. Other structural biomarkers merit further research, such as ellipsoid zone reflectivity and choriocapillaris flow features. The measures of visual function that best detect change in iAMD and correlate with risk of progression remain under intense investigation, with tests such as dark adaptometry and cone-specific contrast tests being explored. Evidence on blood and plasma markers is preliminary, but there are indications that changes in levels of C-reactive protein and high-density lipoprotein cholesterol may be used to stratify patients and predict risk. With further research, some of these biomarkers may be used to monitor progression. Emerging artificial intelligence methods may help evaluate and validate these biomarkers; however, until we have large and well-curated longitudinal data sets, using artificial intelligence effectively to inform clinical trial design and detect outcomes will remain challenging. This is an exciting area of intense research, and further work is needed to establish the most promising biomarkers for disease progression and their use in clinical care and future trials. Ultimately, a multimodal approach may yield the most accurate means of monitoring and predicting future progression towards vision-threatening, late-stage AMD.
- Published
- 2023
- Full Text
- View/download PDF
3. Biomarkers for the Progression of Intermediate Age-Related Macular Degeneration.
- Author
-
Lad, Eleonora M., Finger, Robert P., and Guymer, Robyn
- Subjects
MACULAR degeneration ,EYE diseases ,HDL cholesterol ,VISION testing ,OPTICAL coherence tomography ,CLINICAL trials monitoring ,EXPERIMENTAL design ,VISION - Abstract
Age-related macular degeneration (AMD) is a leading cause of severe vision loss worldwide, with a global prevalence that is predicted to substantially increase. Identifying early biomarkers indicative of progression risk will improve our ability to assess which patients are at greatest risk of progressing from intermediate AMD (iAMD) to vision-threatening late-stage AMD. This is key to ensuring individualized management and timely intervention before substantial structural damage. Some structural biomarkers suggestive of AMD progression risk are well established, such as changes seen on color fundus photography and more recently optical coherence tomography (drusen volume, pigmentary abnormalities). Emerging biomarkers identified through multimodal imaging, including reticular pseudodrusen, hyperreflective foci, and drusen sub-phenotypes, are being intensively explored as risk factors for progression towards late-stage disease. Other structural biomarkers merit further research, such as ellipsoid zone reflectivity and choriocapillaris flow features. The measures of visual function that best detect change in iAMD and correlate with risk of progression remain under intense investigation, with tests such as dark adaptometry and cone-specific contrast tests being explored. Evidence on blood and plasma markers is preliminary, but there are indications that changes in levels of C-reactive protein and high-density lipoprotein cholesterol may be used to stratify patients and predict risk. With further research, some of these biomarkers may be used to monitor progression. Emerging artificial intelligence methods may help evaluate and validate these biomarkers; however, until we have large and well-curated longitudinal data sets, using artificial intelligence effectively to inform clinical trial design and detect outcomes will remain challenging. This is an exciting area of intense research, and further work is needed to establish the most promising biomarkers for disease progression and their use in clinical care and future trials. Ultimately, a multimodal approach may yield the most accurate means of monitoring and predicting future progression towards vision-threatening, late-stage AMD. Plain Language Summary: Age-related macular degeneration, or AMD, is an eye disease that causes vision loss. Worldwide, the number of people with AMD is increasing. It is difficult for doctors to know who, among those with AMD, will get worse and lose some of their sight, and who will not. Researchers are trying to find early signs that predict whether AMD will get worse and ways to track AMD progression over time. These signs are known as "biomarkers." They can be structural (seen in the structures inside the eye), functional (a change in how well someone sees), genetic, or proteins found in the blood. Being able to identify people with AMD that are most at risk of losing their vision will help to make sure they get more frequent review so that interventions can be started quickly before vision is lost permanently. Some structural and functional biomarkers are already well known, while others may be useful and are being intensively researched. Changes in the blood markers need much more research to be useful. Researchers are also looking at how to combine data from different biomarkers. This may be a better way to follow worsening of AMD over time compared to using a single biomarker. In the future, we may also be able to use artificial intelligence to help combine all biomarker data. This is an exciting area of research that will be important to help improve the vision outcomes for people with AMD. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
