Outcomes of global coagulation assays in patients with Philadelphia-negative myeloproliferative neoplasms with respect to genetic determinants of clonal progression

Classical myeloproliferative neoplasms (MPNs) are hematopoietic stem cell disorders that manifest with inflammation, promotion of atherosclerosis, hypercoagulability, fibrosis, and clonal evolution. The complex biological background lends itself to multi-omics studies. We have previously shown that reduced platelet fibrinogen receptor (PFR) expression may follow hyperactivation of plasma-dependent mechanisms, such as tissue factor (TF) release, unbalanced thrombin generation, involvement of protease-activated receptors (PARs). Acetylsalicylic acid (ASA) helped to restore the expression of PFRs. In this study, we enrolled 53 MPN patients, subjecting them to advanced genetic testing (panel of 30 genes in NGS), global coagulation testing (Rotational Thromboelastometry - ROTEM) and cytofluorometric determination of PFRs. ROTEM parameters appear to differ considerably depending on the type of pathology under investigation, cell count, and selected mutations. Essential thrombocythemia (ET) and CALR mutation appear to correlate with increased efficiency of both classical coagulation pathways, with significantly more contracted clot formation times (CFTs). In contrast, primary myelofibrosis (PMF) and polycythemia vera (PV) show greater imbalances in the hemostatic system. PV, probably due to its peculiar hematological features, shows a lengthening of the CFT and, at the same time, a selective contraction of parameters in INTEM with the increase of platelets and white blood cells. PMF - in contrast - seems to exploit the extrinsic pathway more to increase cell numbers. The presence of DNMT3A mutations is associated with reduced clotting time (CT) in EXTEM, while ASXL1 causes reduced maximal lysis (ML). EZH2 could be responsible for the elongation of CFT in INTEM assay. In addition, increased PFR expression is associated with history of hemorrhage and sustained CT time in FIBTEM under ASA prophylaxis. Our findings corroborate the existing models on the connection between fibrosis, genetic complexity, clonal progression, and hypercoagulability. Global coagulation assays and PFR expression are potentially useful tools for dynamic evaluation of treatments’ outcomes.

Access to climate justice: the main procedural hurdles, and possible solutions, within the italian legal framework and the IBA Model Statute

The thesis deals with standing and justiciability in climate litigation against governments and the private sector. The first part addresses the impacts of climate change on human rights, the major developments in international climate law, and the historical reasons for climate litigation. The second part analyses several cases, divided into categories. It then draws to a comparative conclusion with regard to each category. The third part deals with the Italian legal tradition on standing and justiciability – starting from the historical roots of such rules. The fourth part introduces the ‘Model Statute’ drafted by the International Bar Association, arguing that the 'ratio legis' of this proposal could be implemented in Italy or the EU. The thesis develops arguments, based on the existing legal framework, to help plaintiffs establish standing and justiciability in proceedings pending before Italian courts. It further proposes the idea that 'citizen suits' are consistent with the Italian and EU legal tradition and that the EU could rely on citizen suits to privately enforce its climate law and policies under the ‘European Green Deal.’

Evaluation of clinical implications correlate to genetic polymorphisms and pharmacokinetic of transdermal fentanyl

