Literatura académica sobre el tema "Dole effect"
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Artículos de revistas sobre el tema "Dole effect"
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Hoffmann, Georg, Matthias Cuntz, Christine Weber, et al. "A model of the Earth's Dole effect." Global Biogeochemical Cycles 18, no. 1 (2004): n/a. http://dx.doi.org/10.1029/2003gb002059.
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Žukovec Topalović, Dijana, Lada Živković, Andrea Čabarkapa, et al. "Dry Olive Leaf Extract Counteracts L-Thyroxine-Induced Genotoxicity in Human Peripheral Blood LeukocytesIn Vitro." Oxidative Medicine and Cellular Longevity 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/762192.
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The thyroid hormones change the rate of basal metabolism, modulating the consumption of oxygen and causing production of reactive oxygen species, which leads to the development of oxidative stress and DNA strand breaks. Olive (Olea europaeaL.) leaf contains many potentially bioactive compounds, making it one of the most potent natural antioxidants. The objective of this study was to evaluate the genotoxicity of L-thyroxine and to investigate antioxidative and antigenotoxic potential of the standardized oleuropein-rich dry olive leaf extract (DOLE) against hydrogen peroxide and L-thyroxine-induced DNA damage in human peripheral blood leukocytes by using the comet assay. Various concentrations of the extract were tested with both DNA damage inducers, under two different experimental conditions, pretreatment and posttreatment. Results indicate that L-thyroxine exhibited genotoxic effect and that DOLE displayed protective effect against thyroxine-induced genotoxicity. The number of cells with DNA damage, was significantly reduced, in both pretreated and posttreated samples (P< 0.05). Comparing the beneficial effect of all tested concentrations of DOLE, in both experimental protocols, it appears that extract was more effective in reducing DNA damage in the pretreatment, exhibiting protective role against L-thyroxine effect. This feature of DOLE can be explained by its capacity to act as potent free radical scavenger.
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Goenka, Shilpi, and Sanford R. Simon. "A Novel Pro-Melanogenic Effect of Standardized Dry Olive Leaf Extract on Primary Human Melanocytes from Lightly Pigmented and Moderately Pigmented Skin." Pharmaceuticals 14, no. 3 (2021): 252. http://dx.doi.org/10.3390/ph14030252.
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Benolea® (EFLA®943) is a standardized dry olive leaf extract (DOLE) considered safe for food consumption and has demonstrated superior pharmaceutical benefits such as antioxidant, anti-obesity, and anti-hypertensive activities. However, there is no study on its effects on melanogenesis yet. Disruption in the sequence of steps in melanogenesis can lead to hypopigmentary disorders which occur due to reduced production or export of pigment melanin in the skin. There is a need for safe and nontoxic therapeutics for the treatment of hypopigmentation disorders. Herein, we studied the effects of DOLE over a concentration range of 10–200 µg/mL on melanin synthesis and melanin secretion in B16F10 mouse melanoma cells and MNT-1 human melanoma cells and validated our results in primary human melanocytes (obtained from lightly pigmented (LP) and moderately pigmented (MP) cells) as well as their cocultures with keratinocytes. The capacity of melanocytes to export melanosomes was also estimated indirectly by the quantitation of melanocyte dendrite lengths and numbers. Our results show that DOLE significantly enhanced levels of extracellular melanin in the absence of effects on intracellular melanin, demonstrating that this plant extract’s pro-melanogenic activity is primarily based on its capacity to augment melanin secretion and stimulate melanocyte dendricity. In summary, our preliminary results demonstrate that DOLE may hold promise as a pro-pigmenting agent for vitiligo therapy and gray hair treatment by its exclusive and novel mechanism of functioning as a dendrite elongator. Further studies to elucidate the mechanisms of action of the pro-melanogenic activity and effects of DOLE on melanosome export as well as the last steps of melanogenesis are warranted.
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Angert, A., J. Muhr, R. Negron Juarez, et al. "The contribution of respiration in tree-stems to the Dole Effect." Biogeosciences Discussions 9, no. 1 (2012): 1097–114. http://dx.doi.org/10.5194/bgd-9-1097-2012.
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Abstract. Understanding the variability and the current value of the Dole Effect, which has been used to infer past changes in biospheric productivity, requires accurate information on the discrimination associated with respiratory oxygen consumption in each of the biosphere components. Respiration in tree stems is an important component of the land carbon cycle. Here we measured, for the first time, the discrimination associated with tree stem oxygen uptake. The measurements included tropical forest trees, which are major contributors to the global fluxes of carbon and oxygen. We found discrimination in the range of 12.6–21.5 ‰, indicating both diffusion limitation, resulting in O2 discrimination values below 20 ‰, and alternative oxidase respiration, which resulted in discrimination values greater than 20 ‰. Discrimination varied seasonally, between and within tree species. Calculations based on these results show that variability in woody plants discrimination can result in significant variations in the global Dole Effect.
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Angert, A., J. Muhr, R. Negron Juarez, et al. "The contribution of respiration in tree stems to the Dole Effect." Biogeosciences 9, no. 10 (2012): 4037–44. http://dx.doi.org/10.5194/bg-9-4037-2012.
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Abstract. Understanding the variability and the current value of the Dole Effect, which has been used to infer past changes in biospheric productivity, requires accurate information on the isotopic discrimination associated with respiratory oxygen consumption in each of the biosphere components. Respiration in tree stems is an important component of the land carbon cycle. Here we measured, for the first time, the discrimination associated with tree stem oxygen uptake. The measurements included tropical forest trees, which are major contributors to the global fluxes of carbon and oxygen. We found discrimination in the range of 12.6–21.5‰, indicating both diffusion limitation, resulting in O2 discrimination values below 20‰, and alternative oxidase respiration, which resulted in discrimination values greater than 20‰. Discrimination varied seasonally, between and within tree species. Calculations based on these results show that variability in woody plants discrimination can result in significant variations in the global Dole Effect.
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Malaizé, B., D. Paillard, J. Jouzel, and D. Raynaud. "The Dole effect over the last two glacial-interglacial cycles." Journal of Geophysical Research: Atmospheres 104, no. D12 (1999): 14199–208. http://dx.doi.org/10.1029/1999jd900116.
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Famiglietti, Michela, Alessandro Savastano, Rosa Gaglione, Angela Arciello, Daniele Naviglio, and Loredana Mariniello. "Edible Films Made of Dried Olive Leaf Extract and Chitosan: Characterization and Applications." Foods 11, no. 14 (2022): 2078. http://dx.doi.org/10.3390/foods11142078.
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Nowadays a possible strategy in food preservation consists of the use of active and functional packaging to improve safety and ensure a longer shelf life of food products. Many studies refer to chitosan-based films because of the already-known chitosan (CH) antibacterial and antifungal activity. In this work, we developed CH-based films containing Dried Olive Leaf Extract (DOLE) obtained by Naviglio extractor, with the aim to investigate the polyphenols yield and the antioxidant activity of this extract entrapped in CH-based-edible films. Olive tree cultivation produces a huge amount of byproducts that are usually simply burned. Phenolic compounds are already studied for their beneficial effects on human health. Some studies reported that phenols isolated from olive leaves have been shown to inhibit the growth of different strains of microorganisms. Thus, the antimicrobial effect of DOLE-containing films against bacterial strains (Salmonella enterica subsp. enterica serovar Typhimurium ATCC® 14028, Salmonella enteritidis RIVM 706, and Enterococcus faecalis ATCC® 29212) was tested in vitro. The DOLE component of the films is effective in inhibiting all the bacteria tested in a dose-dependent manner. Thus, it was demonstrated that these edible films can act as active bioplastics when used to wrap hamburgers in substitution for baking paper, which is normally used.
