Activity in Geriatric acute CARe (AGECAR): Rationale, design and methods

The Activity in GEriatric acute CARe (AGECAR) is a randomised control trial to assess the effectiveness of an intrahospital strength and walk program during short hospital stays for improving functional capacity of patients aged 75 years or older. Patien

Pratiques d’infirmière clinicienne et obésité

Tese apresentada à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Doutor em Ciências Sociais, especialidade em Psicologia

Targeting aberrant kinase activity in myeloid leukaemias

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults. Its treatment has remained largely unchanged for the past 30 years. Chronic myeloid leukaemia (CML) represents a tremendous success story in the era of targeted therapy but significant challenges remain including the development of drug resistance and disease persistence due to presence of CML stem cells. The Aurora family of kinases is essential for cell cycle regulation and their aberrant expression in cancer prompted the development of small molecules that selectively inhibit their activity. Chapter 2 of this thesis outlines the efficacy and mechanism of action of alisertib, a novel inhibitor of Aurora A kinase, in preclinical models of CML. Alisertib possessed equipotent activity against CML cells expressing unmutated and mutated forms of BCR-ABL. Notably, this agent retained high activity against the T315I and E255K BCR-ABL mutations, which confer the greatest degree of resistance to standard CML therapy. Chapter 3 explores the activity of alisertib in preclinical models of AML. Alisertib disrupted cell viability, diminished clonogenic survival, induced expression of the forkhead box O3 (FOXO3a) targets p27 and BCL-2 interacting mediator (BIM), and triggered apoptosis. A link between Aurora A expression and sensitivity to ara-C was established. Chapter 4 outlines the role of the proto-oncogene serine/threonine-protein (PIM) kinases in resistance to ara-C in AML. We report that the novel small molecule PIM kinase inhibitor SGI-1776 disrupted cell viability and induced apoptosis in AML. We establish a link between ara-C resistance and PIM over-expression. Finally, chapter 5 explores how the preclinical work outlined in this thesis may be translated into clinical studies that may lead to novel therapeutic approaches for patients with refractory myeloid leukaemia.

Comportamiento de las semillas de Ambrosia tenuifolia (Altamisa) en un pastizal de la Depresión del Salado (Provincia de Buenos Aires)

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Structural and functional vulnerability to elevated pCO2 in marine benthic communities

The effect of elevated pCO(2)/low pH on marine invertebrate benthic biodiversity, community structure and selected functional responses which underpin ecosystem services (such as community production and calcification) was tested in a medium-term (30 days) mesocosm experiment in June 2010. Standardised intertidal macrobenthic communities, collected (50.3567A degrees N, 4.1277A degrees W) using artificial substrate units (ASUs), were exposed to one of seven pH treatments (8.05, 7.8. 7.6, 7.4, 7.2, 6.8 and 6.0). Community net calcification/dissolution rates, as well as changes in biomass, community structure and diversity, were measured at the end of the experimental period. Communities showed significant changes in structure and reduced diversity in response to reduced pH: shifting from a community dominated by calcareous organisms to one dominated by non-calcareous organisms around either pH 7.2 (number of individuals and species) or pH 7.8 (biomass). These results were supported by a reduced total weight of CaCO3 structures in all major taxa at lowered pH and a switch from net calcification to net dissolution around pH 7.4 (a"broken vertical bar(calc) = 0.78, a"broken vertical bar(ara) = 0.5). Overall community soft tissue biomass did not change with pH and high mortality was observed only at pH 6.0, although molluscs and arthropods showed significant decreases in soft tissue. This study supports and refines previous findings on how elevated pCO(2) can induce changes in marine biodiversity, underlined by differential vulnerability of different phyla. In addition, it shows significant elevated pCO(2)-/low pH-dependent changes in fundamental community functional responses underpinning changes in ecosystem services.

Scientifi c discourses on chronic pain without organic cause Incorporating gender perspective for pain resignifyng-repoliticizing

Chronic pain, without any organic or physical cause (DC), which in psycho-medical terminology is known as fi bromyalgia, (FM), is diagnosed each year to a considerable number of women in capitalistic societies. Our main interest in the following paper is to go in depth in the elaboration of this symptom, its treatment and the psychosocial effects, both in the social order as well as in the lives of the people who suffer from it. Our main goal in the following paper is to look deeper in the elaboration (conceptualization) of this symptom, its treatment and psychological affects, both in the social order as well as in the lives of the people who suffer from it, we are using linked speeches in Spanish magazines publications. The result has been the emergence of three hegemonic discourse positions: One position “scientist”, one “therapeutic of the conformity” position and one “economic and legalistic” position. Each of these has a specifi c feature, but on the whole, is enhanced, producing effects such as the absence of social context to explain the disease; disregard of gender differences in the management and treatment; the instrumentalization of pain to legitimize their practices and the subjection of women to the “psycho-biomedical” paradigm. In that way, a new signifi cance and politicization of the concept of pain is proposed.