ABSTRACT Background:Strong opioids are the treatment of choice for moderate to severe cancer-related pain. Fentanyl is a synthetic opioid with high affinity for the μ-opioid receptor and is 75–100 times more potent than morphine. Fentanyl is metabolised rapidly, particularly in the liver and only 10% is excreted as intact substance. The use of CYP3A4 inhibitors and inducers, impaired liver function, and heating of the patch potentially influence fentanyl pharmacokinetics in a clinically relevant way. The influence of BMI and gender on fentanyl pharmacokinetics is questionable. Pharmacogenetic, may influence fentanyl pharmacokinetic and other factors have been studied but did not show significant and clinically relevant effects on fentanyl pharmacokinetic. Method: This is a biological interventional prospective, single-center study in 49 patients with solid or haematological neoplasm treated with transdermal fentanyl undergoing 5-step pharmacokinetic and pharmacogenetic withdrawals from administration of the fentanyl patch. Objective:to evaluate the pharmacokinetic and pharmacogenetic of transdermal fentanyl in relation to the patient's clinical response on pain Results: Sex was the only parameter with evidence of different distribution between responders and non-responders , showing a major chance for male to be responders than females. We found some correlation with pharmacokinetic parameters and sex, regarding adverse events and NRS correlation with BPI. NAT2 and UGT2B7 polymorphisms are associated with AUC and Cmax kinetics parameters, NAT2 and CYP4F2 showed some evidence of association with the fentanyl dosage and CYP2B6 polymorphism seemed to be correlate with side effects. Conclusion: Small sample size of study population make difficult do find some significant correlation between pharmacogenetic, pharmacokinetic and clinical response. Larger studies are needed to increase knowledge about response to opioid treatment in cancer patients to better individualized pain treatment.

Ciclimo de velocidade : uma proposta de controle da preparação fisica especial

Universidade Estadual de Campinas . Faculdade de Educação Física

Macro-botanical evidence for plant use at Neolithic Catalhoyuk, south-central Anatolia, Turkey

Analysis of charred plant macro-remains, including wood charcoals, cereals, seeds, tubers and fruits from the Neolithic site of Catalhoyuk has indicated complex patterns of plant resource use and exploitation in the Konya plain during the early Holocene. Evidence presented in this paper shows that settlement location was not dictated by proximity to high quality arable land and direct access to arboreal resources (firewood, timber, fruit producing species). A summary of the patterns observed in sample composition and species representation is outlined here together with preliminary interpretations of these results within their broader regional context.

O mar não está para peixe : uma etnografia dos conflitos socioambientais em torno da Zona de Proteção Marinha e da comunidade pesqueira do Bugigão – RESEXMAR do Corumbau/Bahia.

A Reserva Extrativista Marinha (RESEXMAR) do Corumbau foi criada no ano de 2000, a partir de uma ação coletiva, iniciada em 1997 por meio das lideranças de pescadores locais, na busca de instrumento jurídico que garantisse o acesso exclusivo dos recursos pesqueiros contra a atividade da pesca comercial de camarão sete-barbas que se instalou na década de 1980. Durante o processo de criação da RESEXMAR do Corumbau, os pescadores obtiveram apoio de órgãos governamentais, como a Coordenação Nacional de Populações Tradicionais (CNPT) e de entidades ambientalistas do terceiro setor – Associação Pradense de Proteção Ambiental (APPA), e posteriormente a Conservation International do Brasil (CI-Brasil). Entretanto, após a criação da RESEXMAR do Corumbau – entre os anos 2000 e 2002 – foi elaborado o Plano de Manejo que orientaria a gestão da Unidade de Conservação (UC). O documento foi capitaneado pela equipe técnica e científica vinculada à CI-Brasil, tendo como ponto de destaque a criação de áreas de exclusão total da atividade da pesca, por meio da Zona de Proteção Marinha (ZPM). A ideia de uma ZPM, para a CI-Brasil, era que de forma indireta e em médio e longo prazo, os pescadores se beneficiariam com o possível aumento de produção de pescado, contanto que 30% de cobertura de recifes tivesse algum tipo de proteção dos processos ecológicos, tais como reprodução e crescimento de espécies. Durante as discussões do Plano de Manejo e atualmente uma parcela de pescadores locais contestaram os limites da ZPM, pois iria restringir o acesso aos recursos pesqueiros. No entanto, tal contestação foi suprimida pelas relações não formais que os membros da CI-Brasil possuíam com o núcleo familiar principal da Vila do Corumbau, forçando os demais em um acordo formal temporário. Tal questionamento evidenciou um conflito de conjunto de normas distintas entre pescadores artesanais em relação à CI-Brasil e IBAMA: a pesca artesanal ‒ um tipo de ação que segue normas específicas das quais elementos humanos e não humanos interagem conjuntamente, evidenciando um conhecimento prático e corporizado constituindo um modelo compreensivo de mundo e de natureza; conceitos modernos e globalizantes de uma natureza totalmente desvinculada das práticas locais artesanais, com forte articulação de uma entidade ambientalista de alcance internacional, guiada pela emergência das questões ambientais, imprimindo no local (o lugar da prática da pesca tradicional) a ideia de um espaço (Áreas Marinhas Protegidas), desencaixado de formas específicas de natureza/culturas.

