Academic literature on the topic 'MDRS'
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Journal articles on the topic "MDRS"
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Sobreira, Emmanuelle Silva Tavares, Marina Ceres Silva Pena, José Humberto Silva Filho, Carolina Pinto Souza, Guiomar Nascimento Oliveira, Vitor Tumas, and Francisco de Assis Carvalho do Vale. "Executive cognitive tests for the evaluation of patients with Parkinson's disease." Dementia & Neuropsychologia 2, no. 3 (September 2008): 206–10. http://dx.doi.org/10.1590/s1980-57642009dn20300008.
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Abstract Parkinson's disease (PD) is characterized by changes in movement, which are later followed by cognitive, behavioral and psychological changes. The objective of the present study was to correlate different tests used to examine executive functions in PD patients followed at a specialized outpatient clinic. Methods: Thirty-five patients with idiopathic PD aged 63.0 years on average and with mean schooling of 5.5±4.2 years, were examined using the following tests: Mattis Dementia Rating Scale (MDRS), Scales for Outcomes of Parkinson's Disease-Cognition (SCOPA-COG), Wisconsin Card Sorting Test (WCST), Frontal Assessment Battery (FAB), Digit Span - Inverse Order (IO) (a subtest of the WAIS III) and Verbal Fluency Test (category animals). Results: Significant correlations were detected between FAB and MDRS Conceptualization (0.814), MDRS Initiation/Perseveration (I/P) and SCOPA-COG Executive Function (0.643), FAB and MDRS I/P (0.601), FAB and Verbal Fluency (0.602), MDRS I/P and MDRS Conceptualization (0.558), Verbal Fluency and MDRS I/P (0.529), MDRS Attention and SCOPA-COG Executive Function (0.495), MDRS Conceptualization and SCOPA-COG Executive Function (0.520), FAB and Digit Span (OI) (0.503), Verbal Fluency and MDRS Conceptualization (0.501), and WCST perseverative errors and FAB (-0.379), WCST perseverative errors and MDRS Conceptualization (0.445), WCST perseverative errors and MDRS I/P (-0.407) and WCST categories completed and MDRS Conceptualization (0.382). Discussion: The results demonstrated strong correlations between most of the tests applied, but no associations were detected between the WCST and the other tests, a fact that may be explained by the heterogeneity of scores obtained in the tests by the patients evaluated. A difficulty of the present study was the lack of a control groups for the establishment of adequate standards for this population.
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Herreen, Danielle, Simon Rice, and Ian Zajac. "Brief assessment of male depression in clinical care: Validation of the Male Depression Risk Scale short form in a cross-sectional study of Australian men." BMJ Open 12, no. 3 (March 2022): e053650. http://dx.doi.org/10.1136/bmjopen-2021-053650.
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ObjectivesTo develop and validate a short form of the Male Depression Risk Scale (MDRS-22) for use in primary care, examining associations with prototypic depression symptoms, psychological distress and suicidality.DesignCross-sectional study with 8-month follow-up.SettingCommunity-based.ParticipantsA community sample of younger (n=510; 18–64 years) and older (n=439; 65–93 years) men residing in Australia (M age=58.09 years, SD=17.77) participated in the study. A subset of respondents (n=159 younger men; n=169 older men) provided follow-up data approximately eight months later.Primary and secondary outcome measuresQuantitative data were obtained through a survey comprising a range of validated measures, including the MDRS-22, the Patient Health Questionnaire (PHQ-9) and the Kessler Psychological Distress Scale (K10). The MDRS-22 was refined using exploratory and confirmatory factor analysis in line with best practice guidelines. Analysis of variance and generalised linear models were conducted to explore relationships between variables.ResultsThe short-form MDRS consisted of seven items (MDRS-7) and captured all of the domains in the original tool. Participants with mixed symptoms (PHQ-9 ≥ 10 and MDRS-7 > 5) had significantly higher risk of mental illness (K10 ≥ 25) and current suicidality (PHQ-9 item 9 ≥ 1) than those with exclusively prototypic symptoms (PHQ-9 ≥ 10 and MDRS-7 ≤ 5). Furthermore, the MDRS-7 was shown to be effective at predicting elevated symptoms of depression at follow-up, after controlling for previous depression diagnosis.ConclusionsFindings provide preliminary evidence of the potential utility of the MDRS-7 as a screening tool for externalised and male-type symptoms associated with major depression in men. Field trials of the MDRS-7 in primary care settings may facilitate identification of men at risk of suicide and psychological distress who do not meet cut-off scores for existing measures of major depression symptoms.
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Van, Johnson, Alicia Mangram, Christopher Mitchell, Manuel Lorenzo, Dot Howard, and Ernest Dunn. "Is There a Benefit to Multidisciplinary Rounds in an Open Trauma Intensive Care Unit regarding Ventilator-Associated Pneumonia?" American Surgeon 75, no. 12 (December 2009): 1171–74. http://dx.doi.org/10.1177/000313480907501204.
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Multidisciplinary rounds (MDRs) have been instituted for patient care since June 2005. Before June 2005, all care was provided by individual practitioners. MDRs include the surgical intensivist, surgical resident, patient's nurse, case manager, pharmacist, chaplain, nutritionist, and respiratory therapist. Our study examined the effect of MDRs on ventilator-associated pneumonia in trauma patients in open intensive care units (ICUs). Group 1 included patients from June 2003 to May 2005 before the implementation of MDRs, and Group 2 included patients after the institution of MDRs from June 2005 to May 2007. In Group 1, there were 83 ventilator-associated pneumonias (VAPs) during 2414 ventilator days. In Group 2, there were 49 VAPs during 2094 ventilator days. The ratio of VAPs per thousand ventilator days decreased from 34.4 to 23.4 between the two groups ( P = 0.04). When comparing trauma patients in our open ICU with similar mean Injury Severity Score and mean Abbreviated Injury Score for chest and for head and neck, implementing MDRs significantly decreased our incidence of VAP.
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Foss, Maria Paula, Francisco de Assis Carvalho do Vale, and José Geraldo Speciali. "Influência da escolaridade na avaliação neuropsicológica de idosos: aplicação e análise dos resultados da Escala de Mattis para Avaliação de Demência (Mattis Dementia Rating Scale - MDRS)." Arquivos de Neuro-Psiquiatria 63, no. 1 (March 2005): 119–26. http://dx.doi.org/10.1590/s0004-282x2005000100022.
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OBJETIVO: Estimar a influência da baixa escolaridade e do analfabetismo na avaliação das demências através da aplicação da Escala de Mattis para Avaliação de Demência (MDRS). MÉTODO: Aplicou-se a MDRS em 62 idosos normais (64-77 anos), divididos em cinco grupos, segundo a escolaridade: 15-16 anos, 11-12 anos, 8-9 anos, 4 anos, analfabetos. A MDRS abrange o estudo de 36 itens distribuídos em cinco subescalas, sendo que a soma pode representar o grau de comprometimento cognitivo. RESULTADOS: Observou-se diferença significativa (p<0,05) na escala, no desempenho entre os grupos quanto a escolaridade, em 12 dos itens, nas cinco subescalas (analfabetos< os demais grupos e os de 15-16 anos> que os de 4 e/ou 8 anos de escolaridade, p<0,001)e no total de pontos da MDRS (analfabetos<todos os demais e 4 e 8 anos< 15-16 anos, p<0,001). Não houve correlações significativas para a idade e, quanto ao gênero, as diferenças foram significativas em apenas um item. CONCLUSÃO: A escolaridade interferiu no desempenho dos indivíduos no MDRS. O analfabetismo é um fator determinante no rebaixamento nos escores da MDRS, podendo gerar erros diagnósticos.
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Connell, Jian, Shanil Haugen, and Ann Ferriter. "Duodenoscope Medical Device Reports Associated with Patient Infection, Patient Exposure, or Device Contamination." Infection Control & Hospital Epidemiology 41, S1 (October 2020): s196—s197. http://dx.doi.org/10.1017/ice.2020.737.
