O som da Sé Patriarcal de Lisboa no final do século XX: os cânticos do Pe. Manuel Luís e os acompanhamentos de Antoine Sibertin-Blanc

A novidade do cerimonial em língua vernácula, resultante do Concílio Vaticano II, levou a uma vasta actividade composicional em todos os países católicos. Em Portugal, e muito especialmente na região de Lisboa, um dos principais protagonistas desta acção foi o Pe. Manuel Luís (1924-81). Apesar de os seus cânticos (em particular, os Salmos Responsoriais) serem actualmente utilizados de norte a sul de Portugal, a actividade do Pe. Manuel Luís esteve centrada em Lisboa, nomeadamente, no contexto das celebrações realizadas na Sé Patriarcal, onde foi inevitável o contacto assíduo com Antoine Sibertin-Blanc (1930-2012), organista daquele templo desde 1965. As harmonizações de Sibertin-Blanc viriam a tornar-se, para os frequentadores da Catedral lisboeta, indissociáveis das melodias do Pe. Manuel Luís.

Detecting and evaluating land cover change in the eastern half of East Timor (1972-2011)

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

Identificação de biomarcadores de prognóstico e marcadores preditivos de resposta à terapia no cancro do cólon e recto

Mais de 50% dos novos casos de cancro do cólon e recto (CCR) diagnosticados desenvolvem metástases, as quais apresentam uma elevada resistência às terapias convencionais, tornando o CCR uma das principais causas de morte por cancro. Por estas razões, é necessário identificar biomarcadores moleculares de prognóstico e preditivos da resposta ao tratamento. A maioria dos tumores colorectais apresentam mutações em genes que codificam para componentes da via de sinalização WNT. O presente trabalho teve como objectivo estudar o papel de mutações específicas no gene TCF7L2, um importante factor de transcrição desta via, como potenciais factores de prognóstico no cancro do cólon e recto e avaliar a presença de alterações (epi)genéticas e a sua relação com a resposta à quimioradioterapia pré-operatória no cancro do recto, de modo a identificar marcadores preditivos de resposta ao tratamento. Foi efectuada a análise de mutações em exões específicos do TCF7L2 em 68 amostras de CCR, por DGGE, Genescan e sequenciação automática. Foi realizada a análise de perda de heterozigotia por Genescan e de copy-number e metilação por MS-MLPA, para o mesmo gene, em 16 tumores do recto. Foram confirmados alguns destes resultados, ao nível do DNA e RNA, por qPCR. Foram detectadas mutações no gene TCF7L2 em 7/68 (10%) CCR, as quais foram menos frequentes em tumores sem instabilidade de microssatélites (MSS) do que em tumores instáveis (5/56, 11% vs 8/12, 67%). Na maioria dos tumores do recto resistentes à terapia foram detectados ganhos da região upstream e 5´do gene, os quais foram mais frequentes do que em tumores sensíveis (4/6 vs 1/8, p=0,063). Os tumores do recto que responderam melhor à quimioradioterapia apresentaram mais frequentemente ganhos na região 3’ do gene. Em conclusão, as mutações no gene TCF7L2 são pouco frequentes em tumores estáveis, sendo necessário mais estudos para avaliar relação com o prognóstico. As alterações de copy number poderão ser potenciais marcadores de resposta à quimioradioterapia pré-operatória no recto, no entanto os resultados ainda são preliminares, sendo necessária a análise de um maior número de casos.