Representações dos técnicos de intervenção precoce sobre as famílias e práticas de IP em contexto rural e urbano

O presente estudo visou caraterizar as representações que técnicos de intervenção precoce têm sobre famílias que vivem em meio rural e em meio urbano que recebem apoio das equipas. Foram realizadas entrevistas semi-diretivas, os participantes e entrevistados foram dez docentes com intervenção educativa nas equipas, cinco em apoio direto a famílias de meio rural e cinco a realizar intervenções com famílias de meio urbano. Deste estudo resultaram vários dados qualitativos que depois de analisados e discutidos, levaram a diversas conclusões que vem dar respostas às questões e problemática iniciais. As famílias inseridas nestes contextos têm características que as diferenciam; habilitações, recursos, necessidades e comportamentos em comunidade. Tem aspetos culturais que influenciam as suas atitudes, participação e autonomia e são ou não decisivas no desenvolvimento da criança. Em contexto rural as famílias apresentam um maior número de necessidades comparativamente às famílias de meio urbano. As maiores necessidades das famílias em contexto rural situam-se nas questões financeiras, de formação e apoio técnico e especializado. As maiores necessidades das famílias de contexto urbano situam-se ao nível do fraco apoio familiar e das redes sociais. As necessidades comuns situam-se nas necessidades de informação e promoção da autonomia e competências parentais. As visitas e intervenções domiciliares podem permitir melhorar a identificação das necessidades e recursos das famílias e compreender melhor os critérios de referência de algumas crianças. As oportunidades de aprendizagem são maiores nestes encontros em domicílio, estão presentes em muitos casos, elementos da família alargada, que muitas vezes tem um papel fundamental na educação e estimulação destas crianças. Os docentes de IP em intervenção em contexto urbano, comparativamente com os docentes inseridos em contexto rural, apoiam famílias que na generalidade abrangem áreas profissionais mais vantajosas financeiramente. Estas famílias terão á partida melhores condições para aceder a mais recursos e apoios. Nos dois contextos existe uma necessidade comum, falta de informação e alguma autonomia e competências parentais em relação ao crescimento das crianças. A realização de iii encontros de pais ou criação de grupos de pais que tenham por base a partilha de experiencias e informação, estão planeadas mas não são uma realidade nestas equipas. Nas práticas de qualidade, o profissional deve atuar nos contextos naturais como, a família, ou a comunidade, mas pode incluir também rotinas, brincadeiras, festas etc. cenários que facilitem o dia-a-dia. As famílias têm contextos e rotinas próprias que os profissionais devem identificar, os dados que recolhemos indicam essa necessidade de proceder a avaliação mais atenta das necessidades das famílias. As práticas recomendadas e o enquadramento legislativo são tidos em conta pelos docentes e profissionais das equipas, os recursos documentais são na sua maioria comuns, a todas as equipas participantes, seguindo as orientações e documentos/minutas facultadas pela comissão coordenadora do SNIPI (Sistema Nacional de Intervenção Precoce na Infância) Apesar das recomendações teóricas para práticas de qualidade centradas na família, verificamos que estas fazem parte das preocupações destes docentes, mas nem sempre são implementadas. A problemática da criança parece ser ainda o ponto mais importante dos programas e planos de intervenção e mesmo o critério decisivo para delinear a duração e frequência das intervenções, seja em contexto urbano ou rural. - ABSTRACT This study aimed to characterize the families of rural and urban areas that receive support from Early Intervention Teams. It has been proposed yet whether professionals IP suit their practices to the characteristics of these families and communities integrated in different cultural contexts. Interviews were conducted semidirective, participants were ten respondents and teachers with educational intervention teams, five in direct support to families in rural areas and five interventions with families in urban areas. This study resulted in a number of qualitative data that then analyzed and discussed, led to several conclusions that comes to answer the questions and problems early. The families included in these contexts have characteristics that differentiate them; qualifications, resources, needs and behaviors in the community. Has cultural aspects that influence their attitudes, participation and autonomy and are not decisive in the development of the child. In the rural households have a greater number of needs compared to urban families. The greatest needs of families in rural settings are located in financial matters, training and technical support and expertise. The greatest needs of the urban households are located at the level of weak family support and social networks. Common needs lie in information needs and promoting autonomy and parenting skills. The home visits and interventions may allow improved identification of needs and resources of families and understand the benchmarks of some children. Learning opportunities are greater in these meetings at home, are present in many cases, elements of the extended family, which often plays a key role in education and stimulation of these children. Teachers IP intervention in the urban compared with rural teachers placed in context, support families in general include professional areas more financially advantageous. These families will have better starting conditions for access to more resources and support. In both contexts there is a common need, lack of information and some autonomy and parenting skills in relation to the growth of children. The meetings of parents or creating parent groups that are based on the sharing of information and experiences are planned but are not a reality in these teams. In quality practices, the professional must act in natural contexts like the family or the community, but may also include routines, jokes, and parties’ etc. scenarios that v facilitate the day-to-day. Families have their own contexts and routines that professionals should identify, collect the data indicate that the need for more careful assessment of the needs of families. Best practices and legislative environment are taken into account by teachers and professional teams, the documentary resources are mostly common to all participating teams, following the guidelines and documents / drafts provided by the coordinating committee SNIPI (National Intervention Early Childhood) Despite the theoretical recommendations for quality practices family-centered, we see that these are part of the concerns of teachers, but are not always implemented. The issue of child seems to be still the most important programs and plans and even the decisive criterion for delineating the duration and frequency of interventions whether in urban or rural.