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Background: Each year, the FDA receives more than a million reports of suspected device-associated deaths, serious injuries, and malfunctions. Medical device reports (MDRs) are submitted to the FDA by mandatory reporters (manufacturers, importers, and device user facilities) and voluntary reporters such as healthcare professionals, patients, and consumers. The FDA uses MDRs to monitor device performance, including monitoring reports of infection or device contamination to detect potential device-related safety issues and to share this information in public communications. In this analysis, the FDA presents MDRs for duodenoscopes, which are a type of flexible endoscope that have been associated with infections in patients. Methods: For this analysis, we searched the MDR database for duodenoscope reports submitted between January 2015 and July 1, 2019. MDRs were classified into clinical risk categories based on the MDR’s text narratives as patient infection (indicated the presence of infection in patients potentially transmitted by the device), patient exposure (indicated a contaminated device has been used in a patient, but the MDR lacks clear mention of patient infection), or device contamination (indicated that the device was contaminated, but no mention of device use in patients or patient infection). Results: Overall, 1,115 duodenoscope reports related to a patient infection, patient exposure, or device contamination for devices marketed inside and outside the United States were received from January 2015 to mid-2019. Among them, 79 MDRs were received for deaths in patient infection, patient exposure, or device contamination reports. The number of reported infections decreased from 247 MDRs in 2015 to 55 MDRs in the first half of 2019. Furthermore, the number of reported deaths decreased from 25 MDRs in 2015 to 2 MDRs reported in the first half of 2019. Conclusions: The MDR data indicate a decrease in the number of reported infections. The decrease in infections suggests that efforts to reduce the risk of infection from duodenoscopes have yielded improvements; however, additional improvements are necessary to further decrease the risk of infection.Funding: NoneDisclosures: None
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Li, Yaqiong, Pascale Carayon, Ann Schoofs Hundt, and Peter Hoonakker. "Team Interactions and Health IT Use during Hospital Multidisciplinary Rounds." Proceedings of the Human Factors and Ergonomics Society Annual Meeting 60, no. 1 (September 2016): 513–17. http://dx.doi.org/10.1177/1541931213601117.
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Multidisciplinary rounds (MDRs) are an important form of team-based process in health care. Team members coordinate patient care and make decisions on care plans jointly. Health IT used during MDRs should be designed to facilitate the team interactions given the specific context or work system where MDRs occur. This study examines and compares team interactions and health IT use in three hospital services (contexts): hospitalist, cardiology and critical care. There were few differences in team interactions and health IT use across services. However, health IT use was different for different rounding tasks and team members. Therefore, health IT should be designed to support team interactions and users’ needs during MDRs in different contexts.
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Gilbert, David N. "Influence of an Infectious Diseases Specialist on ICU Multidisciplinary Rounds." Critical Care Research and Practice 2014 (2014): 1–4. http://dx.doi.org/10.1155/2014/307817.
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Objective. To ascertain the influence of a physician infectious diseases specialist (IDS) on antibiotic use in a medical/surgical intensive care unit.Method. Over a 5-month period, the antibiotic regimens ordered by the ICU multidisciplinary team were studied. The days of antibiotic therapy (DOT) when management decisions included an IDS were compared to DOT in the absence of an IDS. The associated treatment expense was calculated.Results. Prior to multidisciplinary rounds (MDRs), 79-80% of the patients were receiving one or more antibiotic. IDS participation occurred in 61 multidisciplinary rounding sessions. There were 384 patients who before MDRs had orders for 669 days of antimicrobial therapy (DOT). After MDRs, the antimicrobial DOT were reduced to 511 with a concomitant cost saving of $3772. There were 51 MDR sessions that occurred in the absence of the IDS. There were 352 patients who before MDRs had orders for 593 DOT. After MDRs, the DOT were reduced to 572 with a cost savings of $727. The results were normalized by number of patients evaluated with statistically greater reductions when MDRs included the IDS. In addition, the number of rounding sessions with a reduction in DOT was greater with the participation of the IDS.Conclusion. The addition of an IDS to multidisciplinary ICU patient rounds resulted in a reduction in antibiotic DOT and attendant drug expense.
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Rice, Simon M., David Kealy, Zac E. Seidler, John L. Oliffe, Ronald F. Levant, and John S. Ogrodniczuk. "Male-Type and Prototypal Depression Trajectories for Men Experiencing Mental Health Problems." International Journal of Environmental Research and Public Health 17, no. 19 (October 7, 2020): 7322. http://dx.doi.org/10.3390/ijerph17197322.
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Growing interest in gender-sensitive assessment of depression in men has seen the development of male-specific screening tools. These measures are yet to be subject to longitudinal latent modelling, which limits evidence about the ability of these tools to detect change, especially relative to established screening scales. In this study, three waves of data were collected from 234 men (38.35 years, SD = 14.09) including 3- and 6-month follow-up. Analyses focused on baseline differences and symptom trajectories for the Patient Health Questionnaire (PHQ; prototypic symptoms) and the Male Depression Risk Scale (MDRS; male-type symptoms). At baseline, men not accessing treatment reported higher MDRS scores relative to treatment-engaged men. There was no group difference for the PHQ. Internal consistency (α, ω) coefficients indicated comparable reliability for both measures across the three waves. Multidomain latent growth modelling, including current treatment engagement as a covariate, reported good model fit (CFI = 0.964, TLI = 0.986, RMSEA = 0.081, SRMR = 0.033) with differential findings for the PHQ and MDRS. Consistent with the baseline between-group analysis, current treatment effects were observed for the MDRS, but not the PHQ. Trajectory modelling for the MDRS indicated that greater severity resulted in slower improvement by 6 months. In contrast, there was no difference in the PHQ rate of change between baseline and 6 months. Findings support the psychometric utility of the MDRS as a male-specific symptom domain measure sensitive to both longitudinal change and potential treatment effects for symptomatic men, in ways not discernible by the PHQ. The MDRS may be a useful adjunctive screening tool for assessing men’s depression.
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Owsiany, Montgomery, and Amy Fiske. "VALIDITY EVIDENCE FOR THE MALE DEPRESSION RISK SCALE-22 (MDRS-22) IN YOUNGER AND OLDER ADULT MALES." Innovation in Aging 6, Supplement_1 (November 1, 2022): 792–93. http://dx.doi.org/10.1093/geroni/igac059.2862.
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Abstract Men are two times less likely to be diagnosed with major depressive disorder (MDD) than women. However, suicide rates are nearly four times higher in men than women, increasing to six times or more when comparing older men to older women. Masculine depression is characterized by symptoms that are not usually assessed by diagnostic criteria for MDD, including drug and alcohol abuse, anger and aggression, and risk-taking. Previous studies have largely neglected to consider the possibility of age-related differences in the presentation of masculine depression. Given research on age-related differences in MDD, there may be age-related differences in the presentation of masculine depression as well. The present study assessed age invariance of the MDRS-22 through a multi-group confirmatory factor analysis (CFA), evaluated validity evidence of the MDRS-22, and tested the MDRS-22’s ability to assess suicidal ideation and behaviors. There was a significant difference between the configural and first-order metric models of the CFA showing that the MDRS-22 was not age invariant (ΔX2 = 451.47, Δdf = 16, p < .001). The MDRS-22 showed convergent validity evidence with assessments of MDD, alignment with masculine norms, suicidal behaviors, problematic alcohol use, and aggression. The MDRS-22 showed concurrent validity evidence with another assessment of masculine depression. Finally, MDRS-22 scores significantly predicted suicide risk above PHQ-9 scores (F(2,440) = 138.774, p < .001, R2 = .385). Overall, the study highlights the importance of screening males for masculine depression. Further research is needed to determine if masculine depression presents differently in younger and older males.
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Kalkbrenner, Michael T., and Emily Goodman-Scott. "Peer-to-Peer Mental Health Support: Validating Scores on the Mental Distress Response Scale With High School Students." Professional School Counseling 25, no. 1 (January 1, 2021): 2156759X2110066. http://dx.doi.org/10.1177/2156759x211006631.
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This investigation tested the internal structure of scores on the Mental Distress Response Scale (MDRS), a peer-to-peer mental health support screening tool, with a national sample of 237 adolescents from 111 high schools in 30 states. Results revealed psychometric support for the scores on the MDRS and demographic differences in students’ responses. We discuss implications for how school counselors can use the MDRS to enhance peer-to-peer mental health support as part of a comprehensive school counseling program.
Dissertations / Theses on the topic "MDRS"
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Costa, Cesar Augusto Sam Tiago Vilanova. "Avaliação da expressão de genes de resistência às múltiplas drogas (MDRs) e de metabolização em diferentes linhagens celulares tratadas com complexos metálicos de rutênio." Universidade Federal de Goiás, 2013. http://repositorio.bc.ufg.br/tede/handle/tede/3769.