4. Plasma Metabolomics of Intermediate and Neovascular Age-Related Macular Degeneration Patients
- Author
-
Sabrina L. Mitchell, Chunyu Ma, William K. Scott, Anita Agarwal, Margaret A. Pericak-Vance, Jonathan L. Haines, Dean P. Jones, Karan Uppal, and Milam A. Brantley
- Subjects
age-related macular degeneration ,IAMD ,NVAMD ,metabolomics ,acylcarnitines ,carnitine shuttle ,Cytology ,QH573-671 - Abstract
To characterize metabolites and metabolic pathways altered in intermediate and neovascular age-related macular degeneration (IAMD and NVAMD), high resolution untargeted metabolomics was performed via liquid chromatography-mass spectrometry on plasma samples obtained from 91 IAMD patients, 100 NVAMD patients, and 195 controls. Plasma metabolite levels were compared between: AMD patients and controls, IAMD patients and controls, and NVAMD and IAMD patients. Partial least-squares discriminant analysis and linear regression were used to identify discriminatory metabolites. Pathway analysis was performed to determine metabolic pathways altered in AMD. Among the comparisons, we identified 435 unique discriminatory metabolic features. Using computational methods and tandem mass spectrometry, we identified 11 metabolic features whose molecular identities had been previously verified and confirmed the molecular identities of three additional discriminatory features. Included among the discriminatory metabolites were acylcarnitines, phospholipids, amino acids, and steroid metabolites. Pathway analysis revealed that lipid, amino acid, and vitamin metabolism pathways were altered in NVAMD, IAMD, or AMD in general, including the carnitine shuttle pathway which was significantly altered in all comparisons. Finally, few discriminatory features were identified between IAMD patients and controls, suggesting that plasma metabolic profiles of IAMD patients are more similar to controls than to NVAMD patients.
- Published
- 2021
- Full Text
- View/download PDF
5. Deutschlands schwache Führungsrolle bei der europäischen Luftverteidigung
- Author
-
Arnold, Sven, Arnold, Torben, and Stiftung Wissenschaft und Politik -SWP- Deutsches Institut für Internationale Politik und Sicherheit
- Subjects
air force ,Politikwissenschaft ,Friedens- und Konfliktforschung, Sicherheitspolitik ,Peace and Conflict Research, International Conflicts, Security Policy ,Federal Republic of Germany ,IAMD ,Luftwaffe ,Sicherheitspolitik ,SAMP/T ,Luftverteidigung ,Luftverteidigungseinheiten ,Militärische Stärke, materiell ,Militärische Stärke, personell ,Neue Waffen/neues Gerät ,Modernisierung von Waffen/Waffensystemen ,Einsatzkonzeption für Waffensysteme ,Einsatzkonzeption für Streitkräfte ,security policy ,Deutschlands Führungsrolle ,Patriot ,European Sky Shield Initiative ,Arrow 3 ,defense policy ,European cooperation ,Political science ,military ,Militär ,Verteidigungspolitik ,THAAD ,IRIS-T ,Bundesrepublik Deutschland ,europäische Zusammenarbeit ,neue Technologie ,ddc:320 ,new technology ,europäische Luftverteidigung ,EU - Abstract
Mit der European Sky Shield Initiative hat Deutschland seinen Führungsanspruch bei der europäischen Luftverteidigung angemeldet. Verteidigung gemeinsam zu denken ist begrüßenswert, aber schwierig umzusetzen. Wichtige europäische Partner, allen voran Frankreich und Italien, sind derzeit nicht gewillt, Deutschland zu folgen. Die fehlende politische Einigkeit zeigt, dass der deutsche Vorstoß die europäischen Sicherheitsinteressen nicht genug berücksichtigt, Partner nicht überzeugt und viele Fragen zur strategischen, militärischen, industriellen und ökonomischen Ebene offen lässt. Soll die ESSI Europas Schutz im Bereich Luftverteidigung spürbar verbessern, muss Berlin Antworten zum strategischen Gleichgewicht, zur Entwicklung der europäischen Rüstungsindustrie und zu militärisch sinnvollen Lösungen geben. Der Aufwuchs einzelner militärischer Fähigkeiten wird keinen europäischen Sky Shield ermöglichen. (Autorenreferat)
- Published
- 2023
- Full Text
- View/download PDF
6. OPTIMIZING VLS FIRING POLICY: AN ENUMERATION OF HETEROGENEOUS SEQUENCES TO INFORM EXPENDITURE
- Author
-
Kress, Moshe, Atkinson, Michael P., Salmeron-Medrano, Javier, Operations Research (OR), Templin, Steel J., Kress, Moshe, Atkinson, Michael P., Salmeron-Medrano, Javier, Operations Research (OR), and Templin, Steel J.
