Apical hypertrophic cardiomyopathy : a review

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Avaliação do impacto do horizonte temporal nas estimativas de EAD de linhas de crédito com limites explícitos a PME

Tese de mestrado em Matemática Aplicada à Economia e Gestão, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2016

Common Security and Defence in 2014: Revise and resubmit. CEPS Commentaries, 27 March 2014

The conclusions of the December 2013 European Council on defence sounded like a ‘revise and resubmit’ recommendation for the Common Security and Defence Policy (CSDP). That outcome was not too disappointing in itself, because precise technical guidelines were provided to revamp Europe’s defence, with good prospects of real progress. But it was not too ambitious either, as a clear indication of Europe’s future role in global security was in effect postponed until 2015, thus requiring ‘resubmission’ at a later date. Furthermore, member states did not seem particularly committed to reaching a formal agreement on a common strategic narrative; a sign that the governance gap continues to affect CSDP. Giovanni Faleg asks whether the European Council on defence marked the twilight of CSDP, or whether we will now see a new phase of cooperation, characterised by escalating external pressures in the southern neighbourhood and a resurgent Russian threat in the east.

Migration and Integration. Common Challenges and Responses from Europe and Asia

With the signing of the ASEAN Framework Agreement for the Integration of Priority Sectors (FA) in 2004, migration and integration issues gained significance on the agenda. Primarily concerned with increasing economic growth, this framework excludes the integration of low and unskilled migrant workers; instead, ASEAN efforts to address migration and integration issues have been limited to Mutual Recognition Agreements for skilled labour and professionals. After an analysis of migration policy in the region, we highlight specific barriers to the integration of labour migrants in two priority sectors – nursing, which is highly regulated by the state, and Information, Communications and Technology (ICT), which is typically selfregulated and privately run. Despite a MRA for nursing allowing registered nurses to practice in another ASEAN country under supervision of local nurses without registering with the host country’s nursing regulatory authority, in practice, there are major barriers to the free movement of nurses within ASEAN in terms of skills recognition, licensure requirements and other protectionist measures. Although regulations governing the inflow of ICT professionals are not as stringent as those for healthcare professionals, private costs associated with job search and gaining foreign employment are higher in the ICT sector, largely due to limited information on international mobility within the industry. Three sets of barriers to greater integration are discussed. First, the economic and political diversity within ASEAN makes integration more problematic than in the European Union. Second, the primary concern with value-adding economic growth means that regional agreements are focused on skilled and professional labour migration only. Third, the “ASEAN way” of doing things – via a strong emphasis on consensus and non-interference with domestic policies – often means that the FA provision for the free movement of labour is usually trumped by domestic policies that do not reflect the same desire for labour integration.

Greater TTIP Ambition in Chemicals: Why and how. CEPS Special Report, 28 July 2015. Paper No. 10 in the CEPS-CTR project ‘TTIP in the Balance’ and CEPS Special Report No. 114/July 2015.

To date, the negotiations over chemicals in the Translatlantic Trade and Investment Partnership (TTIP) have not shown sufficient ambition. The talks have focused too much on the differences in the two ‘systems’, rather than on the actual levels of health and environmental protection for substances regulated by both the US and the EU. Given the accomplishments within the OECD and the UN Globally Harmonised System of Classification and Labelling of Chemicals (GHS), the question is whether TTIP can be any more ambitious in the area of chemicals? We find that there is no detailed or systematic knowledge about how the two levels of protection in chemicals compare, although caricatures and stereotypes abound. This is partly due to an obsessive focus on a single US federal law, the Toxic Subtances Control Act (TSCA), whereas in practice US protection depends on many statutes and regulations, as well as on voluntary withdrawals (under pressure from the Environmental Protection Agency) and severe common law liability. This paper makes the economic case for firmly addressing the regulatory barriers, discusses the EU’s proposals, finds that the European Parliament’s Resolution on TTIP of July 2015 lacks a rationale (for chemicals), argues that both TSCA and REACH ought to be improved (based on ‘better regulation’), discusses the link with a global regime, advocates significant improvement of market access where equivalence of health and environmental objectives is agreed and, finally, proposes to lower the costs for companies selling in both markets by allowing them to opt into the other party’s more stringent rules, thereby avoiding duplication while racing-to-the-top. The ‘living agreement’ on chemicals ought to be led by a new TTIP institution authorised to establish the level of health and environmental protection on both sides of the Atlantic for substances regulated on both sides. These findings will lay the foundation for a highly beneficial lowering of trading costs without in any way affecting the level of protection. Indeed, this is exactly what TTIP is, or should be, all about.This paper is the 10th in a series produced in the context of the “TTIP in the Balance” project, jointly organised by CEPS and the Center for Transatlantic Relations (CTR) in Washington, D.C. It is published simultaneously on the CEPS (www.ceps.eu) and CTR websites (http://transatlantic.sais-jhu.edu).