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Foi com a descoberta da atividade antimitótica da cisplatina por Rosenberg na década se 1960 e 70, em seu célebre estudo com bactérias Escherichia coli, que surgiu o interesse em sintetizar e entender as bases moleculares responsáveis pelo mecanismo de ação biológica dos compostos metálicos, visto que a própria cisplatina foi inicialmente sintetizada por Peyrone nos idos de 1840. Os primeiros estudos envolvendo o uso de complexos metálicos de rutênio como agentes antitumorais foram realizados por Tochter no final dos anos 1980 (Dale et al., 1992). Àquela época, foi inferido que todos os compostos de rutênio apresentavam como mecanismo de ação, a sua ligação com o DNA, formando adutos e desencadeando processos celulares de natureza deletéria que, por fim, levariam a morte celular. É interessante lembrar que esse é o mesmo mecanismo de ação dos compostos de platina mais aceitos nos dias atuais. Sadler e Dyson (2003) estudando compostos de rutênio que continham cloro em sua estrutura, como o cloreto de cis-(dicloro)tetraaminorutênio(III) [cis-[RuCl2(NH3)4]Cl], observaram que estes compostos apresentavam mecanismos de ação biológica muito parecidos com os apresentados pela cisplatina [Pt(NH3)2Cl2], onde a hidrólise da ligação Ru–Cl pode ser fortemente influenciada pela natureza dos coligantes presentes na estrutura do rutenato, como grupamentos amino ou até mesmo pela presença de átomos de carbono. A alta concentração de cloretos no sangue permite a esses compostos metálicos, levados por proteínas séricas, chegar até as células e atravessar sua membrana celular e nuclear. Uma vez no interior do núcleo, a ligação Ru–Cl é hidrolisada, devido a queda abrupta da concentração de cloretos (que é cerca de 25 vezes menor), levando o composto a se ligar ao DNA, mais especificamente à posição N7 da base nitrogenada guanina. Por outro lado, compostos que não possuem cloro em sua estrutura, parecem apresentar mecanismos de ação diferentes ao padrão "ligação ao DNA". Sabe-se que compostos que apresentam carboxilatos em sua molécula, como a carboplatina, oxaliplatina e o próprio ditionato de cis-tetraammino(oxalato)rutênio(III) [Cis-[Ru(C2O2)(NH3)4]2(S2O6)], uma vez no interior das células, são hidrolisados muito mais lentamente do que os compostos ricos em cloretos, o que leva a um acúmulo desses compostos no citoplasma, diminuindo sua migração até o núcleo e, assim reduzindo a sua capacidade de se ligar ao DNA. Mas se o DNA não é o alvo desses compostos, então, quem poderia ser? Essa pergunta está sendo respondida com recentes estudos, que revelaram a interação desses compostos, ricos em carboxilatos, com uma miríade de proteínas e enzimas, que vão desde catepsinas, chegando até mesmo à Pgp (Melchart & Sadler, 2008). Estudos realizados por Dyson e colaboradores (2007), utilizando alguns inibidores da proteína Pgp, como fenoxazinas e antracenos, coordenados com compostos de rutênio, observaram que estes novos complexos não somente inibiram a ação da enzima, como também induziram morte celular, demonstrando uma multifuncionalidade. Seguindo essa linha de pensamento, acreditamos que a capacidade do composto ditionato de cistetraammino(oxalato)rutênio(III) em induzir apoptose nas células tumorais, assim como os baixos níveis de expressão de Pgp apresentados pelas células tratadas, corroboram os resultados previamente observados por outros grupos, utilizando compostos de rutênio similares. A resistência a fármacos mediada por Pgp é o mecanismo de MDR mais estudado atualmente. Apesar do desenvolvimento de novos agentes antitumorais, a MDR mediada pela Pgp protege as células de possíveis agentes citotóxicos, limitando a eficácia dos tratamentos quimioterápicos em pacientes com câncer. Atualmente, a extensa maioria dos inibidores da Pgp disponíveis estão associados a vários inconvenientes, que limitam o seu uso no reestabelecimento da eficácia da quimioterapia antineoplásica, após o aparecimento do fenótipo MDR. A procura de inibidores de Pgp alternativos, com um processo sintético exequível e efeitos secundários reduzidos, continua a ser um desafio para os químicos, farmacêuticos e pesquisadores. É nesse contexto que estão sendo desenvolvidos e estudados novos agentes antitumorais que possam agir como inibidores de Pgp, apresentando um efeito dual, ou até mesmo multifuncional, no tratamento clínico das neoplasias malignas. Muito tem se discutido que a próxima geração de fármacos antitumorais poderá ser formada por substâncias que se ligam a mais do que um único alvo terapêutico, o que poderia acelerar tratamento contra a doença, reduzindo o número e a concentração de fármacos que deveriam ser administrados, como os coquetéis atualmente utilizados, e até mesmo aumentando a adesão ao tratamento por parte do paciente. No presente trabalho, estudamos dois complexos de rutênio, o cloreto e o ditionato de rutênio(III), que se apresentam como promissores no possível desenvolvimento de um novo fármaco antitumoral. Essa promessa transparece no fato de ambos serem de síntese química relativamente simples (processo sintético exequível) e, principalmente, por apresentarem efeito biológico de interesse em células tumorais, como citotoxicidade e indução de morte celular, especialmente por apoptose. Pelo que foi observado nos resultados de nossa pesquisa, os complexos aqui estudados, podem constituir um modelo para o estudo de novos agentes anticancerígenos com concomitante capacidade de não induzir MDR. Esta característica se mostrou muito evidente sobre a linhagem leucêmica K-562, onde os níveis de expressão de MDR1, após o tratamento com os rutenatos, foram muito inferiores aos apresentados pelas células tumorais tratadas com o fármaco controle Cisplatina. Ainda, é importante pontuar que o composto ditionato de cistetraammino(oxalato)rutênio(III) apresentou efeito citotóxico em ambas as linhagens tumorais K-562 e A549, sem contudo induzir altos níveis de expressão de Pgp (MDR1), apresentados pelos fármacos platinados. Assim, estudos mais aprofundados sobre a estrutura e funcionamento biológico desses complexos de rutênio, representam um ponto de partida interessante para o desenvolvimento de fármacos multifuncionais e de efeito desejável, auxiliando na delineação de estudos clínicos dirigidos a grupos selecionados de pacientes que reúnam características genotípicas e fenotípicas preditivas de máxima resposta terapêutica com mínima toxicidade. Posteriormente, estes estudos podem levar às realizações de testes diagnósticos e farmacológicos mais eficazes que poderão ser estabelecidos como rotina voltada para uma melhor definição de tratamentos. Isso traria um maior sucesso no teste de novos medicamentos e reduziria os custos e riscos, minimizando o tempo gasto para aprovação de um novo medicamento e a sua disponibilização para a sociedade.
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Stege, Alexandra Eva. "Überwindung der P-Glykoprotein (MDR1)-abhängigen Multidrugresistenz mittels RNA-Interferenz." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2007. http://dx.doi.org/10.18452/15578.
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P-Glykoprotein als Produkt des MDR1-Gens stellt einen gut untersuchten Mediator der Multidrugresistenz (MDR) in humanen Malignomen dar. Die Überexpression dieses ABC-Transporters steht in Korrelation zu einer erniedrigten Tumorremission und einer kürzeren Überlebensrate der Patienten. Bisherige Versuche, das Protein über niedermolekulare Substanzen (MDR-Modulatoren) zu inhibieren, vermochten in allen bisherigen klinischen Studien nicht zu überzeugen, so daß diese bis heute keinen Eingang in Standardtherapieschemata gefunden haben. Ziel dieser Arbeit war es, mittels RNA-Interferenz Strategien die Expression von MDR1 zu hemmen und eine Reversion der zellulären Chemoresistenz sowohl im Zellkultur- als auch im Tiermodell zu erreichen. Für die in vitro Untersuchungen an drei humanen multidrug-resistenten Karzinomzellinien wurden verschiedene siRNA (short interfering) Duplexe und shRNA (short hairpin)-exprimierende Vektoren gegen die MDR1 mRNA entwickelt. Die Behandlung der Zellen mit siRNAs führte zu einer bis zu 91 %igen Inhibition der MDR1 mRNA-Expression und zu einer Sensitivierung der Zellen gegenüber dem Anthrazyklin um 89 %. Diese Effekte konnte über einen Zeitraum von drei bis fünf Tagen aufrechterhalten werden. Die stabile Expression von anti-MDR1 shRNAs führte in zwei der untersuchten Zellmodelle zu einer dauerhaften und kompletten Überwindung des MDR1-abhängigen Resistenzphänotyps. Im Mausmodell konnte durch intratumorale Applikation des anti-MDR1 shRNA-kodierenden Vektors mittels low-volume Jet-Injektion eine komplette Reversion der MDR1-Überexpression sowie eine Wiederherstellung der Chemosensitivität gegenüber Doxorubicin in dem resistenten Tumormodell erreicht werden. Die Effizienz der kombinierten Gen- und Chemotherapie wird durch die Verminderung des in vivo Tumorwachstums auf das Volumen des von der sensiblen Zellinien-abgeleiteten Tumors reflektiert.Multidrug resistance (MDR) is the major cause of failure of effective chemotherapeutic treatment of disseminated neoplasms. The "classical" MDR phenotype of human malignancies is mediated by drug extrusion by the adenosine triphosphate binding cassette (ABC)-transporter P-glycoprotein (MDR1/P-gp). For stable reversal of "classical" MDR in three human cancer cell lines by RNA interference (RNAi) technology, two small interfering RNA (siRNA) constructs and four H1-RNA gene promoter-driven expression vectors encoding anti-MDR1/P-gp short hairpin RNA (shRNA) molecules were constructed. In all cellular systems, siRNAs could specifically inhibit MDR1 expression up to 91% at the mRNA and protein levels. Resistance against daunorubicin was decreased to a maximum of 89%. The introduction of anti-MDR1/P-gp shRNA expression vectors leads in two of the three human cancer cell lines to a complete reversion of the MDR phenotype. The reversal of MDR was accompanied by a complete suppression of MDR1/P-gp expression on mRNA and protein level, and by a considerable increased intracellular anthracyline accumulation in the anti-MDR1/P-gp shRNA-treated cells. In a mouse xenograft model a complete in vivo restoration of MDR1 overexpression and chemosensitivity to doxorubicin could be obtained by intratumorally jet-injected anti-MDR1 shRNA in a multidrug resistant human cancer tumor model.
