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1رسالة جامعية
المؤلفون: Malek, Karim
مرشدي الرسالة: Grenoble Alpes, Balosso, Jacques, Foray, Nicolas
مصطلحات موضوعية: Hypersensibilité du groupe 2, Radiothérapie, Réparation de l' ADN, Tests de radiosensibilité, Transfert clinique, Redaction, Hypersensitivity of group 2, Radiation, DNA reparation, Hypersensitivity tests, Translational research, 610
الوصف: La réponse tissulaire des patients soumis à une radiothérapie, malgré des protocoles de traitement identiques, est variable avec des extrêmes importants. Une des questions posées à la radiobiologie est d'expliquer ces variations (approche a posteriori) et si possible de les prévoir (approche a priori). La réponse d'un organisme et de tissus complexes à la radiothérapie est la résultante de nombreux déterminants. Certains appartiennent à la dynamique et à l'homéostasie tissulaire (inflammation, cytokines, etc.) d'autre à la sensibilité et à la réponse cellulaire (sensibilité intrinsèque, réparation de l'ADN, régulation de la mort cellulaire, etc.). Concernant les déterminants cellulaires, l'Equipe d'Accueil a proposé de classer les humains en 3 groupes de radiosensibilités différentes, le premier considéré comme normal est de loin le plus important (près de 75% des individus), le groupe II de radiosensibilité intermédiaire représente la majeure partie des individus pour lesquels une réponse anormale est constatée après radiothérapie. Le groupe III rassemble des pathologies particulièrement rares associées à une hyper-radiosensibilité marquée, voire très marquée. Les patients du groupe II présentent donc une réponse thérapeutique inattendue et / ou des effets secondaires précoces ou tardifs sévères à des doses d'irradiation dont on attend une tolérance normale. Les patients du groupe II peuvent aussi être caractérisés par une forte prédisposition au cancer et aux tumeurs radio induites. Il existe une variabilité intrinsèque liée à des facteurs endogènes tels que la qualité de réparation de l'ADN, ou la production spontanée de micronoyaux ; et des facteurs exogènes. A cet égard, certaines médications sont susceptibles de modifier la réponse cellulaire à la radiothérapie, telles que les statines, les anticoagulants ou les antiagrégants plaquettaires. Approche a posteriori : par une étude clinique unicentrique de 65 patients atteints de cancers de la prostate et traités par le même radiothérapeute dans les mêmes conditions, la fréquence et la gravité des effets secondaires rectaux par rapport à la prise ou non de statines ont été étudiées : un effet radioprotecteur des statines vis-à-vis de la rectite radique a été mis en évidence in vivo sur des arguments statistiques pertinents. Approche a priori : par l'étude de la réponse cellulaire et moléculaire aux radiations de fibroblastes humains (notamment issus de tissus intestinaux sains). Ont été étudiés : la réparation et la signalisation des cassures double-brin de l'ADN par l'analyse des foci nucléaires H2AX et pATM ; le transit radioinduit de la protéine ATM du cytoplasme vers le noyau a été observé pour la première fois sur des fibroblastes humains rectaux. Les statines semblent accélérer ce transit, produisant un effet modérateur de la sévérité des rectites. L’étude des différents produits antioxydants et stimulateurs de la réparation de l’ADN a permis de montrer que les statines ont effet non équivoqué sur la réparation cellulaire après irradiation. Ces résultats ouvrent des perspectives pour des études plus approfondies de l'usage de médications facilement accessibles capables de moduler la gravité des effets secondaires de la radiothérapie.
