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Uznanski, Slawosz. "Monte-Carlo simulation and contribution to understanding of Single-Event-Upset (SEU) mechanisms in CMOS technologies down to 20nm technological node." Thesis, Aix-Marseille 1, 2011. http://www.theses.fr/2011AIX10222/document.
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L’augmentation de la densité et la réduction de la tension d’alimentation des circuits intégrés rend la contribution des effets singuliers induits par les radiations majoritaire dans la diminution de la fiabilité des composants électroniques aussi bien dans l’environnement radiatif spatial que terrestre. Cette étude porte sur la modélisation des mécanismes physiques qui conduisent à ces aléas logiques (en anglais "Soft Errors"). Ces modèles sont utilisés dans une plateforme de simulation,appelée TIARA (Tool suIte for rAdiation Reliability Assessment), qui a été développée dans le cadre de cette thèse. Cet outil est capable de prédire la sensibilité de nombreuses architectures de circuits (SRAM,Flip-Flop, etc.) dans différents environnements radiatifs et sous différentes conditions de test (alimentation, altitude, etc.) Cette plateforme a été amplement validée grâce à la comparaison avec des mesures expérimentales effectuées sur différents circuits de test fabriqués par STMicroelectronics. La plateforme TIARA a ensuite été utilisée pour la conception de circuits durcis aux radiations et a permis de participer à la compréhension des mécanismes des aléas logiques jusqu’au noeud technologique 20nmAggressive integrated circuit density increase and power supply scaling have propelled Single Event Effects to the forefront of reliability concerns in ground-based and space-bound electronic systems. This study focuses on modeling of Single Event physical phenomena. To enable performing reliability assessment, a complete simulation platform named Tool suIte for rAdiation Reliability Assessment (TIARA) has been developed that allows performing sensitivity prediction of different digital circuits (SRAM, Flip-Flops, etc.) in different radiation environments and at different operating conditions (power supply voltage,altitude, etc.) TIARA has been extensively validated with experimental data for space and terrestrial radiation environments using different test vehicles manufactured by STMicroelectronics. Finally, the platform has been used during rad-hard digital circuits design and to provide insights into radiation-induced upset mechanisms down to CMOS 20nm technological node
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Walldén, Johan. "Radiation Induced Effects in Electronic Devices and Radiation Hardening By Design Techniques." Thesis, Linköpings universitet, Elektroniska komponenter, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-109343.
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The aim with this thesis has been to make a survey of radiation hardened electronics, explaining why and how radiation affects electronics and what can be done to harden it. The effects radiation have on electronics in general and in specific commonly used devices are explained qualitatively. The effects are divided into Displacement Damage (DD), Total Ionizing Dose (TID) and Single Event Effects (SEEs). The devices explained are MOSFETs, Silicon On Insulator (SOI) transistors, 3D-transistors, Power transistors, Optocouplers, Field Programmable Gate Arrays (FPGAs), three dimensional circuits (3D-ICs) and Flash memories. Different radiation hardening by design (RHBD) techniques used to reduce or to remove the negative effects radiation induces in electronics are also explained. The techniques are Annular transistors, Enclosed source/drain transistors, Guard rings, Triple Modular Redundancy (TMR), Dual Interlocked Storage Cells (DICE), Guard gates, Temporal filtering,Multiple drive, Charge dissipation, Differential Charge Cancellation (DCC), Scrubbing, Lockstep, EDAC codes and Watchdog timers.
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Vaz, Pablo Ilha. "Efeitos da radiação ionizante e técnicas de proteção aplicadas a projetos de dispositivos MOS customizados." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/129819.
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Os efeitos produzidos pela interação da radiação ionizante com os circuitos integrados podem ser classificados em efeitos de eventos únicos (Single Event Effects - SEE), comumente relacionados a problemas transientes, e efeitos de dose total ionizante (Total Ionization Dose - TID), os quais se originam em decorrência do longo tempo de exposição à radiação ionizante. Com relação à proteção desses circuitos, técnicas, como redundâncias temporais e espaciais, podem ser aplicadas a fim de reduzir a ocorrência de eventos transientes. Por outro lado, efeitos de TID e mesmo alguns SEE específicos, como os que causam degradações permanentes do circuito, podem ser atenuados drasticamente através de técnicas propostas em nível de layout. Nesse contexto, este trabalho analisa os conceitos básicos envolvidos na interação da radiação com o transistor MOS, desvios de suas características elétricas e técnicas de atenuação dos efeitos acumulativos aplicadas em níveis de arquitetura de sistemas, de processo de fabricação e de dispositivo. Contudo, este trabalho realiza uma abordagem mais detalhada de técnicas de tolerância em nível de layout. A tolerância em nível de layout do transistor é o resultado da combinação entre tecnologia escolhida agregada ao uso de anéis de guarda (guard rings) e aplicação de técnicas em nível de dispositivo como, por exemplo, a de geometria fechada (enclosed-gate). Este trabalho explora diferentes topologias de geometria fechada analisando diferentes modelagens e estimativas de razão de aspecto (W⁄L). Além disso, todas as análises e propostas apresentadas ao longo deste trabalho levam em conta o ambiente de projeto comercial, de forma que os dispositivos e técnicas propostas possam ser aplicadas e fabricadas utilizando ferramentas de projeto comerciais, respeitando restrições quando a dimensões e espaçamentos entre estruturas de acordo com requisitos comerciais de litografia. Os resultados obtidos corroboram o fato de que ao custo de área é possível que se obtenha um dispositivo mais tolerante à radiação e, neste caso, técnicas de mais alto nível ainda podem ser aplicadas de forma a atingir uma maior eficiência de proteção.Studies related to ionizing radiation effects into MOS transistors are usually classified into two main groups, Single Event Effects (SEE) and Total Ionization Dose (TID). The former is related to transient effects and the later to the permanent effects which occurs during the whole lifetime of integrated circuits and devices. Architecture level for SEE mitigation techniques usually involves redundancy and majority voters, on the other hand, TID mitigation techniques act avoiding or reducing the weak and critical regions in the layout perspective. In this context this work proposes the analysis of primary physical mechanisms of radiation effects in semiconductor components and MOS transistors by exploring the electrical properties and related degradations. The mitigation (or hardening) techniques are explored not only at the architectural level but also by processes improvements. Nonetheless, this work is primarily focused to achieve a radiation hardened circuit by applying specific changes in the layout perspective making the design named as Radiation Hardened by Design (RHBD). Trading the area and circuit density it is possible to harden the most basic building block of electrical circuits (MOS transistors) and, in this case, by applying higher levels of mitigation techniques it is even possible to harden the entire circuit. Hardening by device is a combination of technology node, use of guard rings and techniques such as Enclosed Layout Transistor (ELT). Thus, this work realizes a comparative study of different proposed models to estimate the effective W/L aspect ratio in ELTs. Moreover, the analysis and approaches presented throughout this work take into account the commercial context, i.e., respecting the commercial Process Design Kits rules.
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Glorieux, Maximilien. "Durcissement par conception (RHBD) et modélisation des évènements singuliers dans les circuits intégrés numériques en technologies Bulk 65 nm et FDSOI 28 nm." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM4725.
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La miniaturisation des circuits intégrés numériques tend à augmenter leur sensibilité aux radiations. Ainsi le rayonnement naturel peut induire des événements singuliers et porter atteinte à la fiabilité des circuits.Cette thèse porte sur la modélisation des mécanismes à l'origine de ces événements singuliers et sur le développement de solutions de durcissement par conception permettant de limiter l'impact des radiations sur le taux d'erreur.Dans une première partie, nous avons notamment développé une approche dénommée RWDD (Random-Walk Drift- Diffusion) modélisant le transport et la collection de charges au sein d'un circuit, sur la base d'équations physiques sans paramètre d'ajustement. Ce modèle particulaire et sa résolution numérique transitoire permettent de coupler le transport des charges avec un simulateur circuit, tenant ainsi compte de l'évolution temporelle des champs électriques dans la structure. Le modèle RWDD a été intégré avec succès dans une plateforme de simulation capable d'estimer la réponse d'un circuit suite à l'impact d'une particule ionisante.Dans une seconde partie, des solutions de durcissement permettant de limiter l'impact des radiations sur la fiabilité des circuits ont été développées. A l'échelle des cellules élémentaires, de nouvelles bascules robustes aux radiations ont été proposées, en limitant leur impact les performances. Au niveau système, une méthodologie de duplication de l'arbre d'horloge a été développée. Enfin, un flot de triplication a été conçu pour les systèmes dont la fiabilité est critique. L'ensemble de ces solutions a été implémenté en technologie 65 nm et UTBB-FDSOI 28 nm et leur efficacité vérifiée expérimentalementThe extreme technology scaling of digital circuits leads to increase their sensitivity to ionizing radiation, whether in spatial or terrestrial environments. Natural radiation can now induce single event effects in deca-nanometer circuits and impact their reliability.This thesis focuses on the modeling of single event mechanisms and the development of hardening by design solutions that mitigate radiation threat on the circuit error rate.In a first part of this work, we have developed a physical model for both the transport and collection of radiation-induced charges in a biased circuit, derived from pure physics-based equations without any fitting parameter. This model is called Random-Walk Drift-Diffusion (RWDD). This particle-level model and its numerical transient solving allows the coupling of the charge collection process with a circuit simulator, taking into account the time variations of the electrical fields in the structure. The RWDD model is able to simulate the behavior of a circuit following a radiation impact, independently of the implemented function and the considered technology.In a second part of our work, hardening solutions that limit radiation impacts on circuit reliability have been developed. At elementary cell level, new radiation-hardened latch architectures have been proposed, with a limited impact on performances. At system level, a clock tree duplication methodology has been proposed, leaning on specific latches. Finally, a triplication flow has been design for critical applications. All these solutions have been implemented in 65 nm and UTBB-FDSOI 28nm technologies and radiation test have been performed to measure their hardening efficiency
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Phillips, Stanley David. "Single event effects and radiation hardening methodologies in SiGe HBTs for extreme environment applications." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/45854.
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Field-effect transistor technologies have been critical building blocks for
satellite systems since their introduction into the microelectronics industry. The
extremely high cost of launching payloads into orbit necessitates systems to have
small form factor, ultra low-power consumption, and reliable lifetime operation,
while satisfying the performance requirements of a given application. Silicon-based
complementary metal-oxide-semiconductors (Si CMOS) have traditionally been able to
adequately meet these demands when coupled with radiation hardening techniques that
have been developed over years of invested research. However, as customer demands
increase, pushing the limits of system throughput, noise, and speed, alternative
technologies must be employed. Silicon-germanium BiCMOS platforms have been
identfied as a technology candidate for meeting the performance criteria of these
pioneering satellite systems and deep space applications, contingent on their ability to
be hardened to radiation-induced damage. Given that SiGe technology is a relative new-
comer to terrestrial and extra-terrestrial applications in radiation-rich environments,
the same wealth of knowledge of time-tested radiation hardening methodologies has
not been established as it has for Si CMOS. Although SiGe BiCMOS technology has
been experimentally proven to be inherently tolerant to total-ionizing dose damage
mechanism, the single event susceptibility of this technology remains a primary concern.
The objective of this research is to characterize the physical mechanisms that drive the
origination of ion-induced transient terminal currents in SiGe HBTs that subsequently
lead to a wide range of possible single event phenomena. Building upon this learning,
a variety of device-level hardening methodologies are explored and tested for efficacy.
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Hopkins, Thomas A. "An Automated Approach to a 90-nm CMOS DRFM DSSM Circuit Design." Wright State University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=wright1281645939.
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Rodrigues, Artemis Socorro do Nascimento. "Caracterização molecular dos antigenos RhD, (RhD fraco e RhD parcial) e sua aplicação na pratica transfusional." [s.n.], 2005. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310418.
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Orientador: Lilian Maria de CastilhoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Considerando a imunogenicidade e importância clínica do antígeno RhD bem como o grande número de variantes RhD identificadas, estudos que possam esclarecer sua expressão e mecanismos moleculares envolvidos são importantes para a padronização de técnicas moleculares e sorológicas em diferentes populações. Assim foram nossos objetivos: padronizar técnicas moleculares para realização da genotipagem RHD fraco e determinar sua ocorrência na população brasileira; associar os tipos de RhD fracos encontrados com os haplótipos Rh presentes; e avaliar a aplicação da determinação do antígeno RhD na prática transfusional. Estudamos 503 amostras de DNA de doadores voluntários de sangue fenotipados como RhD ftaco. Destas amostras de DNA estudadas, 415 (82,5%) foram caracterizadas como RhD ftaco, 65 (12,9%) como RhD parcial, 15 (3%) apresentaram associações de RhD parcial e RhD ftaco e 8 (1,6%) foram RhD normal. I Os antígenos RhD fraco tipos 1, 3 e 4 foram os mais fteqüentes em nossa população. Como estes três tipos de RhD fraco não apresentam risco de aloimunização anti-D, pacientes assim classificadospodem ser transfundidos com sangue RhD-positivo. Nossos resultados demonstraram que 12,~A>das amostras fenotipadas como RhD fraco eram na verdade RhD parcial. Os antígenos RhD parciais encontrados em nosso estudo foram D~ DHMi e DVI. Quarenta (7,9%) amostras de DNA foram caracterizadas como D~ 16 (3,2%) como DHMi e 9 (1,8%) como DVI. A caracterização dos antígenos RhD parciais que reagem sorologicamente como RhD ftaco, tais como D DHMi e RhD categoria VI pode ser de grande auxilio na prevenção da aloimunização anti-D em pacientes politransfundidos e gestantes. A freqüência dos antígenos RhD parciais D~ DHMi e DVI encontrada em nossas amostras sugere um elevado risco de aloimunização ao antígeno RhD em pacientes fenotipados como RhD ftaco. - Das 503 amostras estudadas, 15 apresentaram mutações responsáveis pela expressão do antígeno RhD fraco e ao mesmo tempo mutações características de antígenos RhD parciais, ou seja, estas amostras possuíam os antígenos RhD fraco e RhD parcial associados. Estudamos quatro amostras de DNA de pacientes fenotipados como RhD :fraco que apresentavam anti-D. Nosso estudo demonstrou que a aloimunização anti-D nestes pacientes estava relacionada à presença de um antígeno RhD parcial e não a um antígeno RhD :fraco como diagnosticado sorologicamente. Duas amostras foram classificadascomo RhD parcial DAR, 1 como RhD parcial DHMi e 1 como DVI. Os resuhados demonstraram que os tipos de RhD fraco 1, 2, 3 e 4 que foram detectados à TA ou à 3'te e apresentaram grau de aglutinação superior a 1+ na AGH podem ser considerados como RhD positivo, pois não foram associados ao antígeno RhD parcial. Apesar deste trabalho ter sido o único que relacionou os tipos de RhD ftaco com o grau de aglutinação, a literatura revela que ainda não foi demonstrada aloimunização anti-D em pacientes portadores dos antígenos RhD fraco tipos 1,2 e 3. De acordo com os nossos resultados pode-se concluir que: 1. A transfusão com sangue RhD-positivo pode ser recomendada para todos os pacientes que apresentam os tipos do antígeno RhD :ftaco 1, 3 e 4 identificados por técnicas moleculares e para aqueles que apresentarem grau de aglutinação superior a 1+ na fenotipagem RhD. 2. A utilização de métodos de fenotipagem mais sensíveis em combinação com reagentes anti-D de alta afinidade é recomendada na detecção de antígenos RhD ftaco com baixa densidade antigênica em doadores de sangue; 3. Há necessidade da utilização de dois anti-soros monoc1onais (IgM e IgG) na determinação do antígeno RhD :ftacoem pacientes; 4. As genotipagens RHD, RHD ftaco e RHD parcial devem ser rea1i73dasquando os resuhados sorológicos não forem claros ou quando o paciente for politransfundido. 5. A biologia molecular associada à hemaglutinação pode aumentar consideravelmente a segurança transfusional pela mellior caracterização dos antígenos RhD em nossa população
Abstract: The purpose of this study was to characterize by molecular studies theRhD antigens (weak D and partial D) in Brazilian blood donors. DNA samples ftom 503 blood donors phenotyped as weak D were tested by two different sequence-specific primers (pCR-SSP) assays to determine the presence or absence of RHD gene (PCR-SSP intron 4 and exon 10) and to detect the common weak D types. Ofthe 503 weak D samples studied, 415 (82,5%) were identified as weak D, 65 (12,9%) as partial D, 15 (3%) showed association ofweak D and partial D and 8 (1,6%) were normal D. Weak D types 1, 3 and 4 contributed more than 85% of alI molecular weak D types. For these 3 types, D-positive transfusion can be considered safe because no immunization events have been documented yet. These findings show for the first time the frequency of weak D types in Brazilians. Molecular analysis showed that 12,9% of the weak D phenotype samples studied carried a partia! D alIele. The partial Ds found in our study were DAR, DVI and DHMi. Forty (7,9%) DNA samples were characterized as DAR, 16 (3,8%) as DHMi and 9 (1,8%) as DVI. The characterization of the partia! D antigens DAR, DHMi and DVI may avoid alIoimmunization in patients phenotyped as weak D. Fiffeteen patients showed mutations to weak D and partia! D showing that these samples had the weak D and partia! D antigens associated. We also studied 4 DNA samples of patients phenotyped as weak D who had developed anti-D. Our study showed that anti-D alIoimmunization in these patients was associated with the presence of partia! D antigens. Two samples were classified as partia!, D DAR, 1 as DHMi and 1 was DVI.AlI the weak D types identified in our study were associated with the intensity of agglutination obtained at room temperature (RT), 3'fC and AGH. The sensitivity of detecting weak D depends on the anti-D reagent and on the exact conditions of the methods. Our results showed that the weak D types 1, 2, 3 and 4 were frequently detected at RT and 3'fC and therefore could be considered as D-positive for transfusion. According to our results we could recommend the use ofmonoclonal anti-DIgM with high avidity to detect weak D antigen with low antigen density in blood donors and two monoclonals, one IgM and one IgG in combination with AGT to detect the weak D antigen in patients
Doutorado
Ciencias Basicas
Doutor em Clínica Médica
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Axelsson, Lena. "Karakterisering av blodgruppsgenen RHD hos patienter med svagt RhD-antigenuttryck." Thesis, Malmö högskola, Fakulteten för hälsa och samhälle (HS), 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-24168.