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Baja, Karine Gehlen. "Farmacocinética do cloridrato de tramadol administrado por via oral em cães com a mutação nt230(del4) no gene MDR1." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2013. http://hdl.handle.net/10183/79520.
Full textAbstract:
A P-glicoproteína (P-gp) é uma transportadora transmembrana de múltiplos fármacos, produto do gene MDR1 (ABCB1). A P-gp contribui para a função de barreira de vários tecidos e órgãos, funcionando como uma bomba de efluxo para muitos substratos. Diminuição na expressão desta proteína é associada à sensibilidade a fármacos. Cães da linhagem dos Collies possuem uma alta incidência de uma mutação no gene MDR1, denominada nt230(del4). Animais homozigotos para a mutação apresentam a supressão total de uma P-gp funcional e um animal heterozigoto apresenta uma maior sensibilidade para substratos da P-gp, devido a uma diminuição na expressão da mesma. Alguns fármacos opioides, como a morfina e a metadona, foram identificados como substratos da P-gp. O tramadol é um dos analgésicos opioides mais utilizados em cães. No presente trabalho, a mutação MDR1 nt230(del4) foi analisada em vinte cães Collie, utilizando reação em cadeia de polimerase (PCR). A identificação foi realizada por eletroforese em gel de poliacrilamida de alta resolução, sendo o resultado confirmado por análise de sequênciamento de DNA. Como resultado, seis cães apresentaram normalidade nos dois alelos e 14 apresentaram heterozigose para a mutação. Estes animais foram submetidos à segunda fase do experimento, quando se administrou uma dose única de 100 mg de tramadol oral de liberação prolongada (SR), objetivando investigar o tramadol como sendo substrato da P-gp. Outro objetivo foi avaliar a farmacocinética deste tipo de formulação, pois ainda não foi estabelecida para cães. A análise farmacocinética do tramadol foi realizada utilizando cromatografia líquida de alta eficiência (CLAE) com detecção por espectrometria de massas para a determinação e quantificação de tramadol no soro canino. O analito e o padrão interno foram extraídos do soro por método líquido-líquido. A separação cromatográfica foi obtida a partir de uma coluna analítica C18, mantida a 30°C, sob condições isocráticas de uma fase móvel constituída por uma mistura de acetonitrila e ácido fórmico a 0,1% (80:20). A concentração de tramadol no soro foi maior do que o limite de quantificação (LOQ), em 17 cães. Os cães foram divididos em dois grupos, cães normais (MDR1 +/+) e heterozigotos (MDR1 +/-). Os cálculos farmacocinéticos para o tramadol oral SR obtiveram valores médios de concentração máxima no soro (Cmax) de 63,12 ng/mL ± 33,35 para o grupo normal e 58,00 ng/mL ± 27,29 para o grupo heterozigoto. Tmax (tempo de concentração plasmática maxima) foi de 4 h para ambos os grupos e t ½ (meia-vida) foram 2,85 h ± 1,61 e 2,81 ± 1,46 h para os cães normais e heterozigotos, respectivamente. A área sob a curva (AUC) média para o tramadol oral SR para o grupo normal e heterozigoto foram 350,20 ± 216,61 e 312,15 ± 155,43 ng.h/mL, respectivamente. A biodisponibilidade foi de 22% e 23% para os cães normais e heterozigotos, respectivamente. Não houve diferença estatística entre os grupos em todos os parâmetros farmacocinéticos. Os resultados sugerem que o tramadol não é um substrato da Pgp. A quantidade de dados farmacocinéticos do tramadol oral na formulação de liberação prolongada (SR) em cães é escassa, sendo necessários mais estudos farmacocinéticos e farmacodinâmicos para o tramadol oral de liberação prolongada em cães para estabelecer adequada dose e frequência de administração em cães.The P-glycoprotein (P-gp) is a transmembrane multidrug transporter, product of the MDR1 (ABCB1) gene. P-gp contributes to the barrier function of several tissues and organs, acting as an efflux pump for many substrates. Decreased expression of this protein is associated with sensitivity to drugs. Collie dogs have a high incidence of a mutation in MDR1 gene, denominated MDR1 nt230 (del4). In homozygosis, this mutation results in the total absence of a functional P-gp and a heterozygote animal presents a greater sensibility to P-gp substrates, probably due to a decrease in the expression thereof. Some opioid drugs such as morphine and methadone were identified as P-gp substrates. Tramadol is one of the most commonly opioid used in dogs. In the present work MDR1nt230 (del4) mutation was analyzed in 20 healthy Collie dogs using allele-specific polymerase chain reaction (PCR) method. Thereby, 6 homozygous intact and 14 heterozygous mutated MDR1 genotypes can be differentiated by high resolution polyacrylamide gel electrophoresis, confirmed by DNA sequence analysis. These animals underwent the second phase of the experiment, when a single oral administration of 100 mg of sustained release (SR) tramadol was administrated to investigate the tramadol as P-gp substrate. In addition, another aim was evaluate the pharmacokinetics of sustained release formulation, which has not been established for dogs. Pharmacokinetic analysis of tramadol was evaluated using high performance liquid chromatography (HPLC) with tandem mass spectrometry for determination and quantification of tramadol in canine serum. The analyte and internal standard (IS) were extracted from serum using liquid-liquid method. Chromatographic separation was achieved on a C18 analytical column, kept at 30°C, under isocratic conditions of a mobile phase consisted by a mixture of acetonitrile and water contained 0,1% formic acid (80:20). Serum tramadol concentration was greater than the limit of quantification (LOQ) in 17 dogs. The dogs were divided into two groups, normal dogs (MDR1 +/+) and heterozygous (MDR1 +/-) according to the MDR1 genotype. The median values of maximum serum concentration (Cmax) were 63.13 ng/mL ± 33.35 for the normal group and 58.01 ng/mL ± 27.29 for the heterozygous group. Tmax (time to maximum serum concentration) was 4 h for both groups and t ½ (half-life) were 2,85h ± 1,61 e 2,81h ± 1,46 for normal and heterozygous dogs, respectively. The mean area-under-the-curve (AUC) values for the sustained release tramadol compounds for the normal and heterozygous group were 350,20 ±216,61 and 312,15 ± 155,43 ng.h/mL, respectively. The bioavailability was 22% and 23% for normal and heterozygous dogs respectively. There was no statistic difference between groups in all pharmacokinetics parameters. The findings suggest that tramadol is not a P-gp substrate. The amount of pharmacokinetics data of SR formulation of tramadol in dogs is sparse. Therefore, more studies of oral SR tramadol in dogs are needed to establish appropriate dose and frequency of administration in dogs.
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Xie, Song [Verfasser], and Ulrich [Akademischer Betreuer] Landgraf. "A gas monitoring chamber for ATLAS MDTs = Eine Gas Monitoring Chamber für ATLAS MDTs." Freiburg : Universität, 2011. http://d-nb.info/1123464561/34.
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Huchton, Scott. "Secure mobile distributed file system (MDFS)." Thesis, Monterey, California. Naval Postgraduate School, 2011. http://hdl.handle.net/10945/5758.
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Approved for public release; distribution is unlimitedThe goal of this research is to provide a way for frontline troops to securely store and exchange sensitive information on a network of mobile devices with resiliency. The first portion of the thesis is the design of a file system to meet military mission specific security and resiliency requirements. The design integrates advanced concepts including erasure coding, Shamir's threshold based secret sharing algorithm, and symmetric AES cryptography. The resulting system supports two important properties: (1) data can be recovered only if some minimum number of devices are accessible, and (2) sensitive data remains protected even after a small number of devices are compromised. The second part of the thesis is to implement the design on Android mobile devices and demonstrate the system under real world conditions. We implement and demonstrate a functional version of MDFS on Android hardware. Due to the device's limited resources, there are some issues that must be explored before MDFS could be deployed as a viable distributed file system.
