The Oncological and Functional Risks of the Organ Preservation Experimental Treatment Approach

We increasingly face conservative surgery for rectal cancer and even the so called ‘wait and see’ approach, as far as 10–20% patients can reach a complete pathological response at the time of surgery. But what can we say to our patients about risks? Standard surgery with mesorectal excision gives a <2% local recurrence with a post operative death rate of 2–8% (may reach 30% at 6 months in those over 85), but low AR has some deterioration in bowel function and in low cancer a permanent stoma may be required. Also a long-term impact on urinary and sexual function is possible. Distant metastasis rate seem to be identical in the standard and conservative approach. It is difficult to evaluate conservative approach because a not clear standardization of surgery for low rectal cancer. Rullier et al tried to clarify, and they found identical results for recurrence (5–9%), disease free survival (70%) at 5y for coloanal anastomosis and intersphinteric resection. Other series have found local recurrence higher than with standard approach and functional results may be worse and, in some situations, salvage therapy is compromised or has more complications. In this context, functional outcomes are very important but most studies are incomplete in measuring bowel function in the context of conservative approach. In 2005 Temple et al made a survey of 122/184 patient after sphinter preserving surgery and found a 96.9% of incomplete evacuation, 94.4% clustering, 93.2% food affecting frequency, 91.8% gas incontinence and proposed a systematic evaluation with a specific questionnaire. In which concerns ‘Wait and see’ approach for complete clinical responders, it was first advocated by Habr Gama for tumors up to 7cm, with a low locoregional failure of 4.6%, 5y overall survival 96%, 72% for disease free survival; one fifth of patients failed in the first year; a Dutch trial had identical results but others had worse recurrence rates; in other series 25% of patients could not be salvaged even with APR; 30% have subsequent metastatic disease what seems equal for ‘wait and see’ and operated patients. In a recent review Glynne Jones considers that all the evaluated ‘wait and see’ studies are heterogeneous in staging, inclusion criteria, design and follow up after chemoradiation and that there is the suggestion that patients who progress while under observation fare worse than those resected. He proposes long-term observational studies with more uniform inclusion criteria. We are now facing a moment where we may be more aggressive in early cancer and neoadjuvant treatment to be more conservative in the subsequent treatment but we need a better stratification of patients, better evaluation of results and more clear prognostic markers.

The Hybrid Approach for Palliation of Hypoplastic Left Heart Syndrome: Intermediate Results of a Single-Center Experience

INTRODUCTION: Hypoplastic left heart syndrome (HLHS) is a major cause of cardiac death during the first week of life. The hybrid approach is a reliable, reproducible treatment option for patients with HLHS. Herein we report our results using this approach, focusing on its efficacy, safety and late outcome. METHODS: We reviewed prospectively collected data on patients treated for HLHS using a hybrid approach between July 2007 and September 2014. RESULTS: Nine patients had a stage 1 hybrid procedure, with seven undergoing a comprehensive stage 2 procedure. One patient completed the Fontan procedure. Five patients underwent balloon atrial septostomy after the hybrid procedure; in three patients, a stent was placed across the atrial septum. There were three deaths: two early after the hybrid procedure and one early after stage two palliation. Overall survival was 66%. CONCLUSIONS: In our single-center series, the hybrid approach for HLHS yields intermediate results comparable to those of the Norwood strategy. The existence of dedicated teams for the diagnosis and management of these patients, preferably in high-volume centers, is of major importance in this condition.

Portuguese investor profile in Poland, a managerial approach

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

Comparative effects of sediments contaminated by carcinogenic and non-carcinogenic PAHs in Dicentrarchus labrax: a semi-quantitative histopathological approach

Dissertação para obtenção do Grau de Mestre em Engenharia do Ambiente

From a project to an organisation: a Strategic Communication’s approach

Relatório de Estágio apresentado para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Ciências da Comunicação, área de especialização em Comunicação Estratégica

Development of an integrative approach for the characterization of ecological risk on marine transition ecosystems: the Sado Estuary as a case study