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Huang, Enqing, Pinxian Wang, Yue Wang, et al. "Dole effect as a measurement of the low-latitude hydrological cycle over the past 800 ka." Science Advances 6, no. 41 (2020): eaba4823. http://dx.doi.org/10.1126/sciadv.aba4823.
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The quest of geological proxies to evaluate low-latitude hydrological changes at a planetary scale remains an ongoing issue. The Dole effect is such a potential proxy owing to its global character. We propose a new approach to recalculate the fluctuation of the Dole effect (∆DE*) over the past 800 thousand years (ka). The ∆DE* calculated this way is dominated by precession cycles alone, with lesser variance in the obliquity bands and almost no variance in the eccentricity bands. Moreover, the ∆DE* is notably correlated with Chinese stalagmite δ18O record over the past 640 ka; simulated terrestrial rainfall changes between 30°N and 30°S over the past 300 ka. Our findings highlight the predominant role of the low-latitude hydroclimate in governing the ∆DE* on orbital time scales, while high-latitude climate impacts are negligible. In turn, we argue that the ∆DE* can be used to indicate low-latitude hydrological changes at a global extent.
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Nevile, J. W. "Employment Outcomes of Work for the Dole: An Analysis of the DEWRSB Net Impact Report." Economic and Labour Relations Review 14, no. 1 (2003): 127–42. http://dx.doi.org/10.1177/103530460301400110.
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Since the data necessary to make a formal quantitative analysis of Work for the Dole employment outcomes is not available to researchers who are independent of Commonwealth Government Departments, this article examines the (then) Department of Employment, Workplace Relations and Small Business (DEWRSB) net impact report, finding in it a number of weaknesses. The combined effect of these is to inflate the estimated value for net impact but a corrected estimate is still higher than many consider likely. Any figure for the net impact estimate of an Australian labour market program can only be a broad indicator. This article argues that in the case of Work for the Dole the net impact is definitely positive and by more than a trivial amount.
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Leydesdorff, Loet, and Martin Meyer. "The decline of university patenting and the end of the Bayh–Dole effect." Scientometrics 83, no. 2 (2009): 355–62. http://dx.doi.org/10.1007/s11192-009-0001-6.
Texto completoTesis sobre el tema "Dole effect"
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Paul, Clémence. "Fractionnement du dioxygène lors des processus biologiques : application à la reconstruction de la productivité passée de la biosphère." Electronic Thesis or Diss., université Paris-Saclay, 2024. http://www.theses.fr/2024UPASJ002.
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La composition isotopique du dioxygène piégé dans les bulles d'air des carottes de glace peut être utilisée pour reconstituer la productivité globale de la biosphère dans le passé ainsi que pour documenter l'évolution du cycle de l'eau aux basses latitudes. Le travail de cette thèse a été d'améliorer l'interprétation du δ18O de l'O2. Pour cela, nous avons affiné la détermination des différents coefficients de fractionnement associés au cycle de l'oxygène au niveau de la biosphère terrestre, c'est-à-dire pendant les processus de respiration et de photosynthèse. Afin de quantifier ces coefficients de fractionnement, nous avons développé un nouveau dispositif expérimental qui repose sur un système de chambres biologiques fermées multiplexées dans lesquelles tous les paramètres environnementaux sont contrôlés, stabilisés et mesurés. Ces chambres biologiques fermées ont un volume de 120 L permettant d'étudier un système « plante + sol ». La première étape a été de développer un prototype avec une seule chambre biologique et de faire une première étude sur la fétuque. Ensuite, un deuxième développement a permis de travailler sur plusieurs chambres biologiques via un système multiplexé. Nous avons aussi développé un instrument de spectrométrie optique (SARA-O2) afin de mesurer en continu la concentration et composition isotopique de l'O2 pendant les expériences en chambres multiplexées. Ceci remplace la mesure par spectrométrie de masse d'échantillons prélevés dans les chambres de façon manuelle. Ce système a permis d'étudier les coefficients de fractionnement pour plusieurs plantes (fétuque, bananier, laurier, maïs). Nous avons notamment mis en évidence un fractionnement isotopique associé à la photosynthèse terrestre. Les fractionnements biologiques trouvés lors de ces expériences ont finalement été intégrés dans des calculs globaux de composition isotopique du dioxygène de l'air et comparés aux mesures effectuées sur la dernière déglaciation. Ceci permet de conclure que les variations passées de δ18O de l'O2 dans l'atmosphère sont principalement liées aux variations du cycle hydrologique aux basses latitudes<br>The isotopic composition of oxygen trapped in air bubbles in ice cores can be used to reconstruct the global productivity of the biosphere in the past, as well as to document the evolution of the water cycle at low latitudes. The aim of this thesis was to improve the interpretation of δ18O de l'O2. Thus, we improved the determination of the various fractionation coefficients associated with the oxygen cycle at the level of the terrestrial biosphere, i.e. during the processes of respiration and photosynthesis. To quantify these fractionation coefficients, we have developed a new experimental set-up based on a system of multiplexed closed biological chambers in which all environmental parameters are controlled, stabilized and measured. These closed biological chambers have a volume of 120 L, enabling us to study a "plant + soil" system. The first step was to develop a prototype with a single biological chamber and carry out an initial study on fescue. This was followed by a second development, enabling us to work on several biological chambers via a multiplexed system. We also developed an optical spectrometry instrument (SARA-O2) for continuous measurement of O2 concentration and isotopic composition during multiplexed chamber experiments. This replaces manual mass spectrometry measurements of samples taken from the chambers. This system has enabled us to study fractionation coefficients for several plants (fescue, banana, laurel, maize). In particular, we highlighted isotopic fractionation associated with terrestrial photosynthesis. The biological fractionations found in these experiments were finally integrated into global calculations of the isotopic composition of atmospheric oxygen, and compared with measurements taken during the last deglaciation. This led to the conclusion that past variations in the δ18O of the O2 in the atmosphere are mainly linked to variations in the hydrological cycle at low latitudes
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Alfvén, Tobias. "Bone and kidney effects from cadmium exposure : dose effect and dose response relationships /." Stockholm : Karolinska Univ. Press, 2002. http://diss.kib.ki.se/2002/91-7349-341-4.
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Kafrouni, Marilyne. "Relation dose-effet et optimisation de la dosimétrie en radiothérapie interne sélective du carcinome hépatocellulaire." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTT007/document.