A calculus for modeling and analyzing conversations in service-oriented computing

Dissertação apresentada para a obtenção do Grau de Doutor em Informática pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

A proof system for lock-free concurrency

Dissertação para obtenção do Grau de Mestre em Engenharia Informática

Data-centric concurrency control on the java programming language

Dissertação para obtenção do Grau de Mestre em Engenharia Informática

The strategic drivers of the 'revolution': Harley-Davidson and Porsche

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Gestão da manutenção de edifícios em unidades hospitalares

Dissertação de mestrado em Construção e Reabilitação Sustentáveis

Creació de recursos digitals per a la innovació docent en Geologia Estructural i Tectònica

El projecte ha estat dedicat a l’elaboració d’una sèrie de recursos didàctics en format digital per a l’ensenyament de les matèries de Geologia Estructural i Tectònica en titulacions universitàries relacionades amb les Ciències de la Terra. L’objectiu és la millora de la formació i del rendiment dels estudiants mitjançant l’elaboració d’activitats de suport no presencials que fomentin l’autoaprenentatge i l’autoregulació per part de l’estudiant. Les activitats intenten aprofitar les noves eines informàtiques disponibles i fomentar l’accés mitjançant la xarxa. El material que s’elabora en el marc del projecte consisteix en: 1) un fons documental d’imatges relacionades amb la Geologia Estructural i la Tectònica amb explicació, disponibles en xarxa i accessibles per motors específics de cerca, 2) un conjunt d’exercicis i casos pràctics, alguns d’ells resolts, i 3) sortides de camp virtuals d’una regió geològica que permeten proposar activitats prèvies a una pràctica presencial de camp o desenvolupar la pràctica a nivell completament autònom. Per aconseguir aquests objectius, les tasques realitzades són: la compilació i digitalització de la base d'imatges d'exemples naturals d'estructures geològiques de deformació de que disposàvem, junt amb la redacció de material explicatiu (text i figures), la selecció d'un conjunt d'exercicis de la disciplina, i la preparació de dades de camp per a la realització de les sortides virtuals. Paral•lelament, aquest material s'ha estat processant per a la seva disposició en xarxa com un recurs lliure y obert, accessible en una website i domini específics (plataforma REDITEC).