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Barry, Jennifer L. (Jennifer Lynn). "Fast approximate hierarchical solution of MDPs." Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/53202.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2009.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 89-91).
In this thesis, we present an efficient algorithm for creating and solving hierarchical models of large Markov decision processes (MDPs). As the size of the MDP increases, finding an exact solution becomes intractable, so we expect only to find an approximate solution. We also assume that the hierarchies we create are not necessarily applicable to more than one problem so that we must be able to construct and solve the hierarchical model in less time than it would have taken to simply solve the original, flat model. Our approach works in two stages. We first create the hierarchical MDP by forming clusters of states that can transition easily among themselves. We then solve the hierarchical MDP. We use a quick bottom-up pass based on a deterministic approximation of expected costs to move from one state to another to derive a policy from the top down, which avoids solving low-level MDPs for multiple objectives. The resulting policy may be suboptimal but it is guaranteed to reach a goal state in any problem in which it is reachable under the optimal policy. We have two versions of this algorithm, one for enumerated-state MDPs and one for factored MDPs. We have tested the enumerated-state algorithm on classic problems and shown that it is better than or comparable to current work in the field. Factored MDPs are a way of specifying extremely large MDPs without listing all of the states. Because the problem has a compact representation, we suspect that the solution should, in many cases, also have a compact representation. We have an implementation for factored MDPs and have shown that it can find solutions for large, factored problems.
by Jennifer L. Barry.
S.M.
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Kaszubiak, Alexander. "Adenoviraler Transfer von anti-MDR1 shRNAs." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2007. http://dx.doi.org/10.18452/15644.
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Tumoren entwickeln während einer Chemotherapie häufig Resistenzen gegen strukturell und funktionell unabhängige Zytostatika - ein Phänomen, das als Multidrug-Resistenz (MDR) bezeichnet wird und die Hauptursache für das Scheitern einer Chemotherapie ist. Die klassische MDR ist mit einer Überexpression des ABC-Transporters MDR1/P-gp assoziiert. Der vorliegende gentherapeutische Ansatz beinhaltet eine selektiv gegen MDR1/P-gp gerichtete und vor allem effiziente Strategie zur Überwindung des MDR-Phänotyps humaner Tumorzellen. Basierend auf der Integration verschiedener anti-MDR1 shRNA Expressionskassetten in adenovirale Gentherapievektoren, konnte mit Hilfe der RNA-Interferenz Technologie (RNAi) die MDR1/P-gp Expression selektiv inhibiert werden. Mittels des hoch effizienten Adenovirus Ad5U6/MDR-C wurde die MDR1 mRNA- sowie Protein-Expression soweit reprimiert, dass eine vollständige Aufhebung der biologischen Aktivität der Effluxpumpe MDR1/P-gp und eine Reversion des Resistenz Phänotyps gegenüber den typischen MDR1/P-g-Substraten Daunorubicin (87 % in EPP85-181RDB bzw. 66 % in EPG85-257RDB) sowie Vincristin (96 % bzw. 82 %) resultierte. Zudem wurde gezeigt, dass E1-deletierte und damit replikationsinkompetente Adenoviren in multidrug-resistenten Tumorzellen replizieren können. Damit wirkt Ad5U6/MDR-C in MDR-Tumorzellen onkolytisch. Zwar konnte die Adenovirusreplikation mit dem DNA-Synthese-Hemmer Hydroxyurea (HU) zu 94 % inhibiert werden, die anti-MDR1 Effizienz von Ad5U6/MDR-C wurde dennoch erhöht (+5 % in HeLaRDB, +12 % in EPG85-257RDB), was für eine erfolgreiche und niedrig dosierte Ad-Gentherapie multidrug-resistenter Tumoren in Kombination mit HU ausgenutzt werden kann. Außerdem wurde der entscheidende Einfluss des regulatorischen Proteins YB-1 auf die selektive Replikation von Ad5U6/MDR-C in MDR1/P-gp überexprimierenden Tumorzellen gezeigt. Eine 90 %ige Inhibition von YB-1 bedingt eine Hemmung der Adenovirusreplikation um 70 % und damit eine verringerte Effizienz der RNAi-vermittelten Inhibition von MDR1/P-gp um 40 %. Mit diesem gentherapeutischen Ansatz können die Effekte der YB-1-abhängigen und der die Zelllyse bedingenden Adenovirusreplikation sowie der anti-MDR1 shRNA vermittelten Chemosensitivierung kombiniert und zu einer verbesserten Eliminierung von MDR-Tumorzellen führen.Simultaneous resistance of cancer cells to multiple cytotoxic drugs, multidrug resistance (MDR), is the major limitation to the successful chemotherapeutic treatment of disseminated neoplasms. The ‘classical’ MDR phenotype is conferred by MDR1/P-glycoprotein (MDR1/P-gp) that is expressed in almost 50% of human cancers. Recent developments in the use of small interfering RNAs for specific inhibition of gene expression have highlighted their potential use as therapeutic agents. DNA cassettes encoding RNA polymerase III promoter-driven siRNA-like short hairpin RNAs (shRNAs) allow long-term expression of therapeutic RNAs in targeted cells. A variety of viral vectors have been used to deliver such cassettes to mammalian cells. In this study, the construction of different adenoviruses for anti- MDR1/P-gp shRNA delivery in different human multidrug-resistant cancer cells was investigated. It could be demonstrated that MDR1/P-gp mRNA and protein expression could be completely inhibited by adenoviral delivery of anti-MDR1/P-gp shRNAs. This down regulation in mRNA and protein expression was accompanied by a complete inhibition of the pump activity of MDR1/P-gp and a reversal of the multidrug-resistant phenotype. Moreover, it could be demonstrated that MDR-tumour cells facilitate adenoviral replication of originally E1- and E3-deleted and thus replication deficient adenoviral vectors through stable relocation of the fundamental regulatory factor YB-1 to the nucleus. To analyse the impact of YB-1 on adenoviral replication, two specific in vitro MDR models were used which stably trigger YB-1 posttranscriptional gene-silencing via the RNA interference (RNAi) pathway, i.e. the MDR cell line EPG85-257RDB well as its drug-sensitive counterpart EPG85-257P. The YB-1 gene-silencing effects of 90 % were accompanied by a reduction of adenoviral gene expression of 70 %. In conclusion, the data demonstrate that an highly efficient adenoviral delivery of shRNAs can chemosensitise human cancer cells and that YB-1 is involved in the regulation of adenoviral gene expression of originally replication deficient Ad-vectors in MDR cancer cells.
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Marthinet, Eric. "Modulation du phénotype typique de multichimiorésistance (MDR) des cellules cancéreuses humaines par des leurres transcriptionnels et étude de la régulation transcriptionnelle du gène MDR1 au niveau de la région MED-1." Lyon 1, 2001. http://www.theses.fr/2001LYO10021.
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Le phenotype de multichimioresistance mdr est une cause majeure de l'echec de la chimiotherapie anticancereuse. Le phenotype dit typique s'explique entre autres par la surexpression de proteines membranaires parmi lesquelles la plus importante est la glycoproteine-p (p-gp) codee par le gene mdr1 chez l'homme. La modulation du phenotype mdr est une priorite majeure du traitement clinique anticancereux. Dans cette optique, nous developpons au laboratoire des strategies innovantes et efficaces pour moduler le phenotype mdr en agissant non pas sur la proteine elle-meme mais sur son gene. Ces approches sont basees sur l'utilisation de leurres transcriptionnels (destines a devier la fixation de proteines regulatrices sur ces leurres plutot que sur leur region regulatrice) et de ribozymes (petits arn capables de cliver l'arn messager du gene mdr1) pour reduire l'expression de la p-gp. Les resultats positifs de modulation obtenus avec les leurres transcriptionnels sur les modeles cellulaires construits au laboratoire ont ete transposes avec succes a des cellules tumorales mdr in vitro et seront testees prochainement sur des cellules in situ. L'issue de ces tests permettra d'envisager serieusement l'usage de ces approches pour le traitement clinique des cancers. De plus, afin de mieux comprendre la regulation de la transcription du gene mdr1, nous avons isole et identifie une proteine qui interagit specifiquement avec une region regulatrice specifique du gene mdr1, appelee med-1. Le role de cette region consisterait a initier correctement la transcription du gene. Nous avons identifie cette proteine par spectrometrie de masse maldi-tof comme etant la proteine lrp130. Nous avons egalement entrepris l'etude du role de cette region
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Dias, Michele Carrett. "Mecanismo de ação do ácido acetilsalicílico em linhagens celulares leucêmicas MDR e não MDR." reponame:Repositório Institucional da FURG, 2007. http://repositorio.furg.br/handle/1/229.