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La radiothérapie interne sélective (RTIS), en plein développement ces dernières années, constitue une alternative thérapeutique pour les cancers primaires et secondaires inopérables du foie. Le principe repose sur l’administration intra-artérielle de microsphères chargées d’yttrium-90 avec pour objectif la destruction des cellules tumorales par l’irradiation.L’activité d’yttrium-90 à administrer au patient est actuellement généralement prescrite à partir d’approches semi-empiriques ou peu personnalisées, faciles à mettre en place cliniquement. De nouveaux outils sont aujourd'hui disponibles semblables à ceux utilisés en radiothérapie externe. Leur utilisation encore peu répandue nécessite un retour d'expérience clinique pour mettre en avant leurs bénéfices et guider l'application clinique. Par ailleurs, le traitement RTIS est précédé d'une étape de simulation. Des différences inhérentes à cette procédure en deux temps (type de particules utilisées, modalité d’imagerie, modifications de flux vasculaires, etc.) existent et pourraient potentiellement conduire à des écarts dosimétriques entre la planification et le traitement. C’est dans ce contexte que s’inscrit le projet de cette thèse qui porte sur l'optimisation de la dosimétrie pour le traitement du carcinome hépatocellulaire par RTIS.Les doses délivrées au cours de 42 traitements par microsphères de résine réalisés entre 2012 et 2015 au CHU de Montpellier, ont été rétrospectivement calculées à l’échelle du voxel sur un logiciel de dosimétrie dédié (PLANET Dose, DOSIsoft, Cachan). Les doses délivrées ont été calculées pour le volume tumoral et le volume de foie sain définis anatomiquement, à partir de l’imagerie post-traitement TEP aux microsphères d’yttrium-90. Ce travail a mené à deux études complémentaires. La première analyse a consisté à confronter les données dosimétriques recueillies (doses moyennes, histogrammes dose-volume) à la réponse tumorale, la toxicité hépatique et la survie du patient. Les résultats obtenus, en accord avec ceux de la littérature, ont confirmé l’existence d’une relation dose-effet en RTIS. La deuxième étude a mis en évidence les limites du modèle BSA (body surface area pour surface corporelle) qui avait été utilisé pour planifier l’activité à administrer, à prédire la dose délivrée et par conséquent l’efficacité du traitement. L’absence de considérations dosimétriques et de prise en compte de l’hétérogénéité de distribution, de ce modèle ont notamment été discutées. Ces deux études ont ainsi souligné l'intérêt de planifier l'activité d'yttrium-90 à administrer en se basant sur des données dosimétriques individualisées.Une troisième étude a été conduite sur une population de 23 patients atteints de CHC, traités par microsphères de verre traités entre 2015 et 2018 au CHU de Montpellier. L’objectif a été de comparer les dosimétries prédictives et post-traitement calculées à l’échelle du voxel. Les résultats cliniques obtenus ont été appuyés par des expérimentations sur fantômes physiques (simple et anthropomorphique). Une bonne corrélation a été montrée, mettant en avant la valeur prédictive de la dosimétrie de planification. En revanche, un écart significatif a été observé et semble lié en partie à la quantification de l’imagerie TEP à l’yttrium-90. De plus, il a été montré que le geste radiologique peut influencer la distribution de particules et donc de dose, d’où la nécessité d’une reproductibilité aussi parfaite que possible entre les deux étapes<br>Selective internal radiation therapy (SIRT) is a growing therapeutic alternative for unresectable primary and secondary liver cancer. The principle is based on the intra-arterial administration of yttrium-90 loaded microspheres for tumor cell destruction through irradiation.Yttrium-90 activity to be administered to the patient is, at the moment, usually prescribed using semi-empirical or barely personalized approaches that can be easily clinically implemented. New tools, similar to the ones used in external beam radiotherapy, are available today. These tools, which are not yet widely spread, require clinical feedback to show their benefits and guide the clinical application. Besides, a simulation stage is always performed before SIRT treatment itself. This two-step procedure implies differences (in terms of particles used, imaging modality, vascular flow modifications, etc.) that could potentially lead to dose deviations between planning and treatment. The thesis project comes within this scope, dealing with dosimetry optimization for hepatocellular carcinoma SIRT.Delivered doses during 42 treatment procedures performed between 2012 and 2015 at Montpellier University Hospital, were retrospectively calculated at the voxel level using a dosimetry dedicated software (PLANET Dose, DOSIsoft, Cachan). Two complementary studies were carried out from this work. The first one analyzed dose data (average dose, dose volume histograms) versus patient follow-up including tumor response, liver toxicity and patient survival. The results obtained are consistent with the other teams, confirming the dose-effect relationship in SIRT. The second study highlighted the limitations of the BSA (body surface area) model that was used for activity planning. In particular, the limitations of this model to predict delivered dose and consequently treatment efficiency were quantitatively demonstrated. The lack of dosimetry and heterogeneity distribution considerations were also discussed. These two studies emphasized the interest for yttrium-90 activity planning based on individualized dose data.A third study was conducted on a population of 23 patients treated between 2015 and 2018 at Montpellier University Hospital. The aim was to compare predictive and post-treatment dosimetry calculated at the voxel level. The clinical results were supported by phantom (simple and anthropomorphic) experimentations. A good correlation was observed highlighting the predictive value of dosimetry planning. However, a significant deviation was noticed and seems to be partly related to yttrium-90 TEP quantification. In addition, it was also noted that the radiological gesture can affect particle distribution and consequently dose distribution, this is why reproducibility as perfect as possible is required between the two stages
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Rostand, Neil. "Modélisation compacte de l'effet des radiations naturelles des dispositifs sub-28nm pour des applications automobiles et aéronautiques." Thesis, Toulouse, ISAE, 2019. http://www.theses.fr/2019ESAE0035.
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L’objectif de cette thèse était le développement de modèles SET (Single Event Transient) et TID (Total Ionizing Dose) pour les MOSFETs de technologies fortement intégrées, reposant notamment sur la technologie SOI. Ces modèles devaient respecter les standards de la modélisation compacte afin d’assurer leur utilisation dans les simulateurs de circuits SPICE (ELDO, SPECTRE, PSPICE …) tout en assurant la justesse du contenu physique. Le langage d’implémentation est alors le Verilog-A. En 1A, l’investigation physique des SET a été effectuée à l’aide de simulations TCAD. Cette tâche a supporté le développement d’un premier modèle physique SET (validé par la TCAD) adapté aux technologies BULK.En 2A, le modèle physique a été rendu compact et implémenté en Verilog-A. Ce travail a nécessité le développement d’une méthode d’implémentation faisant appel à la considération d’un circuit électrique équivalent au phénomène SET. Le modèle ainsi implémenté en SPICE a été capable de prédire l’occurrence de SEUs (Single Event Upset) dans les mémoires et des erreurs plus fonctionnelles dans les registres à décalage. En parallèle, l’investigation physique du TID a été effectuée à l’aide simulations TCAD. Par ailleurs, les effets TID ont été modélisés et implémentés dans le modèle standard compact LETI – UTSOI décrivant le fonctionnement des transistors FDSOI. Le modèle a été validé à l’aide de simulations TCAD et a été utilisé pour extraire les paramètres TID sur des MOSFETs FDSOI irradiés au CEA/DAM.En 3A, un modèle compact SET pour technologies fortement intégrées (reposant sur la technologie SOI) a été développé. Ce modèle prend en compte l’amplification bipolaire inhérente à ce type de structure ainsi que la morphologie 3D de la charge générée par la particule ionisante. Des validations TCAD de ce modèle ont été effectuées. Par ailleurs, ce modèle SET a été interfacé avec le simulateur multi-physiques MUSCA SEP3 afin d’estimer le risque SEE sur des matrices mémoires FDSOI. L’apport du modèle SET a été mis en évidence dans la fiabilité de cette estimation<br>The purpose of the PhD was to develop "Single Event Transient"(SET) and "Total Ionizing Dose" (TID) models for sub-28nm MOS technologies. These models have been developed according to standards of compact modeling in order to be used into SPICE simulators (ELDO, SPECTRE, PSPICE ...) while main physical features are taken into account. The implementation has been done in Verilog-A langage.During the first year, SET physical investigation has been done performing TCAD simulations. It supported model development of SET applied to BULK technologies. During the second year, this model has been turned into a compact model and implemented in Verilog-A, which required the development of an implementation method involving equivalent electrical circuit. The resulting model has been able to predict "Single Event Upsets" (SEUs) in memories and functional errors in shift registers. Moreover, physical investigation of TID has been performed through TCAD simulations of FDSOI MOSFETs. TID effects have been included into standard FDSOI transistor model LETI-UTSOI. The model has been validated through TCAD simulations and has been used to extract TID parameters on experimental devices irradiated in CEA/DAM. The third year has been partly dedicated to SET model development for very integrated technologies (relying on SOI technology).This model takes bipolar amplification into account as well as 3D charge deposit morphology induced by the ionizing particle. TCAD validations have been performed in order to validate the model. Moreover, this model has been included into multi-physics simulator MUSCA SEP3 in order to assess SEE risk in FDSOI memory matrix. it has been found that the physical features the model is able to model can influence reliability of this assessment
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Morency, Catherine-Ève. "Effets de l'estradiol et de la progestérone sur le contrôle respiratoire en situation hypoxique chez le raton nouveau-né et impacts à long terme." Thesis, Université Laval, 2006. http://www.theses.ulaval.ca/2006/23851/23851.pdf.
