Expression of eight genes of nuclear factor-kappa B pathway in multiple myeloma using bone marrow aspirates obtained at diagnosis

Purpose: To evaluate the expression of NF-kappa B pathway genes in total bone marrow samples obtained from MM at diagnosis using real-time quantitative PCR and to evaluate its possible correlation with disease clinical features and survival. Material and methods: Expression of eight genes related to NF-kappa B pathway (NFKB1, IKB, RANK, RANKL, OPG, IL6, VCAM1 and ICAM1) were studied in 53 bone marrow samples from newly diagnosed MM patients and in seven normal controls, using the Taqman system. Genes were considered overexpressed when tumor expression level was at least four times higher than that observed in normal samples. Results: The percentages of overexpression of the eight genes were: NFKB1 0%, IKB 22.6%, RANK 15.1%, RANKL 31.3%, OPG 7.5%, IL6 39.6%, VCAM1 10% and ICAM1 26%. We found association between IL6 expression level and International Staging System (ISS) (p = 0.01), meaning that MM patients with high ISS scores have more chance of overexpression of IL6. The mean value of ICAM1 relative expression was also associated with the ISS score (p = 0.02). Regarding OS, cases with IL6 overexpression present worse evolution than cases with IL6 normal expression (p = 0.04). Conclusion: We demonstrated that total bone marrow aspirates can be used as a source of material for gene expression studies in MM. In this context, we confirmed that IL6 overexpression was significantly associated with worse survival and we described that it is associated with high ISS scores. Also, ICAM1 was overexpressed in 26% of cases and its level was associated with ISS scores.

Corruption and the size of government: causality tests for OECD and Latin American countries

The purpose of this article is to examine the causality between government size and corruption, and to verify if there is a different pattern of causality between developed Organization for Economic Co-operation and Development (OECD) countries (excluding Mexico) and developing countries (Latin American countries) during the period 1996 to 2003. Applying Granger and Huang`s (1997) methodology we find evidence that size of government Granger causes corruption in both samples. Since a larger government involvement in private markets today will be followed in future by a higher level of corruption a policy advice would be to enhance governance. The promotion of good governance helps to combat corruption given that it complements efforts to reduce corruption more directly, and it is strongly recommended by the International Monetary Fund, other multilateral institutions, and all worried with the negative impacts of corruption on economic activity.

Imaging and lung cancer

Lung cancer remains the most common cause of cancer-related mortality in Scotland, accounting for 28.9% of all cancer deaths in 2007. Current guidelines recommend assessment of patient fitness and operability by a multidisciplinary team when selecting management options. Two of the most important prognostic markers are the stage of disease and ECOG performance status. In 1996, the International Association for the Study of Lung Cancer (IASLC) launched a worldwide TNM staging project to create international databases that would be used to continue the excellent efforts of Dr. Cliff Mountain, who pioneered this approach to lung cancer staging in 1973. Successive iterations of tumor, nodule, metastasis (TNM) staging for lung cancer have addressed shortcomings identified by the oncology community. Similarly, the IASLC recognized that it is important that further revisions continue to be made to ensure that the international staging system for lung cancer remains fit for its purpose. The last work of the International Staging Committee (ISC) was the conduct of the study that informed the seventh edition of the international staging system for lung cancer, in 2010. This review of image and staging in non small cell lung cancer (NSCLC), includes a summary of the different noninvasive tests currently available for staging non small cell lung cancer.

Frequency and prognostic relevance of cancer testis antigen 45 expression in multiple myeloma

Objective. This study aims to analyze the expression of cancer testis antigen 45 (CT45) in normal tissues and in plasma cell disorders and to identify possible associations with clinical data and prognosis in multiple myeloma (MM) patients. Materials and Methods. Expression of CT45 was studied in 20 normal tissues (testis, placenta, skeletal muscle, bladder, lung, spleen, heart, brain and fetal brain, thymus, uterus, stomach, mammary gland, pancreas, prostate, small intestine, kidney, adrenal gland, spinal cord, colon, and one pool of 10 normal bone marrow samples) and bone marrow aspirates from 3 monoclonal gammopathies of undetermined significance, 5 solitary plasmacytomas, 61 newly diagnosed MM patients and MM cell line U266 by reverse transcriptase polymerase chain reaction. Results. CT45 was positive in 3 of 20 (15%) normal tissues tested: lung, brain (both fetal and adult), and spinal cord. Among monoclonal gammopathies, CT45 was positive in 2 of 5 (40%) solitary plasmacytomas bone marrow aspirates, 10 of 61 (16%) MM bone marrow aspirates, and in the U266 MM cell line. Conclusions. We did not find associations between bone marrow histology and CT45 expression. However, we demonstrated for the first time that positive expression of CT45 was associated with poor prognostic (international Staging System) and poor outcomes in MM patients, meaning that CT45-positive cases presented seven times more chance of worse evolution than the negative ones. (C) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

Higher education of tourism in Spain and its adaptation to the European higher education area

The international tourism system has deeply undergone structural changes in the last decades which not remain outside the subsystem higher education in tourism, especially in the European case. This article has two objectives: firstly, describes the European higher education area and the objectives, skills and subjects taught in the main Spanish universities that offer higher education in tourism. On the other hand, in the light of knowledge that researchers' descriptive models, provide experience of the implementation of European credit and thorough a deeply review of the literature on the topic higher education in tourism, to propose strategies that will enable other tourism higher education systems approach to the European reality. These policy proposals are aimed at agents and elements from higher education in tourism subsystem and they specifically include: the institutions providing education in tourism, the curriculum, the teaching methods, teachers and students.