Functionally characterization of the most common LDLR missense alterations found in Portuguese FH patients

Aims: Mutations in the LDLR gene are the major cause of familial hypercholesterolaemia (FH), which results in defective catabolism of LDL leading to premature coronary heart disease. Presently, more than 1700 different mutations in the LDLR gene have been described as causing FH but the majority of them remain without functional characterization. In the Portuguese Familial Hypercholesterolemia Study (PFHS), 123 LDLR alterations were found in 243 index patients and their relatives up to date. Until now, 70 of these alterations already have a final classification of pathogenic and 15 have been proved by in vitro studies to be non-pathogenic. The aim of the present work is to functionally characterize 16 LDLR missense alterations found in Portuguese FH patients and worldwide.

Intraperitoneal bevacizumab for control of malignant ascites due to advanced-stage gastrointestinal cancers: A multicentre double-blind, placebo-controlled phase II study - AIO SUP-0108

PURPOSE: Malignant ascites is debilitating for patients with advanced cancer. As shown previously, tumour cell production of vascular endothelial growth factor might be a major cause of the formation of malignant ascites. Intraperitoneal bevacizumab could therefore be an option for symptom control in refractory ascites. PATIENTS AND METHODS: Patients with advanced gastrointestinal cancer and malignant ascites who had undergone paracentesis at least twice within the past 4 weeks were randomly assigned in a 2:1 ratio to intraperitoneal bevacizumab (400 mg absolute) or placebo after paracentesis. During the 8-week treatment period, a minimum interval of 14 d was kept between the applications of the study drug. Primary end-point was paracentesis-free survival (ParFS). RESULTS: Fifty-three patients (median age 63 years) were randomised. Forty-nine patients received at least one study drug application and qualified for the main analysis. The proportion of patients with at least one common toxicity criteria grade III-V event was similar with 20/33 (61%) on bevacizumab and 11/16 (69%) on placebo. Median ParFS was 14 d (95% confidence interval [CI]: 11-17) in the bevacizumab arm and 10.5 d (95% CI: 7-21) on placebo (hazard ratio 0.74, 95% CI: 0.40-1.37; P = 0.16). The longest paracentesis-free period was 19 d on bevacizumab (range 6-66 d) and 17.5 d in the placebo arm (range 4-42) (P = 0.85). Median overall survival was 64 d (95% CI: 45-103) on bevacizumab compared to 31.5 d (95% CI: 20-117) on placebo (P = 0.31). CONCLUSION: Intraperitoneal bevacizumab was well tolerated. Overall, treatment did not result in a significantly better symptom control of malignant ascites. However, patients defined by specific immune characteristics may benefit.

(Table 2) Trace metal concentrations in ODP Hole 169-1033B

We measured the concentrations of redox-sensitive trace metals (Mn, V, Mo, U, Cd and Re) in sediments from ODP Leg 169S Hole 1033B in Saanich Inlet, British Columbia, to determine changes in redox conditions associated with the onset of laminated sediments at ~12.5 kyr. The most striking result is a large peak in authigenic Re along with detrital levels of Mo at the glacial terrigenous clay-diatomaceous sediment transition. In contrast, the underlying glacial terrigenous clay, which extends throughout the bottom section of the core, is chemically similar to detrital concentrations, either Cowichan River particulates or average shale values. These data suggest a period of oxic bottom waters but reducing pore-waters. This could be due to the dramatic transformation of Saanich Inlet during the late deglaciation from an open bay to an inlet, which restricted circulation and slowed bottom water oxygen renewal. A peak and gradual increase in authigenic Mn in younger sediments subsequent to the Re peak suggests that increasingly oxic conditions followed the authigenic enrichment in Re. These conditions could be connected to the Younger Dryas cooling period, which was coincident with an increase in well oxygenated upwelled waters on the west coast of North America that form the bottom waters of Saanich Inlet. Metal concentrations in a gray clay bed (~11 kyr) are similar to their concentrations in the glacial terrigenous clay, implying that they have a common source. Authigenic enrichments of Re with little authigenic Mo and Cd suggest that before the deposition of this bed, bottom waters were oxic and pore-water oxygen was consumed in the top centimeter or less. Laminations above the clay layer suggest anoxic conditions, which are also indicated by higher authigenic Mo and Cd and slightly lower Re/Mo ratios in these sediments. The basin remained mostly anoxic after the gray clay was emplaced, as seen by continuous authigenic enrichment of the redox-sensitive trace metals. These results are consistent with increased stratification of the water column, brought about by an influx of fresh water to the basin by a large flood.