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Sutton, Akil K. "Displacement Damage and Ionization Effects in Advanced Silicon-Germanium Heterojunction Bipolar Transistors." Thesis, Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/7217.
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A summary of total dose effects observe in advanced Silicon Germanium (SiGe) Heterojunction Bipolar Transistors (HBTs) is presented in this work. The principal driving froces behin the increased use of SiGe BiCMOS technology in space based electronics systems are outlined in the motivation Section of Chapter I. This is followed by a discussion of the strained layer Si/SiGe material structure and relevant fabrication techniques used in the development of the first generation of this technology. A comprehensive description of the device performance is presented.
Chapter II presents an overview of radiation physics as it applies to microelectronic devices. Several sources of radiation are discussed including the environments encountered by satellites in different orbital paths around the earth. The particle types, interaction mechanisms and damage nomenclature are described.
Proton irradiation experiments to analyze worst case displacement and ionization damage are examined in chapter III. A description of the test conditions is first presented, followed by the experimental results on the observed dc and ac transistor performance metrics with incident radiation. The impact of the collector doping level on the degradation is discussed.
In a similar fashion, gamma irradiation experiments to focus on ionization only effects are presented in chapter IV. The experimental design and dc results are first presented, followed by a comparison of degradation under proton irradiation. Additional proton dose rate experiments conducted to further investigate observed differences between proton and gamma results are presented.
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Rossouw, Maria Susanna. "Validation of endpoints as biomarkers of low-dose radiation damage." Thesis, Cape Technikon, 2004. http://hdl.handle.net/20.500.11838/1461.
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Thesis (MTech (Biomedical Technology))--Cape Technikon, Cape Town, 2004<br>The need for radiobiological research was bom from the discovery that high doses of
radiation could cause cancer and other health effects. However, recent
developments in molecular biology uncovered the effects of low doses of radiation on
different biological systems and as a result new techniques have been developed to
measure these effects.
The aim of this study was thus to validate biomarkers of initial DNA strand breaks,
micronucleus formation, and the different pt ;ases of apoptosis as biological indicators
of low-dose radiation damage. Furthermore, the difference in response of blood cells
to different qualities and doses of radiation was investigated by irradiating cells with
low- and high-LET radiation simultaneously.
Blood from one donor was irradiated with doses between 0 and 4 Gy gamma- and
neutron radiation. The alkaline single-cell gel electrophoresis (comet) assay was
performed on different cell preparations directly after irradiation for the detection of
initial DNA strand breaks. Radiation-induced cytogenetic damage was investigated
using the cytokinesis-blocked micronucleus assay while different features of
apoptosis were investigated by measuring caspase activation, enzymatic DNA
fragmentation, and cellular morphology.
The comet assay was sensitive enough to detect DNA strand breaks above 0.25 Gy
and showed that the Iymphocyte isolation process induced some endogenous
damage in cells, detected by the formation of highly damaged cells and hedgehogs in
isolated cell preparations only.
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Ferraro, Rudy. "Development of Test Methods for the Qualification of Electronic Components and Systems Adapted to High-Energy Accelerator Radiation Environments." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTS118.
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Le Grand collisionneur de hadrons (LHC), le plus grand et le plus puissant au monde, a démarré en 2008 et constitue la dernière étape du complexe des accélérateurs du CERN. Le LHC consiste en un anneau de 27 kilomètres d'aimants supraconducteurs permettant d'accélérer deux faisceaux jusqu'à 7 TeV avant de les faire entrer en collision à 14 TeV dans l'une des cinq expériences de contrôle du résultat de la collision. Le LHC a notamment permis la découverte du boson de Higgs et d'autres particules baryoniques prédites par le modèle standard. L'environnement de rayonnement du LHC et de ses lignes d'injection est composé de différentes particules sur un large spectre d'énergies, du niveau GeV jusqu'au niveau meV (par exemple le neutron thermique). L'équipement électronique fonctionnant dans un environnement de rayonnement aussi rude, principalement basé sur des composants commerciaux prêts à l'emploi (COTS), peut subir des défaillances induites par des effets de rayonnement. La criticité de l'équipement peut être très élevée, dans le meilleur des cas, la défaillance d'un système de contrôle peut conduire à une chute du faisceau, ce qui peut drastiquement rendre le faisceau disponible pour la science et dans le pire des cas, la défaillance d'un système de sécurité peut conduire à la destruction d'une partie de la machine. La nouvelle mise à niveau du LHC prévue pour 2025, le LHC à haute luminosité (HL-LHC) atteindra une luminosité annuelle cinq fois supérieure à celle de la version actuelle du LHC. Par conséquent, les niveaux de rayonnement générés par le fonctionnement de la machine vont également augmenter considérablement. Avec des niveaux de rayonnement aussi élevés, un nombre important de systèmes commerciaux seront exposés à des niveaux de rayonnement auxquels ils ne peuvent résister. Cela impliquera soit de concevoir des systèmes plus robustes et tolérants à base de COTS, soit de remplacer préventivement les systèmes avant leur fin de vie utile. Ainsi, alors qu'au cours des années précédentes, les effets singuliers (EEI) étaient la principale cause de défaillance, à l'avenir, l'effet cumulatif du rayonnement deviendra également une préoccupation majeure. Bien qu'un effort considérable ait été fait dans le passé sur le processus de qualification contre les défaillances induites par les SEE, le processus de qualification pour les effets cumulatifs du rayonnement est resté pratiquement inchangé. L'objectif de ces travaux était donc d'étudier comment la Radiation Hardness Assurance (RHA) du CERN pourrait être améliorée pour répondre à ce nouveau défi et s'assurer qu'aucune défaillance de système n'aura d'impact sur les opérations du LHC. Plusieurs activités ont été menées à cet effet : (i) l'étude des particularités de l'environnement radiatif du LHC et de son impact sur les composants et les systèmes qui y sont exposés, (ii) l'étude de l'adéquation des méthodes de qualification actuelles et le développement d'approches adaptées aux besoins du CERN et (iii) l'étude des méthodes fiables pour estimer la durée de vie des systèmes<br>The Large Hadron Collider (LHC), the largest and most powerful in the world, started in 2008 and is the last stage of CERN's accelerator complex. The LHC consists in a 27-kilometer ring of superconducting magnets allowing to accelerate two beams up to 7 TeV before colliding them at 14 TeV in one of the five experiments monitoring the result of the collision. The LHC allowed notably the discovery of the Higgs boson and other baryonic particles predicted by the standard model. The radiation environment of the LHC and its injection lines is composed of different particles over a large spectrum of energies, from GeV level down to meV level (e.g. thermal neutron). The electronic equipment operating in such a harsh radiation environment, mostly based on Commercial Off The Shelf (COTS) components, can experience failures induced by radiation effects. The criticality of the equipment can be very high, in the best case, the failure of a control system can lead to a beam dump, which can drastically the availability of the beam for science and in the worst case, the failure of a safety system can lead to the destruction of part of the machine. The new upgrade of the LHC planned for 2025, the High Luminosity LHC (HL-LHC) will achieve an annual luminosity five time higher than the current version of the LHC. Consequently, the levels of the radiation generated by the operation of the machine will also drastically increase. With such high radiation levels, a significant number of COTS-based systems will be exposed to radiation levels they cannot withstand. This will imply to either design more robust tolerant COTS-based systems and/or substitute preventively systems before their end of life. Thus, while in the previous years the Single Event Effects (SEEs) where the dominant cause of failure, in the future, cumulative radiation effect will as well become a major preoccupation. While a huge effort has been done in the past on the qualification process against SEE-induced failures, the qualification process for cumulative radiation effects, remained mostly unchanged. The aim of this work was, therefore, to investigate how the CERN’s Radiation Hardness Assurance (RHA) could be improved to respond to this new challenge and ensure that no system failures will impact the LHC operations. This involved several activities; (i) the study of the particularities of the LHC radiative environment and its impact on the components and systems exposed to it, (ii) the study of the suitability of current qualification methods and the development of approaches adapted to CERN’s needs and (iii) the study of reliable system lifetime estimation methods
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Erekson, David McConkie. "Scheduled Healing: The Relationship Between Session Frequency and Psychotherapy Outcome in a Naturalistic Setting." BYU ScholarsArchive, 2013. https://scholarsarchive.byu.edu/etd/4037.