Microsatellite instability in solitary and sporadic gastric cancer

Recently, the presence of microsatellite instability (MSI) has been reported in gastric cancer and associated with older age of presentation, distal tumor location, early disease staging, and better overall prognosis. Different characteristics in presentation and in tumor behavior may be explained by different genetic alterations during carcinogenesis of gastric cancer. Identification of specific genetic pathways in gastric cancer may have direct impact on prognosis and selection of treatment strategies. PATIENTS AND METHODS: All 24 patients were treated by radical surgery. Fragments of normal and tumor tissues were extracted from the specimen and stored at -80ºC before DNA purification and extraction. PCR amplification utilizing microsatellite markers was performed. Tumors presenting PCR products of abnormal sizes were considered positive for microsatellite instability (MSI+). RESULTS: Five patients (21%) had tumors that were MSI+ in at least 1 marker. In the group of patients with Lauren's intestinal-type gastric carcinoma, 3 had tumors that were MSI+ (23%), while in the group of diffuse-type gastric cancer, 2 patients had tumors that were MSI+ (19%). The mean age of presentation and the male:female ratio was similar in both groups. Tumors that were MSI+ were more frequently located in proximal portion of the stomach compared to microsatellite-stable (MSS) tumors (40% vs. 16%). Although there was a trend of patients with MSI+ tumors towards a proximal gastric tumor location, early staging, and negative lymph node metastasis, there was no statistical significance compared to those with MSS tumors (P >.1). Comparison of overall and disease-free survival between gastric tumors that were MSI+ and those that were MSS found no statistically significant differences (P >.1). CONCLUSIONS: Microsatellite instability is a frequent event in gastric carcinogenesis and shows a trend towards distinct clinical and pathological characteristics of gastric cancer.

Integrated management systems as complex adaptive systems

It is a difficult task to avoid the “smart systems” topic when discussing smart prevention and, similarly, it is a difficult task to address smart systems without focusing their ability to learn. Following the same line of thought, in the current reality, it seems a Herculean task (or an irreparable omission) to approach the topic of certified occupational health and safety management systems (OHSMS) without discussing the integrated management systems (IMSs). The available data suggest that seldom are the OHSMS operating as the single management system (MS) in a company so, any statement concerning OHSMS should mainly be interpreted from an integrated perspective. A major distinction between generic systems can be drawn between those that learn, i.e., those systems that have “memory” and those that have not. These former systems are often depicted as adaptive since they take into account past events to deal with novel, similar and future events modifying their structure to enable success in its environment. Often, these systems, present a nonlinear behavior and a huge uncertainty related to the forecasting of some events. This paper seeks to portray, for the first time as we were able to find out, the IMSs as complex adaptive systems (CASs) by listing their properties and dissecting the features that enable them to evolve and self-organize in order to, holistically, fulfil the requirements from different stakeholders and thus thrive by assuring the successful sustainability of a company. Based on the revision of literature carried out, this is the first time that IMSs are pointed out as CASs which may develop fruitful synergies both for the MSs and for CASs communities. By performing a thorough revision of literature and based on some concepts embedded in the “DNA” of the subsystems implementation standards it is intended, specifically, to identify, determine and discuss the properties of a generic IMS that should be considered to classify it as a CAS.

Analysis of integrated management systems from various perspectives

This article compiles the main topics addressed by management systems (MSs) literature concerningMSs integration by performing a systematic literature review. In this paper, it is intended to present themain limitations of non-integratedmanagement systems (IMSs), the main motivations driving an IMS implementation, the major resistances faced, the most common resultant benefits, the suitable guidelines and standards and the critical success factors. In addition, this paper addresses the issues concerning integration strategies and models, the integration levels or degrees achieved by an IMS and the audit function in an integrated context. The motivations that drive companies to integrate their management subsystems, the obstacles faced and the benefits collected may have internal or external origins. The publishing of standards guiding companies on how to integrate their management subsystems has been done mainly at a national level. There are several models that could be used in order to support companies in their management subsystems integration processes, and a sequential or an all-in strategy may be adopted. Four audit typologies can be distinguished, and the adoption of any of these typologies should consider resource availability and audit team know-how, among other features.

Integrated management systems: A model for maturity assessment

Maturity models are adopted to minimise our complexity perception over a truly complex phenomenon. In this sense, maturity models are tools that enable the assessment of the most relevant variables that impact on the outputs of a specific system. Ideally a maturity model should provide information concerning the qualitative and quantitative relationships between variables and how they affect the latent variable, that is, the maturity level. Management systems (MSs) are implemented worldwide and by an increasing number of companies. Integrated management systems (IMSs) consider the implementation of one or several MSs usually coexisting with the quality management subsystem (QMS). It is intended in this chapter to report a model based on two components that enables the assessment of the IMS maturity, considering the key process agents (KPAs) identified through a systematic literature review and the results collected from two surveys.

A mathematical model to describe fat oxidation kinetics during graded exercise.