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Dissertação (mestrado)-Universidade Federal do Rio Grande, Programa de Pós-Graduação em Ciências Fisiológicas – Fisiologia Animal Comparada, Instituto de Ciências Biológicas, 2007.Submitted by Barbara Milbrath (barbaramilbrath@yahoo.com.br) on 2010-10-21T22:25:55Z No. of bitstreams: 1 tese michele carrett dias.pdf: 355404 bytes, checksum: 04e1becf311e23c5da6492386ffd6c33 (MD5)
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As estatísticas com relação ao câncer são impiedosas. Uma em cada cinco pessoas desenvolverá uma forma de câncer em determinado momento de sua vida e ainda é importante considerar que tumores malignos já foram constatados também em plantas e em outros animais. Além das ferramentas convencionais para o tratamento do câncer, que incluem radioterapia, quimioterapia e cirurgia, outras terapias alternativas têm sido propostas, como a terapia fotodinâmica. Uma outra tentativa promissora no combate ao câncer vem sendo demonstrada com o uso do ácido acetilsalicílico (AAS). O AAS, o salicilato mais importante da família de drogas antiinflamatórias não-esteróides (NSAIDs), adquiriu popularidade em 1899, quando foram reconhecidas suas propriedades antiinflamatórias. Dados experimentais sugerem que AAS e outros membros da família de NSAIDs inibem o crescimento de células cancerosas in vitro e in vivo. É atribuído às prostaglandinas o poder de iniciar e promover o câncer por causar a proliferação celular, inibição da apoptose (morte celular programada), estimulação da angiogênese ou supressão da resposta imune. Inibir a enzima Cox está relacionado com a ini bição da produção de prostaglandinas, sugerindo assim a inibição do processo de cancerização. O AAS inibe irreversivelmente a enzima Cox em determinados tipos celulares, sendo que esta inibição é não -seletiva para ambas as isoformas da Cox; Cox-1 (isoforma constitutiva) e Cox-2 (isoforma induzida). Entretanto, estudos sugerem que o efeito antiproliferativo de AAS não está correlacionado exclusivamente com a ação inibitória da enzima Cox, já que existem relatos mostrando que NSAIDs podem induzir apoptose em células de câncer de cólon que não expressam a proteína Cox-2. Neste sentido, alguns autores demonstraram uma inibição no crescimento in vitro de células tumorais do endométrio humano pelo AAS, de uma maneira dose-dependente, sendo a apoptose um dos mecanismos envolvidos nesta resposta, mediada em parte pela “downregulation” do gene bcl-2. A redução no número de apoptoses contribui para o desenvolvimento do câncer sendo o gene bcl-2 o primeiro membro de uma família de genes que regulam este processo. Foi demonstrado que a superexpressão do gene bcl-2 aumenta a sobrevida das células tumorais protegendo-as da toxicidade causada pelos quimioterápicos, não permitindo que a apoptose ocorra. Por outro lado, a indução da apoptose é uma das ações centrais pela qual a proteína P53 exerce função na supressão do tumor. Esta proteína previne a transmissão da informação genética defeituosa para a geração das células seguintes, sendo denominada “a guardiã do genoma” e a perda desta função é um achado freqüente em câncer. A mutação do gene p53 provavelmente inativa a função supressora da proteína P53, conferindo vantagem de crescimento celular, podendo contribuir para o desenvolvimento de tumores, dentre eles, as leucemias. Também a propriedade antioxidants das NSAIDs tem si do investigada, sendo que alguns autores também atribuem a isso os efeitos antitumorais do AAS. Também é de extrema relevância considerar a possibilidade de que determinadas células tumorais podem adquirir resistência a múltiplas drogas, caracterizando o f enótipo MDR. Atualmente, a procura de novas drogas capazes de vencer o mecanismo MDR e conduzir a morte de células tumorais é de extrema importância para a terapia do câncer. Assim, criar um modelo biológico que permita estudos comparativos entre uma linhagem tumoral MDR e uma não MDR é pertinente. Com base nas informações levantadas sobre a possível atividade antitumoral do AAS, objetivamos analisar como parâmetros de estudo sua citotoxicidade (em células tumorais e não tumorais); morte celular; atividade antioxidante e alterações de expressão nos genes cox-2, bcl2 e p53, utilizando como modelos biológicos linhagens celulares normais e tumorais MDR e não MDR. AAS inibiu a proliferação celular ou induziu toxicidade nas linhagens celulares K562 e Lucena desco nsiderando o fenótipo MDR. O tratamento com AAS provocou morte, nas células K562, principalmente por apoptose inicial e por necrose, nas células Lucena. Também AAS mostrou uma capacidade antioxidante em ambas linhagens. A expressão do gene bcl-2 não apresentou diferenças significativas, considerando as células controle e tratadas com AAS, bem como as duas linhagens celulares. Para os genes p53 e cox-2, a expressão foi concentração dependente para as células K562. Já para as células Lucena, a expressão de ambos os genes foi aumentada nas menores concentrações e, para o gene p53, diminuída na maior concentração quando comparadas as células controle. Como o perfil das expressões foi similar para os genes p53 e cox-2 foi possível sugerir um fator de transcrição comum, justificando esta resposta. Por outro lado, os linfócitos normais tratados com as mesmas concentrações de AAS foram mais resistentes do que as linhagens tumorais. Os resultados deste trabalho mostraram que as duas linhagens celulares foram sensíveis ao tratamento com AAS, mas permitem sugerir que o mecanismo de ação foi diferenciado nas linhagens MDR e não MDR.
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Garnier, France. "Study of transcription regulation of the gene mdr1." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=56986.
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In order to characterize cis-acting sequences and trans-acting factors important in regulating the expression of the mouse mdr1 gene, in vitro DNAsel footprinting experiments were carried out on a mdr1 promoter segment between positions $-$245 and +84, using nuclear protein extracts prepared from cell lines expressing different endogenous amounts of mdr1 mRNAs. Three footprinted sequences were detected on the non-coding strand of the $-$245 to +84 mdr1 promoter fragment (between -77 to -56, between -46 to -24, and between +5 and +15) with nuclear extracts from mdr1 expressing cells (CMT-93, LTA, and Y-1 cells). In addition, a specific footprinted sequence ($-$14 to +5) was detected on both strands only with nuclear extracts from the mdr1 non-expressing cell line (RAG cells) suggesting the presence and binding of a putative negative regulatory factor in these cells. However, replacement of this sequence in the mdr1 basal promoter ($-$93 to +84) by a heterologous, although similar positioned SV40 sequence did not restore promoter activity in RAG cells. The basal mdr1 promoter was further characterized in bidirectional deletion mutants, in order to identify cis-acting elements important for general transcriptional regulation. These studies further localized the mdr1 basal promoter between positions $-$74 and +84, and also suggested the presence of possible positive and negative cis-acting sequence elements modulating the activity of this basal promoter.
Books on the topic "MDRS"
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Byrne, Dorena Orlagh. Data warehousing within MDS Harris. [s.l: The author], 1999.
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Reyes, Anselmo, and Weixia Gu, eds. Multi-Tier Approaches to the Resolution of International Disputes. Cambridge University Press, 2021. http://dx.doi.org/10.1017/9781108854306.
Full textAbstract:
Multi-tier dispute resolution (MDR) entails an early attempt at mediation followed by arbitration or litigation if mediation is unsuccessful. Seemingly, everyone acknowledges MDR's attractiveness as a means of resolving disputes due to its combination of the flexibility and informality of mediation with the rigour and formality of arbitration or litigation. Yet, the question is why, except in China and some Asian jurisdictions, MDR is not resorted to around the world and MDR clauses in commercial contracts remain relatively uncommon. This book responds to that question by (1) surveying global regulatory approaches frameworks for MDR, (2) comparing MDR trends in Asia and the wider world, (3) identifying MDR's strengths and weaknesses, and (4) prescribing ways to address MDR's weaknesses (the enforceability of MDR clauses, the difficulties arising when the same person acts as mediator and decision-maker in the same dispute, and the enforcement of mediated settlement agreements resulting from MDR).
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Agere, Sam. Strengthening MDIs. Commonwealth, 1999. http://dx.doi.org/10.14217/9780850925852-en.
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Provan, Drew, Trevor Baglin, Inderjeet Dokal, and Johannes de Vos. Myelodysplasia. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199683307.003.0006.
Full textAbstract:
Myelodysplastic syndromes (MDS) - Classification of MDS - Clinical features of MDS - Prognostic factors in MDS - Clinical variants of MDS - Management of MDS - Response criteria - Myelodysplastic/myeloproliferative diseases (MDS/MPD)
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Provan, Drew, Trevor Baglin, Inderjeet Dokal, Johannes de Vos, and Mammit Kaur. Myelodysplasia. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199683307.003.0006_update_001.