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The dose-effect relationship in psychotherapy has been examined extensively, but few studies have included session frequency as a component of psychotherapy "dose." Those studies that have examined the effects of session frequency have indicated that it may affect both the total amount of recovery and the speed of recovery. No studies were found examining the clinical significance of this construct in a naturalistic setting. The change trajectories of 16,003 clients were examined using multi-level modeling and including session frequency as a fixed effect. Of these clients, subgroups were identified that were scheduled approximately once a week or approximately once every two weeks. These groups were compared to each other for differences in speed of recovery and clinically significant change. Results indicated that more frequent therapy was associated with steeper recovery curves. When comparing groups scheduled once a week to those scheduled once every two weeks, more clinically significant gains were identified in those attending once a week, and more significant deterioration was identified in those attending once every two weeks. These findings are discussed in light of the existing literature and the implications for future psychotherapy research and clinical practice.
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Jaillet, Cyprien. "Modifications du glycome endothélial vasculaire dans le contexte d'une irradiation à forte dose." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066021/document.
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La radiothérapie constitue l’un des principaux traitements pour l’éradication des cancers. Cependant, elle présente un risque d’effets secondaires aux tissus sains environnant la tumeur. Dans ce processus, le système vasculaire et plus particulièrement l’endothélium jouent un rôle clé. Les cellules endothéliales activées favorisent le recrutement chronique des thrombocytes et des leucocytes, contribuant ainsi aux effets secondaires. D’autre part, dans les maladies inflammatoires, les glycanes exprimés à la surface des cellules endothéliales sont modifiés et influencent le recrutement des cellules immunitaires. Dans cette étude, nous avons évalué la modification des glycanes endothéliaux en réponse à une irradiation à forte dose, et étudié les effets fonctionnels de ces modifications sur le recrutement des leucocytes en utilisant un modèle de cellules endothéliales (HUVECs) in vitro. Nos résultats apportent les premières preuves d’une modification du glycome des cellules endothéliales en réponse à l’irradiation. Les N-glycanes hautement mannosylés, les O-glycanes et les motifs sialylées sont surexprimés. Parallèlement, le glycocalyx endothélial semble subir une dégradation. Nous avons évalué l’effet fonctionnel des modifications glycanique des cellules endothéliales irradiées sur l’adhésion d’une lignée de monocyte (THP-1). Nos résultats montrent que l’adhésion radio-induite est en partie due à la surexpression endothéliale des N-glycanes hautement mannosylés. Nous avons aussi évalué le glycome sur un modèle de souris irradiées et sur des pièces opératoires de patients traités par radiothérapies. Nos résultats de transcriptomiques sur la souris suggèrent l’existence de modifications glycaniques radio-induites in vivo. L’intégration de la composante glycanique permet de porter un regard nouveau sur le continuum d’évènement qui conduit aux lésions tissulaires radio-induites. A l’avenir, l’étude du glycome pourrait ouvrir de nouvelles pistes thérapeutiques pour une meilleure prise en charge des effets secondaires de la radiothérapie<br>Radiotherapy is one of the main treatments against cancers. However, it presents a risk of adverse effects for the normal tissues surrounding the tumors. The vascular network and especially the endothelium are considered as main targets to limit normal tissue damages and prevent side effects of radiotherapy. Activated endothelial cells are involved in the chronic recruitment of thrombocytes and leukocytes, resulting in tissue complications. On the other hand, in inflammatory diseases, the glycans expressed on the surface of endothelial cells are modified and lead to immune cells recruitment. We sought to evaluate changes in endothelial glycome in a context of exposure to high dose of radiation, and studied the functional consequences on the recruitment of leukocytes. In vitro, the characterization of the glycome was performed on a primary endothelial cell model (HUVEC). Our results provide the first evidences of an endothelial modification of the glycome after exposure to ionizing radiation. We report an overexpression of high mannose N-glycans, O-glycans and syalilated motifs. At the same time, endothelial glycocalyx appeared to be damaged by exposure to radiation. Next, we evaluated these radiation-induced modifications of endothelial glycans on monocyte adhesion. We show that the radiation induced adhesion was mediated by overexpression of high mannose N-glycans. We also investigated changes in glycome in an irradiated mouse model of enteropathy and in resections of patients treated with radiotherapy. In mice, a transcriptomic study suggests changes in glycans following radiation exposure. Collectively, these findings on glycome changes provide a new perspective of the continuum of events leading to normal tissue complications. In the future, the study of the glycome should open new therapeutics opportunities for better management of tissue damages induced by radiation
Libros sobre el tema "Dole effect"
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1946-, Calabrese Edward J., ed. Biological effects of low level exposures: Dose-response relationships. Lewis Publishers, 1994.
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1923-, Upton Arthur C., National Research Council (U.S.). Committee on the Biological Effects of Ionizing Radiations., National Research Council (U.S.). Board on Radiation Effects Research., and National Research Council (U.S.). Commission on Life Sciences., eds. Health effects of exposure to low levels of ionizing radiation. National Academy Press, 1990.
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Hormesis: A revolution in biology, toxicology, and medicine. Springer, 2010.
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I, Rudnev M., and Akademii͡a︡ medychnykh nauk Ukraïny, eds. Vlii͡a︡nie nizkikh doz ionizirui͡u︡shcheĭ radiat͡s︡ii i drugikh faktorov okruzhai͡u︡shcheĭ sredy na organizm. Nauk. dumka, 1994.
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1924-, Moseley Robert D., ed. Medical effects of ionizing radiation. Grune & Stratton, 1985.
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A, Mettler Fred. Medical effects of ionizing radiation. 2nd ed. W.B. Saunders, 1995.
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1923-, Upton Arthur C., ed. Medical effects of ionizing radiation. 3rd ed. Saunders / Elsevier, 2008.