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Rh-blodgruppssystemet är mycket komplext med 54 blodgruppsantigen som kodas av två nära varandra belägna gener på kromosom 1 – RHD och RHCE. RHD-genen kodar för RhD-proteinet, ett membranbundet protein på erytrocyter vars antigen utgör de kliniskt viktigaste och mest immunogena efter ABOsystemets, och som kan ge upphov till transfusionskomplikationer och hemolytisk sjukdom hos foster och nyfödda. Vissa individer har varianter av RhD-protein som uttrycks svagare än normalt (”svaga D”), eller där vissa epitoper saknas (”partiella D”), och för vilka serologiska metoder inte kan ge enhetliga resultat. Detta orsakar problem vid blodtransfusion, graviditet och bloddonation, och leder ofta till användning av det redan knappa lagret av RhD-negativa blodenheter för att skydda patienten. I detta projekt har åtta prover med svaga RhD-antigenuttryck sekvenserats med avseende på RHD-genen i syfte att fastställa individernas RhDfenotyp. I sex av proverna hittades sex nukleotidpolymorfismer och två deletioner, som alla är sällsynta men dock är kända sedan tidigare. I två prover kunde inga mutationer i exon eller intilliggande intron påvisas som förklaring till de svaga uttrycken av RhD hos dessa individer.The Rh blood group system is very complex with 54 blood group antigens encoded by two adjacent genes on chromosome 1 – RHD and RHCE. The RHD gene encodes the RhD protein, a membrane bound protein on erythrocytes whose antigens are the most clinically important and immunogenic after those of the ABO system, and which can result in transfusion complications and haemolytic disease of the fetus and newborn. Some individuals have variants of the RhD proteins that are expressed more weakly than normal (“weak D”), or have some of the epitopes missing (“partial D”), and for which serological methods cannot give a uniform result. This provides a problem in blood transfusion, pregnancy, and blood donation, and often results in the use of the already sparse supply of RhDnegative blood units for the safety of the patient. In this project, eight samples with weak RhD antigen expression have been sequenced with regard to the RHD gene in order to determine the RhD phenotype of the individuals. In six of the samples, six single nucleotide polymorphisms and two deletions were found, all of which are rare but are previously known. For two of the samples, no mutations in exons or adjacent introns could be detected to explain the weak expression of RhD in those individuals.
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Phillips, Stanley D. "Developing radiation hardening by design." Thesis, Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/29640.
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Thesis (M. S.)--Electrical and Computer Engineering, Georgia Institute of Technology, 2010.Committee Chair: Cressler, John; Committee Member: Citrin, David; Committee Member: Shen, Shyh-Chiang. Part of the SMARTech Electronic Thesis and Dissertation Collection.
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Bustamante-Gallardo, Pedro. "Molecular studies on Rice hoja blanca virus (RHBV)." Thesis, University of East Anglia, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338096.
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Lüttringhaus, Timo. "RHD-Genotypisierung bei D-negativen Ostasiaten." [S.l. : s.n.], 2008. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-61148.
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Diestelhorst, Ryan M. "Silicon-germanium BiCMOS device and circuit design for extreme environment applications." Thesis, Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/28180.
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Thesis (M. S.)--Electrical and Computer Engineering, Georgia Institute of Technology, 2009.Committee Chair: Cressler, John; Committee Member: Papapolymerou, John; Committee Member: Ralph, Stephen.
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Amaral, Daphne Renata Tavares. "Determinação do genótipo RHD fetal através do plasma materno em gestantes RhD-negativo de uma população do Brasil." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310413.
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Orientador: Lilian Maria de CastilhoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A análise de plasma materno para a determinação do genótipo RHD fetal é uma importante ferramenta no acompanhamento de gestantes RhD-negativo, especialmente em pacientes aloimunizadas. Este trabalho verificou a acurácia da genotipagem RHD fetal pela análise do plasma materno em uma população do Brasil. Foram analisadas 88 gestantes RhD-negativo entre 11 e 39 semanas de gestação, com idade mediana de 28 anos. Treze (14,78%) pacientes encontravam-se aloimunizadas com anti-D. Foram utilizados primers e sondas para detecção do gene RHD (exons 4, 5 e 10) por PCR em tempo real. Como controle interno, utilizou-se um conjunto de primers e sondas para identificar o genes SRY e CCR5. Sangue periférico ou sangue de cordão umbilical dos respectivos neonatos foram coletados durante o parto para a realização da fenotipagem RhD. A genotipagem RHD convencional foi realizada em todas as 88 amostras de DNA materno. Oitenta e três (94,32%) gestantes apresentaram a deleção do gene RHD e em 5 (5,68%) amostras foram identificadas variantes do gene RHD (3 RHD e 2 DFR). A genotipagem RHD convencional foi também realizada em 17 amostras de DNA paternas. Quinze amostras (88,24%) foram genotipadas como RHD+ (5 RHD+/RHD+ e 10 RHD+/RHD-) e 2 (11,76%), como RHD-. Cinqüenta e oito (65,91%) fetos foram genotipados como RHD+. Vinte e sete (30,68%) amostras apresentaram ausência completa do gene RHD e três fetos apresentaram amplificação apenas para o exon 10, demonstrando a presença de uma possível variante RHD ou RHD-CE-Ds. Todos os resultados da genotipagem RHD fetal foram concordantes com a fenotipagem neonatal incluindo os 3 fetos com a variante RHD, fenotipados como RhD-. Nossos resultados indicam que a genotipagem RHD fetal através da análise do plasma materno amplificando 3 regiões do gene RHD (exons 4, 5 e 10) é adequada para a aplicação clínica. Este protocolo pode-se tornar prática em um futuro próximo
Abstract: Maternal plasma analysis for determination of the fetal RHD status is an important tool for the management of RhD-negative pregnant, specially alloimunized women. We assessed the accuracy of fetal RHD genotyping by analysis of maternal plasma in a multi-ethnic population. We analyzed plasma samples from 88 RhD-negative pregnant women between 11 and 39 weeks of gestation, median age of 28 years old to determine the fetal RHD genotype. This population was from Southeastern Brazil with high mixed ethnic background. Thirteen patients (14,78%) had anti-D alloantibody. We used TaqMan primers and probes to detect exons 4, 5 and 10 of RHD, by real-time PCR. As internal controls, we used primers/probes sets to SRY and CCR5. Peripheral or umbilical cord bloods from respective neonates were collected during delivery and hemagglutination was performed. Conventional RHD genotyping was realized in all pregnant. Eighty-three patients had a deletion of RHD gene and five samples were identified RHD variants (3 RHD and 2 DFR). The conventional RHD genotyping was also performed on 17 DNA samples from fathers. Fifteen samples were genotyped as RHD+ (5 RHD+/RHD+ and 10 RHD+/RHD-) and 2 RHD-negative. Fifty-eight (65,91%) fetuses were genotyped as RHD+. Twenty-seven (30,68%) samples showed completely absence of RHD and three fetuses showed amplification only for the exon 10, demonstrating the presence of a possible variant (RHD or RHD-CE-Ds). All fetal RHD results agreed with the neonatal typing including the 3 fetuses with RHD variant, phenotyped as RhD-negative. Thus, the accuracy of the fetal RHD genotyping in this population was 100%. The earliest pregnancy in which fetal RHD was detected was 11 weeks. Our findings indicate that the accuracy of fetal RHD genotyping from maternal plasma using 3 regions (exons 4, 5 and 10) can be sufficient for clinical application in a multi-ethnic population. This knowledge helped us on the development of a feasible protocol for fetal RHD genotyping on DNA from maternal plasma in our population and should become practice in the near future
Mestrado
Ciencias Basicas
Mestre em Clinica Medica
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Rosdahl, Karl Joakim. "Cosmological RHD simulations of early galaxy formation." Thesis, Lyon 1, 2012. http://www.theses.fr/2012LYO10075/document.
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Avec l’essor actuel de la sophistication et de l’efficacité des codes de cosmologie hydrodynamique,il est devenu possible d’inclure le transfert radiatif (RT) des photons ionisants dansles simulations cosmologiques, soit en post-traitement, soit en simulations couplées rayonnement+hydrodynamique (RHD). Malgré de nombreux obstacles, il y a eu cette derniéredécennie beaucoup de recherches menées sur les différentes stratégies et implémentations,dû au fait qu’un nombre de problèmes intéressants peuvent être désormais abordés par laRT et RHD, par exemple comment et quand l’Univers s’est réionisé, comment l’émissionradiative des étoiles et des noyaux actifs de galaxies se comportent pour réguler la formationdes structures à des échelles petites et grandes, et quelles prédictions et interprétationsnous pouvons faire des phénomènes observés, tels que la forêt Lyman-alpha et des sourcesdiffuses de rayonnement.Cela coïncide avec l’avènement du télescope spatial James Webb (JWST) et d’autresinstruments de pointe qui sont sur le point de nous donner un aperçu sans précédent sur lafin des âges sombres de l’Univers, quand le cosmos est passé d’un état froid et neutre à unétat chaud et ionisé, à la suite de l’apparition des sources radiatives.Notre préoccupation principale étant les rétroactions radiatives des premieres structures,nous avons mis en place une version RHD du code cosmologique Ramses, que nous appelonsRamsesRT, basée sur la méthode des moments. Ce code nous permet d’étudier les effets durayonnement ionisant dans les simulations cosmologiques RHD qui tirent pleinement profitdes stratégies de raffinement adaptif de grille et de parallélisation de Ramses. Pour rendreauto-cohérent le RHD nous avons également mis en oeuvre une thermochimie hors-équilibreincluant des espèces de l’Hydrogène et de l’Hélium qui interagissent avec le rayonnementtransporté.Je présente dans cette thèse une description détaillée de RamsesRT et de nombreux testscontribuant à sa validation.Jusqu’à présent nous avons utilisé RamsesRT pour étudier l’émission Lyman-alpha decourants d’accrétion, qui sont prédits à grand redshift par les simulations cosmologiques,mais n’ont jamais été clairement identifiés par les observations. Nous avons également étudiéle chauffage gravitationnel dans ces courants pour déterminer si ce dernier pouvait être lasource motrice principale des Lyman-alpha blobs, un phénomène observé qui a été beaucoupétudié et débattu au cours de la dernière décennie. Cet étudie nous permet de conclure queles Lyman-alpha blobs peuvent, en principe, être alimentés par le chauffage gravitationnel,et que d’autre part, les courants d’accrétion sont sur le point d’être directement détectablesavec des instruments à venir.Mes intentions futures sont d’utiliser RamsesRT dans les simulations cosmologiques àhaute résolution, de la formation des premiéres galaxies jusqu’à l’époque de la réionisation,et ainsi étudier comment la rétroaction radiative affecte la formation et l’évolution de cesgalaxies et de faire des prévisions d’observation qui peuvent être testées avec des instrumentssophistiqués tels que le JWSTWith the increasing sophistication and efficiency of cosmological hydrodynamics codes, ithas become viable to include ionizing radiative transfer (RT) in cosmological simulations,either in post-processing or in full-blown radiation-hydrodynamics (RHD) simulations. Inspite of the many hurdles involved, there has been much activity during the last decade or soon different strategies and implementations, because a number of interesting problems canbe addressed with RT and RHD, e.g. how and when the Universe became reionized, howradiation from stars and active galactic nuclei plays a part in regulating structure formationon small and large scales, and what predictions and interpretations we can make of observedphenomena such as the Lyman-alpha forest and diffuse sources of radiation.This coincides with the advent of the James Webb space telescope (JWST) and otherstate-of-the-art instruments which are about to give us an unprecedented glimpse into theend of the dark ages of the Universe, when the cosmos switched from a cold and neutralstate to a hot and ionized one, due to the turn-on of ionizing radiative sources.With a primary interest in the problem of radiative feedback in early structure formation,we have implemented an RHD version of the Ramses cosmological code we call RamsesRT,which is moment based and employs the local M1 Eddington tensor closure. This code allowsus to study the effects of ionizing radiation on-the-fly in cosmological RHD simulationsthat take full advantage of the adaptive mesh refinement and parallelization strategies ofRamses. For self-consistent RHD we have also implemented a non-equilibrium chemistry ofthe atomic hydrogen and helium species that interact with the transported radiation.I present in this thesis an extensive description of the RamsesRT implementation andnumerous tests to validate it.Thus far we have used the RHD implementation to study extended line emission fromaccretion streams, which are routinely predicted to exist at early redshift by cosmologicalsimulations but have never been unambiguously verified by observations, and to investigatewhether gravitational heating in those streams could be the dominant power source ofso-called Lyman-alpha blobs, an observed phenomenon which has been much studied anddebated during the last decade or two. Our conclusions from this investigation are thatLyman-alpha blobs can in principle be powered by gravitational heating, and furthermorethat accretion streams are on the verge of being directly detectable for the first time withupcoming instruments.My future intent is to use RamsesRT for high-resolution cosmological zoom simulations ofearly galaxy formation, up to the epoch of reionization, to study how radiative feedbackaffects the formation and evolution of those galaxies and to make observational predictionsthat can be tested with upcoming instruments such as the JWST
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Perera, W. Shermal. "Binding and molecular characterisation of monoclonal RhD antibodies." Thesis, University of Aberdeen, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342706.