Risco de crédito na banca face ao novo enquadramento normativo em contexto de crise : o caso do crédito a particulares

Mestrado em Auditoria

A importância do contrato de compra e venda internacional de mercadorias pelo empresariado de Cabinda em Angola

Dissertação de Mestrado apresentado ao Instituto Superior de Contabilidade e Administração do Porto para obtenção de grau de Mestre em Empreendedorismo e Internacionalização, sob a orientação da Professora Doutora Manuela Maria Ribeiro da Silva Patrício

Modelo de avaliação de risco no sector bancário português

A globalização dos sistemas financeiros, ao longo dos anos, tem estimulado uma crescente necessidade de supervisão bancária nas instituições financeiras. O Comité de Supervisão Bancária de Basileia tem tido um papel crucial nesta área, estabelecendo princípios por via dos seus acordos entre as várias entidades nacionais de regulação e supervisão das maiores economias mundiais. Em 1988, foi criado o Acordo de Basileia (Basileia I) pelo Comité de Supervisão Bancária de forma a harmonizar os padrões de supervisão bancária. Este acordo estabeleceu mínimos de solvabilidade para o sistema bancário internacional no sentido de reforçar a sua solidez e estabilidade. Com o desenvolvimento de novas potências económicas e novas necessidades regulamentares, em Junho de 2004, foi publicado o novo Acordo de Capital – o Basileia II. Este acordo pretendia tornar os requisitos de capital mais sensíveis ao risco, promover a atuação das autoridades de supervisão e a disciplina de mercado (através do seu Pilar II) e encorajar a capacidade de cada instituição mensurar e gerir o seu risco. Em Setembro de 2010, o Acordo de Basileia III, com adoção prevista até 2019, veio reforçar estas medidas com a criação de um quadro regulamentar e de supervisão mais sólido, por parte das instituições de crédito. Surge, assim neste contexto, o Modelo de Avaliação de Risco (MAR) para o sector bancário. Em Portugal, o MAR tem como objetivo avaliar o perfil de risco das instituições de crédito, sujeitas à supervisão do Banco de Portugal, assim como apresentar o perfil de risco e a solidez da situação financeira de cada instituição de crédito. Este trabalho pretende avaliar o surgimento e a caracterização deste modelo e identificar as variáveis a ter em conta nos modelos de avaliação de risco a nível qualitativo e quantitativo.

Portugal no conselho de segurança das Nações Unidas

The United Nations is an international organization that was created after World War II, whose main objective is to promote cooperation, social and economic development, as well as to ensure international peace and security. The Member States are key actors in the international political system. For that reason they have strategic interests in what regards taking part in the international organizations. They see it as an opportunity to achieve those goals. The United Nations Security Council has a very important role in preserving international peace and security. It is the organ of the United Nations in which fifteen member states are represented: five permanently and ten non-permanently, being that the latter are elected for two years. Participating in the Security Council is a unique opportunity for middle powers like Portugal to promote their national interests and to increase their international visibility. In addition, they can contribute to the world’s destiny during their mandate period. Portugal has exercised his third term as a non-permanent member of the Security Council in 2011-2012 biennium, defeating Canada after a successful campaign carried out by the Portuguese diplomacy. This study analyses the participation of Portugal in the Security Council´s 2011-2012 biennium. It will focus the application process and election and the role of Portugal in the Security Council, especially in its the presidency and its intervention in the presidency of the Sanctions Committee on Libya. Its aim is to show the impact of Portuguese participation in the Security Council for international peace and security, as well as the geopolitical importance for the country of being part of the Security Council.

Does the euro dominate Central and Eastern European money markets?

The so-called German Dominance Hypothesis (GDH) claimed that Bundesbank policies were transmitted into other European Monetary System (EMS) interest rates during the pre-euro era. We reformulate this hypothesis for the Central and Eastern European (CEE) countries that are on the verge of accessing the eurozone. We test this \Euro Dominance Hypothesis (EDH)" in a novel way using a global vector autoregressive (GVAR) approach that combines country-speci c error correction models in a global system. We nd that euro area monetary policies are transmitted into CEE interest rates which provides evidence for monetary integration between the eurozone and CEE countries. Our framework also allows for introducing global monetary shocks to provide empirical evidence regarding the e ects of the recent nancial crisis on monetary integration in Europe.