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Colloque Les Relations dose-effet de l'alcool (1984 Esclimont, France). Colloque Les Relations dose-effet de l'alcool: Esclimont, France, 20-21 mars 1984. Documentation française, 1985.
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Tsutomu, Sugahara, Sagan Leonard A, and Aoyama Takashi, eds. Low dose irradiation and biological defense mechanisms: Proceedings of the International Conference on Low Dose Irradiation and Biological Defense Mechanisms, Kyoto, Japan, 12-16 July 1992. Excerta Medica, 1992.
Buscar texto completoCapítulos de libros sobre el tema "Dole effect"
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Tallarida, Ronald J., Robert B. Raffa, and Paul McGonigle. "Dose-Effect Relations." In Springer Series in Pharmacologic Science. Springer New York, 1988. http://dx.doi.org/10.1007/978-1-4612-3778-5_2.
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van der Kogel, Albert J., and Michael C. Joiner. "The dose-rate effect." In Basic Clinical Radiobiology. CRC Press, 2018. http://dx.doi.org/10.1201/9780429490606-13.
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Messenger, George C., and Milton S. Ash. "Dose-Rate Effects." In The Effects of Radiation on Electronic Systems. Springer Netherlands, 1986. http://dx.doi.org/10.1007/978-94-017-5355-5_7.
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Simola, Nicola, Micaela Morelli, Tooru Mizuno, et al. "Drug (Dose)-Effect Function (Curve)." In Encyclopedia of Psychopharmacology. Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-68706-1_1086.
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Cherruault, Y. "Relations Between Dose and Effect." In Mathematical Modelling in Biomedicine. Springer Netherlands, 1986. http://dx.doi.org/10.1007/978-94-009-5492-2_5.
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Fiedler, H. "High-Dose-Hook-Effekt." In Lexikon der Medizinischen Laboratoriumsdiagnostik. Springer Berlin Heidelberg, 2018. http://dx.doi.org/10.1007/978-3-662-49054-9_1446-1.
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Fiedler, H. "High-Dose-Hook-Effekt." In Springer Reference Medizin. Springer Berlin Heidelberg, 2019. http://dx.doi.org/10.1007/978-3-662-48986-4_1446.
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Kalra, Mannudeep K., and Thomas L. Toth. "Patient Centering in MDCT: Dose Effects." In Radiation Dose from Multidetector CT. Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/174_2011_447.
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Sapareto, Stephen A. "Practical concepts of thermal dose." In Thermal Effects on Cells and Tissues. CRC Press, 2023. http://dx.doi.org/10.1201/9780429070365-8.
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Preskorn, S. H. "Dose-Effect and Concentration-Effect Relationships with New Antidepressants." In Clinical Pharmacology in Psychiatry. Springer Berlin Heidelberg, 1993. http://dx.doi.org/10.1007/978-3-642-78010-3_17.
Texto completoActas de conferencias sobre el tema "Dole effect"
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Prahardi, R., and Arundito Widikusumo. "Zero Dose." In Seminar Si-INTAN. Badan Pengawas Tenaga Nuklir, 2021. http://dx.doi.org/10.53862/ssi.v1.062021.008.
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Ionizing radiation in the medical world has long been used, both for diagnostic and therapeutic purposes. But the use of ionizing radiation, besides helping a lot in diagnosis and therapy, ionizing radiation is also hazardous for us. The effects of ionizing radiation on humans are divided into two types, namely stochastic effects, and non-stochastic (deterministic) effects. Of the two kinds of effects caused by ionizing radiation, the stochastic effect needs special attention. Because the dose-limiting parameter does not exist, how much radiation dose can cause the stochastic effect. We only have the principle that no matter how small the radiation that hits us, it will still impact us. The mechanism for this effect is either a direct effect or an indirect effect, or a newly discovered effect, namely the bystander effect, all of which lead to DNA damage. This DNA damage will cause various kinds of health problems for us. Keywords: Stochastic Effect, DNA Damage. Gene Mutation, Bystander Effect
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Bartoloni, Alessandro, and Lidia Strigari. "Dose-effects models for space radiobiology: An overview on dose-effect relationships." In RAD Conference. RAD Centre, 2022. http://dx.doi.org/10.21175/rad.sum.abstr.book.2022.25.1.
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Pease, Ronald, Gary Dunham, and John Seiler. "Total Dose and Dose Rate Response of Low Dropout Voltage Regulators." In 2006 IEEE Radiation Effects Data Workshop. IEEE, 2006. http://dx.doi.org/10.1109/redw.2006.295473.
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Bogorad, Alexander L., Justin J. Likar, Stephen K. Moyer, Audrey J. Ditzler, Graham P. Doorley, and Roman Herschitz. "Total Ionizing Dose and Dose Rate Effects in Candidate Spacecraft Electronic Devices." In 2008 IEEE Radiation Effects Data Workshop. IEEE, 2008. http://dx.doi.org/10.1109/redw.2008.29.
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Wang, Zujun, Zhigang Xiao, Baoping He, Shaoyan Huang, Benqi Tang, and Minbo Liu. "Total Dose Radiation Effects on COTS Array CCDs at Low Dose Rate." In 2014 IEEE Radiation Effects Data Workshop (REDW). IEEE, 2014. http://dx.doi.org/10.1109/redw.2014.7004605.
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Hansen, D. L., M. J. Robinson, and F. Lu. "Total-Dose Effects in InP Devices." In 2007 IEEE Radiation Effects Data Workshop. IEEE, 2007. http://dx.doi.org/10.1109/redw.2007.4342542.
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Harris, Richard D., Steven S. McClure, Bernard G. Rax, et al. "ELDRS Characterization for a Very High Dose Mission." In 2010 Radiation Effects Data Workshop. IEEE, 2010. http://dx.doi.org/10.1109/redw.2010.5619505.
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Avery, Keith, Jeffery Finchel, Jesse Mee, et al. "Total Dose Test Results for CubeSat Electronics." In 2011 IEEE Radiation Effects Data Workshop. IEEE, 2011. http://dx.doi.org/10.1109/redw.2010.6062504.
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Chen, Dakai, James D. Forney, Ronald L. Pease, et al. "The Effects of ELDRS at Ultra-Low Dose Rates." In 2010 Radiation Effects Data Workshop. IEEE, 2010. http://dx.doi.org/10.1109/redw.2010.5619506.
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Hiemstra, D. M., S. Shi, Z. Yang, and L. Chen. "Total Dose Performance at High and Low Dose Rate of a CMOS, Low Dropout Voltage Regulator showing Enhanced Low Dose Rate Sensitivity." In 2021 IEEE Nuclear and Space Radiation Effects Conference (NSREC). IEEE, 2021. http://dx.doi.org/10.1109/nsrec45046.2021.9679352.
Texto completoInformes sobre el tema "Dole effect"
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Abdulla, Sara, and Jack Corrigan. Bayh-Dole Patent Trends. Center for Security and Emerging Technology, 2023. http://dx.doi.org/10.51593/20230012.
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This brief examines trends in patents generated through federally funded research, otherwise known as Bayh-Dole patents. We find that while Bayh-Dole patents make up a small proportion of U.S. patents overall, they are much more common in certain fields, especially in biosciences and national defense related fields. Academic institutions are major recipients of Bayh-Dole patents, and the funding landscape for patent-producing research has shifted since Bayh-Dole came into effect in 1980.
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Li, Xiao, GX Xu, FY Ling, et al. The dose-effect association between electroacupuncture sessions and its effect on chronic migraine: a protocol of a meta-regression of randomized controlled trials. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, 2022. http://dx.doi.org/10.37766/inplasy2022.12.0085.