Full textAbstract:
Monoclonal RhD antibodies (anti-RhD) may potentially be used in preventing Rh alloimmunisation of women delivering RhD-positive babies, and thereby preventing haemolytic disease of the newborn (HDN). Binding and molecular analyses were performed on a range of monoclonal anti-RhDs to understand the interaction between the antibody and antigen. A flow cytometry (FCM) assay system was developed to analyse the binding of the anti-RhD to human group O R1R2 red blood cells (RBC). A panel of 30 anti-RhD preparations were studied using this assay and Vmax (maximum binding) and KD (equilibrium constant) were determined for each antibody. The antibodies were categorised into 3 groups (low, medium and high binders) according to their Vmax. Furthermore, the Vmax was converted to the number of antibody molecules bound per RBC (NMBR) by using a correlation curve generated from running parallel FCM and radioiodination assays (RIA). Scatchard analysis of the RIA data indicated that the total NMBR for O R1R2 RBC was 27,300 antigen sites/cell. Molecular analysis involved cloning and sequencing of 11 anti-RhD. Heavy chains (HC) preferentially used gene segments from the VH3 and VH4 families, and kappa chain (κ LC) usage was restricted to DPK9. Four sets of antibodies, showed restricted D gene segments (encode part of the HCDR3) which indicated possible importance for epitope specificity. Analysis of V gene sequence indicated that common VH and VL pairings were found used by the medium binders. The high and low binders had unique VH and VL pairings, although the high binders also showed greater somatic mutations from their respective germline genes. It was concluded that the fit of the antibody to the RhD antigen is dependent on both the VH and VL usage and pairing, and that the precise epitope specificity of these antibodies may require HCDR3 interaction.
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Credidio, Débora Castilho. "Variantes do antígeno RhD = estudo sorológico e molecular." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310414.
Full textAbstract:
Orientador: Lilian Maria de CastilhoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Discrepâncias na tipagem Rh ocorrem devido à presença de variantes do antígeno RhD, em especial D fraco e D parcial. Diferentes reagentes anti-D monoclonais tem sido desenvolvidos para identificar estas variantes, mas a caracterização molecular pode garantir um resultado mais específico com melhor definição do tipo de variante presente. O fenótipo D fraco ocorre por alterações de nucleotídeos que levam a substituição de aminoácidos na região transmembranar e intracelular da proteína Rh enquanto que o fenótipo D parcial ocorre por alterações de nucleotídeos ou rearranjos gênicos que levam a substituição de aminoácidos na região extracelular da proteína Rh, resultando em fenótipos sorológicos distintos e aloimunização anti-D. Nossos objetivos foram avaliar reagentes anti-D e métodos sorológicos e moleculares na detecção e identificação destas variantes. Foram estudadas 335 amostras de sangue e DNA de doadores e pacientes fenotipados previamente como RhD fraco, ou que apresentaram resultados discrepantes na tipagem RhD. Das 335 amostras estudadas, 215 (64,1%) foram identificadas como D fraco, 89 (26,5%) como D parcial, 3 (1%) como DEL, 11 como RhD-positivo e 17 como RhD-negativo. Entre as amostras D fraco, 76 eram DF1 (35,3%); 75 DF2 (34,9%); 13 DF3 (6,1%); 49 DF4 (22,8%) e 2 DF5 (0,9%). Entre as amostras D parcial, 9 (10,1%) eram DAR, 25 (28,1%) DFR, 6 (6,7%) DBT, 1 (1,1%) DHMi, 1(1,1%) RoHAR, 26 (29,2%) DVI, 14 (15,8%) DVa, 5 DIVb (6,6%) e 2 (2,3%) DVII . Nas amostras DEL, duas foram identificadas molecularmente como RHD(IVS5-38DEL4) e uma como RHD(K409K). Nossos resultados demonstram que a utilização de diferentes reagentes anti-D e métodos na rotina sorológica pode indicar a presença de uma variante do antígeno RhD que deve ser investigada por análise molecular. Esta estratégia pode auxiliar na diferenciação entre D fraco e D parcial e caracterizar as variantes que levam a aloimunização anti-D. Esta distinção é importante na seleção de sangue para pacientes e na prevenção da doença hemolítica do feto e recém-nascido
Abstract: Rh discrepancies are becoming a problem during routine testing due to partial D or weak D phenotypes. Panels of monoclonal antibodies (MoAb) are being developed in order to identify D variants such as partial D and weak D when there are anomalous RhD typing results but molecular characterization offers a more specific grouping of weak and partial D. The weak D phenotype is caused by many different RHD alleles encoding aberrant RhD proteins, resulting in distinct serologic phenotypes and anti-D immunizations. We evaluated currently used serologic methods and reagents to detect and identify D variants and correlated the results with molecular analyses. A total of 335 blood samples from Brazilian blood donors and patients with discrepant results of D typing in routine were analyzed. In total, 215 (64.1%) weak D, 89 (26.5%) partial D, 3 (1%) DEL, 11 RhD-positive and 17 RhD-negative were identified. Among weak D samples, 76 weak D Type 1 (35.3%); 75 weak D Type 2 (34.9%); 13 weak D Type 3 (6.1%); 49 weak D Type 4 (22.8%) and 2 weak D Type 5 (0.9%) alleles were found. Among the partial D samples, 9 (10.1%) DAR, 25 (28.1%) DFR, 6 (6.7%) DBT, 1 (1.1%) DHMi, 1(1.1%) RoHAR, 26 (29.2%) DVI, 14 (15.8%) DVa, 5 DIVb (6.6%) and 2 (2.3%) DVII were observed. Two samples identified as DEL by adsorption/elution were characterized by molecular analyses as RHD(IVS5-38DEL4) and one sample as RHD(K409K). Our results showed that the use of different methods and anti-D reagents in the serologic routine reveal some D variants that can be further investigated. Molecular methods can help to differentiate between partial D and weak D and characterize the weak D types providing additional information of value in the RhD typing. This distinction is important for selection of blood products and to prevent anti-D hemolytic disease of the fetus and newborn
Mestrado
Ciencias Basicas
Mestre em Clinica Medica
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Mota, Mariza Aparecida 1956. "Identificação do gene RHD em doadores voluntários de sangue fenotipados como RHD negativo utilizando pools de DNA = RHD allelic identification among D-brazilian blood donors as a routine test using pools of DNA." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310410.
Full textAbstract:
Orientador: Lilian Maria de CastilhoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Alelos RHD que levam à redução da expressão do antígeno D na superfície dos eritrócitos podem levar à tipagem errônea como D- por técnica sorológica e podem causar imunização anti-D quando transfundidos em pacientes. A fim de determinar a ocorrência de tais alelos em doadores de sangue aparentemente D-, foi implementada técnica molecular de rotina utilizando um pool de DNAs de doadores de sangue. Um total de 2450 amostras previamente tipadas como D- foram testadas em pools de 10 amostras para o polimorfismo RHD específico, intron 4 e éxon 7. Nos pools que apresentaram resultado de PCR positivo, as amostras foram reavaliadas individualmente utilizando PCR exon-específico, métodos sorológicos e sequenciamento genético. Dentre as 2.450 amostras de doadores D- testadas, 101 (4,1%) carreavam o gene RHD. Foi identificada a presença de RHD não funcional (RHD'psi', RHD*CE(2-9)-D e RHD*CE(3-7)-D), diferentes alelos de D fraco tais como RHD*weak D type 1, RHD*weak D type 4.3, RHD*weak D type 5, RHD*weak D type 38 e RHD*DEL. Uma metodologia utilizando a técnica de PCR foi empregada como teste de rotina para o gene RHD utilizando pools de 10 amostras de DNA de doadores de sangue. Foi possível a integração da genotipagem RHD em programas de triagem de rotina utilizando pools de DNA. Como resultado, 19 (0,8%) dos doadores de sangue que carreavam fenótipos D fraco ou Del, com potencial de causar imunização anti-D em receptores, foram reclassificados como D+. Entretanto, seria necessário adaptar a estratégia de genotipagem RHD ao espectro de alelos prevalente em cada população
Abstract: RHD alleles leading to a reduced expression of D antigen of the red blood cell (RBC) surface may be erroneously typed as D negative by serology and may cause anti-D immunizations when transfused to recipients. We have therefore investigated the occurrence of such alleles among apparent D negative blood donors, molecular typing was implemented as a routine test using a pool of DNA. A total of 2,450 pretyped D negative samples was tested in pools of 10 for the RHD-specific polymorphism in intron 4 and exon 7. Samples in PCR positive pools were individually reevaluated by exon-specific PCRs, sequencing and serologic methods. Our results showed that among 2,450 serologically D negative blood donor samples tested, 101 (4.1%) carried the RHD gene. Nonfunctional RHD (RHD*'psi', RHD*CE(2-9)-D and RHD*CE(3- 7)-D), different weak D alleles such as RHD*weak D type 1, RHD*weak D type 4.3, RHD*weak D type 5, RHD*weak D type 38 and RHD*DEL were identified. We employed a PCR-based assay for RHD as a routine test using pools of 10 DNA blood donor samples. The integration of RHD genotyping into the routine screening program using pools of DNA samples was straightforward. As a consequence, 19 (0.8%) blood donors carrying a weak D and Del phenotypes with the potential of causing anti-D immunizations in recipients were reclassified as RhD positive. For each population, it would be necessary to adapt the RHD genotyping strategy to the spectrum of prevalent alleles
Doutorado
Clinica Medica
Doutora em Ciências
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Schmidt, Luciana Cayres. "Genotipagem RHD fetal no plasma materno como ferramenta não invasiva na predição do risco da doença Hemolítica Perinatal em gestantes RHD negativo." Universidade Federal de Minas Gerais, 2011. http://hdl.handle.net/1843/BUOS-8L7MQ6.
Full textAbstract:
The management of RhD negative pregnant women is based on the premise that their fetuses may be at risk of developing hemolytic disease (DHPN), which could bring serious risks to the fetus. Invasive procedures such as amniocentesis or cordocentesis can be used to define the fetal RhD phenotype, however, it offers risks to both fetus and pregnant woman. The ability to detect fetal RHD gene in DNA from maternal plasma allowed a major advance in the care protocol to RhD negative pregnant women for being a non-invasive procedure and therefore carries no risk to the mother or fetus. Methods: 55 blood samples from RhD negative pregnants were processed for extraction of fetal DNA. Real time PCR was performed to amplify segments of exons 5 and 7 of RHD gene. The results of fetal genotyping using maternal plasma were compared with the RhD phenotype of newborns, performed in cord blood sample obtained at birth. PCR for detection of SRY gene and for the study of RHD zygosity was also performed, when the paternal sample was available. Results: The results of fetal RHD genotyping could be compared with 43 RhD phenotypes of newborn. There were five inconclusive results, no false negative and one false positive due to a probable incorrect RhD phenotyping. The test sensitivity was 100%, specificity was 94,1% and concordance between molecular and serological tests was 97,7% if we consider that the only discordant serological results was correct. However, in this case, genotyping from maternal plasma was concordant to that determined from the newborn buccal cells. Conclusion: The test for noninvasive fetal RHD genotyping was a sensitive and viable tool in management of RhD negative pregnants.O acompanhamento a gestantes RhD negativo é baseado na premissa de que seus fetos podem estar em risco de desenvolver a doença hemolítica perinatal (DHPN), o que pode trazer sérios riscos ao feto. Procedimentos invasivos como amniocentese ou cordocentese podem ser utilizados para se conhecer o fenótipo RhD fetal, entretanto, oferecem riscos ao feto e à gestante. A possibilidade de se detectar o gene RHD no DNA fetal extraído do plasma materno possibilitou um grande avanço no protocolo de atendimento a gestantes RhD negativo por ser um procedimento não invasivo e que, portanto, não acarreta qualquer risco à mãe ou ao feto. Material e métodos: 55 amostras de sangue de gestantes RhD negativo foram processadas para purificação do DNA fetal. PCR em tempo real foi realizada para amplificar segmentos dos exons 5 e 7 do gene RHD. Os resultados da genotipagem fetal no plasma materno foram comparados com a fenotipagem RhD dos recém-nascidos, realizada em amostras de sangue umbilical colhida ao nascimento. Também foram realizadas PCR para detecção do gene SRY e para estudo da zigozidade RHD paterna, quando a amostra paterna estava disponível. Resultados: Os resultados da genotipagem RHD fetal puderam ser comparados com 43 fenótipos RhD dos recém-nascidos. Houve cinco resultados inconclusivos, nenhum falso negativo e um falso positivo, devido a uma provável fenotipagem RhD incorreta. A sensibilidade do teste foi de 100%, a especificidade foi de 94,1% e a concordância dos resultados moleculares com os sorológicos foi de 97,7%, se considerarmos que o único resultado sorológico discordante estava correto. Entretanto, este não parece ser o caso, uma vez que a genotipagem usando DNA fetal extraído de plasma materno foi concordante com a genotipagem RHD a partir de células da mucosa bucal do recém-nascido. Conclusão: O teste para a genotipagem RHD fetal não invasiva mostrou-se sensível e viável como ferramenta auxiliar na rotina de atendimento a gestantes RhD negativo.
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Schweidler, Kerstin. "Pränatale RhD- und AB0-Diagnostik aus Fruchtwasser mittels Polymerasekettenreaktionen." [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=965811506.
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Machado, Isabela Nelly. "Genotipagem RHD fetal atraves da analise do plasma materno." [s.n.], 2004. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313178.