- Abstract
The U.S. Navy (USN) utilizes the Vertical Launch System (VLS) to store and launch both their offensive and defensive missiles. Since the number of VLS silos on a given ship is fixed, to maximize offensive capability the USN needs to minimize the number of interceptors required to combat incoming anti-surface missiles. Current firing policies may be overly conservative and expend too many interceptors per incoming threat, which results in a substantial fraction of VLS silos dedicated to defensive missiles. Decision makers need an analysis tool to explore the trade-off between missile consumption and probability of raid annihilation (PRA) for various firing policies and would also benefit from a prescriptive algorithm to help inform missile expenditure. This thesis provides a model to optimize VLS firing policy using a set of multiple interceptor types while accounting for range limitations, travel time, multi-interceptor salvos, battle damage assessment, and range dependent probability of kill. Additionally, the thesis derives analytical results for the optimal, lowest-cost allocation of interceptors in the single interceptor case, which, in turn, generates insight into how to structure sequential salvos., N81, Washington DC, Ensign, United States Navy, Approved for public release. Distribution is unlimited.
- Published
- 2022
7. OPTIMIZING VLS FIRING POLICY: AN ENUMERATION OF HETEROGENEOUS SEQUENCES TO INFORM EXPENDITURE
- Author
-
Templin, Steel J., Kress, Moshe, Atkinson, Michael P., Salmeron-Medrano, Javier, and Operations Research (OR)
- Subjects
Vertical Launch System ,pk ,probability of raid annihilation ,ship ,SSLSS ,probability of engagement kill ,IAMD ,integrated air and missile defense ,VLS ,BMD ,SLS ,ASCM ,mix ,distributed maritime operations ,interceptor ,DMO ,loadout ,salvo ,battle damage assessment ,expenditure ,counterfire ,low cost ,PEK ,PIP ,missile ,defense ,probable impact point ,BDA ,PRA ,anti-ship cruise missile ,range ,hard kill ,SLSS ,shoot look shoot ,optimization - Abstract
The U.S. Navy (USN) utilizes the Vertical Launch System (VLS) to store and launch both their offensive and defensive missiles. Since the number of VLS silos on a given ship is fixed, to maximize offensive capability the USN needs to minimize the number of interceptors required to combat incoming anti-surface missiles. Current firing policies may be overly conservative and expend too many interceptors per incoming threat, which results in a substantial fraction of VLS silos dedicated to defensive missiles. Decision makers need an analysis tool to explore the trade-off between missile consumption and probability of raid annihilation (PRA) for various firing policies and would also benefit from a prescriptive algorithm to help inform missile expenditure. This thesis provides a model to optimize VLS firing policy using a set of multiple interceptor types while accounting for range limitations, travel time, multi-interceptor salvos, battle damage assessment, and range dependent probability of kill. Additionally, the thesis derives analytical results for the optimal, lowest-cost allocation of interceptors in the single interceptor case, which, in turn, generates insight into how to structure sequential salvos. N81, Washington DC Ensign, United States Navy Approved for public release. Distribution is unlimited.