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Review question / Objective: We will use a meta-regression approach to verify the dose-effect relationship between the number of electroacupuncture sessions and its effects on migraine. Condition being studied: Migraine is recurrent and chronic, requiring long-term control, but the side effects caused by long-term use limit the use of pharmacotherapy, like non-steroidal anti-inflammatory drugs (NSAIDS), ergoamines and opioids. With fewer side effects and lower cost, acupuncture is becoming a more attractive option for migraine. Relevant studies have confirmed the clinical effects of electroacupuncture on migraine and its effects on intracranial blood flow velocity, functional brain imaging and neuroinflammation. However, uncertainty exists regarding the dose-effect between electroacupuncture and migraine. In recent years, inspired by the dose-effect researches in pharmacology and epidemiology, researches focusing on the dose-effect association between acupuncture and diseases has also begun to emerge. So in this protocol, we designed to use a meta-regression approach to explore the optimal electroacupuncture dose for migraine.
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Worgul, B. V. Low dose neutron late effects: Cataractogenesis. Office of Scientific and Technical Information (OSTI), 1991. http://dx.doi.org/10.2172/5816375.
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Jordan, Jacob. On-treatment changes in pediatric parameningeal rhabdomyosarcoma treated with upfront proton therapy. University of Tennessee Health Science Center, 2022. http://dx.doi.org/10.21007/com.lsp.2022.0008.
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The project is focused on the effects of longitudinal changes in patient and tumor anatomy on the delivered treatment plan during proton radiotherapy for the treatment of pediatric Para meningeal rhabdomyosarcoma. The study will investigate the effects of change on dose delivered to organs-at-risk near the tumor. This effort will extend the analysis of changes to the organs-at-risk to all the cases in the study and add an additional case meeting the study criteria.
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Azmy, Y. Y. Effect of Workbench Shielding on Nagasaki Factory Workers' Dose. Office of Scientific and Technical Information (OSTI), 2001. http://dx.doi.org/10.2172/777636.
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Sopori, Mohan L. Neuroimmune Effects of Inhaling Low Dose Sarin. Defense Technical Information Center, 2005. http://dx.doi.org/10.21236/ada442264.
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Brust. L51576 Crack Growth Behavior and Modeling. Pipeline Research Council International, Inc. (PRCI), 1989. http://dx.doi.org/10.55274/r0010642.
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The objective of the Crack Growth/Modeling effort of the NG-18 Line Pipe Supervisory Committee's Stress-Corrosion Phase is to develop an understanding of the factors that control stress-corrosion crack growth. This information can be used to develop models for predicting crack growth and to mitigate crack growth through control of metallurgical parameters and operating conditions. This effort has been divided into the following four main tasks: (1) Characterization of crack shape,(2) Identification of a crack force driving parameter,(3) Determination of the effects of mechanical properties on crack growth and shape, and(4) Examination of the effects of crack interaction on overall crack growth. The background, procedures, and results of the work done in each of these tasks will be described separately.
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E, Flemyng, and Mitchell D. Increased versus stable doses of inhaled steroids for exacerbations of chronic asthma in adults and children: Protocol. Epistemonikos Interactive Evidence Synthesis, 2022. http://dx.doi.org/10.30846/ies.b984bf9656.v3.
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Abstract Rationale Early treatment of asthma exacerbations with inhaled corticosteroids is the best strategy for management, although use of an increased or stable dose is questioned. Objectives To compare the clinical effectiveness and safety of increased versus stable doses of inhaled corticosteroids as part of a patient-initiated action plan for the home management of exacerbations in children and adults with persistent asthma. Search methods We searched the Cochrane Airways Group Specialised Register (part of CENTRAL), MEDLINE, Embase, CINAHL, major trials registries and handsearched abstracts up to 20 December 2021. Eligibility criteria Parallel and cross-over blinded randomised controlled trials (RCTs) Outcomes Treatment failure (the need for rescue oral steroids) in the randomised population and in the subset who initiated the study inhaler, unscheduled physician visits, unscheduled acute care, emergency department or hospital visits, serious and non-serious adverse events, and duration of exacerbation. Risk of bias We used Risk of Bias 2 (RoB 2)and the tool's extension for cross-over trials. Synthesis methods We conducted meta-analyses using fixed-effect models to calculate odds ratios (OR) and 95% confidence intervals (CI) for all but one outcome, which used random-effects models due to heterogeneity (treatment failure in the subset who initiated the study inhaler). We summarised certainty of evidence according to GRADE methods. Included studies We included nine RCTs (seven parallel and two cross‐over) with a total of 1923 participants. The studies were conducted in Europe, North America, and Australasia and were published between 1998 and 2018. Five studies evaluated adult populations (1247 participants; ≥ 15 years), and four studies evaluated child or adolescent populations (676 participants; < 15 years). Approximately 50% of randomised participants initiated the study inhaler (range 23% to 100%). The studies reported treatment failure in various ways, so we made assumptions to allow us to combine data. Synthesis of results People randomised to increase their inhaled corticosteroids dose at the first signs of an exacerbation probably had similar odds of needing rescue oral corticosteroids to those randomised to a placebo inhaler (OR 0.97, 95% CI 0.76 to 1.25; 8 studies, 1774 participants; moderate-certainty evidence). Results for the same outcome in the subset of participants who initiated the study inhaler (approximately 50%) gives a different point estimate with very low certainty due to heterogeneity, imprecision and risk of bias (OR 0.84, 95% CI 0.54 to 1.30; 7 studies, 766 participants; random-effects model used). For adverse effects, imprecision and risk of bias from missing data, outcome measurement and reporting meant we were very uncertain about the effect estimate (serious adverse events OR 1.69, 95% CI 0.77 to 3.71; 2 studies, 394 participants; non-serious adverse events OR 2.15, 95% CI 0.68 to 6.73; 2 studies, 142 participants). We had very low confidence in the effect estimates for unscheduled physician visits, unscheduled acute care, emergency department or hospital visits and duration of exacerbation due to risk of bias. Authors' conclusions Evidence suggests that adults and children with mild to moderate asthma are unlikely to have an important reduction in the need for oral steroids from increasing a patient's inhaled corticosteroid dose at the first sign of an exacerbation. Other clinically important benefits and potential harms cannot be ruled out due to wide confidence intervals, risk of bias in the studies, and assumptions made for synthesis when combining data. Included studies reflect evolving clinical practice and study methods, and the data do not support thorough investigation of effect modifiers such as baseline dose, fold increase, asthma severity and timing. The review does not include recent evidence from pragmatic, unblinded studies showing benefits of larger dose increases in those with poorly controlled asthma. Differences between the blinded and unblinded studies should be investigated. Funding This Cochrane Review had no dedicated funding. Registration Protocol (2009): doi.org/10.1002/14651858.CD007524 Original review (2010): doi.org/10.1002/14651858.CD007524.pub3 Review update (2014): doi.org/10.1002/14651858.CD007524.pub4
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E, Flemyng, and Mitchell D. Increased versus stable doses of inhaled steroids for exacerbations of chronic asthma in adults and children: Protocol. Epistemonikos Interactive Evidence Synthesis, 2022. http://dx.doi.org/10.30846/ies.b984bf9699.v2.