3D models created from ROV videos and their corresponding subtransect dimensions

Underwater video transects have become a common tool for quantitative analysis of the seafloor. However a major difficulty remains in the accurate determination of the area surveyed as underwater navigation can be unreliable and image scaling does not always compensate for distortions due to perspective and topography. Depending on the camera set-up and available instruments, different methods of surface measurement are applied, which make it difficult to compare data obtained by different vehicles. 3-D modelling of the seafloor based on 2-D video data and a reference scale can be used to compute subtransect dimensions. Focussing on the length of the subtransect, the data obtained from 3-D models created with the software PhotoModeler Scanner are compared with those determined from underwater acoustic positioning (ultra short baseline, USBL) and bottom tracking (Doppler velocity log, DVL). 3-D model building and scaling was successfully conducted on all three tested set-ups and the distortion of the reference scales due to substrate roughness was identified as the main source of imprecision. Acoustic positioning was generally inaccurate and bottom tracking unreliable on rough terrain. Subtransect lengths assessed with PhotoModeler were on average 20% longer than those derived from acoustic positioning due to the higher spatial resolution and the inclusion of slope. On a high relief wall bottom tracking and 3-D modelling yielded similar results. At present, 3-D modelling is the most powerful, albeit the most time-consuming, method for accurate determination of video subtransect dimensions.

Sea surface temperature (Mg/Ca) from ODP Hole 161-977A

Mg/Ca, Sr/Ca, and stable isotope measurements have been performed on tests from the planktonic foraminifers Globigerinoides ruber (white), Globigerina bulloides, and Neogloboquadrina pachyderma (right coiling) in samples from Ocean Drilling Program site 977A in the Alboran Sea (Western Mediterranean). The evolution of different water masses between 250 and 150 ka is described. Warm substages were characterized by strong seasonality and thermal stratification of the water column. By contrast, less pronounced seasonality and basin stratification seem to prevail during cold substages. Several periods of stratification due to the low salinity of the upper water mass occurred during the formation of organic-rich layers and also during a possible Heinrich-like event at 220 ka. The three foraminifer species studied show a common and large shell Sr/Ca variability in short timescales, suggesting changes in the global ocean Sr/Ca ratio as one of the main causes of variations in shell composition.

Astronomical time scale for Paleocene and early Eocene sediments

The astronomical-tuned time scale is rapidly extended into the Paleogene but, due to the existence of an Eocene gap, different tuning options had to be presented for the Paleocene. These options differ both in number and tuning of ~405-kyr eccentricity related cycles and are only partially consistent with recalculated 40Ar/39Ar constraints for the Cretaceous/Paleogene (K/Pg) and Paleocene/Eocene (P/E) boundaries. In this paper, we evaluate the cyclostratigraphic interpretation of records from ODP Leg 198 and 208 sites, and the Zumaia section to solve the problem of the different tuning options. We found that the interval between the K/Pg boundary and the early Late Paleocene biotic event (ELPE) comprises 17 instead of 16 * ~405-kyr eccentricity related cycles as previously proposed, while the entire Paleocene contains 25 * ~405-kyr cycles. Starting from 40Ar/39Ar age constraints for the K/Pg boundary, a new tuning to 405-kyr eccentricity is presented for the Paleocene and earliest Eocene, which results in ages of ~66.0 and ~ 56.0 Ma for the K/Pg and P/E boundaries, respectively. This tuning introduces considerable differences in age for a number of nannofossil events at ODP Sites 1209 and 1262 in the interval between 61 and 63 Ma, but eliminates large and abrupt changes in the seafloor spreading rate. The tuning seems further consistent with recalculated 40Ar/39Ar ages for ash layer -17 of early Eocene age. However, despite this apparent consistency with existing radio-isotopic constraints, an alternative 405-kyr younger or, less likely, older tuning cannot be excluded at this stage.