Estuaries and other transitional waters are complex ecosystems critically important as nursery and shelter areas for organisms. Also, humans depend on estuaries for multiple socio-economical activities such as urbanism, tourism, heavy industry, (taking advantage of shipping), fisheries and aquaculture, the development of which led to strong historical pressures, with emphasis on pollution. The degradation of estuarine environmental quality implies ecologic, economic and social prejudice, hence the importance of evaluating environmental quality through the identification of stressors and impacts. The Sado Estuary (SW Portugal) holds the characteristics of industrialized estuaries, which results in multiple adverse impacts. Still, it has recently been considered moderately contaminated. In fact, many studies were conducted in the past few years, albeit scattered due to the absence of true biomonitoring programmes. As such, there is a need to integrate the information, in order to obtain a holistic perspective of the area able to assist management and decision-making. As such, a geographical information system (GIS) was created based on sediment contamination and biomarker data collected from a decade-long time-series of publications. Four impacted and a reference areas were identified, characterized by distinct sediment contamination patterns related to different hot spots and diffuse sources of toxicants. The potential risk of sediment-bound toxicants was determined by contrasting the levels of pollutants with available sediment quality guidelines, followed by their integration through the Sediment Quality guideline Quotient (SQG-Q). The SQG-Q estimates per toxicant or class was then subjected to georreferencing and statistical analyses between the five distinct areas and seasons. Biomarker responses were integrated through the Biomarkers Consistency Indice and georreferenced as well through GIS. Overall, in spite of the multiple biological traits surveyed, the biomarker data (from several organisms) are accordant with sediment contamination. The most impacted areas were the shipyard area and adjacent industrial belt, followed by urban and agricultural grounds. It is evident that the estuary, although globally moderately impacted, is very heterogeneous and affected by a cocktail of contaminants, especially metals and polycyclic aromatic hydrocarbon. Although elements (like copper, zinc and even arsenic) may originate from the geology of the hydrographic basin of the Sado River, the majority of the remaining contaminants results from human activities. The present work revealed that the estuary should be divided into distinct biogeographic units, in order to implement effective measures to safeguard environmental quality.

Real convergence in per capita output and growth in Eurozone: A time-series approach

The real convergence hypothesis has spurred a myriad of empirical tests and approaches in the economic literature. This Work Project intends to test for real output and growth convergence in all N(N-1)/2 possible pairs of output and output growth gaps of 14 Eurozone countries. This paper follows a time-series approach, as it tests for the presence of unit roots and persistence changes in the above mentioned pairs of output gaps, as well as for the existence of growth convergence with autoregressive models. Overall, significantly greater evidence has been found to support growth convergence rather than output convergence in our sample.

A practical approach to execute and test a lean startup

This paper practically applies the “Lean Startup Approach” by identifying, analyzing and executing a newly developed web-based business idea. Hypotheses were designed and tested with the construction of a minimum viable product – i.e. a landing page. In-depth interviews allowed deciding either to pivot or persevere the initial launch strategy. Overall, the aim was to collect as much valuable response as possible from customers and ultimately decide for a superior strategy while devoting the smallest amount of time and money.

To be or not to be a pseudogene: a molecular epidemiological approach to the mclx genes and its impact in tuberculosis

Tuberculosis presents a myriad of symptoms, progression routes and propagation patterns not yet fully understood. Whereas for a long time research has focused solely on the patient immunity and overall susceptibility, it is nowadays widely accepted that the genetic diversity of its causative agent, Mycobacterium tuberculosis, plays a key role in this dynamic. This study focuses on a particular family of genes, the mclxs (Mycobacterium cyclase/LuxR-like genes), which codify for a particular and nearly mycobacterial-exclusive combination of protein domains. mclxs genes were found to be pseudogenized by frameshift-causing insertion(s)/deletion(s) in a considerable number of M. tuberculosis complex strains and clinical isolates. To discern the functional implications of the pseudogenization, we have analysed the pattern of frameshift-causing mutations in a group of M. tuberculosis isolates while taking into account their microbial-, patient- and disease-related traits. Our logistic regression-based analyses have revealed disparate effects associated with the transcriptional inactivation of two mclx genes. In fact, mclx2 (Rv1358) pseudogenization appears to be primarily driven by the microbial phylogenetic background, being mainly related to the Euro-American (EAm) lineage; on the other hand, mclx3 (Rv2488c) presents a higher tendency for pseudogenization among isolates from patients born on the Western Pacific area, and from isolates causing extra-pulmonary infections. These results contribute to the overall knowledge on the biology of M. tuberculosis infection, whereas at the same time launch the necessary basis for the functional assessment of these so far overlooked genes.

A network approach to brain aging through multimodal neuroimaging

Tese de Doutoramento em Ciências da Saúde.