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Orientadores: Ricardo Barini, Lilian Maria de CastilhoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A Doença Hemolítica Perinatal ainda contribui para as taxas de morbi-mortalidade perinatal, a despeito do amplo uso da imunoprofilaxia. A determinação da tipagem sanguínea RhD fetal é útil para o acompanhamento pré-natal das gestantes RhD-negativo sensibilizadas e para a profilaxia da Doença Hemolítica Perinatal, evitando-se desnecessários procedimentos invasivos, investigações sorológicas e administração da imunoglobulina humana nos casos de fetos RhD-negativo. A análise molecular do plasma matemo abriu novas possibilidades para o diagnóstico pré-natal não invasivo, onde a genotipagem RHD fetal é uma das aplicações clínicas mais relevantes até o momento. Objetivo: Avaliar o desempenho da genotipagem RHD fetal através da análise do plasma matemo como método diagnóstico pré-natal não invasivo. Método: Foi conduzido um estudo de validação de teste diagnóstico a partir de 81 amostras sangüneas obtidas de gestantes RhD-negativo, entre 4 e 41 semanas de gestação. O DNA fetal foi extraído dos respectivos plasmas matemos utilizando kits comercialmente disponíveis. As regiões exon 10 e intron 4 do gene RHD foram testadas através da reação em cadeia da polimerase alelo- específica (AS-PCR) convencional. Os resultados da genotipagem fetal foram comparados com a tipagem sanguínea neonatal e os dados analisados pelo softwware SAS - versão 8.2@ (1999-2001). Resultados: 15 amostras foram obtidas no primeiro trimestre, 37 no segundo trimestre e 29 no terceiro trimestre. Houve falha de amplificação em 6 amostras, 3 RhD-negativo e 3 RhD-positivo à tipagem neonatal. A concordância entre os resultados da genotipagem e da tipagem neonatal foi de 97,3%, sensibilidade de 98,3% e especificidade de 93,8%. Foi observado 1 falso positivo no terceiro trimestre e 1 falso negativo no primeiro trimestre. Conclusão: AS-PCR convencional é um método com bom desempenho para a genotipagem RHD fetal através da análise do plasma matemo, como método diagnóstico pré-natal não invasivo
Abstract: Hemolytic Disease of the Fetus and Newborn still contributes to perinatal morbidity and mortality, in spite of the widespread munoprophylaxis. Prenatal identification of fetal RHD status is a goal of obstetrical practice, in order to prevent maternal immunization and to help in the management of alloimmunized pregnant women. The analysis of the maternal plasma opened up new posibilities for noninvasive prenatal diagnosis and the determination of fetal RHD genotype is one of the most relevant application of this molecular analysis. Objective: To establish the performance of conventional PCR analysis of the maternal plasma as a method to genotype fetal RHD. Method: A validity of diagnostic test was conduced with 81 peripheral blood samples obtained from RhD-negative pregnant women, between 4 and 41 weeks of gestation. Commercially available kits were used to extract DNA from the maternal plasma. Exon 10 and intron 4 RHD gene regions were tested using conventional Allele-Specific Polymerase Chain Reaction (AS-PCR). Fetal RHD genotyping by PCR on maternal plasma was compared to conventional Rh typing in neonatal period and data analysed by SAS- 8.2 version@ (1999-2001). Results: Samples were obtained as follows: 15 on 1 si, 37 on 2nd and 29 on 3rd trimester. Amplification failed in six of the specimens, 3 were RhD-negative and 3 RhD-positive at neonatal typing. Concordance between the genotyping and neonatal typing was 97.3%, sensitivity of 98.3% and specificity of 93.8%. One false positive in the third trimester and one false negative in the first trimester were observed. Conclusion: Conventional AS-PCR is an accurate method for fetal RHD genotyping on maternal plasma, as a noninvasive prenatal dignosis
Mestrado
Tocoginecologia
Mestre em Tocoginecologia
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Coutinho, Conrado Milani. "Diagnóstico do fator RhD utilizando a reação em cadeia da polimerase convencional." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/17/17145/tde-14012009-183745/.
Full textAbstract:
A aplicação dos métodos de biologia molecular tem acrescentado benefícios aos métodos convencionais de diagnóstico do grupo sangüíneo Rhesus (Rh). Alguns estudos evidenciaram a superioridade prática da genotipagem RhD por reação em cadeia da polimerase (PCR) em relação às técnicas de identificação do fenótipo dos antígenos do grupo Rh obtidas pela hemaglutinação. Esta análise molecular tem sido realizada utilizando-se várias seqüências cromossômicas e diferentes tipos de técnicas. O grupo Rh contém dois genes homólogos, um codificando o antígeno D e o outro os antígenos C/c e E/e. Os objetivos deste projeto foram: (1) Detectar a presença de seqüência RhD específica dos indivíduos Rh positivo; (2) Comparar a presença/ausência destas seqüências com o grupo sanguíneo detectado pela hemaglutinação e calcular a sensibilidade e a especificidade da PCR. Para cumprir estes objetivos, foram analisadas amostras de DNA extraídas de sangue periférico de 23 indivíduos (4 homens e 19 mulheres) Rh positivo (11) e negativo (12) para amplificação de seqüências dos genes RhD e RhCE utilizando a técnica de PCR convencional. Nestas amostras, a comparação dos resultados da PCR com os da hemaglutinação demonstrou total concordância entre os testes. A sensibilidade do método foi avaliada pela realização da PCR em amostras de sangue Rh positivo diluídas em água e em sangue Rh negativo, amplificando o DNA na concentração de até 4 pg/l. Estes resultados indicaram que a técnica de PCR mostrou-se efetiva no diagnóstico da genotipagem do fator Rh, vislumbrando-se a possibilidade de sua utilização em outros tecidos de origem êmbrio-fetal para orientação de diagnóstico fetal invasivo e do uso profilático da imunoglobulina anti-D apenas nos casos de incompatibilidade Rh materno-fetal. Adicionalmente, indicaram que havendo melhora da sensibilidade desta técnica será possível detectar quantidades objetivamente menores de DNA fetal na circulação materna, fundamentando um importante passo rumo ao diagnóstico do fator Rh fetal por técnica não invasiva.Molecular biology techniques have added some advantages to conventional diagnosis of the Rhesus (Rh) blood group. Many researches have demonstrated the practical superiority of RhD genotyping using polymerase chain reaction (PCR) over phenotypic identification tests obtained by hemagglutination. The use of different kinds of molecular analysis techniques and genetic sequences has been described. The Rh blood group contains two homologous genes, one encoding the D antigen and the other one coding C/c and E/e antigens. This study objectives were: (1) Detect the RhD sequence specific for the Rh positive individuals; (2) Compare the presence/absence of these sequences with the blood group identified by hemagglutination to calculate PCRs sensitivity and specificity rates. To accomplish these objectives, DNA extracted from venous blood of 23 individuals (4 men and 19 women), Rh positive (11) and negative (12), were analyzed using conventional PCR to amplify RhD and RhCE gene sequences. The comparison of PCR with hemagglutination results has shown total agreement. The sensitivity of this PCR method was evaluated using progressive dilutions of Rh positive samples on water and also on Rh negative samples, which demonstrated successful amplification of until 4 pg/l DNA concentration. These results have indicated that PCR was effective for the RhD genotyping, foreseeing the possibility of its utilization with other embryofetal tissues for invasive diagnosis orientation and anti-D immunoglobulin use only in cases of maternal-fetal incompatibility. Also, with an increase of this techniques sensitivity, fewer DNA amounts could be detected, which will certainly be an important step towards noninvasive fetal RhD diagnosis.
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Jiménez, Divins Núria. "Catalytic hydrogen production over RhPd/CeO2 catalysts and CO purification over Au/TiO2 catalysts." Doctoral thesis, Universitat Politècnica de Catalunya, 2015. http://hdl.handle.net/10803/346926.
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This Thesis focuses on the study of the catalytic production of hydrogen from a biofuel, namely the bioethanol. It also studies the subsequent purification of pre-cleaned reformate streams. The end use of the hydrogen produced is to feed fuel cells to power portable and mobile applications. In this Thesis, two types of catalysts have been developed. One consisting of RhPd/CeO2 catalysts aimed at generating hydrogen via the ethanol steam reforming. On the other hand, Au/TiO2 catalysts have been investigated to eliminate carbon monoxide from reformate streams. The developed catalysts have been tested under practical operational conditions. The developed catalysts have been characterized ex situ, in situ and under reaction conditions. The operando studies allowed for the investigation of the reorganization of the metals driven by the reactive atmosphere. Finally, the miniaturization of the hydrogen production and purification scale has been investigated. To achieve this goal, the developed catalysts have been implemented on microreactors composed of channels measuring only few microns.A la present Tesi doctoral s'estudien la producció catalítica d'hidrogen a partir d'un biocombustible, el bioetanol, i la seva posterior purificació per alimentar piles de combustible que proporcionin energia a aplicacions portàtils i mòbils. S'han desenvolupat dues famílies de catalitzadors, una de RhPd/CeO2 per generar hidrogen a partir de la reformació amb vapor d'etanol, i l'altra d'Au/TiO2 per eliminar el monòxid de carboni dels corrents de reformació pre-purificats. Els catalitzadors han estats estudiats en condicions de reacció properes a la indústria. En aquesta tesi s'han caracteritzat els catalitzadors ex situ, in situ i també en condicions “operando” o de reacció. L'estudi en “operando” dels catalitzadors ha permès investigar la reorganització induïda pels reactius dels components del catalitzador. Finalment, també s'ha estudiat la miniaturització tant del sistema de generació com de purificació de l'hidrogen per tal d'alimentar aplicacions de petit consum. Per això, s'han utilitzat microreactors composats de canals en l'escala del micròmetre.
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Zidi-Yahiaoui, Nedjma. "Propriétés structurales et fonctionnelles des protéines RhBG et RhCG, transporteur d'ammonium chez les mammifères." Paris 7, 2008. http://www.theses.fr/2008PA077133.
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Les protéines Rhésus des mammifères appartiennent à la superfamille Amt/Mep/Rh des transporteurs d'ammonium identifiés chez les bactéries, les levures, les plantes et les animaux. Alors que RhCE, RhD et RhAG sont spécifiquement érythroïdes, les protéines RhBG et RhCG sont exprimées dans divers organes impliqués dans le métabolisme et le transport de l'ammonium. Nous avons étudié les propriétés fonctionnelles des transporteurs RhBG et RhCG humains exprimés dans les cellules HEK293 et MDCK. La fonction de transport d'ammonium dans les cellules transfectées et sauvages a été analysée par le suivi des variations du pH intracellulaire en présence d'un gradient d'ammonium. Cette étude a été réalisée par spectrofluorimétrie en flux interrompu en utilisant une sonde fluorescente sensible au pH. Nous avons observé une alcalinisation très rapide et une énergie d'activation plus faible des cellules transfectées comparées aux cellules sauvages. Nos résultats montrent que les protéines RhBG et RhCG facilitent les mouvements de NH₃ à travers la membrane plasmique des cellules et apparaissent ainsi comme des canaux à NH₃. Sur la base de la structure 3D des canaux à NH3 bactériens, l'AmtB d'Escherichia coli et la Rh50 de Nitrosomonas europaea, et d'une modélisation par homologie des protéines Rh humaines selon la méthode HCA, nous avons identifié les différents acides aminés critiques pour la fonction du canal RhCG et comparé les mécanismes de transport d'ammonium des canaux Rh et de l'EcAmtB. Cette étude a permis de mettre en évidence des similitudes et des différences dans le mécanisme de transport d'ammonium via les transporteurs de la famille Amt et les protéines RhThe mammalian Rh (Rhesus) proteins (RhCE, RhD, RhAG, RhBG and RhCG) belong to the Amt/Mep/Rh superfamily of ammonium transportera identified in bacteria, yeasts, plants and animals. Whereas RhCE, RhD and RhAG are erythroid specific, RhBG and RhCG are expressed in key organs associated with ammonium transport and metabolism particularly in kidney and liver. We have investigated the ammonium transport function of human RhBG and RhCG by comparing intracellular pH variation in wild type and transfected MDCK and HEK293 cells in the presence of an ammonium (NH₄⁺/NH₃) gradient. Stopped-flow spectrofluorimetry analysis, using a pH-sensitive probe, revealed, as compared with wild type cells, a low temperature-dependence of ammonium transport and a faster alkalinisation phase in RhBG and RhCG-transfected cells. Our results show that NH₃ movement across the plasma membrane is facilitated by RhBG and RhCG indicating that these proteins behave as NH₃ channels. Homology models based on crystallographic structures o the bacterial NH₃ channels Escherichia coli AmtB (EcAmtB) and Nitrosomonas europaea Rh5( (A/eRh50) confirms a channel structure for human Rh glycoproteins. Based on the 3D structure, we have highlighted critical residues involved in Rh channel activity and specific mechanistics of NH transport as compared to EcAmtB. This study reveals similarities and differences in ammonia transport mechanism through EcAmtB and human Rh proteins. These functional specificities might be related to the different physiological nitrogen roles in bacteria and mammals
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Chen, Qing [Verfasser]. "Random survey for RHD alleles among D positive Europeans / Qing Chen." Ulm : Universität Ulm. Medizinische Fakultät, 2004. http://d-nb.info/1015471439/34.
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Evans, Rachael Yvonne. "The production of anti-idiotopic antibodies to monoclonal anti-RhD antibodies." Thesis, Lancaster University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274194.
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Lobo, Guilherme Antonio Rago [UNIFESP]. "O desfecho perinatal da aloimunização eritrocitária não-relacionada ao antígeno RhD." Universidade Federal de São Paulo (UNIFESP), 2007. http://repositorio.unifesp.br/handle/11600/23554.
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Previous issue date: 2007Objetivos: Analisar o desfecho perinatal da Aloimunização eritrocitária não-relacionada ao antígeno RhD. De forma complementar, confrontar os resultados perinatais com os da Aloimunização RhD e com aqueles de gestantes Rh- não-sensibilizadas. Método: Estudo observacional descritivo realizado no período de Janeiro de 2000 a Julho de 2005. Foram avaliadas 15 gestantes sensibilizadas por anticorpos não-D (grupo A), 55 grávidas Rhsensibilizadas pelo anti-D (grupo B) e 130 gestantes Rh- não-sensibilizadas (grupo controle C). Foram apurados os seguintes parâmetros relativos à gestante e ao recémnascido: título do anticorpo, alterações ultra-sonográficas ao longo do acompanhamento pré-natal, transfusão intra-uterina, via de parto, idade gestacional ao nascimento, peso ao nascimento, índice de Apgar no quinto minuto, hematócrito do recém-nascido, necessidade de transfusão e/ou exsanguino transfusão no período neonatal, tempo de internação no berçário, natimortalidade e mortalidade no período neonatal. Resultados: No grupo A encontramos sete gestantes sensibilizadas por anticorpos do sistema Lewis, três por anticorpos do sistema Kell, três por anticorpos relacionados ao sistema MNS e duas pelo sistema Diego. Título de anticorpo ≥ 1/16 foi encontrado em todas as pacientes do grupo B e em 27% do grupo A. As alterações ultra-sonográficas estiveram presentes de maneira semelhante entre as grávidas dos grupos A e B (20% e 25%). Transfusão intra-uterina, embora mais freqüente no grupo B, em relação ao grupo A (20% e 7%), não apresentou significância estatística. O parto cesáreo foi realizado de forma crescente nos grupos C, A e B (44%, 53% e 78%). O parto pré-termo teve maior incidência no grupo B em comparação aos grupos A e C (40%, 27% e 7%), assim como o baixo peso ao nascer (39%, 27% e 7%). Índice de Apgar < 7 no 5º minuto foi semelhante entre os três grupos. O hematócrito médio, obtido de sangue do cordão umbilical, foi significativamente maior entre os recém-nascidos do grupo A, em relação ao grupo B (43% e 40,5%). Transfusão e/ou exsanguino transfusão foram indicadas mais vezes nos infantes do grupo B em relação àqueles dos grupos A e C (69%, 14% e 1%). Internação prolongada no berçário (maior que três dias) foi mais encontrada também no grupo B, quando comparada aos grupos A e C ( 75%, 14% e 2%). Verificaram-se quatro óbitos intra-uterinos, um no grupo A, dois no grupo B e um no grupo C. Nenhum óbito foi registrado no período neonatal entre infantes dos grupos A e C, enquanto no grupo B, três recém-nascidos tiveram êxito letal. Conclusões: A Aloimunização eritrocitária não-relacionada ao antígeno D pode determinar quadro de Doença hemolítica perinatal grave, com necessidade de tratamento intra-uterino. Em comparação à Aloimunização RhD, no entanto, determina melhor desfecho perinatal, considerando-se o hematócrito ao nascimento, a necessidade de transfusão e/ou exsanguino transfusão no período neonatal, o tempo de internação no berçário e o decesso perinatal.