PURPOSE: The purpose of this study was to develop a mathematical model (sine model, SIN) to describe fat oxidation kinetics as a function of the relative exercise intensity [% of maximal oxygen uptake (%VO2max)] during graded exercise and to determine the exercise intensity (Fatmax) that elicits maximal fat oxidation (MFO) and the intensity at which the fat oxidation becomes negligible (Fatmin). This model included three independent variables (dilatation, symmetry, and translation) that incorporated primary expected modulations of the curve because of training level or body composition. METHODS: Thirty-two healthy volunteers (17 women and 15 men) performed a graded exercise test on a cycle ergometer, with 3-min stages and 20-W increments. Substrate oxidation rates were determined using indirect calorimetry. SIN was compared with measured values (MV) and with other methods currently used [i.e., the RER method (MRER) and third polynomial curves (P3)]. RESULTS: There was no significant difference in the fitting accuracy between SIN and P3 (P = 0.157), whereas MRER was less precise than SIN (P < 0.001). Fatmax (44 +/- 10% VO2max) and MFO (0.37 +/- 0.16 g x min(-1)) determined using SIN were significantly correlated with MV, P3, and MRER (P < 0.001). The variable of dilatation was correlated with Fatmax, Fatmin, and MFO (r = 0.79, r = 0.67, and r = 0.60, respectively, P < 0.001). CONCLUSIONS: The SIN model presents the same precision as other methods currently used in the determination of Fatmax and MFO but in addition allows calculation of Fatmin. Moreover, the three independent variables are directly related to the main expected modulations of the fat oxidation curve. SIN, therefore, seems to be an appropriate tool in analyzing fat oxidation kinetics obtained during graded exercise.

Maximal Physiological Parameters during Partial Body-Weight Support Treadmill Testing.

PURPOSE: This study investigated maximal cardiometabolic response while running in a lower body positive pressure treadmill (antigravity treadmill (AG)), which reduces body weight (BW) and impact. The AG is used in rehabilitation of injuries but could have potential for high-speed running, if workload is maximally elevated. METHODS: Fourteen trained (nine male) runners (age 27 ± 5 yr; 10-km personal best, 38.1 ± 1.1 min) completed a treadmill incremental test (CON) to measure aerobic capacity and heart rate (V˙O2max and HRmax). They completed four identical tests (48 h apart, randomized order) on the AG at BW of 100%, 95%, 90%, and 85% (AG100 to AG85). Stride length and rate were measured at peak velocities (Vpeak). RESULTS: V˙O2max (mL·kg·min) was similar across all conditions (men: CON = 66.6 (3.0), AG100 = 65.6 (3.8), AG95 = 65.0 (5.4), AG90 = 65.6 (4.5), and AG85 = 65.0 (4.8); women: CON = 63.0 (4.6), AG100 = 61.4 (4.3), AG95 = 60.7 (4.8), AG90 = 61.4 (3.3), and AG85 = 62.8 (3.9)). Similar results were found for HRmax, except for AG85 in men and AG100 and AG90 in women, which were lower than CON. Vpeak (km·h) in men was 19.7 (0.9) in CON, which was lower than every other condition: AG100 = 21.0 (1.9) (P < 0.05), AG95 = 21.4 (1.8) (P < 0.01), AG90 = 22.3 (2.1) (P < 0.01), and AG85 = 22.6 (1.6) (P < 0.001). In women, Vpeak (km·h) was similar between CON (17.8 (1.1) ) and AG100 (19.3 (1.0)) but higher at AG95 = 19.5 (0.4) (P < 0.05), AG90 = 19.5 (0.8) (P < 0.05), and AG85 = 21.2 (0.9) (P < 0.01). CONCLUSIONS: The AG can be used at maximal exercise intensities at BW of 85% to 95%, reaching faster running speeds than normally feasible. The AG could be used for overspeed running programs at the highest metabolic response levels.

A robust genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency.