The Importance of Graduates for the Scottish Economy: A “Micro-to-Macro” Approach

There have been numerous attempts to assess the overall impact of Higher Education Institutions on regional economies in the UK and elsewhere. There are two disparate approaches focussing on: demand-side effects of HEIs, exerted through universities’ expenditures within the local economy; HEIs’ contribution to the “knowledge economy”. However, neither approach seeks to measure the impact on regional economies that HEIs exert through the enhanced productivity of their graduates. We address this lacuna and explore the system-wide impact of the graduates on the regional economy. An extensive and sophisticated literature suggests that graduates enjoy a significant wage premium, often interpreted as reflecting their greater productivity relative to non-graduates. If this is so there is a clear and direct supply-side impact of HEI activities on regional economies through the employment of their graduates. However, there is some dispute over the extent to which the graduate wage premium reflects innate abilities rather than the impact of higher education per se. We use an HEI-disaggregated computable general equilibrium model of Scotland to estimate the impact of the growing proportion of graduates in the Scottish labour force that is implied by the current participation rate and demographic change, taking the graduate wage premium in Scotland as an indicator of productivity enhancement. We conduct a range of sensitivity analyses to assess the robustness of our results. While the detailed results do, of course, vary with alternative assumptions about future graduate retention rates and the size of the graduate wage premium, for example, they do suggest that the long-term supply-side impacts of HEIs provide a significant boost to regional GDP. Furthermore, the results suggest that the supply-side impacts of HEIs are likely to be more important than the expenditure impacts that are the focus of most “impact” studies.

The system-wide impacts of the external benefits to higher education on the Scottish economy: An exploratory “micro-to-macro” approach

The private market benefits of education, i.e. the wage premia of graduates, are widely studied at the micro level, although the magnitude of their macroeconomic impact is disputed. However, there are additional benefits of education, which are less well understood but could potentially drive significant macroeconomic impacts. Following the taxonomy of McMahon (2009) we identify four different types of benefits of education. These are: private market benefits (wage premia); private non market benefits (own health, happiness, etc.); external market benefits (productivity spillovers; and external non-market benefits (crime rates, civic society, democratisation, etc.). Drawing on available microeconometric evidence we use a micro-to-macro simulation approach (Hermannsson et al, 2010) to estimate the macroeconomic impacts of external benefits of higher education. We explore four cases: technology spillovers from HEIs; productivity spillovers from more skilled workers in the labour market; reduction in property crime; and the potential overall impact of external and private non-market benefits. Our results suggest that the external economic benefits of higher education could potentially be very large. However, given the dearth of microeconomic evidence this result should be seen as tentative. Our aim is to illustrate the links from education to the wider economy in principle and encourage further research in the field.

Investigation of Postmortem Gases: A Forensic Imaging and Analytical Chemistry Approach

Background: Distinguishing postmortem gas accumulations in the body due to natural decomposition and other phenomena such as gas embolism can prove a difficult task using purely Multi-Detector Computed Tomography (MDCT). The Radiological Alteration Index (RAI) was created with the intention to be able to identify bodies undergoing the putrefaction process based on the quantity of gas detected within the body. The flaw in this approach is the inability to absolutely determine putrefaction as the origin of gas volumes in cases of moderate alteration. The aim of the current study is to identify percentage compositions of O2, N2, CO2 and the presence of gases such as H2 and H2S within these sampling sites in order to resolve this complication. Materials and methods: All cases investigated in our University Center of Legal Medicine are undergoing a Post-Mortem Computed Tomography (PMCT)-scan before external examination or autopsy as a routine investigation. In the obtained images, areas of gas were characterized as 0, I, II or III based on the amount of gas present according to the RAI (1). The criteria for these characterizations were dependent of the site of gas, for example thoracic and abdominal cavities were graded as I (1 - 3cm gas), II (3 - 5cm gas) and III (>5cm gas). Cases showing gaseous sites with grade II or III were selected for this study. The sampling was performed under CT-guidance to target the regions to be punctured. Luer-lock PTFE syringes equipped with a three-way valve and needles were used to sample the gas directly (2). Gaseous samples were then analysed using gas chromatography coupled to a thermal conductivity detector (GC-TCD). The components present in the samples were expressed as a percentage of the overall gas present. Results: Up to now, we have investigated more than 40 cases using our standardized procedure for sampling and analysis of gas. O2, N2 and CO2 were present in most samples. The following distributions were found to correlate to gas origins of gas embolism/scuba diving accidents, trauma and putrefaction: ? Putrefaction → O2 = 1 - 5%; CO2 > 15%; N2 = 10 - 70%; H2 / H2S / CH4 variable presence ? Gas embolism/Scuba diving accidents → O2 and N2= varying percentages; CO2 > 20% ? Trauma → O2 = small percentage; CO2 < 15%; N2 > 65% H2 and H2S indicated levels of putrefaction along with methane which can also gauge environmental conditions or conditions of body storage/burial. Many cases showing large RAI values (advanced alteration) did reveal a radiological diagnosis which was in concordance with the interpretation of the gas composition. However, in certain cases (gas embolism, scuba divers) radiological interpretation was not possible and only chemical gas analysis was found to lead to the correct diagnosis, meaning that it provided complementary information to the radiological diagnosis. Conclusion: Investigation of postmortem gases is a useful tool to determine origin of gas generation which can aid the diagnosis of the cause of death. Levels of gas can provide information on stage of putrefaction and help to perform essential medico-legal diagnosis such as vital gas embolism.