Objectives: Evaluate perinatal outcomes of non-D alloimmunization. Additionally to compare perinatal results with those of D alloimmunized pregnancies and RhD negative not sensitized. Methods: Descriptive observational study with a control group. The study involved 200 women examined between January 2000 and July 2005. Patients were divided in three groups: 15 non-D alloimmunized pregnant (group A), 55 D alloimmunized pregnant (group B) and 130 RhD negative women not sensitized (control group – C). Obstetric and neonatal variables analyzed were: antibody titer, ultrasound findings during pregnancy, intrauterine transfusion, mode and timing of delivery, birthweight, 5-minute Apgar score, neonatal hematocrit, need for neonatal transfusion or exchange transfusion, duration of neonatal stay, intrauterine and neonatal death. Results: Group A comprised 7 patients with Lewis sensitization, 3 with Kell sensitization, 3 with MNS sensitization and 2 with antibodies against Diego system antigens. Antibody titer ≥ 1/16 were seen in all group B patients and in 27% of group A pregnant. Abnormal ultrasound findings were similar between group A and B (20% and 25%). Intrauterine transfusion although more frequent in group B, compared to group A, did not reach statistically significance (20% e 7%). Rate of cesarean deliveries was crescent in C, A and B groups (44%, 53% and 78%). Prematurity was more incident in group B, compared to A and C groups (40%, 27% and 7%), and the same was found related to the low birthweight (39%, 27% e 7%). There were no significant differences regarding the 5-minute Apgar score between all groups. Mean neonatal hematocrit was higher in group B than in group A (43% and 40,5%). The need for neonatal transfusion or exchange transfusion was higher among group B infants, compared to A and C groups (69%, 14% and 1%). Neonatal stay was longer in group B newborn, in comparison to A and C groups (75%, 14% and 2%). There were 4 intrauterine deaths, one in group A, two in group B and one in group C. No death in the neonatal period was registered in group A and C infants while it occurred in three liveborns of group B. Conclusions: Non-D alloimmunization may cause hemolytic disease severe enough to require intrauterine treatment. Compared to D alloimmunization, yelds better perinatal results taking into consideration neonatal hematocrit, need for neonatal transfusion or exchange transfusion, duration of neonatal stay and perinatal mortality
BV UNIFESP: Teses e dissertações
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Pacheco, Cynthia Amaral Moura Sá. "Doença hemolítica perinatal Rhd: um problema de saúde pública no Brasil." Instituto Nacional de Saúde da Mulher e da Criança Fernandes Figueira, 2013. https://www.arca.fiocruz.br/handle/icict/7929.
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Previous issue date: 2013Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do AdolescenteFernandes Figueira. Departamento de Ensino. Programa de Pós-Graduação em Saúde da Criança e da Mulher. Rio de Janeiro, RJ, Brasil.
Introdução: A Doença Hemolítica Perinatal RhD (DHPN-RhD) é decorrente da passagem transplacentária de anticorpos maternos anti Rh positivo causando hemólise no feto e recém-nascido. Este processo pode ser prevenido pela administração de imunoglobulina anti-Rh D, no entanto, quando instalada, é irreversível. Os pacientes afetados poderão desenvolver anemia e icterícia que se não tratadas adequadamente, levam a dano cerebral irreversível, clinicamente conhecido como Kernicterus ou morte. Apesar da existência de profilaxia adequada, a DHPN-RhD ainda é prevalente no Brasil, mas não é considerada para cálculo nos Estudos de Carga de Doença. Considerando que ela possa representar uma fração importante da morbidade e mortalidade perinatal e neonatal este trabalho propõe o cálculo da carga da DHPN-RhD no Brasil Objetivo: Calcular a Carga da DHPN-RhD no Brasil e Regiões do País Método: O indicador utilizado neste estudo foi o número de anos de vida perdidos ajustados por incapacidade DALY (DisabilityAdjusted Life Years). O número de DALY foi calculado a partir da soma de duas parcelas: Anos de Vida Perdidos por Morte Prematura (YLL -Years of Life Lost,) e os Anos de Vida Perdidos devido à Incapacidade (YLD - Years Lived with Disability. Os dados para o cálculo do YLL foram obtidos através do Sistema de Informação sobre Mortalidade (SIM/DATASUS). No processo de estimação do YLD, foram utilizados, como parâmetros clínicos epidemiológicos, os casos incidentes, a duração e o peso médio das incapacidades. O considerada foi de até 30 dias. Devido à gravidade do Kernicterus, considerou-se como duração 50% da expectativa de vida estimada para o País e para as macrorregiões. Para avaliar as estimativas dos pesos das incapacidades optou-se utilizar o peso 0,894 para os casos de DHPN-RhD sem sequelas e 0,459 para os casos de Kernicterus, considerando as sequelas neurológicas relacionadas ao quadro. Resultados: A DHPN-RhD possui as menores taxas de DALY em todas as regiões do País comparando com os outros eventos perinatais. As regiões Norte e Nordeste tiveram as maiores taxas para todos os eventos neonatais com exceção da DHPN-RhD cuja segunda maior taxa foi a da região Sul. Quando analisados o componente YLL, as maiores taxas estão nas regiões Norte e Nordeste e a menor no Sudeste. Em relação ao YLD, observa-se uma inversão em relação aos valores encontrados para o componente YLL, isto é, as maiores taxas foram aquelas das regiões Sudeste e Sul. Conclusão: Apesar de a Carga da DHPN-RhD no Brasil ser muito inferior aos outros eventos perinatais ele demonstra uma herança histórica de ausência de investimentos no Norte e Nordeste como demonstrado em nosso trabalho, onde o risco de morrer por DHPN-RhD é maior que nas regiões Sul e Sudeste. Assim, para o declínio da DHPN-RhD no nosso país há necessidade de melhorar a assistência perinatal e também de um reconhecimento político da contingência dessas desigualdades regionais e da necessidade de priorizar a profilaxia ao invés de tratamento.
Introduction: Rhesus Haemolytic Disease (RHD) occurs due passage of maternal antibodies anti RhD by placenta causing hemolysis in fetus and newborn. This can be prevented by administration of anti-Rh D immunoglobulin, however, when installed, is irreversible. Affected patients may develop anemia and jaundice which if not treated, lead to irreversible brain damage known as kernicterus or death. Despite the existence of appropriate prophylaxis to RhD-DHPN is still prevalent in Brazil, but is not considered for calculating the Burden of Disease Study. Whereas it may represent an important fraction of perinatal morbidity and mortality and neonatal this paper proposes calculation the burden of Rhesus Haemolytic Disease in Brazil Objective: To calculate burden of Rhesus Haemolytic Disease in Brazil and Macroregions Methods: The indicator used in this study was the number of years of life lost disability-adjusted DALY (Disability Adjusted Life Years). The number of DALYs was calculated from the sum of two components: Years of Life Lost to Premature Death (YLL-Years of Life Lost) and Years of Life Lost due to Disability (YLD - Years Lived with Disability. Data for the calculation of YLL was obtained through the Information System (SIM / DATASUL.) In the process of estimation of YLD were used as clinical epidemiological incident cases, the length and weight of disabilities. The number of incident cases calculated through analysis of the Hospital Information System of the Unified Health System (SIH-SUS). In the case of RhD without sequelae was considered the duration of up to 30 days due but to the severity of kernicterus it was considered as 50% of the duration estimated life expectancy. To evaluate the estimates of the weights of disabilities we use the weight to 0,894 cases of RHD without sequelae and 0.459 for cases of kernicterus considering neurological sequelae. Results: RHD has the lowest rates of DALYs in all regions of the country compared to other perinatal events. The North and Northeast had the highest rates for all events with the exception in the South were the rates RHD DALYS was the second highest. When analyzed the component YLL rates are the highest in the North and Northeast and the lowest rate in the Southeast. Regarding the YLD observed a reversal of the values found for the YLL component is the highest rates were those from Southeast and South Conclusion: Despite the burden of RhD Hemolytic Disease Perinatal in Brazil is much lower than the other perinatal events there is a historical legacy of lack of investment in the North and Northeast as demonstrated in our work where the risk of dying from DHPN-RhD is higher than in the South and Southeast. So for the decline of DHPN-RhD in our country there is a need to improve perinatal care and also a political recognition of the contingency of these regional inequalities and the need to prioritize the prevention rather than treatment.
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Stott, Lisa M. "Characterisation of the alloreactive T helper epitopes on the RhD protein." Thesis, University of Aberdeen, 2002. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU170746.
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The Rhesus (Rh) D antigen is important in transfusion medicine and is the major target in haemolytic disease of the newborn (HDN). The aims of this project were to characterise the helper-T (Th) cell response that drives anti-D alloantibody production in HDN as a first step towards developing an improved or alternative strategy to the current programme of prophylaxis, based on the manipulation the T-cell response. Peripheral blood mononuclear cells (PBMC) were obtained from 22 individuals, who had developed anti-RhD alloantibodies following natural or deliberate immunisation, and from 22 RhD negative and from 12 RhD positive control donors who had not been immunised with RhD. A panel of 69 overlapping synthetic 15-mer peptides, spanning the sequence of the RhD protein, was screed for the ability to stimulate recall proliferation and cytokine production from T-cells in cultures of the PBMC. T cells from all 22 of the alloimmunised donors proliferated in response to RhD peptides and typically multiple peptides were stimulatory. In contrast, only a few minor responses were observed in the control donors. RhD peptides 6, 13, 17, and 28 were identified as immunodominant peptides that stimulated proliferation in over 50% of the alloimmunised donors. Each of these peptides were promiscuous in their ability to stimulate T-cells from donors of the common HLA allotypes in this study. Each immunodominant peptide contains multiple core epitopes and multiple sets of MHC/TCR contacts. Preliminary findings indicate that neither peptides shorter than 15mer length nor analogues can be designed to boost or tolerise alloimmunised donors. The RhD peptides induced a complex pattern of cytokine production from alloreactive T cells. Both IFN-gamma and IL-4 could be produced to the RhD peptides indicative of a Th0 response. In addition, particular peptides elicited the production of the potentially inhibitory cytokines IL-10 or TGFb and not proliferation.
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Heldin, Johan. "Identification and Characterization of Proteins and MicroRNAs that Modulate Receptor Signaling, Vesicular Trafficking and Cell Migration in Vascular Cells." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-212949.
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Blood vessels deliver nutrients and oxygen to tissues. Importantly, the functions and growth of blood vessels are commonly altered in disease. The inside of all blood vessels are lined with endothelium, a thin specialized layer of endothelial cells that separate the blood from other tissues. This thesis deals with the identification and functional characterization of proteins and microRNAs that have key roles as modulators of growth factor signaling and directed cell migration of endothelial cells and other vascular cells. A previously uncharacterized protein of the exocyst complex, Exocyst complex component 3-like 2 (ExoC3L2) was identified and shown to be highly expressed in endothelial cells of sprouting vessels. Suppression of ExoC3L2 resulted in reduced VEGF-A signaling together with reduced chemotaxis in response to VEGF-A gradients. VEGF-A-signaling via its receptor VEGFR-2 is thus modulated by the exocyst complex and ExoC3L2. Expression profiling of highly vascularized tissues were used to identify several microRNAs selectively expressed in blood vessels. miR-145, targeting the transcription factor Fli1, was shown to be expressed in pericytes and mural cells. Elevated levels of miR-145 reduced chemotaxis of both endothelial cells and fibroblasts in response to growth factor gradients. miR-145 depletion in fibroblasts was shown to inhibit chemotaxis in response to PDGF-BB. The guanine nucleotide exchange factor FGD5 was shown to be selectively expressed in endothelial cells and to regulate Cdc42 activity. FGD5 was shown to regulate the turnover of activated VEGF-receptors. Suppression of FGD5 impaired endothelial cell chemotaxis, suggesting that FGD5 is required for efficient and sustained VEGF-A signaling. Inactivation of RhoD, a regulator of endosomal trafficking, resulted in an increased pool of acetylated and stable microtubules. Knockdown of RhoD in human fibroblasts resulted in a loss of cell polarity. A link between PDGFR-β and RhoD was implicated by the finding that PDGF-BB was shown to trigger formation of GTP-bound RhoD. Chemotaxis towards PDGF-BB was severely inhibited in cells with reduced RhoD expression, suggesting a role for RhoD in chemotaxis via its regulation of microtubule dynamics.
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Ziza, Karen Nogueira Chinoca. "Determinação do genótipo RHD fetal no plasma materno: acurácia do teste semiautomatizado." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5139/tde-03022016-093418/.