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Myelodysplastic syndromes (MDS) - Classification of MDS - Clinical features of MDS - Prognostic factors in MDS - Clinical variants of MDS - Management of MDS - Response criteria - Myelodysplastic/myeloproliferative diseases (MDS/MPD)
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Mdr's National School Directory (Mdr's School Directory Complete Set). Market Data Retrieval, 1996.
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Pieth, Mark. Beyond Criminal Law. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780190458331.003.0018.
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This chapter discusses administrative sanctions and preventive measures that go beyond criminal law to fight corruption such as states and Multilateral Development Banks (MDBs). They have developed a set of regulatory sanctions more directly aiming at the prevention of abuses by companies and individuals and protecting the interests of their respective institutions. Domestic procurement rules as well as the regulations developed by MDBs foresee cancellation of loans in the face of concrete misbehavior. Domestic agencies would also be able to stay subsidies or export insurance. Furthermore, domestic agencies and MDBs have introduced detailed sanctions procedures allowing debarment of corporations and individuals from future participation in procurement or from eligibility for export insurance. The debarment procedures established by MDBs may be regarded as a worldwide example of such administrative sanctioning, and one of the largest is the World Bank.
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Mdr's School Directory Alabama 1999-2000 (Mdr's School Directory Alabama). Market Data Retrieval, 1999.
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Mdr's School Directory Pennsylvania 2002-2003 (Mdr's School Directory Pennsylvania). Market Data Retrieval, 2002.
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MDR's School Directories, 1998-99: Iowa (MDR's School Directory Iowa). Market Data Retrieval, 1998.
Find full textBook chapters on the topic "MDRS"
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Cinelli, I., and S. Rupert. "MDRS Lessons Learned." In Handbook of Life Support Systems for Spacecraft and Extraterrestrial Habitats, 1–18. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-319-09575-2_146-1.
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Bhardwaj, Ashima Kushwaha, and Kittappa Vinothkumar. "Evolution of MDRs." In Quorum Sensing vs Quorum Quenching: A Battle with No End in Sight, 9–22. New Delhi: Springer India, 2014. http://dx.doi.org/10.1007/978-81-322-1982-8_2.
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Morgan, Michael M., MacDonald J. Christie, Thomas Steckler, Ben J. Harrison, Christos Pantelis, Christof Baltes, Thomas Mueggler, et al. "MDAS." In Encyclopedia of Psychopharmacology, 751. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-68706-1_4344.
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Mehlhorn, Heinz. "MDOs." In Encyclopedia of Parasitology, 1612. Berlin, Heidelberg: Springer Berlin Heidelberg, 2016. http://dx.doi.org/10.1007/978-3-662-43978-4_3696.
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Mehlhorn, Heinz. "MDOs." In Encyclopedia of Parasitology, 1. Berlin, Heidelberg: Springer Berlin Heidelberg, 2015. http://dx.doi.org/10.1007/978-3-642-27769-6_3696-1.
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Kolobov, Mausam, and Andrey Kolobov. "MDPs." In Planning with Markov Decision Processes, 7–29. Cham: Springer International Publishing, 2012. http://dx.doi.org/10.1007/978-3-031-01559-5_2.
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Bensard, Denis D., Philip F. Stahel, Jorge Cerdá, Babak Sarani, Sajid Shahul, Daniel Talmor, Peter M. Hammer, et al. "MDR." In Encyclopedia of Intensive Care Medicine, 1362. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-00418-6_3200.
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Oette, Mark, Marvin J. Stone, Hendrik P. N. Scholl, Peter Charbel Issa, Monika Fleckenstein, Steffen Schmitz-Valckenberg, Frank G. Holz, et al. "MDS." In Encyclopedia of Molecular Mechanisms of Disease, 1270. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-540-29676-8_6247.
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Byskov, Morten Fibieger, Babette Olga Rump, and Marcel Verweij. "Conceptualizing the Impact of MDRO Control Measures Directed at Carriers: A Capability Approach." In Ethics and Drug Resistance: Collective Responsibility for Global Public Health, 203–24. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-27874-8_13.
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Abstract Many countries have implemented specific control measures directed at carriers of multidrug-resistant organisms (MDRO) in order to prevent further introduction and transmission of resistant organisms into hospitals and other healthcare related settings. These control measures may in many ways affect the lives and well-being of carriers of MDRO, resulting in complex ethical dilemmas that often remain largely implicit in practice. In this chapter, we propose to conceptualize the impact of MDRO control measures on the well-being of individual carriers in terms of capabilities and functionings. A capabilitarian framework for the ethical treatment of MDRO carriers commits us to conceptualize the harm done to carriers in terms of the impact that MDRO control measures have on what they are able to do or be. Adopting and adapting Nussbaum’s list of ten central human capabilities, we present a taxonomy of capabilities and functionings that are normatively relevant for the design and evaluation of MDRO control measures.
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Ehrenfeucht, Andrzej, Tero Harju, Ion Petre, David M. Prescott, and Grzegorz Rozenberg. "MDS Arrangements and MDS Descriptors." In Natural Computing Series, 67–73. Berlin, Heidelberg: Springer Berlin Heidelberg, 2004. http://dx.doi.org/10.1007/978-3-662-06371-2_6.
Full textConference papers on the topic "MDRS"
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Doule, Ondrej. "MDRS - Mars Analog Outpost Growth." In AIAA SPACE 2014 Conference and Exposition. Reston, Virginia: American Institute of Aeronautics and Astronautics, 2014. http://dx.doi.org/10.2514/6.2014-4407.
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Rouverand, Léa, Cerise Cuny, Elena López-Contreras González, Marine Prunier, Mathéo Fouchet, Nicolas Wattelle, Valentine Bourgeois, Quentin Royer, and Marie Delaroche. "Experiment collaboration program during a Martian analogue mission to introduce young students to human space exploration." In Symposium on Space Educational Activities (SSAE). Universitat Politècnica de Catalunya, 2022. http://dx.doi.org/10.5821/conference-9788419184405.090.
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The last decade has demonstrated an increased public and private interest towards crewed missions through the emergence of New Space and the Artemis program. There is therefore a need to form the next generation of scientists to prepare future crewed space exploration missions. In this context, it is important to familiarize teenagers with the scientific issues of today’s world and to inspire them to engage in the space sector. Crew 263 is a group of seven students preparing a Martian analogue mission at the Mars Desert Research Station (MDRS) in the desert of Utah (United States). A Martian analogue mission at the MDRS, because is the perfect set-up to introduce young students to human space exploration. In the context of their mission, Crew 263 has organized a program of space educational activities for middle and high school students surrounding the topics of altered gravity, astronomy, health and safety procedures and robotic systems. Precisely, a set of four experiments that will be performed by the students was conceived to bring into light the various scientific topics surrounding space exploration missions.
The experiment “Plants in Microgravity” aims to illustrate the influence of gravity on plant growth by planting seeds in pots mounted on a rotating platform in a vertical plane, which will disturb their gravitational cues. “Beginner Astronomer” aims to introduce students to astronomy and astrophotography by establishing with the students a list of galaxies/nebulas to be observed during the Mission. Then, for “Emergency situation at the MDRS” students will put into practice the scientific approach by creating protocols to mitigate risk situations during space exploration missions. Finally, for the “Perseverance’s little brother” experiment, students will develop a small rover to analyze the atmosphere condition around the MDRS station.
To maximize their involvement, prior to the mission at the MDRS, the middle and high school students prepare the experiments with the support of the crew. Then, the prepared experiment will be performed in parallel with the crew while they are simulating Martian life. To allow students to be immersed in the mission when the crew will be at the MDRS, short podcasts will be recorded describing the crew’s daily life and the evolution of the different experiments. This podcast will be sent to the classes during the simulation, thus allowing the students to have an insight on the daily life of the analogue astronauts at the station.
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Cocchiara, Chiara. "Mars Analogue Mission Crew 159 at MDRS: Christmas on Mars." In SpaceOps 2016 Conference. Reston, Virginia: American Institute of Aeronautics and Astronautics, 2016. http://dx.doi.org/10.2514/6.2016-2351.
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"ISMICT 2020 Workshop: Medical Device Regulatory Science（MDRS) and ROVER Workshop." In 2020 14th International Symposium on Medical Information Communication Technology (ISMICT). IEEE, 2020. http://dx.doi.org/10.1109/ismict48699.2020.9152748.
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Aoki, Naoshi, Shogo Narahara, Tsukasa Nishiki, Akihisa Takahashi, and Shinsuke Kikuchi. "Structural delineation in geologically complex area using MDRS (multi-dip reflection surfaces)." In Proceedings of the 10th SEGJ International Symposium. Society of Exploration Geophysicists of Japan, 2011. http://dx.doi.org/10.1190/segj102011-001.41.