99mTc-sestamibi imaging and bone marrow karyotyping in the assessment of multiple myeloma and MGUS

AIM: The first pathogenetic step in multiple myeloma is the emergence of a limited number of clonal plasma cells, clinically known as monoclonal gammopathy of undetermined significance (MGUS). Patients with MGUS do not have symptoms or end-organ damage but they do have a 1% annual risk of progression to multiple myeloma or related malignant disorders. With progression of MGUS to multiple myeloma, complex genetic events occur in the neoplastic plasma cell. Karyotyping and fluorescence in-situ hybridization (FISH) were shown to be of prognostic value in patients with multiple myeloma. Tc-sestamibi imaging reflects myeloma disease activity in bone marrow with very high sensitivity and specificity predicting disease evolution. This study was undertaken to evaluate the role of Tc-sestamibi imaging and cytogenetic analysis in prognosis prediction of MGUS and multiple myeloma. METHODS: We enrolled 30 consecutive patients with a confirmed diagnosis of multiple myeloma or MGUS. Bone marrow biopsy and biochemical staging according to the International Staging System (ISS) were performed in all cases. Karyotype analysis and FISH were performed in 11 of 12 patients with MGUS and in 17 of 18 patients with multiple myeloma having adequate metaphases. RESULTS: The karyotype was abnormal in four of 11 MGUS and in six of 17 multiple myeloma. Abnormalities of chromosome 13 were present in one case of MGUS and in six cases of multiple myeloma whereas the involvement of immunoglobulin was observed in one case of multiple myeloma. An abnormal FISH panel was found in four MGUS and nine multiple myeloma patients. All patients with MGUS showed a normal MIBI scan (score 0). Among patients with multiple myeloma only three, all with ISS stage I, showed a normal scan while a positive scan was obtained in others (score range, 1-7). The MIBI uptake was strongly related to the bone marrow plasma cell infiltration and to cytogenetic abnormalities. Particularly, a MIBI uptake score above 5 identified patients with poor prognosis encompassing all stage III multiple myeloma and three of seven stage II multiple myeloma. On the other hand all stage I and II patients having a MIBI score less than 5 showed a good prognosis. CONCLUSION: Both cytogenetic analysis and a MIBI scan add no relevant prognostic information to the ISS in patients with stage I and III multiple myeloma. The MIBI scan was of prognostic value in stage II multiple myeloma patients. Additionally, MIBI imaging may be useful to guide bone marrow biopsy in order to obtain adequate samples for cytogenetic analysis.

Achievement of at least very good partial response is a simple and robust prognostic factor in patients with multiple myeloma treated with high-dose therapy: long-term analysis of the IFM 99-02 and 99-04 Trials.

PURPOSE: The prognostic impact of complete response (CR) achievement in multiple myeloma (MM) has been shown mostly in the context of autologous stem-cell transplantation. Other levels of response have been defined because, even with high-dose therapy, CR is a relatively rare event. The purpose of this study was to analyze the prognostic impact of very good partial response (VGPR) in patients treated with high-dose therapy. PATIENTS AND METHODS: All patients were included in the Intergroupe Francophone du Myelome 99-02 and 99-04 trials and treated with vincristine, doxorubicin, and dexamethasone (VAD) induction therapy followed by double autologous stem-cell transplantation (ASCT). Best post-ASCT response assessment was available for 802 patients. RESULTS: With a median follow-up of 67 months, median event-free survival (EFS) and 5-year EFS were 42 months and 34%, respectively, for 405 patients who achieved at least VGPR after ASCT versus 32 months and 26% in 288 patients who achieved only partial remission (P = .005). Five-year overall survival (OS) was significantly superior in patients achieving at least VGPR (74% v 61% P = .0017). In multivariate analysis, achievement of less than VGPR was an independent factor predicting shorter EFS and OS. Response to VAD had no impact on EFS and OS. The impact of VGPR achievement on EFS and OS was significant in patients with International Staging System stages 2 to 3 and for patients with poor-risk cytogenetics t(4;14) or del(17p). CONCLUSION: In the context of ASCT, achievement of at least VGPR is a simple prognostic factor that has importance in intermediate and high-risk MM and can be informative in more patients than CR.

Update of the BIPM comparison BIPM.RI(II)-K1.Ho-166m activity measurements to include the IRA and the NPL and a re-evaluation of the degrees of equivalence for the APMP.RI(II)-K2.Ho-166m comparison

The IRA and the NPL have submitted ampoules of 166Hom to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures, thus becoming the third and fourth participants since 1989. The five samples of known activity of 166Hom now recorded in the SIR have activities between about 70 kBq and 500 kBq. The new results have enabled a re-evaluation of the key comparison reference value, and the degrees of equivalence between each equivalent activity measured in the SIR and the key comparison reference value (KCRV) have been calculated. The results are given in the form of a matrix for these four NMIs together with the recalculated degrees of equivalence of an APMP regional comparison held in 2000, comparison identifier APMP.RI(II)-K2.Ho-166m for six other NMIs. A graphical presentation is also given.

Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome.

Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myélome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p). Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC translocations did not influence the prognosis. Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In myeloma, the genomic aberrations t(4;14) and del(17p), together with beta2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.