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INTRODUÇÃO: A determinação do genótipo RHD fetal no plasma materno é um teste de diagnóstico pré-natal não invasivo oferecido a gestantes RhD negativo que apresentam potencial de sensibilização e/ou Doença Hemolítica Perinatal. Atualmente, este exame é realizado de rotina em diversos países, mas não no Brasil. A Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) oferece atendimento terciário a gestantes RhD negativo, com monitorização dos títulos de anticorpos irregulares, administração da imunoglobulina anti-D e/ou terapêutica fetal, quando necessários. OBJETIVO: Avaliar a acurácia do teste semiautomatizado para determinação do genótipo RHD fetal no plasma materno. METODOLOGIA: Foram coletadas prospectivamente amostras de sangue de 220 gestantes RhD negativo, com idade gestacional entre 8-28 semanas. O plasma foi obtido em no máximo 2 horas após a coleta, e uma alíquota de 1 mL foi submetida à extração de ácidos nucléicos no equipamento automatizado MagNA Pure Compact (Roche), empregando o kit Large Volume. O DNA extraído foi submetido a PCR em tempo real (Step One Plus - Applied Biosystems), usando o protocolo do grupo SAFE, que tem como alvos os éxons 5 e 7 do gene RHD. RESULTADOS: Ocorreu exclusão de 35 amostras devido a problemas pré-analíticos, aborto ou desconhecimento do fenótipo do recém-nascido. Entre as 185 amostras analisadas, 130 (70,2%) foram genotipadas como RHD+ e 55 (29,8%) RHD-. Os resultados obtidos foram comparados com a fenotipagem do cordão umbilical, e houve concordância completa (100%). Sete amostras exibiram amplificação exclusiva para o éxon 7. Essas amostras foram submetidas aos protocolos em PCR convencional, e PCR em tempo real específico para o pseudogene RHD. Ambos os ensaios apresentaram os mesmos resultados: cinco positivos e dois negativos. Nesses mesmos 7 casos, após extração da camada de leucócitos materna, os protocolos foram repetidos, e o resultado confirmou que cinco mães eram RHD. As duas amostras com resultado negativo foram submetidas ao protocolo Multiplex, envolvendo os éxons 3-9 do gene RHD, com resultados negativos, confirmando que as mães são verdadeiramente RHD- portanto o sinal do éxon 7 é provindo dos fetos que são D variantes. CONCLUSÃO: O método para a determinação do RHD fetal no plasma materno descrito demonstrou ser rápido, de fácil execução, alta precisão e reprodutível, além de indicar possíveis variantes RHD em nossa populaçãoBACKGROUND: Fetal RHD genotype determination in maternal plasma is a noninvasive prenatal diagnostic test performed in RhD negative pregnant women at risk of alloimmunization and/or Hemolytic Disease of Fetus and Newborn. Currently, this test is routinely performed in many countries but not in Brazil. The Department of Obstetrics at Hospital das Clínicas, São Paulo University Medical School provides tertiary antenatal care for RhD negative pregnant women including anti-D immunoglobulin administration, antibody levels monitoring and intrauterine treatment if necessary. AIMS: To validate the accuracy of a semi-automated test for fetal RHD genotype determination in maternal plasma. METHODS: Two-hundred and twenty blood samples were prospectively collected between 8 and 28 weeks of gestational age. Plasma processing was performed within 2 hours after blood collection, and nucleic acids were extracted from 1mL aliquots with an automated extraction platform (MagNA Pure Compact Roche) and the Large Volume kit. RHD gene exons 5 and 7 were amplified with real-time PCR (Step One Plus - Applied Biosystems) using the SAFE group protocol. RESULTS: Thirty-five samples were excluded due to pre-analytical problems, miscarriage and missing follow-up. In the remaining 185 samples, 130 (70.2%) were genotyped as RhD+ and 55 (29.8%) RhD-. Comparison with umbilical cord blood group phenotype showed 100% concordance. Seven samples showed amplification for exon 7 only. These were further investigated with conventional and real-time PCR with an specific protocol for RHD? pseudogene: 5 were positive and 2, negative. In these 7 cases, maternal buffy-coat DNA analysis also confirmed that 5 women were RHD?. In the remaining 2 cases, a multiplex protocol directed at RHD gene exons 3-9 confirmed that both mothers were truly RhD negative so exon 7 signal comes from the fetuses, further found to harbor D variants. CONCLUSION: The present study demonstrates that fetal RHD determination in maternal plasma is a fast, easy-to-perform and reproducible technique with high accuracy in our population. Moreover, it helps in the identification of possible RHD variants in our population
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Oyebamiji, Oyeleke. "The household economic impact of Rheumatic Heart Disease (RHD) in South Africa." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29377.
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Background: Rheumatic heart disease (RHD) remains a major public health concern in African countries due to the high rates of complications such as atrial fibrillation, stroke, infective endocarditis, and heart failure, all of which can result in premature death. In 2015, RHD was estimated to affect 33 million people globally and resulted in at least 320,000 deaths, nearly all of which were in low and middle-income countries. Comparing to other non-communicable diseases (NCDs), RHD imposes economic burden on households that if measures are not in place to mitigate this, it can impoverish such household. However, there are several literatures on the intergenerational economic consequences of other chronic diseases. But, there is no study regarding the household economic of RHD. This mini-dissertation sets out to estimate the household economic impact of RHD. Methods: This study was a follow-on study from the Global Rheumatic Heart Disease Registry (REMEDY), which was a multi-center, international, hospital-based prospective registry of patients with RHD. It was designed as a cohort study to document the disease characteristics and outcomes of individuals with RHD across many countries. We recruited participants in the REMEDY study who were resident in Cape Town and received care at Groote Schuur Hospital (GSH). This study made use of patient and household member surveys to estimate the economic consequences of RHD among households in which REMEDY participants reside. REMEDY registry participants (index cases), their caregivers, and other household members were considered as respondents. 100 REMEDY participants receiving care at GSH was sampled. This sample size was chosen to balance feasibility and precision and to align with a parallel study of the cost of RHD to the health system that aimed to sample medical records from the same 100 REMEDY participants. Patient and household data collection was carried out between September 2017 to December 2017. Direct costs, indirect costs, and the downstream economic behaviors (coping strategies) that lead to medical impoverishment and other consequences were estimated. Cost of illness (COI) was used to assess the effect of ill-health and health-related expenditure on the consumption possibilities of households. Direct costs comprise both medical and nonmedical costs, which may include both the financial cost of resources as well as opportunity costs (e.g., of capital items). Human capital approach was used to calculate indirect cost. Implicit in the human capital approach is the assumption that changes in health status of household members can be reflected by losses in productivity, and losses in income generation. Productivity losses was estimated using the new South Africa minimum wage rate per month as proxy. Coping was estimated with the direct costs (e.g., borrowing from friends or relatives, or taking out formal loans) or indirect costs (e.g., intra-household labor substitution) and can be cost prevention strategies (e.g., ignoring illness, non-treatment) to cost management strategies (e.g., borrowing, selling assets, or labor substitution). Economic costs were valued in United State dollar (USD) converted from South African rand (ZAR) in 2017. Results: Direct medical cost was estimated to ZAR 0, because all patients were exempt from medical fees. Total direct non-medical cost for outpatient and inpatient visits was estimated to be ZAR 27,000 (USD 2000) and 29,000 (USD 2200) (respectively) over 302 and 74 encounters (respectively), an average of ZAR 270 (USD 20) and ZAR 290 (USD 22) per patient (respectively). Indirect costs incurred over the 302 outpatient encounters and 74 hospital admissions were estimated to be ZAR 41,000 (USD 3100) and ZAR 26,000 (USD 1900) (respectively), an average of ZAR 410 (USD 31) and ZAR 260 (USD 19) per patient. Direct cost had a very high impact on the household and they were compelled to adopt coping. Households observed in the study recorded that seventeen percent of households took out loans at an average of ZAR 1200 (USD 91) per loan (range ZAR 100 to ZAR 7000) (range USD 7 to 500). Fifteen percent received financial gifts at an average of ZAR 800 (USD 61) per gift. Two percent sold assets valued at ZAR 5600 (USD 120) on average. Five percent engaged in multiple coping strategies. Also, HH had to cope with indirect cost of illness as 15% of household caregivers changed jobs and 10% worked extra hours. About 4% of household members dropped out of school. Four percent adopted more than one coping strategy. A considerable share of participants reported that they had reduced education to take care of the affected patient. Most of the caregivers of patients with RHD were spouses and children, and 6 % were heads of household. The total cost of RHD to the average affected household is valued at about ZAR 1600 annually. In total, the overall annual economic impact of RHD in this sample of 100 households affected by RHD was estimated at ZAR 160,000 (USD 12200) (ZAR 1600 per household) (USD 120), representing 4.4% of annual household income or 4.9% of annual household expenditure patient spending that exceeded 10% threshold was estimated to be 8% and increasing the threshold to 40 % of non- food expenditure reduced the prevalence of catastrophic spending to 4%. Conclusions: The economic impact of RHD in South Africa is substantial despite government efforts to provide free care. The total cost of RHD to the average affected household is valued at about ZAR 1600 annually. A broader and more robust range of social policies will be required to mitigate non-medical and indirect costs and reduce distortions in household economic activity.
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Kacem, Narjess. "Détermination de la zygotie du gène RHD dans la population tunisienne : impacts des polymorphismes des "boîtes Rhésus" dans la pertinence des analyses moléculaires." Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM5093/document.
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La prédiction de la zygotie à partir du génotype le plus probable en la comparant à la PCR-SSP, n’était pas fiable liée à la possibilité d’avoir d’autres génotypes possibles pour le même phénotype. En effet, la fréquence très proche de l’haplotype R0 et r dans la population tunisienne rend la déduction du génotype le plus probable très aléatoire. Dans un deuxième temps, l’évaluation de la méthode moléculaire la plus convenable à la détermination de la zygotie RHD a été réalisée par comparaison des trois techniques moléculaires (PCR-SSP, PCR-RFLP et Q-PCR) et par l’analyse des résultats discordants par séquençage du gène RHD et des « boîtes Rhésus ». L’analyse de 370 échantillons RH:1 à l'aide de ces trois tests moléculaires a montré que 81,9% des résultats étaient en concordance alors que 18,1% en discordance. L’analyse des cas discordants a montré que notre cohorte se compose de 193 sujets dizygotes et 145 hémizygotes et 32 dont la zygotie reste inconnue. Cette étude a révélé 19 nouveaux polymorphismes des « boîtes Rhésus » et a permis aussi de décrire trois nouveaux allèles RHD: RHD(Trp185Stop), RHD(Ala176Thr) et RHD(Ile342Ile). Cette étude a également mis en valeur l’hétérogénéité des « boîtes Rhésus » et la complexité des allèles RHD en décrivant les nouveaux polymorphismes obtenus, ce qui met en évidence les limites des approches moléculaires de la détermination de la zygotie. La Q-PCR a été la méthode la plus adaptée à la détermination de la zygotie, mais en raison des contraintes économiques locales, la PCR-RFLP pourrait être une alternative malgré l’hétérogénéité des « boîtes Rhésus » et la complexité du gène RHDDetermination of paternal RHD zygosity can help the clinician to assess the risk of HDN. It was determined initially by both assignment of the most probable genotype and PCR-SSP. The prediction of zygosity based on the most probable genotype was not reliable due to the possibility of other genotypes for the same phenotype. In fact, the frequencies of R0 and r haplotypes in the Tunisian population are approached and make the deduction of the most probable genotype very aleatory. Secondly, the evaluation of the most convenient molecular method for RHD zygosity determination was realized by comparison of three molecular techniques (PCR-SSP, PCR-RFLP and RQ-PCR) and analysis of discordant results by sequencing of the RHD gene and Rhesus boxes. Analysis of 370 RH:1 samples by these three molecular tests showed concordant results in 81.9% and discordant results in 18.1%. Molecular investigations revealed that our cohort consists of 193 dizygous and 145 hemizygous samples and 32 which zygosity remains unknown. This study revealed 19 novel Rhesus boxes polymorphisms, and described 3 novel RHD alleles: RHD(Trp185Stop), RHD(Ala176Thr) and RHD(Ile342Ile). This study also underlined Rhesus boxes heterogeneity and RHD alleles complexity by describing of new polymorphisms which showed the limits of molecular approaches for RHD zygosity determination. RQ-PCR is the most convenient method for first intension paternal RHD zygosity determination in Tunisians. However taking into account local economic constraints PCR-RFLP could be an alternative despite the Rhesus boxes heterogeneity and RHD complexity
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Johansson, Jimmy. "A first principles study of the thermodynamics of phase separating systems -The examples RhPd and AlZn-." Thesis, Linköping University, Department of Physics, Chemistry and Biology, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-18517.
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A screened GPM approach in an EMTO-CPA framework was investigated in order to study its ability of describing transition temperatures in phase separating systems, i. e. systems giving either a random or a cluster structure depending on the temperature and the relative concentration of the ingoing atoms of the binary alloy used for the study. A motivation for the study is that the method works well for ordering systems, i. e. systems giving either a random or ordered structure dependent on the temperature and the relative concentration of the components in the binary alloy. Thereby is it of interest to find out the methods capacity in phase separating systems. The so called GPM potentials derived in the approach were applied in statistical Monte Carlo simulations for this purpose. The systems chosen for the investigation were the RhPd and the AlZn binary alloy systems. For both systems the method showed acceptable accuracy when properties as lattice parameter and mixing enthalpy were calculated. The quality of the derived GPM potentials has also been checked by calculating ordering energy for different ordered structures; directly from first principles calculations and from the GPM approach. The results were in acceptable agreement and thereby indicating that the GPM potentials were reliable. The transition temperatures in the RhPd phase diagram, derived by the statistical Monte Carlo simulations showed anyway deviation from experimental results. The error in the predictions might be due to the existing concentration dependencies in the GPM potentials.The conclusion from this study is that the Monte Carlo scheme might be inconvenient in order to handle the concentration dependencies seen in the GPM potentials.
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Lamego, Neto Luiz Gonzaga. "Tratamento de esgoto urbano em reator híbrido operado em baleladas sequenciais (RHBS) submetido a variações de cargas." Florianópolis, SC, 2008. http://repositorio.ufsc.br/xmlui/handle/123456789/91619.
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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia Ambiental.Made available in DSpace on 2012-10-24T00:50:50Z (GMT). No. of bitstreams: 1 262290.pdf: 5604703 bytes, checksum: f86dd0bb71388f0bf6aae1e9316b613c (MD5)
Neste trabalho foi realizado o estudo do comportamento de um reator híbrido operado em bateladas seqüenciais (RHBS), no tratamento de esgoto urbano. O reator piloto RHBS possuía 2,20 m de altura e 0,95 m de diâmetro interno, com um volume útil para tratamento de 1,42 m3. Na parte inferior do reator foram instalados dois difusores de ar do tipo membrana circular, com 20 cm de diâmetro cada, que foram alimentados por um compressor de ar. O funcionamento do reator era automatizado, controlando assim o número e o tempo de cada fase que compõe um ciclo padrão de tratamento (enchimento, reação anóxica e aeróbia, decantação e retirada), por meio de um painel de comandos elétricos. Em cada ciclo padrão, com duração de oito (8) horas, foram realizados três enchimentos e três fases de reação anóxica e aeróbia. O material suporte empregado no sistema híbrido foi a rede de nylon, escolhida entre os materiais testados em estudos anteriores (SOUTO, 2007). Foram realizadas quatro (4) estratégias operacionais, com duração total de 294 dias, testando-se diferentes cargas carbonáceas (0,20 a 1,35 kgDQO/m3.dia); nitrogenadas (42 a 60 gNH4-N/m3.dia); e de fósforo (50 a 70 gPO4-P/m3.dia). Foram avaliados os processos de degradação carbonácea, nitrificaçãodesnitrificação e biodesfosfatação, e também a velocidade de consumo de oxigênio por meio de respirometria, a fim de determinar a composição (heterótrofa e autótrofa) da biomassa bacteriana e sua distribuição no interior do reator (fixa e em suspensão). O reator apresentou eficiências médias de remoção de: ~80% de SST e DQO; 90% a 95% de DBO5; 60% a 87% de Nitrificação; 80% a 90% de Desnitrificação; ~70% de Nitrogênio Total; ~50% de PO4-P. Em condições de funcionamento normal, o lodo do reator apresentou flocos compactos e bem estruturados, com boa sedimentação; por sua vez, o biofilme apresentou-se denso e com presença de muitas Amebas e Rotíferos em sua superfície. A biomassa fixa apresentou maior atividade que a biomassa em suspensão, sendo que a biomassa ativa era composta, predominantemente, por microrganismos heterótrofos (~90%). A biomassa autótrofa estava principalmente fixa no suporte (58%-62%). The intent of this research is to historicize the moment when the issue of trafficking in women for sexual exploitation was raised in media coverage in Brazil and in Spain. The object of the investigation is discourses that constituted human trafficking as a problematic phenomenon around the turn of the twenty first century. The sources are news reports from two widely-read newspapers, Brazil's Folha de São Paulo, and Spain's El País, analysed using a comparative approach. The time outlined is the period in between 1997 and 2007, which is when references to trafficking were made regularly in the media discourse. The most widely-reported modality of trafficking was the trafficking in women for sexual exploitation, and this information does not constitute simple evidence of reality, but rather is the result of a certain way of understanding women, prostitution and ntemporary migration. This work shows the study of the behavior of hybrid sequencing batch reactor (HSBR), in urban wastewater treatment. The pilot HSBR reactor was 2.20 m high and had a diameter of 0.95 m, with a volume of 1.42 m3. In the base of the reactor two air diffusers, membrane type, of the 20 cm, were installed and fed by an air compressor. The operation of the reactor was automated, with time control in each phase of the standard cycles (fill, anoxic, aerobic, settle and drawl) through an electronic command panel. Each standard cycle lasted 8 hours, with three (3) fillings and three (3) phases of anoxic and aerobic reaction. The support material used in the hybrid system was a net of nylon, chosen from materials tested in previous studies of hybrid sequencing batch reactor (SOUTO, 2007). The experiment was carried out in four (4) operational strategies, which lasted 294 days, each one with different operational conditions regarding applied carbonaceous loads (0,20 a 1,35 kgCOD/m3.day); nitrogen (42 a 60 gNH4-N/m3.day); and phosphate (50 a 70 gPO4-P/m3.day). For each strategy, the process of biological carbon, nitrogen and phosphorus removal, and also the oxygen uptake rate (OUR) were evaluated through respirometry, in order to determine composition (heterotrophic and phototrophic) of bacterial biomass and its distribution inside the reactor (fixed and suspended). During the four strategies, the reactor presented average efficiencies: ~80% for total solids and COD; 90% at 95% for BOD5; 60% at 87% for nitrification; 80% at 90% for denitrification; ~70% for total nitrogen; ~50% for PO4-P. In normal operation conditions, the reactor sludge presented compact and well structured granules, and good sedimentation; the biofilm was thick and presented a large amount of amoebae and rotifers in its surface. The fixed biomass demonstrated higher activity when compared to suspended biomass, and the total biomass was composed by heterotrophic microorganisms (~90%). The phototrophic biomass was in fix support mostly (58%-62%).