Current millennium biotechniques for biomedical research on parasites and host-parasite interactions

The development of biotechnology in the last three decades has generated the feeling that the newest scientific achievements will deliver high standard quality of life through abundance of food and means for successfully combating diseases. Where the new biotechnologies give access to genetic information, there is a common belief that physiological and pathological processes result from subtle modifications of gene expression. Trustfully, modern genetics has produced genetic maps, physical maps and complete nucleotide sequences from 141 viruses, 51 organelles, two eubacteria, one archeon and one eukaryote (Saccharomices cerevisiae). In addition, during the Centennial Commemoration of the Oswaldo Cruz Institute the nearly complete human genome map was proudly announced, whereas the latest Brazilian key stone contribution to science was the publication of the Shillela fastidiosa genomic sequence highlythed on a Nature cover issue. There exists a belief among the populace that further scientific accomplishments will rapidly lead to new drugs and methodological approaches to cure genetic diseases and other incurable ailments. Yet, much evidence has been accumulated, showing that a large information gap exists between the knowledge of genome sequence and our knowledge of genome function. Now that many genome maps are available, people wish to know what are we going to do with them. Certainly, all these scientific accomplishments will shed light on many more secrets of life. Nevertheless, parsimony in the weekly announcements of promising scientific achievements is necessary. We also need many more creative experimental biologists to discover new, as yet un-envisaged biotechnological approaches, and the basic resource needed for carrying out mile stone research necessary for leading us to that "promised land"often proclaimed by the mass media.

An efficient use of virtualization in grid/cloud environments

Grid is a hardware and software infrastructure that provides dependable, consistent, pervasive, and inexpensive access to high-end computational resources. Grid enables access to the resources but it does not guarantee any quality of service. Moreover, Grid does not provide performance isolation; job of one user can influence the performance of other user’s job. The other problem with Grid is that the users of Grid belong to scientific community and the jobs require specific and customized software environment. Providing the perfect environment to the user is very difficult in Grid for its dispersed and heterogeneous nature. Though, Cloud computing provide full customization and control, but there is no simple procedure available to submit user jobs as in Grid. The Grid computing can provide customized resources and performance to the user using virtualization. A virtual machine can join the Grid as an execution node. The virtual machine can also be submitted as a job with user jobs inside. Where the first method gives quality of service and performance isolation, the second method also provides customization and administration in addition. In this thesis, a solution is proposed to enable virtual machine reuse which will provide performance isolation with customization and administration. The same virtual machine can be used for several jobs. In the proposed solution customized virtual machines join the Grid pool on user request. Proposed solution describes two scenarios to achieve this goal. In first scenario, user submits their customized virtual machine as a job. The virtual machine joins the Grid pool when it is powered on. In the second scenario, user customized virtual machines are preconfigured in the execution system. These virtual machines join the Grid pool on user request. Condor and VMware server is used to deploy and test the scenarios. Condor supports virtual machine jobs. The scenario 1 is deployed using Condor VM universe. The second scenario uses VMware-VIX API for scripting powering on and powering off of the remote virtual machines. The experimental results shows that as scenario 2 does not need to transfer the virtual machine image, the virtual machine image becomes live on pool more faster. In scenario 1, the virtual machine runs as a condor job, so it easy to administrate the virtual machine. The only pitfall in scenario 1 is the network traffic.