The tissue response of patients undergoing radiotherapy, despite identical treatment protocols, could have important variations. One of the questions asked to the radiobiology is to explain these variations (a posteriori approach) and if possible to predict it (a priori approach). The response of an organism and complex tissues to radiotherapy is the result of many determinants. Some belong to the tissue dynamics and homeostasis (inflammation, cytokines, etc.) and others to the sensitivity and cellular response (intrinsic sensitivity, DNA repair, regulation of cell death, etc.). About cellular determinants, our research team proposed to classify humans into three groups of different radiosensitivity levels, the first considered as normal is by far the largest (almost 75% of individuals), group II of intermediate radiosensitivity represents the majority of individuals having an abnormal response to radiotherapy. Group III gathers extremely rare conditions associated with marked or very marked hyper-radiosensitivity which are usually life threatening. Therefore patients in group II show either unexpected therapeutic response or severe radiation early or late side effects after doses for which normal tolerance is expected. Patients in group II can also be characterized by a strong predisposition to cancer and radiation-induced tumors. There is an inherent variability related to endogenous factors, such as the quality of DNA repair, or the spontaneous production of micronuclei; and exogenous factors. In this regard, certain medications may alter the cellular response to radiation therapy, such as statins, antiplatelet agents or anticoagulants. A posteriori approach: a single-center clinical study of 68 patients with prostate cancer treated by the same radiation oncologist in the same conditions, the frequency and severity of rectal side effects are compared to the use or not of statins : a radioprotective effect of statins toward radiation proctitis cannot be excluded. A priori approach: by studying the cellular and molecular radiation response in human fibroblasts (especially from healthy bowel tissue). Were studied: signaling and repair of DNA double-strand breaks by analysis of nuclear foci of MRE11; H2AX and pATM; radiation induced ATM protein transit from the cytoplasm to the nucleus was observed for the first time in rectal tissue fibroblasts. Statins appear to speed up this transit, making possible a radioprotective effect. These results open perspectives for further studies for the use of medications readily available that can modulate the severity of side effects of radiotherapy. -
2مؤتمر
المؤلفون: Lingaraj, Trupti, Timothy, Marissa, Ortiz-Otero, Nerymar, Bartolini, Wilmin, Kacena, Katherine, Malek, Karim, Santillana, Sergio
المصدر: Regular and Young Investigator Award Abstracts
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3مؤتمر
المؤلفون: Aggen, David, McKean, Meredith, Lakhani, Nehal, Bashir, Babar, Hoffman-Censits, Jean, Alhalabi, Omar, Guancial, Elizabeth, Bowman, Isaac, Tan, Alan, Lingaraj, Trupti, Timothy, Marissa, Ortiz-Otero, Nerymar, Bartolini, Wilmin, Kacena, Katherine, Malek, Karim, Santillana, Sergio, Luke, Jason
المصدر: Regular and Young Investigator Award Abstracts
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4دورية أكاديمية
المؤلفون: Moore, Kathleen N, Vergote, Ignace, Oaknin, Ana, Colombo, Nicoletta, Banerjee, Susana, Oza, Amit, Pautier, Patricia, Malek, Karim, Birrer, Michael J
المصدر: Future Oncology ; volume 14, issue 17, page 1669-1678 ; ISSN 1479-6694 1744-8301
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5دورية أكاديمية
المؤلفون: Arora, Jasbir, Liu, Yuk Ming, Abdel Malek, Karim, Baek, Stephen, Liu, Tina C., Bhatt, Rajan, Farrell, Kimberly D.
المصدر: International Journal of Human Factors Modelling and Simulation ; volume 6, issue 1, page 81 ; ISSN 1742-5549 1742-5557
مصطلحات موضوعية: General Medicine
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6دورية أكاديمية
المؤلفون: Liu, Tina C., Bhatt, Rajan, Farrell, Kimberly D., Baek, Stephen, Liu, Yuk Ming, Malek, Karim Abdel, Arora, Jasbir
المصدر: International Journal of Human Factors Modelling and Simulation ; volume 6, issue 1, page 81 ; ISSN 1742-5549 1742-5557
مصطلحات موضوعية: General Medicine
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7دورية أكاديمية
المؤلفون: Moore, Kathleen N., O'Malley, David M., Vergote, Ignace, Martin, Lainie P., Gonzalez-Martin, Antonio, Malek, Karim, Birrer, Michael J.
المصدر: Gynecologic Oncology ; volume 151, issue 1, page 46-52 ; ISSN 0090-8258
مصطلحات موضوعية: Obstetrics and Gynecology, Oncology
الإتاحة: https://doi.org/10.1016/j.ygyno.2018.07.017Test
https://api.elsevier.com/content/article/PII:S0090825818310813?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0090825818310813?httpAccept=text/plainTest -
8دورية أكاديمية
المؤلفون: Malek, Karim, Fink, Aliza K., Thwin, Soe Soe, Gurwitz, Jerry H., Ganz, Patricia A., Silliman, Rebecca A.
المساهمون: Department of Medicine, Division of Geriatric Medicine, Meyers Primary Care Institute
المصدر: Medical care ; 42 ; 7 ; 700-6
مصطلحات موضوعية: Age Factors, Aged, 80 and over, Antineoplastic Agents, Hormonal, Breast Neoplasms, Chemotherapy, Adjuvant, Decision Making, Female, Humans, Logistic Models, Male, Medicine, Patient Selection, Prospective Studies, Risk Assessment, Specialization, Tamoxifen, United States, Health Services Research, Primary Care
الوصف: OBJECTIVES: The objectives of this study were to determine whether tamoxifen recommendation differs by physician specialty, to determine whether perception affects tamoxifen recommendation, and to investigate the association between the physician's specialty and the perception of risks and benefits of tamoxifen. METHODS: We enrolled a cohort of geographically diverse women aged 65 and older with stage I through IIIa breast cancer in a prospective cohort study. We recruited their surgeons and, when applicable, their medical oncologists to provide patient-specific information about their perceptions of the risks and benefits of tamoxifen and whether they recommended tamoxifen. Each physician also completed a questionnaire regarding his or her demographic and practice characteristics. Patient data were collected through medical record review and a patient interview 3 months after definitive breast cancer surgery. RESULTS: We collected physician treatment recommendation forms for 585 women. Oncologists were 2.5 times more likely to recommend tamoxifen, compared with surgeons, after adjusting for patient and tumor characteristics (95% confidence interval, 1.5-4.2). For both specialties, their perceptions of the risks and benefits of tamoxifen were strong predictors of tamoxifen recommendation. However, there were differences in perception by physician specialty. Distant metastases and tolerance of tamoxifen side effects were more important to oncologists, whereas local recurrence and risk of cataracts were more important to surgeons. CONCLUSION: Physicians' perceptions of the risks and benefits of tamoxifen therapy for older women are important in their decision-making process.