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Biver, Sophie. "Invalidation des gènes codant pour les facteurs Rhésus Rhcg et Rhbg: analyse du phénotype des souris invalidées." Doctoral thesis, Universite Libre de Bruxelles, 2007. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210734.
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Les reins jouent un rôle majeur dans la régulation de l'homéostasie acide-base. La production et l'excrétion rénale d'ammonium assurent environ deux tiers de l'excrétion nette d'acides dans les conditions normales et jusqu'à 90% en situation d'acidose métabolique. Bien que l'excrétion d'ammonium soit un processus finement régulé et capital au maintien de l'équilibre acido-basique, à ce jour aucun transporteur spécifique d'ammonium n'a été décrit chez les mammifères. Les protéines Rhésus Rhcg et Rhbg, membres distants de la famille des transporteurs d'ammonium Mep/Amt, semblaient de bons candidats à cette fonction. L'invalidation du gène Rhcg puis celle de Rhbg ont donc été entreprises chez la souris afin d'estimer leur rôle potentiel dans le transport de l'ammonium.Doctorat en sciences, Spécialisation biologie moléculaire
info:eu-repo/semantics/nonPublished
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Meshi, Abdullah Ahmed. "Characterisation of humoral immune responses to Rhd blood group antigen-derived synthetic peptides." Thesis, University of Aberdeen, 2012. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=186873.
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The aim of this project was to characterise the humoral immune responses to RhD-derived synthetic peptides as a first step towards developing alternative peptide immunogens to replace RBC in immunising donors for anti-D IgG antibody production for clinical use. In the first part, 4 peptides (Dp6, Dp13, Dp17, and Dp28) containing Th-cell epitopes on the RhD protein were used to stimulate PBMC from 2 D-alloimmunised donors in vitro. A mixture of the four peptides was also utilised to boost HLA-DR15 transgenic mice previously immunised with purified RhD protein. The ability of the four peptides to boost anti-D titre significantly varied between the two donors, with a maximum 3-fold increase in anti-D titre induced by Dp17 in donor 2. The mouse antibody response to peptide boosting was also variable, with 4 of the 6 (66.7%) peptide-boosted DR15 mice demonstrating positive changes in anti-RhD antibody levels. The findings from the in vitro and mice studies demonstrated that these four peptides had the potential to boost anti-D titres in D-alloimmunised donors. In the second part of this study, an alternative approach to designing a totally synthetic peptide immunogen was investigated. An RhD mimotope (DM4) was selected from a set of previously identified RhD mimotopes, and its antigenic mimicry for the D antigen was verified. The DM4 peptide was coupled with the Dp6 peptide as a Th-cell epitope, to construct a chimeric T-B peptide immunogen. The immunogenicity of the T-B and DM4 peptides were evaluated in DR15-transgenic mice. Both peptides were able to induce significant DM4-specific IgG antibodies. The immunogenicity of the DM4 was significantly augmented by colinear coupling to the Dp6 peptide. The immunogenic mimicry of the DM4 peptide for the D antigen was examined through the ability of mouse anti-DM4 antibodies to recognise human D antigen on D-positive RBC. However, these antibodies appeared to recognise D antigen non-specifically, reacting with all tested human RBC regardless of their D phenotypes.
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Fabien, Sohet. "Régulation de l'adressage et de la fonction du transporteur d'ammonium RhBG par phosphorylation et liaison à l'ankyrine G." Phd thesis, Université Paris-Diderot - Paris VII, 2008. http://tel.archives-ouvertes.fr/tel-00458374.
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La protéine RhBG humaine est un membre de la famille des protéines Rh (Rhésus), premiers canaux à gaz caractérisés chez les mammifères et par conséquent, de la superfamille Amt/Mep/Rh des transporteurs d'ammonium. Elle facilite le transport de la forme neutre de l'ammonium (NH3) et est ancrée à la membrane plasmique basolatérale de cellules épithéliales rénales, via l'ankyrine G, protéine adaptatrice du squelette membranaire dépendant de la spectrine. Nous avons montré que la mutation du motif d'ancrage à l'ankyrine G, localisé dans l'extrémité C-terminale intracytoplasmique de RhBG, retarde l'adressage, diminue la stabilité à la surface et abolit la fonction de transport de NH3 de la protéine RhBG dans les cellules épithéliales HEK293. Nous avons également montré que la tyrosine Y429, qui appartient au signal d'adressage basolatéral YED de RhBG, est phosphorylée in vitro par les kinases Src et Syk purifiées. D'autre part, le traitement de cellules HEK293 par le pervanadate, un inhibiteur de phosphatases sur phosphotyrosine (donc un activateur indirect des tyrosine kinases) diminue fortement l'activité de transport de la protéine native mais pas celle d'un mutant Y429A (bloquant sa phosphorylation). Ce résultat montre d'une part que Y429 est le seul résidu tyrosine de RhBG impliqué dans la régulation du transport de NH3, via une phosphorylation, d'autre part que la protéine RhBG est phosphorylée ex vivo sur cette tyrosine. Des mutations Y429D et Y429E, mimant une phosphorylation constitutive, abolissent le transport de NH3 et favorisent la solubilisation du RhBG membranaire. À l'inverse, des mutants Y429A et Y429F non phosphorylés et non phosphorylables se comportent comme la protéine RhBG sauvage. En revanche, des études en microscopie confocale montrent que seules les mutations Y429A et Y429F entraînent une dépolarisation de l'expression de RhBG dans des cellules MDCK polarisées, les mutants Y429D et Y429E étant normalement localisés dans le domaine basolatéral des cellules. L'ensemble de ces résultats démontre que l'adressage, l'ancrage au squelette sous-membranaire et la fonction de transport d'ammonium de RhBG sont régulés à la fois par la phosphorylation et la liaison au squelette membranaire de son domaine C-terminal cytoplasmique et nous a conduit à proposer un modèle dans lequel la phosphorylation de la tyrosine Y429 faisant partie du motif YED, serait nécessaire à l'adressage de RhBG vers la membrane basolatérale de cellules épithéliales polarisées, alors que la déphosphorylation de cette tyrosine permettrait l'ancrage de la protéine au squelette membranaire, via l'ankyrine G, et l'activation du canal à NH3 par un changement conformationnel potentiel de l'extrémité C-terminale.
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Sohet, Fabien. "Régulation de l'adressage et de la fonction du transporteur d'ammonium RhBG par phosphorylation et liaison à l'ankyrine G." Paris 7, 2008. http://www.theses.fr/2008PA077154.
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La protéine rhbg, un membre humain de la superfamille amt/mep/rh des transporteurs d'ammonium, facilite le transport de nh3 et est ancrée à la membrane plasmique basolaterale de cellules épithéliales rénales, via l'ankyrine g, protéine adaptatrice du squelette membranaire dépendant de la spectrine. Nous avons montre que la triple substitution en alanine du motif fld qui lie le domaine c-terminal intracytoplasmique de rhbg a l'ankyrine g, détruit l'interaction de rhbg avec le squelette membranaire de lignées de cellules épithéliales recombinantes. Cette mutation retarde également l'adressage, diminue la stabilité à la surface et abolit la fonction de transport de nh3 de la protéine rhbg. Nous avons également montré qu'à la fois l'adressage a la membrane basolatérale, l'ancrage au squelette membranaire et l'activité de transport d'ammonium de la protéine sont régulés par l'état de phosphorylation de la tyrosine y429, qui appartient au signal d'adressage basolateral yed de rhbg localise dans son extrémité c-terminale intracytoplasmique. L'ensemble de ces résultats nous a conduits a proposer un modèle dans lequel l'adressage et la fonction de transport d'ammonium de rhbg sont régulés à la fois par la phosphorylation et la liaison au squelette membranaire de son domaine c-terminal cytoplasmiqueRhbg, a human member of the amt/mep/rh/superfamily of ammonium transporters, has been shown to facilitate nh3 transport and to be anchored to the basolateral plasma membrane of kidney epithelial cells, via ankyrin g. We showed here that triple alanine substitution of the 419-fld-421 sequence, which links the cytoplasmic c-terminal domain of rhbg to ankyrin-g, not only disrupted the interaction of rhbg with the spectrin-based skeleton but also delayed its cell surface expression, decreased its plasma membrane stability and abolished its nh3 transport function in epithelial cell lines. We also demonstrated that basolateral targeting, anchoring to the membrane skeleton and ammonium transport activity are regulated by the phosphorylation status of tyrosine 429, which belongs to the yed basolateral targeting signal of rhbg localized in its c-terminal domain. All these results led to a model in which targeting and ammonium transport function of rhbg are regulated by both phosphorylation and membrane skeleton binding of the c-terminal cytoplasmic domain
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Finning, Kirstin M. "Prediction of fetal RhD blood group status using fetal genetic material in maternal blood." Thesis, University of the West of England, Bristol, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275889.
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Harkness, Mairi. "Policy and practice concerning women with an RhD negative blood type : a midwifery perspective." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/9625.
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In May 2002 the National Institute for Clinical Excellence (NICE) made the recommendation that all pregnant women with an RhD negative blood type should be offered routine antenatal anti-D immunoglobulin (Ig) prophylaxis (RAADP). Midwives were the key professional group who would be involved in administration of anti-D Ig and yet they had little input to formation of policy and contributed little to the evidence base that informs policy and practice. A midwifery perspective is however important and relevant, and forms the basis of this work. The thesis comprises three distinct, but related, pieces of research: a survey conducted in 2005 to determine implementation of RAADP at UK maternity units; secondary analysis of anti-D Ig errors involving midwives that were reported to the Serious Hazards of Transfusion (SHOT) scheme in 2007/8; and focus group interviews conducted in 2010 to explore midwives’ views on issues that impact the care provided for women with an RhD negative blood type. The aim of the RAADP survey was to establish current {2005} policy in the United Kingdom in relation to the NICE recommendation for RAADP (NICE, 2002). The survey formed the foundation on which to build the thesis by determining that by 2005 RAADP had become an integral aspect of maternity care within the UK. However it also found that there were significant variations within local policies and among the information that was provided to pregnant women and healthcare professionals. The aim of the survey was to determine implementation of policy and not to explain findings, raising important questions which were used to inform the subsequent research. The second piece of research was secondary analysis of existing anti-D Ig error reports collated by SHOT. The analysis was unique in that it included only those errors involving midwives. The findings highlight both individual and organisational impact on errors, building on the findings of the RAADP survey. The research identified proximal errors, trigger events and fallible practices providing a framework within which the common pathways to error involving anti-D Ig can be understood. This will allow midwives to better understand and improve the care they provide. This piece of research also raised further questions about midwifery practice and those questions informed the focus group research. The focus group research aimed to consolidate the findings of the previous research by gaining direct input from midwives. Two focus group interviews were held, with clinical midwives as participants. The research found that the midwives and the organisations within which they worked provided care in line with policy and procedure at the apparent expense of a woman centred approach. This appeared to be linked to the midwives’ understanding of their responsibility, accountability and the education and information that underpinned the care they provided. The other important finding from the focus group research was that the midwives regarded RAADP as a less important intervention than they did anti-D Ig given following a potentially sensitising event (PSE) during pregnancy or given following delivery. When considered as a whole body of work, this research provides unique and valuable insight to midwifery involvement in the care of women with an RhD negative blood type. The research highlights the challenge of achieving government objectives for individualised, woman centred care within the present framework of clinical governance and evidence based care. In doing so it also raises questions about how individual midwives and the midwifery profession have engaged with medical colleagues and policy makers to maintain a midwifery context to the care they provide. Although the research findings relate to care provided for women with an RhD negative blood type the findings are pertinent to other aspects midwifery practice, particularly those originating within the medical profession that are now a routine part of midwifery care.
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PANEPINTO, JOHN CARLO. "The role of the Aspergillus fumigatus rheb homologue, rhbA, in nitrogen sensing and the pathogenesis of invasive pulmonary aspergillosis." University of Cincinnati / OhioLINK, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1008598595.
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Frohmajer, Alexander [Verfasser]. "Häufigkeit nicht-funktionaler Allele des RHD-Gens und Ursachen der fehlenden Antigen-Expression / Alexander Frohmajer." Ulm : Universität Ulm. Medizinische Fakultät, 1999. http://d-nb.info/1015269206/34.
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Tezza, Lucianna Corrêa. "Estudo das variantes RHD em pacientes portadores da Doença Falciforme do Estado do Amazonas, Brasil." Universidade Federal do Amazonas, 2014. http://tede.ufam.edu.br/handle/tede/5172.