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Ferreira, Ingrid Jordana Bernardes, and GIOVANNA SANTANA MACHADO E. EDLAINNY ARAÚJO RIBEIRO. "RESULTADO DOS PROGRAMAS DE CONTROLE DE INFECÇÕES RELACIONADAS À ASSISTÊNCIA À SAÚDE E RESISTÊNCIA BACTERIANA." In II Congresso Nacional de Microbiologia Clínica On-line. Revista Multidisciplinar em Saúde, 2022. http://dx.doi.org/10.51161/ii-conamic/40.
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Introdução: A resistência bacteriana é um problema de saúde pública global persistente, seja pelos altos índices de mortalidade que geram ou pelos danos econômicos, principalmente quando é associada à Infecções Relacionadas a Assistência à Saúde (IRAS). Os dados sobre IRAS e cepas multirresistentes (MDRs) passaram a ser mais mapeados e documentados. No entanto, essas estratégias não são executadas de maneira holística, visto que muitos hospitais apresentam dificuldades para implementação. Objetivos: Demonstrar as evidências cientificas acerca do impacto de programas que visam a mitigação de IRAS e MDR bacteriana sobre os prejuízos associados à saúde e econômicos. Material e métodos: Trata-se de uma revisão integrativa da literatura, seguindo os critérios propostos pelo Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a partir de publicações científicas encontradas nas bases de dados Science Direct e Biblioteca Virtual em Saúde (BVS/MEDLINE). Resultados: O estudo contou com uma amostra de 14 artigos. A ocorrência de resistência bacteriana ou de IRAS com aumento da mortalidade e morbidade foi citada em 71% (10/14) dos estudos, já relacionada aos custos econômicos a frequência foi de 64% (9/14). E 43% ressaltaram o aumento de prejuízos à saúde e econômicos concomitantemente. As bactérias gram-negativas multirresistentes 28% (4/14) foram as mais citadas com destaque para o Acinetobacter baumannii. Após a implementação de estratégias como uso racional de antimicrobianos, realização de culturas de vigilância, estudos sobre o perfil epidemiológico local de surtos causados por bactérias resistentes aos antimicrobianos, observou-se diversos benefícios, como a mitigação da incidência de bactérias multirresistentes 50% (7/14) e do tempo de internação dos pacientes 21% (3/14). Conclusão: Dessa maneira, é crucial apresentar as estratégias eficientes e mitigar os entraves relacionados aos programas de controle dessas problemáticas. Os prejuízos associados a IRAS e MDR, traz à tona a importância dos programas e estratégias desenvolvidas para evitar e mitigar esse quadro, ressaltando a necessidade de adequar essas ações considerando as boas práticas assistenciais e os conceitos de saúde única.
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Choi, Andrew, Paul-Camille Kakou, and Oumar Barry. "Considerations for the Testing and Validation of a Mobile Damping Robot for Overhead Power Lines." In ASME 2022 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. American Society of Mechanical Engineers, 2022. http://dx.doi.org/10.1115/detc2022-88415.
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Abstract While analyses have been performed for fixed masses on power line conductors, they have not been in the context of interactions between the conductor and a mobile damping robot (MDR). There is a need to explore the potential impact of the MDR on the power line and the resulting implications for the MDR’s development as current methods of vibration control do not adequately address fatigue failure caused by wind-induced vibrations (WIV). Fixed passive vibration absorbers (FPVAs) are widely used on power lines, but they are inherently limited by their fixed nature since changes in wind conditions affect absorber performance as conductor mode shapes change. An MDR can overcome these limitations by actively transporting a passive absorber to conductor antinodes where the absorbers can most effectively remove energy from the system. In this paper, we experimentally investigate the effects of an untuned suspended mass on the conductor as an analog for the MDR, and we perform numerical analysis in MATLAB using equations of motion obtained via Hamilton’s Principle. The insights gained from this work lay a foundation to guide future experiments that will better define the operating conditions of the MDR and lead to the creation of an appropriate control framework.
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Roy, Rinita, Ruben Mayer, and Hans-Arno Jacobsen. "MDMS." In MM '21: ACM Multimedia Conference. New York, NY, USA: ACM, 2021. http://dx.doi.org/10.1145/3474085.3478551.
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Pais, Denis, Valdinei Freire, and Karina Valdivia-Delgado. "Algoritmo Exato de Avaliação de uma Política Estacionária para CVaR MDP." In Encontro Nacional de Inteligência Artificial e Computacional. Sociedade Brasileira de Computação - SBC, 2019. http://dx.doi.org/10.5753/eniac.2019.9341.
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Processos de decisão Markovianos (Markov Decision Processes -- MDPs) são amplamente utilizados para resolver problemas de tomada de decisão sequencial. O critério de desempenho mais utilizado em MDPs é a minimização do custo total esperado. Porém, esta abordagem não leva em consideração flutuações em torno da média, o que pode afetar significativamente o desempenho geral do processo. MDPs que lidam com esse tipo de problema são chamados de MDPs sensíveis a risco. Um tipo especial de MDP sensível a risco é o CVaR MDP, que inclui a métrica CVaR (Conditional-Value-at-Risk) comumente utilizada na área financeira. Um algoritmo que encontra a política ótima para CVaR MDPs é o algoritmo de Iteração de Valor com Interpolação Linear chamado CVaRVILI. O algoritmo CVaRVILI precisa resolver problemas de programação linear várias vezes, o que faz com que o algoritmo tenha um alto custo computacional. Neste trabalho, é proposto um algoritmo que avalia uma política estacionário para CVaR MDPs de custo constante e que não precisa resolver problemas de programação linear, esse algoritmo é chamado de PECVaR. Além disso, foram realizados experimentos usando o custo total esperado e o custo usando o algoritmo PECVaR de uma política neutra para inicializar o algoritmo CVaRVILI. Os resultados mostram que utilizando essas inicializações é possível diminuir o tempo de convergência do CVaRVILI na maioria dos casos.
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Suprijanto, Djoko, and Mona Elviyenti. "An algorithm to construct new (near-) MDS or (near-) MDR self-dual codes over finite rings Zpm." In THE 5TH INTERNATIONAL CONFERENCE ON RESEARCH AND EDUCATION IN MATHEMATICS: ICREM5. AIP, 2012. http://dx.doi.org/10.1063/1.4724141.
Full textReports on the topic "MDRS"
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Borzatti, J., K. A. Dorsey, and J. Sirmans. Mine Detonation Detection System (MDDS). Fort Belvoir, VA: Defense Technical Information Center, September 1987. http://dx.doi.org/10.21236/ada196830.
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Cooke, Garth, Johnnie Jernigan, Michael Huntington, Theodore Myers, and Colleen Gumienny. Maintenance Diagnostic Aiding System (MDAS) Enhancements. Fort Belvoir, VA: Defense Technical Information Center, January 1990. http://dx.doi.org/10.21236/ada218204.
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Avellán, Leopoldo, Arturo J. Galindo, and Giulia Lotti. Following Public Finances: The Mirage of MDBs Countercyclicality. Inter-American Development Bank, January 2020. http://dx.doi.org/10.18235/0002305.
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This paper investigates the co-movement of sovereign lending from multilateral development banks (MDBs) and private creditors with government expenditure. The paper finds that multilateral sovereign lending follows government expenditure and that this correlation does not change if governments are running a surplus or a deficit. This finding raises doubts on the feasibility of MDBs to be counter-cyclical, unless the governments themselves implement counter-cyclical fiscal policies.
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Clark, Robert R. C-7 Progesterone Analogues and MDR1 in Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, September 2000. http://dx.doi.org/10.21236/ada406203.
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Rao, Shuyun. Study of Rpl22 in MDS and AML. Fort Belvoir, VA: Defense Technical Information Center, October 2014. http://dx.doi.org/10.21236/ada613241.
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Donnenberg, Albert D. Differential MDR in Breast Cancer Stem Cells. Fort Belvoir, VA: Defense Technical Information Center, May 2006. http://dx.doi.org/10.21236/ada473776.
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Puggelli, Alberto A., Wenchao Li, Alberto L. Sangiovanni-Vincentelli, and Sanjit A. Seshia. Polynomial-Time Verification of PCTL Properties of MDPs with Convex Uncertainties. Fort Belvoir, VA: Defense Technical Information Center, April 2013. http://dx.doi.org/10.21236/ada583813.
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Precoda, K., and T. Meng. Long-term Stability of Listening Strategies Determined by MDS. Fort Belvoir, VA: Defense Technical Information Center, May 1998. http://dx.doi.org/10.21236/ada357785.
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Ogier, R. Use of OSPF-MDR in Single-Hop Broadcast Networks. RFC Editor, October 2013. http://dx.doi.org/10.17487/rfc7038.
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Lynn, K., S. Cheshire, M. Blanchet, and D. Migault. Requirements for Scalable DNS-Based Service Discovery (DNS-SD) / Multicast DNS (mDNS) Extensions. RFC Editor, July 2015. http://dx.doi.org/10.17487/rfc7558.
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