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Abstract Rationale Early treatment of asthma exacerbations with inhaled corticosteroids is the best strategy for management, although use of an increased or stable dose is questioned. Objectives To compare the clinical effectiveness and safety of increased versus stable doses of inhaled corticosteroids as part of a patient-initiated action plan for the home management of exacerbations in children and adults with persistent asthma. Search methods We searched the Cochrane Airways Group Specialised Register (part of CENTRAL), MEDLINE, Embase, CINAHL, major trials registries and handsearched abstracts up to 20 December 2021. Eligibility criteria Parallel and cross-over blinded randomised controlled trials (RCTs) Outcomes Treatment failure (the need for rescue oral steroids) in the randomised population and in the subset who initiated the study inhaler, unscheduled physician visits, unscheduled acute care, emergency department or hospital visits, serious and non-serious adverse events, and duration of exacerbation. Risk of bias We used Risk of Bias 2 (RoB 2)and the tool's extension for cross-over trials. Synthesis methods We conducted meta-analyses using fixed-effect models to calculate odds ratios (OR) and 95% confidence intervals (CI) for all but one outcome, which used random-effects models due to heterogeneity (treatment failure in the subset who initiated the study inhaler). We summarised certainty of evidence according to GRADE methods. Included studies We included nine RCTs (seven parallel and two cross‐over) with a total of 1923 participants. The studies were conducted in Europe, North America, and Australasia and were published between 1998 and 2018. Five studies evaluated adult populations (1247 participants; ≥ 15 years), and four studies evaluated child or adolescent populations (676 participants; < 15 years). Approximately 50% of randomised participants initiated the study inhaler (range 23% to 100%). The studies reported treatment failure in various ways, so we made assumptions to allow us to combine data. Synthesis of results People randomised to increase their inhaled corticosteroids dose at the first signs of an exacerbation probably had similar odds of needing rescue oral corticosteroids to those randomised to a placebo inhaler (OR 0.97, 95% CI 0.76 to 1.25; 8 studies, 1774 participants; moderate-certainty evidence). Results for the same outcome in the subset of participants who initiated the study inhaler (approximately 50%) gives a different point estimate with very low certainty due to heterogeneity, imprecision and risk of bias (OR 0.84, 95% CI 0.54 to 1.30; 7 studies, 766 participants; random-effects model used). For adverse effects, imprecision and risk of bias from missing data, outcome measurement and reporting meant we were very uncertain about the effect estimate (serious adverse events OR 1.69, 95% CI 0.77 to 3.71; 2 studies, 394 participants; non-serious adverse events OR 2.15, 95% CI 0.68 to 6.73; 2 studies, 142 participants). We had very low confidence in the effect estimates for unscheduled physician visits, unscheduled acute care, emergency department or hospital visits and duration of exacerbation due to risk of bias. Authors' conclusions Evidence suggests that adults and children with mild to moderate asthma are unlikely to have an important reduction in the need for oral steroids from increasing a patient's inhaled corticosteroid dose at the first sign of an exacerbation. Other clinically important benefits and potential harms cannot be ruled out due to wide confidence intervals, risk of bias in the studies, and assumptions made for synthesis when combining data. Included studies reflect evolving clinical practice and study methods, and the data do not support thorough investigation of effect modifiers such as baseline dose, fold increase, asthma severity and timing. The review does not include recent evidence from pragmatic, unblinded studies showing benefits of larger dose increases in those with poorly controlled asthma. Differences between the blinded and unblinded studies should be investigated. Funding This Cochrane Review had no dedicated funding. Registration Protocol (2009): doi.org/10.1002/14651858.CD007524 Original review (2010): doi.org/10.1002/14651858.CD007524.pub3 Review update (2014): doi.org/10.1002/14651858.CD007524.pub4
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E, Flemyng, and Mitchell D. Increased versus stable doses of inhaled steroids for exacerbations of chronic asthma in adults and children: Update. Epistemonikos Interactive Evidence Synthesis, 2022. http://dx.doi.org/10.30846/ies.b984bf9639.v2.
Texto completoResumen
Abstract Rationale Early treatment of asthma exacerbations with inhaled corticosteroids is the best strategy for management, although use of an increased or stable dose is questioned. Objectives To compare the clinical effectiveness and safety of increased versus stable doses of inhaled corticosteroids as part of a patient-initiated action plan for the home management of exacerbations in children and adults with persistent asthma. Search methods We searched the Cochrane Airways Group Specialised Register (part of CENTRAL), MEDLINE, Embase, CINAHL, major trials registries and handsearched abstracts up to 20 December 2021. Eligibility criteria Parallel and cross-over blinded randomised controlled trials (RCTs) Outcomes Treatment failure (the need for rescue oral steroids) in the randomised population and in the subset who initiated the study inhaler, unscheduled physician visits, unscheduled acute care, emergency department or hospital visits, serious and non-serious adverse events, and duration of exacerbation. Risk of bias We used Risk of Bias 2 (RoB 2)and the tool's extension for cross-over trials. Synthesis methods We conducted meta-analyses using fixed-effect models to calculate odds ratios (OR) and 95% confidence intervals (CI) for all but one outcome, which used random-effects models due to heterogeneity (treatment failure in the subset who initiated the study inhaler). We summarised certainty of evidence according to GRADE methods. Included studies We included nine RCTs (seven parallel and two cross‐over) with a total of 1923 participants. The studies were conducted in Europe, North America, and Australasia and were published between 1998 and 2018. Five studies evaluated adult populations (1247 participants; ≥ 15 years), and four studies evaluated child or adolescent populations (676 participants; < 15 years). Approximately 50% of randomised participants initiated the study inhaler (range 23% to 100%). The studies reported treatment failure in various ways, so we made assumptions to allow us to combine data. Synthesis of results People randomised to increase their inhaled corticosteroids dose at the first signs of an exacerbation probably had similar odds of needing rescue oral corticosteroids to those randomised to a placebo inhaler (OR 0.97, 95% CI 0.76 to 1.25; 8 studies, 1774 participants; moderate-certainty evidence). Results for the same outcome in the subset of participants who initiated the study inhaler (approximately 50%) gives a different point estimate with very low certainty due to heterogeneity, imprecision and risk of bias (OR 0.84, 95% CI 0.54 to 1.30; 7 studies, 766 participants; random-effects model used). For adverse effects, imprecision and risk of bias from missing data, outcome measurement and reporting meant we were very uncertain about the effect estimate (serious adverse events OR 1.69, 95% CI 0.77 to 3.71; 2 studies, 394 participants; non-serious adverse events OR 2.15, 95% CI 0.68 to 6.73; 2 studies, 142 participants). We had very low confidence in the effect estimates for unscheduled physician visits, unscheduled acute care, emergency department or hospital visits and duration of exacerbation due to risk of bias. Authors' conclusions Evidence suggests that adults and children with mild to moderate asthma are unlikely to have an important reduction in the need for oral steroids from increasing a patient's inhaled corticosteroid dose at the first sign of an exacerbation. Other clinically important benefits and potential harms cannot be ruled out due to wide confidence intervals, risk of bias in the studies, and assumptions made for synthesis when combining data. Included studies reflect evolving clinical practice and study methods, and the data do not support thorough investigation of effect modifiers such as baseline dose, fold increase, asthma severity and timing. The review does not include recent evidence from pragmatic, unblinded studies showing benefits of larger dose increases in those with poorly controlled asthma. Differences between the blinded and unblinded studies should be investigated. Funding This Cochrane Review had no dedicated funding. Registration Protocol (2009): doi.org/10.1002/14651858.CD007524 Original review (2010): doi.org/10.1002/14651858.CD007524.pub3 Review update (2014): doi.org/10.1002/14651858.CD007524.pub4