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FAPEAM - Fundação de Amparo à Pesquisa do Estado do Amazonas
Introduction:Studies have demonstrated the presence of RHD variants in sickle cell patients, resulting in subsequent alloimuzation, because of the Rh protein having structural function in membranes of these cells, other factors derived from these polymorphisms may impact on the length of life of the erythrocyte. The frequency of RHD variants is not yet known in sickle cell patients in the state of Amazonas and if there the possibility of association between these variants and blood transfusion in these individuals. Objective: Our aim was to investigate the variants of RHD in sickle cell patients in the State of Amazonas Materials and methods: We performed phenotyping of samples from patients with sickle cell disease by hemagglutination tube method using the reagent anti-D IgG clone MS201 and anti-D IgM clone MS26. The Multiplex PCR genotyping method was performed for characterization RHD regions of the Intron 4 and exon 7 and the exons 3, 4, 5, 6, 7 and 9 for the characterization of vari ant RhD.The statistical method of Chi Square was used for analysis of retrospective information on the number of transfusions and the presence of RhD variants. Results: We analyzed 128 samples, of which 45 (35.15%) showed discrepant results in serology for detec tion of RhD antigen and 12 (9.37%) patients with RhD variants. However 03 of these showed no discrepancies in RhD serology. While 33 discrepant samples in serological test s were not characterized as RhD variant. Among the variants, 07 (58.33%) were characterized as DVa, where such individuals were concentrated up to 32 RhD positive red cells without developing anti-RhD, 01 (8.33%) DFR presenting the frequency of transfusion 18 concentrated RhD positive red cells also without the presence of anti-RhD and 04 (33.33%) samples classified as indeterminate, and 2 of these patients had alloimmunization by anti-RhD. Discussion: Our results demonstrate that not all discrepancies in serological tests is indicative of variant RhD and that these results can be found 4 crosses for two reagents. The DVa variant was more frequent in our sickle cell patients and this is not associated with anti-RhD alloimmunization by patients with multiple transfusions in RhD positive red blood cells, thus contrasting with the frequency of DIIIa found in these type of patients studied in other regions of Brazil and associated with increased risk of alloimmunization. Conclusion: In conclusion, we observed that molecular biology tests are needed to detect the RHD gene. The variations DVa patients may not develop anti-D when transfused with RhD-positive erythrocytes. We found indications that the presence of RhD variants are not associated with the need for transfusions in patients with sickle cell disease.
Introdução: Estudos têm demonstrado a presença de variantes RHD em pacientes falciforme, resultando em aloimunizações subsequentes. Em razão da proteína Rh ter função estrutural na membrana destas Células, outros fatores derivados destes polimorfismos podem impactar na diminuição do tempo de vida do eritrócito. A frequência de variantes RHD ainda não é conhecida, nos pacientes falcêmicos do Estado do Amazonas e nem se há uma possível associação entre estas variantes e a transfusão sanguínea nestes indivíduos. Objetivo: Nosso objetivo foi investigar a as variantes do RHD em pacientes falciformes do Estado do Amazonas Casuísticae métodos: Pacientes falciformes atendidos no Hemocentro do Amazonas, nos quais realizamos a fenotipagem RhD, pelo método de hemaglutinação em tubo, utilizando reagentes anti-RhD IgG clone MS201 e IgM clone MS26 e genotipagem pelo método PCR multiplex para a caracterização de regiões do Intron 4 e exon 7 do gene RHD e outra PCR multiplex para detecção de regiões dos exons3, 4, 5, 6, 7 e 9 para caracterização de variantes RhD. O método estatístico do Qui Quadrado, foi utilizado para análise das informações retrospectivas do número de transfusões e a presença de variantes RhD. Resultados: Foram estudadas 128 amostras, das quais encontramos 45 (35,15%) com resultados discrepantesna sorologia para detecção do antígeno RhD e ainda 12 (9,37%) pacientes com RhD variantes, mas que 03 destes, não apresentaram discrepâncias na sorologia RhD. Ao passo que 33 amostras discrepantes nos testes sorológicos não foram caracterizadas como RhD variante. Dentre as variantes, 07 (5,33%), foram caracterizadas como DVa, em que tais indivíduos receberam até 32 concentrados de hemácias RhD positivo em desenvolver anti-RhD, 01 (8,33%) DFR apresentando a frequência de transfusão de 18 concentrados de hemácias RhD positivo tambémsem presença de anti-RhD e de 04 (33,33%) amostras que classificamos como indeterminados, sendo que 2 (50%) dos pacientes considerados indeterminados, apresentaram alo imunização por anticorpo anti-RhD. Discussão: Nossos resultados demonstram que nem toda discrepância no teste sorológico é indicativo de RhD variante e que estes podem ser encontrados mesmos resultados 4 cruzes nos dois reagentes utilizados. A variante DVa foi a mais frequente em nossos pacientes falciformes não estando associada à aloimunizaçãopor anti-RhD em pacientes politransfundidos com hemácias RhD positivo, contrastando assim com a frequência de DIIIa encontrada nestes tipo de pacientes estudados em outras regiões do Brasil e associada ao aumento de risco de aloimunização. Conclusão: Diante dos nossos resultados, observ amos que testes de biologia molecular são necessários para a detecção do gene RHD e ainda que pacientes com variantes DVa, podem não desenvolver anticorpo anti-D quando transfundidos com hemácias RhD positivo. Encontramos indicativos de que presença de variantes RhD caracterizadas nas amostras estudadas, não estão associadas à necessidade de transfusões em pacientes portadores da doença falciforme.
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Overton, Timothy Graeme. "Minimally invasive prenatal diagnosis." Thesis, Imperial College London, 2000. http://hdl.handle.net/10044/1/7869.
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St-Amour, Isabelle. "Utilisation de banque combinatoire d'anticorps phagiques afin de modifier la réactivité d'un anticorps dirigé contre l'antigène RHD." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0016/MQ49047.pdf.
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Garcia-Chacon, Luis Ernesto. "On the Role of Mitochondria in the Regulation of Calcium in Motor Nerve Terminals During Repetitive Stimulation." Scholarly Repository, 2008. http://scholarlyrepository.miami.edu/oa_dissertations/82.
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During repetitive stimulation of motor nerve terminals, mitochondrial Ca2+ uptake limits increases in free cytosolic [Ca2+] and helps ensure faithful neuromuscular transmission. Changes in cytosolic [Ca2+] and in mitochondrial [Ca2+] as well as changes in mitochondrial membrane potential (Psi m) were studied in mouse motor nerve terminals using Ca2+ sensitive indicator and potentiometric dyes, respectively. Trains of action potentials (APs) at 50 to 100 Hz produced a rapid increase in mitochondrial [Ca2+] followed by a plateau which usually continued beyond the end of stimulation. After stimulation, mitochondrial [Ca2+] decayed back to baseline over the course of tens of seconds to minutes. Increasing the Ca2+ load delivered to the terminal by increasing the number of stimuli (500-2000), increasing bath [Ca2+], or prolonging the AP with 3,4-diaminopyridine (3-4, DAP, 100 micromolar), prolonged the post-stimulation decay of mitochondrial [Ca2+] without increasing the amplitude of the plateau. Inhibiting openings of the mitochondrial permeability transition pore with cyclosporin A (5 micromolar) had no significant effect on the decay of mitochondrial [Ca2+]. Inhibition of the mitochondrial Na+-Ca2+ exchanger with CGP-37157 (50 micromolar) dramatically prolonged the post-stimulation decay of mitochondrial [Ca2+], reduced post-stimulation residual cytosolic [Ca2+], and reduced the amplitude of end-plate potentials evoked after the end of stimulation. Stimulation-induced mitochondrial Ca2+ uptake resulted in Psi m depolarizations that were small or undetectable at near-physiological temperatures (~30 degrees C). Their amplitude became larger at lower temperatures (~20 degrees C), or when AP duration was increased with 3,4-DAP (20 micromolar). Psi m depolarizations were inhibited by lowering bath [Ca2+] or by blocking P/Q-type Ca2+ channels with omega-agatoxin (0.3 micromolar). Partial inhibition of complex I of the electron transport chain (ETC) with rotenone (50 nM) increased the amplitude of stimulation-induced Psi m depolarizations. These findings suggest that: (1) Ca2+ extrusion from motor terminal mitochondria occurs primarily via the Na+-Ca2+ exchanger and helps sustain post-tetanic transmitter release, and (2) that the depolarization of Psi m that accompanies Ca2+ uptake is limited by accelerated proton extrusion via the ETC.
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Akbulut, Derya. "Survival Modelling Approach To Time To First Claim And Actuarial Premium Calculation." Master's thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613113/index.pdf.
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Health problems of the human beings in a society are one of the main components of the social security systems due to the dimension of the financial burden it might bring on individuals, employers, insurance companies and governments. Morbidity measures, such as incidence and prevalence of a specific disease in a certain population enable researchers to estimate for individuals the probability of being diagnosed or being prone to the diseases. This information is usually not tractable because of the non-availability of the convenient data or recordings for many countries as well as Turkey. Even if it is available, it is commonly limited with largely varying characteristics about the type and coverage of the diseases. In this regard, the pattern that a population follows for an acute disease may not be the same for chronic diseases. Having those indicators determined for a group of insureds will enable underwriters to have more profitable and economical premium calculation and precision on required reserve estimation.
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Based on their characteristics such as acute or chronic behaviour, the gender, and the location of residency of people, the diseases show different behaviour on their occurrences. From the insurer
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Hellebo, Assegid Getahun. "The Economic Impact of Rheumatic Heart Disease (RHD) on the Health System of South Africa. A Cost of Illness Study." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29245.
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Background
Rheumatic Heart Disease (RHD) is a disease of poverty that is neglected in developing countries. The consequences of RHD are increasingly becoming huge economic burden to the health system and consecutively the government. Despite RHD being preventable, most of the RHD related deaths happen in children and working age adults where the economic burden of premature death is high. Several strategies have been suggested to advance the escalation of disease severity in order to avoid medical cost including cost of surgery. However, lack of adequate evidence regarding the cost of treating RHD has hindered the needed decisions and interventions to prevent RHD related death. The main objective of this study was to evaluate the utilization of resources and quantify the annual average total cost related to RHD in a tertiary hospital in the Western Cape, South Africa.
Methods
A mixture of ingredients and step-down costing approaches were used to estimate the annual cost of RHD care from health system perspective. All costs were estimated in 2017 (base year) South African Rand (ZAR) and 3% discount rate in order to allow depreciation and opportunity cost. Data on service utilization rates were collected using a randomly selected sample of 100 patient medical records from the Global Rheumatic Heart Disease Registry (the REMEDY study), a registry of individuals living with RHD. Patient-level clinical data, including, prices and quantities of medications and laboratory tests, were collected from Groote Schuur Hospital (GSH). Step-down costing was used to estimate provider time costs and all other facility costs such as overheads. REMEDY and GSH data were aggregated to estimate the total annual costs of RHD care at GSH and the average annual per-patient cost among REMEDY participants. One-way univariate sensitivity analysis was conducted to deal with uncertainty.
Results
The total cost of RHD care at GSH was estimated at $2, 238, 294 (ZAR 27 million) in 2017, with surgery costs accounting for 65% of total costs. Per-patient average annual costs, which included outpatient care, cardiac medical and intensive care unit (ICU) care, cardiac catheterisation lab procedures, and heart valve surgery, was estimated at $4, 311 (ZAR 52, 000) per-patient annually. The cost of medications and consumables related to cardiac catheterisation and heart valve surgery were the main cost drivers.
Conclusions
RHD care consumes a significant level of tertiary hospital resources in South Africa, with annual perpatient costs much higher than many other non-communicable and infectious diseases. This analysis supports the scaling up of primary and secondary prevention programmes at primary health centres in order to reduce the future burden on tertiary services. The study may also inform resource allocation efforts related to RHD at tertiary centres and provide cost estimates for future studies of intervention cost-effectiveness.
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Albuquerque, Sérgio Roberto Lopes. "Estudo das associações entre os sistemas ABO, Duffy, antígenos RhD e a malária vivax em habitantes do Estado do Amazonas, Brasil." Universidade Federal do Amazonas, 2009. http://tede.ufam.edu.br/handle/tede/3111.
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Previous issue date: 2009-02-27Fundação de Amparo à Pesquisa do Estado do Amazonas
A malária é a mais importante doença parasitária do mundo, tendo exercido um forte efeito na evolução humana com um crescente corpo de evidências indicando que tanto o risco de adquirir esta infecção, quanto o de desenvolver severas complicações, tem sido determinado por fatores genéticos do hospedeiro e do parasito infectante. Isolados selvagens de parasitas de malária tem mostrado uma maior variabilidade para invadir hemácias humanas quando comparados com os cultivados em laboratórios, mostrando que em áreas endêmicas, estes podem ter desenvolvido diferentes habilidades para invadir particulares tipos de hemácias. Existem na literatura, resultados controversos quanto a associação entre o sistema ABO, antígenos Rh e a malária vivax, porém já foi bem demonstrada a importância da glicoproteína eritrocitária Duffy na invasão de hemácias humanas por merozoítos de Plasmodium vivax, entretanto ainda sendo pouco conhecido se mutações nesta glicoproteína podem estar associadas à frequência de infecção do P. vivax ou na densidade parasitária da malária vivax. Neste estudo investigamos associações entre o sistema sanguíneo ABO, antígeno RhD, as mutações da proteína Duffy (125 G>A (FYA/FYB) 265 C>T e 298 G>A (antígeno FyX) e do promotor GATA box, -33(T>C),) e a malária vivax, em habitantes do Estado do Amazonas, Brasil. Neste estudo, tanto a identificação do P. vivax, como a verificação das densidades parasitárias na malária vivax, foi determinada por testes microscópicos e leucometria em 497 pacientes infectados, nos quais foram realizadas fenotipagens dos sistemas ABO, Duffy antígeno RhD pela técnica da hemaglutinação, assim como as genotipagens do sistema sanguíneo Duffy pela técnica da PCR/RFLP. As possíveis associações entre as frequências encontradas dos sistemas sanguíneos citados e a malária vivax foram analisadas através do teste qui quadrado, assim como as possíveis associações das genotipagens Duffy com o nível de densidades parasitárias encontradas foram analisadas através do teste de kruskal wallis. Nossos dados mostraram, que a presença do antígeno A, genótipos FYA/FYB-33 e FYB/FYB-33 pode ser uma vantagem seletiva na população, reduzindo a taxa de infecção pelo P. vivax nesta região, porém sem estarem associados ao nível de densidade parasitária das infecções de malária. Não encontramos associação entre o antígeno RhD e a susceptibilidade ao P. vivax, no entanto os genótipos FYA/FYB, FYA/FYA mostraram-se associados ao aumento da frequência de infecção pelo P. vivax na região estudada. Os genótipos FYB/FYX e FYA/ FYX não mostraram-se associados à frequência de infecção pelo P. vivax, mas sim aos baixos níveis de densidades parasitárias encontrada entre os pacientes infectados com este genótipo. Reportamos, ainda, neste estudo, indivíduos com o genótipo FYB-33/FYB-33 com antecedentes de malária vivax. Estes resultados sugerem que, em regiões endêmicas de malária, pode estar havendo adaptações naturais tanto quanto ao surgimento de mecanismos parciais de defesa contra o Plasmodium vivax distintos dos já descritos em descendentes africanos como adaptações que podem estar também levando a um aumento a susceptibilidade a este tipo de malária.
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Siberil, Sophie. "Etude des interactions moléculaires entre RFcγ et IgG : implications fonctionnelles et thérapeutiques." Paris 6, 2005. http://www.theses.fr/2005PA066549.
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