- Published
- 2021
8. Plasma Metabolomics of Intermediate and Neovascular Age-Related Macular Degeneration Patients
- Author
-
William K. Scott, Anita Agarwal, Jonathan L. Haines, Karan Uppal, Margaret A. Pericak-Vance, Sabrina L. Mitchell, Chunyu Ma, Milam A. Brantley, and Dean P. Jones
- Subjects
Male ,QH301-705.5 ,medicine.medical_treatment ,Metabolite ,NVAMD ,Carnitine shuttle ,Pharmacology ,Tandem mass spectrometry ,IAMD ,Article ,Steroid ,chemistry.chemical_compound ,Macular Degeneration ,Metabolomics ,acylcarnitines ,Carnitine ,Medicine ,Humans ,Least-Squares Analysis ,carnitine shuttle ,Biology (General) ,age-related macular degeneration ,phospholipids ,Aged ,chemistry.chemical_classification ,Neovascularization, Pathologic ,business.industry ,Discriminant Analysis ,General Medicine ,Macular degeneration ,Middle Aged ,medicine.disease ,Lipids ,metabolomics ,Amino acid ,Metabolic pathway ,chemistry ,Case-Control Studies ,Linear Models ,Metabolome ,Female ,business ,Metabolic Networks and Pathways - Abstract
To characterize metabolites and metabolic pathways altered in intermediate and neovascular age-related macular degeneration (IAMD and NVAMD), high resolution untargeted metabolomics was performed via liquid chromatography-mass spectrometry on plasma samples obtained from 91 IAMD patients, 100 NVAMD patients, and 195 controls. Plasma metabolite levels were compared between: AMD patients and controls, IAMD patients and controls, and NVAMD and IAMD patients. Partial least-squares discriminant analysis and linear regression were used to identify discriminatory metabolites. Pathway analysis was performed to determine metabolic pathways altered in AMD. Among the comparisons, we identified 435 unique discriminatory metabolic features. Using computational methods and tandem mass spectrometry, we identified 11 metabolic features whose molecular identities had been previously verified and confirmed the molecular identities of three additional discriminatory features. Included among the discriminatory metabolites were acylcarnitines, phospholipids, amino acids, and steroid metabolites. Pathway analysis revealed that lipid, amino acid, and vitamin metabolism pathways were altered in NVAMD, IAMD, or AMD in general, including the carnitine shuttle pathway which was significantly altered in all comparisons. Finally, few discriminatory features were identified between IAMD patients and controls, suggesting that plasma metabolic profiles of IAMD patients are more similar to controls than to NVAMD patients.
- Published
- 2021
9. Plasma Metabolomics of Intermediate and Neovascular Age-Related Macular Degeneration Patients.
- Author
-
Mitchell, Sabrina L., Ma, Chunyu, Scott, William K., Agarwal, Anita, Pericak-Vance, Margaret A., Haines, Jonathan L., Jones, Dean P., Uppal, Karan, and Brantley Jr., Milam A.
- Subjects
AMINO acid metabolism ,MACULAR degeneration ,LIPID metabolism ,LIQUID chromatography-mass spectrometry ,METABOLITES ,TANDEM mass spectrometry ,FISHER discriminant analysis ,METABOLOMICS - Abstract
To characterize metabolites and metabolic pathways altered in intermediate and neovascular age-related macular degeneration (IAMD and NVAMD), high resolution untargeted metabolomics was performed via liquid chromatography-mass spectrometry on plasma samples obtained from 91 IAMD patients, 100 NVAMD patients, and 195 controls. Plasma metabolite levels were compared between: AMD patients and controls, IAMD patients and controls, and NVAMD and IAMD patients. Partial least-squares discriminant analysis and linear regression were used to identify discriminatory metabolites. Pathway analysis was performed to determine metabolic pathways altered in AMD. Among the comparisons, we identified 435 unique discriminatory metabolic features. Using computational methods and tandem mass spectrometry, we identified 11 metabolic features whose molecular identities had been previously verified and confirmed the molecular identities of three additional discriminatory features. Included among the discriminatory metabolites were acylcarnitines, phospholipids, amino acids, and steroid metabolites. Pathway analysis revealed that lipid, amino acid, and vitamin metabolism pathways were altered in NVAMD, IAMD, or AMD in general, including the carnitine shuttle pathway which was significantly altered in all comparisons. Finally, few discriminatory features were identified between IAMD patients and controls, suggesting that plasma metabolic profiles of IAMD patients are more similar to controls than to NVAMD patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
10. Structure–Function Analysis in Macular Drusen With Mesopic and Scotopic Microperimetry
- Author
-
Giovanni Montesano, Giovanni Ometto, Bethany E. Higgins, Costanza Iester, Konstantinos Balaskas, Adnan Tufail, Usha Chakravarthy, Ruth E. Hogg, and David P. Crabb
- Subjects
structure-function analyis ,SD-OCT imaging ,sense organs ,iAMD ,mesopic and scotopic microperimetry ,FAF imaging ,eye diseases ,3. Good health - Abstract
Purpose:To investigate the structure–function relationship in eyes with drusen with mesopic and scotopic microperimetry. Methods:We analyzed structural and functional data from 43 eyes with drusen. Functional data were acquired with mesopic and scotopic two-color (red and cyan) microperimetry. Normative values were calculated using data from 56 healthy eyes. Structural measurements were green autofluorescence and dense macular optical coherence tomography scans. The latter were used to calculate the retinal pigment epithelium elevation (RPE-E) and the photoreceptor reflectivity ratio (PRR). The pointwise structure–function relationship was measured with linear mixed models having the log-transformed structural parameters as predictors and the sensitivity loss (SL, deviation from normal) as the response variable. Results:In the univariable analysis, the structural predictors were all significantly correlated (P< 0.05) with the SL in the mesopic and scotopic tests. In a multivariable model, mesopic microperimetry yielded the best structure–function relationship. All predictors were significant (P< 0.05), but the predictive power was weak (bestR2= 0.09). The relationship was improved when analyzing locations with abnormal RPE-E (bestR2= 0.18). Conclusions:Mesopic microperimetry shows better structure–function relationship compared to scotopic microperimetry; the relationship is weak, likely due to the early functional damage and the small number of tested locations affected by drusen. The relationship is stronger when locations with drusen are isolated for the mesopic and scotopic cyan test. Translational Relevance:These results could be useful to devise integrated structure–function methods to detect disease progression in intermediate age-related macular degeneration.