Appropriate treatment for Crohn's disease: methodology and summary results of a multidisciplinary international expert panel approach--EPACT.

BACKGROUND/AIMS: For many therapeutic decisions in Crohn's disease (CD), high-grade evidence is lacking. To assist clinical decision-making, explicit panel-based appropriateness criteria were developed by an international, multidisciplinary expert panel. METHODS: 10 gastroenterologists, 3 surgeons and 2 general practitioners from 12 European countries assessed the appropriateness of therapy for CD using the RAND Appropriateness Method. Their assessment was based on the study of a recent literature review of the subject, combined with their own expert clinical judgment. Panelists rated clinical indications and treatment options using a 9-point scale (1 = extremely inappropriate; 9 = extremely appropriate). These scenarios were then discussed in detail at the panel meeting and re-rated. Median ratings and disagreement were used to aggregate ratings into three assessment categories: appropriate (A), uncertain (U) and inappropriate (I). RESULTS: 569 specific indications were rated, dealing with 9 clinical presentations: mild/moderate luminal CD (n = 104), severe CD (n = 126), steroid-dependent CD (n = 25), steroid-refractory CD (n = 37), fistulizing CD (n = 49), fibrostenotic CD (n = 35), maintenance of medical remission of CD (n = 84), maintenance of surgical remission (n = 78), drug safety in pregnancy (n = 24) and use of infliximab (n = 7). Overall, 146 indications (26%) were judged appropriate, 129 (23%) uncertain and 294 (52%) inappropriate. Frank disagreement was low (14% overall) with the greatest disagreement (54% of scenarios) being observed for treatment of steroid-refractory disease. CONCLUSIONS: Detailed explicit appropriateness criteria for the appropriate use of therapy for CD were developed for the first time by a European expert panel. Disease location, severity and previous treatments were the main factors taken into account. User-friendly access to EPACT criteria is available via an Internet site, www.epact.ch, allowing prospective evaluation and improvement of appropriateness of current CD therapy.

Physical activity in 22 African countries: results from the World Health Organization STEPwise approach to chronic disease risk factor surveillance.

BACKGROUND: Baseline physical activity data are needed to effectively plan programs and policies to prevent noncommunicable diseases, but for many African countries these data are lacking. PURPOSE: To describe and compare levels and patterns of physical activity among adults across 22 African countries. METHODS: Data from 57,038 individuals from 22 countries (11 national and 11 subnational samples) that participated in the STEPwise approach to chronic disease risk factor surveillance (2003-2009) were analyzed in 2010. The validated Global Physical Activity Questionnaire (GPAQ) was used to assess days and duration of physical activity at work, for transport, and during leisure time in a typical week. RESULTS: Overall, 83.8% of men and 75.7% of women met WHO physical activity recommendations (at least 150 minutes of moderate activity per week or equivalent). Country prevalence ranged from 46.8% (Mali) to 96.0% (Mozambique). Physical activity, both at work and for transport, including walking, had large contributions to overall physical activity, while physical activity during leisure time was rare in the analyzed countries. CONCLUSIONS: Physical activity levels varied greatly across African countries and population subgroups. Leisure time activity was consistently low. These data will be useful to inform policymakers and to guide interventions to promote physical activity.