العلاقة: Link to Article in PubMed; http://www.jstor.org/stable/4640806Test; Med Care. 2004 Jul;42(7):700-6.; 0025-7079 (Linking); http://hdl.handle.net/20.500.14038/36966Test; https://escholarship.umassmed.edu/meyers_pp/355Test; 2407257; meyers_pp/355
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9دورية أكاديمية
المؤلفون: Abdel-Malek, Karim, Bhatt, Rajan, Murphy, Chris, Tena Salais, Marco
المصدر: Volume: 7 ; Issue: 1 ; JournalTitle: Proceedings of the 7th International Digital Human Modeling Symposium
الوصف: Human modeling and simulation environments have become sophisticated, providing capabilities for posturing the digital avatar, conducting dynamic tasks, assessing human performance, and obtaining scientific analysis. Physics-based analysis of human motion has also enabled capabilities for predicting the dynamics of the motion whereby the avatar is able to respond to external effects such as load conditions or the physical environment. However, the behavior of the avatar is typically the same. Indeed, the same input to the system yields the same output. This work is concerned with obtaining more realistic and different behaviors for the human while conducting a task in a physics-based environment.While the Santos1 digital human modeling (DHM) system has been successfully used in the analysis and prediction of human motion, the resulting behavior of a specific soldier is the same. An (avatar) individual doing a task will do the same task exactly the same way if the simulation is executed again. In reality, however, a soldier may adopt a different strategy to accomplish the same task.This paper discusses the development of a rigorous scientific method using human performance functions as the driving force to induce different behavior.The Santos platform uses 215 degrees of freedom to model a human. The research and development of this platform over the past 15 years has made significant strides in the development of predictive dynamics2 as a methodology for predicting behavior and is physics-based. Rather than solving the highly complex and coupled algebraic-differential equations of motion governing the human’s behavior, predictive dynamics uses optimization to solve for the behavior.In this paper we use a new methodology that employs seed scenarios before executing predictive dynamics, thus allowing the system to provide variations in task execution. A tall person will execute a task differently than a short person, if height is an influencing factor.The results of predictive dynamics are autonomous prediction of ...
وصف الملف: 12 pages
العلاقة: info:eu-repo/semantics/reference/isbn/978-0-9840378-4-1; https://doi.org/10.17077/dhm.31790Test; /article/id/31790/
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10دورية أكاديمية
المؤلفون: Frey-Law, Laura A., Bhatt, Rajan, Schneider, Russell, Laguna Mosqueda, Guillermo, Tena Salais, Marco, Evans, Landon, Abdel-Malek, Karim
المصدر: Volume: 7 ; Issue: 1 ; JournalTitle: Proceedings of the 7th International Digital Human Modeling Symposium
الوصف: The US Army recently updated their fitness test from a historical three-task battery to a science-driven six-task battery called the Army Combat Fitness Test (ACFT). The Army chose the six events compared to the time required to complete a battery of commons soldier tasks (CSTs), thus targeting the time-domain aspect of physical requirements and capability. We aimed to critically evaluate the new ACFT using biomechanical analyses and digital human modeling to assess how well specific aspects of the ACFT tasks matched required joint torques to perform common soldier tasks. This paper will focus on one of the ACFT tasks, the dead lift. Five healthy ROTC students (three males, two females) completed simulated CSTs and the ACFT. All were instrumented with markers to use 3D motion analysis coupled with digital human modeling (DHM) using Santos® and Sophia® DHMs to estimate the muscle joint torque requirements (i.e., workloads) needed to complete each task. We assessed five major joints in the body: trunk (low-back extension and abdominal flexion), hip flexion/extension, knee flexion/extension, shoulder flexion/extension, and elbow flexion/extension. The ratio of peak torques needed to complete selective CSTs compared to the torque needed to complete the deadlift at the current passing score were modeled, where < 100% indicates the CSTs were less strenuous than the deadlift. We found examples of less, similar, and greater strength requirements across eight CSTs compared to the dead lift, including 150 – 200% higher torque requirements for select CSTs than the dead lift in some cases. For example, performing simulated casualty extractions required more torque at multiple joints. Overall, we concluded that the muscles involved in the ACFT dead lift often mimic those involved in one or more CSTs. Further, the absolute torques needed to complete the dead lift and simulated CSTs are not notably different between men and women.
وصف الملف: 15 pages
العلاقة: info:eu-repo/semantics/reference/isbn/978-0-9840378-4-1; https://doi.org/10.17077/dhm.31784Test; /article/id/31784/