Microsatellite instability (MSI) occurs in 10-20% of colorectal tumours and is associated with good prognosis. Here we describe the development and validation of a genomic signature that identifies colorectal cancer patients with MSI caused by DNA mismatch repair deficiency with high accuracy. Microsatellite status for 276 stage II and III colorectal tumours has been determined. Full-genome expression data was used to identify genes that correlate with MSI status. A subset of these samples (n = 73) had sequencing data for 615 genes available. An MSI gene signature of 64 genes was developed and validated in two independent validation sets: the first consisting of frozen samples from 132 stage II patients; and the second consisting of FFPE samples from the PETACC-3 trial (n = 625). The 64-gene MSI signature identified MSI patients in the first validation set with a sensitivity of 90.3% and an overall accuracy of 84.8%, with an AUC of 0.942 (95% CI, 0.888-0.975). In the second validation, the signature also showed excellent performance, with a sensitivity 94.3% and an overall accuracy of 90.6%, with an AUC of 0.965 (95% CI, 0.943-0.988). Besides correct identification of MSI patients, the gene signature identified a group of MSI-like patients that were MSS by standard assessment but MSI by signature assessment. The MSI-signature could be linked to a deficient MMR phenotype, as both MSI and MSI-like patients showed a high mutation frequency (8.2% and 6.4% of 615 genes assayed, respectively) as compared to patients classified as MSS (1.6% mutation frequency). The MSI signature showed prognostic power in stage II patients (n = 215) with a hazard ratio of 0.252 (p = 0.0145). Patients with an MSI-like phenotype had also an improved survival when compared to MSS patients. The MSI signature was translated to a diagnostic microarray and technically and clinically validated in FFPE and frozen samples.

Mechanical external work and recovery at preferred walking speed in obese subjects

PURPOSE: The aim of this study was to compare the mechanical external work (per kg) and pendular energy transduction at preferred walking speed (PWS) in obese versus normal body mass subjects to investigate whether obese adults adopt energy conserving gait mechanics. METHODS: The mechanical external work (Wext) and the fraction of mechanical energy recovered by the pendular mechanism (Rstep) were computed using kinematic data acquired by an optoelectronic system and were compared in 30 obese (OG; body mass index [BMI] = 39.6 +/- 0.6 kg m(-2); 29.5 +/- 1.3 yr) and 19 normal body mass adults (NG; BMI = 21.4 +/- 0.5 kg m(-2); 31.2 +/- 1.2 yr) walking at PWS. RESULTS: PWS was significantly lower in OG (1.18 +/- 0.02 m s(-1)) than in NG (1.33 +/- 0.02 m s(-1); P <or= 0.001). There was no significant difference in Wext per unit mass between groups (OG: 0.36 +/- 0.03 J kg(-1) m(-1); NG: 0.31 +/- 0.02 J kg(-1) m(-1); P = 0.12). Rstep was significantly lower in OG (68.4% +/- 2.0%) compared with NG (74.4% +/- 1.0%; P = 0.01). In OG only, Wext per unit mass was positively correlated with PWS (r = 0.57; P < 0.001). CONCLUSION: Obese adults do not appear to alter their gait to improve pendular energy transduction and may select slower PWS to reduce mechanical and metabolic work.

Iconographie de la Mère de Dieu

Après des décennies dʼoubli, un document a été retrouvé, qui avait suscité pendant des années la curiosité dʼétudiants byzantinistes et de bien dʼautres qui étaient à sa recherche. Ilsʼagit de la dernière oeuvre de Nikodim Pavlovic Kondakov, le manuscrit « légendaire » cédé au Vatican dans les années 20 et considéré comme disparu. Après la parution de nombreux textes importants, Kondakov avait commencé à publier ses oeuvres de maturité : la grande monographie sur lʼiconographiedu Christ et les trois volumes de sa célèbre Ikonografija Bogomateri (Iconographie de la Mère de Dieu). Alors que les deux premiers volumes de lʼIconographie de la Mère de Dieu furent publiés à Saint Pétersbourg en 1914-1915, la Révolution Russe de 1917 ne permit pas la publication du troisième volume. Kondakov étant en exil, le troisième volume fut acquis par le Vatican. Le manuscrit fut envoyé à lʼInstitutPontifical Oriental de Rome (PIO) en novembre 1926 où il fut traduit en vue dʼune publication qui nʼeut jamais lieu. Dans les archives du PIO, récemment, la traduction a été retrouvée. Même si nous nʼavons plus la trace de son original en russe, cette traduction complète en français nous permet de retrouver un texte fondamental égaré pendant plus de 80 ans. Ce troisième volume a pour objet lʼiconographie de la Vierge Marie dans lʼart italien, de la fin du Moyen-Âge au début de la Renaissance, un sujet que Kondakov avait en partie affronté dans son premier écrit sur lʼiconographie mariale en 1911, et où il exposait déjà sa proposition de lire la peinture de la Renaissance italienne en lien avec la peinture des icônes russes et grecques. La publication de cette oeuvre nous aidera à connaître une importante page de lʼhistoire concernant le rapport complexe et débattu entre Renaissance italienne et intellectuels russes de lʼ « Âge dʼargent ».