Ecoturismo en comunidades rurales: análisis de los impactos negativos para la población local. Un estudio de caso

En los últimos años han aparecido nuevas formas de turismo más sostenibles, donde existen elementos relacionados con el descanso, el disfrute y la protección del medio ambiente o el conocimiento de la cultura local, a través de políticas que favorecen la sostenibilidad del destino. En este sentido, el ecoturismo se configura como una tipología turística que se desarrolla en contacto con la naturaleza. Este turismo ayuda a mejorar el desarrollo socioeconómico de las comunidades locales, a la vez, que fomenta la conservación de los recursos naturales y el respeto hacia el medio ambiente. Aunque, esta tipología de turismo también genera importantes impactos negativos. El objetivo principal de esta investigación es analizar los impactos socioeconómicos, culturales y medioambientales percibidos por el ecoturismo por parte de los residentes de comunidades rurales de República Dominicana. La técnica de recolección de datos utilizada ha consistido en un cuestionario. Entre las principales conclusiones, cabe destacar que actualmente no se perciben impactos negativos, pero si hay una serie de elementos que hay que ir considerando, con la finalidad de que no se conviertan en un impacto a corto plazo para la comunidad rural.

The maximal C*-algebra of quotients as an operator bimodule

We establish a description of the maximal C*-algebra of quotients of a unital C*-algebra A as a direct limit of spaces of completely bounded bimodule homomorphisms from certain operator submodules of the Haagerup tensor product of A with itself labelled by the essential closed right ideals of A into A. In addition the invariance of the construction of the maximal C*-algebra of quotients under strong Morita equivalence is proved.

Maximal C*-algebras of quotients and injective envelopes of C*-algebras

A new C*-enlargement of a C*-algebra A nested between the local multiplier algebra of A and its injective envelope is introduced. Various aspects of this maximal C*-algebra of quotients are studied, notably in the setting of AW*-algebras. As a by-product we obtain a new example of a type I C*-algebra such that its second iterated local multiplier algebra is strictly larger than its local multiplier algebra.

Sheaves of C*-algebras

We develop the basics of a theory of sheaves of C*-algebras and, in particular, compare it to the existing theory of C*-bundles. The details of two fundamental examples, the local multiplier sheaf and the injective envelope sheaf, are discussed.

When is the second local multiplier algebra of a C*-algebra equal to the first?

We discuss necessary as well as sufficient conditions for the second iterated local multiplier algebra of a separable C*-algebra to agree with the first.

Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival

Better treatment is required for older patients with acute myeloid leukemia (AML) not considered fit for intensive chemotherapy. We report a randomized comparison of lowdose Ara-C (LDAC) vs the novel nucleoside, clofarabine, in untreated older patients with AML and high-risk myelodysplastic syndrome (MDS). A total of 406 patients with de novo (62%), secondary disease (24%), or high-risk MDS (>10% marrow blasts) (15%), median age 74 years, were randomized to LDAC 20 mg twice daily for 10 days every 6 weeks or clofarabine 20 mg/m2 on days 1 to 5, both for up to 4 courses. These patients had more adverse demographics than contemporaneous intensively treated patients. The overall remission rate was 28%, and 2-year survival was 13%. Clofarabine significantly improved complete remission (22% vs 12%; hazard ratio [HR] 5 0.47 [0.28-0.79]; P 5 .005) and overall response (38% vs 19%; HR 5 0.41 [0.26-0.62]; P < .0001), but there was no difference in overall survival, explained by poorer survival in the clofarabine patients who did not gain complete remission and also following relapse. Clofarabine was more myelosuppressive and required more supportive care. Although clofarabine doubled remission rates, overall survival was not improved overall or in any subgroup. The treatment of patients of the type treated here remains a major unmet need. This trial was registered at www.clinicaltrials.gov as #ISRCTN 11036523.