11. Structure–Function Analysis in Macular Drusen With Mesopic and Scotopic Microperimetry
- Author
-
Bethany E. Higgins, Giovanni Ometto, Giovanni Montesano, David P. Crabb, Ruth E Hogg, Adnan Tufail, Costanza Iester, Konstantinos Balaskas, and Usha Chakravarthy
- Subjects
structure–function ,0301 basic medicine ,medicine.medical_specialty ,genetic structures ,Mesopic vision ,Biomedical Engineering ,Retinal Drusen ,Drusen ,FAF imaging ,Retina ,Article ,Macular Degeneration ,03 medical and health sciences ,0302 clinical medicine ,structure-function analyis ,Optical coherence tomography ,Ophthalmology ,medicine ,Humans ,SD-OCT imaging ,iAMD ,Scotopic vision ,age-related macular degeneration ,optical coherence tomography ,Retinal pigment epithelium ,medicine.diagnostic_test ,business.industry ,Structure function ,drusen ,mesopic and scotopic microperimetry ,Macular degeneration ,medicine.disease ,eye diseases ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,microperimetry ,030221 ophthalmology & optometry ,Visual Field Tests ,RE ,sense organs ,business ,Microperimetry ,Tomography, Optical Coherence - Abstract
Purpose: To investigate the structure���function relationship in eyes with drusen with mesopic and scotopic microperimetry. Methods: We analyzed structural and functional data from 43 eyes with drusen. Functional data were acquired with mesopic and scotopic two-color (red and cyan) microperimetry. Normative values were calculated using data from 56 healthy eyes. Structural measurements were green autofluorescence and dense macular optical coherence tomography scans. The latter were used to calculate the retinal pigment epithelium elevation (RPE-E) and the photoreceptor reflectivity ratio (PRR). The pointwise structure���function relationship was measured with linear mixed models having the log-transformed structural parameters as predictors and the sensitivity loss (SL, deviation from normal) as the response variable. Results: In the univariable analysis, the structural predictors were all significantly correlated (P < 0.05) with the SL in the mesopic and scotopic tests. In a multivariable model, mesopic microperimetry yielded the best structure���function relationship. All predictors were significant (P < 0.05), but the predictive power was weak (best R2 = 0.09). The relationship was improved when analyzing locations with abnormal RPE-E (best R2 = 0.18). Conclusions: Mesopic microperimetry shows better structure���function relationship compared to scotopic microperimetry; the relationship is weak, likely due to the early functional damage and the small number of tested locations affected by drusen. The relationship is stronger when locations with drusen are isolated for the mesopic and scotopic cyan test. Translational Relevance: These results could be useful to devise integrated structure���function methods to detect disease progression in intermediate age-related macular degeneration., DPC and GM received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant 116076 (Macustar). This joint undertaking receives support from the European Union's Horizon 2020 research and innovation program and European Federation of Pharmaceutical Industries and Associations (EFPIA). The funding for the NICOLA and NISA studies are reported in the acknowledgments as part of a mandatory statement for these studies. The article was first published in TVST. The final publication is available at https://tvst.arvojournals.org/article.aspx?articleid=2772110
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.