A comprehensive characterization of genome-wide copy number aberrations in colorectal cancer reveals novel oncogenes and patterns of alterations.

To develop a comprehensive overview of copy number aberrations (CNAs) in stage-II/III colorectal cancer (CRC), we characterized 302 tumors from the PETACC-3 clinical trial. Microsatellite-stable (MSS) samples (n = 269) had 66 minimal common CNA regions, with frequent gains on 20 q (72.5%), 7 (41.8%), 8 q (33.1%) and 13 q (51.0%) and losses on 18 (58.6%), 4 q (26%) and 21 q (21.6%). MSS tumors have significantly more CNAs than microsatellite-instable (MSI) tumors: within the MSI tumors a novel deletion of the tumor suppressor WWOX at 16 q23.1 was identified (p<0.01). Focal aberrations identified by the GISTIC method confirmed amplifications of oncogenes including EGFR, ERBB2, CCND1, MET, and MYC, and deletions of tumor suppressors including TP53, APC, and SMAD4, and gene expression was highly concordant with copy number aberration for these genes. Novel amplicons included putative oncogenes such as WNK1 and HNF4A, which also showed high concordance between copy number and expression. Survival analysis associated a specific patient segment featured by chromosome 20 q gains to an improved overall survival, which might be due to higher expression of genes such as EEF1B2 and PTK6. The CNA clustering also grouped tumors characterized by a poor prognosis BRAF-mutant-like signature derived from mRNA data from this cohort. We further revealed non-random correlation between CNAs among unlinked loci, including positive correlation between 20 q gain and 8 q gain, and 20 q gain and chromosome 18 loss, consistent with co-selection of these CNAs. These results reinforce the non-random nature of somatic CNAs in stage-II/III CRC and highlight loci and genes that may play an important role in driving the development and outcome of this disease.

Moderate exercise blunts oxidative stress induced by normobaric hypoxic confinement

PURPOSE: Both acute hypoxia and physical exercise are known to increase oxidative stress. This randomized prospective trial investigated whether the addition of moderate exercise can alter oxidative stress induced by continuous hypoxic exposure. METHODS: Fourteen male participants were confined to 10-d continuous normobaric hypoxia (FIO2 = 0.139 +/- 0.003, PIO2 = 88.2 +/- 0.6 mm Hg, approximately 4000-m simulated altitude) either with (HCE, n = 8, two training sessions per day at 50% of hypoxic maximal aerobic power) or without exercise (HCS, n = 6). Plasma levels of oxidative stress markers (advanced oxidation protein products [AOPP], nitrotyrosine, and malondialdehyde), antioxidant markers (ferric-reducing antioxidant power, superoxide dismutase, glutathione peroxidase, and catalase), nitric oxide end-products, and erythropoietin were measured before the exposure (Pre), after the first 24 h of exposure (D1), after the exposure (Post) and after the 24-h reoxygenation (Post + 1). In addition, graded exercise test in hypoxia was performed before and after the protocol. RESULTS: Maximal aerobic power increased after the protocol in HCE only (+6.8%, P < 0.05). Compared with baseline, AOPP was higher at Post + 1 (+28%, P < 0.05) and nitrotyrosine at Post (+81%, P < 0.05) in HCS only. Superoxide dismutase (+30%, P < 0.05) and catalase (+53%, P < 0.05) increased at Post in HCE only. Higher levels of ferric-reducing antioxidant power (+41%, P < 0.05) at Post and lower levels of AOPP (-47%, P < 0.01) at Post + 1 were measured in HCE versus HCS. Glutathione peroxidase (+31%, P < 0.01) increased in both groups at Post + 1. Similar erythropoietin kinetics was noted in both groups with an increase at D1 (+143%, P < 0.01), a return to baseline at Post, and a decrease at Post + 1 (-56%, P < 0.05). CONCLUSIONS: These data provide evidence that 2 h of moderate daily exercise training can attenuate the oxidative stress induced by continuous hypoxic exposure.