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Cardiac rehabilitation is a class 1 recommendation for acute coronary syndrome (ACS) patients according to the American College of Cardiology/American Heart Association. However, only 1 in 5 ACS patients are referred for cardiac rehabilitation nationally, and even fewer at our institution. We sought to improve the number of referrals to cardiac rehabilitation for post-ACS patients admitted to our inpatient cardiology service, and ultimately their participation in the program. We designed a quality improvement initiative that included education of patients and house staff, automated referral order, and participation of cardiac rehabilitation staff members on multidisciplinary rounds. We compared the number of patients who received a referral to cardiac rehabilitation, had the first appointment scheduled before hospital discharge, and attended the program before and after our intervention. Six months after initiation of the project, the proportion of ACS patients referred to cardiac rehabilitation before hospital discharge increased from 10% to 43% (P < 0.001). The mean number of patients with a cardiac rehabilitation appointment scheduled before discharge was 2 before and 5 after the intervention (P < 0.001), and the mean number of patients who attended their scheduled appointment was 1 before and 3 after the intervention (P = 0.001). Run charts demonstrated that the number of referrals and the number of scheduled appointments remained above the median following the intervention. In conclusion, an initiative that included education, automated referrals, and direct one-on-one contact with cardiac rehabilitation staff before discharge increased the number of cardiac rehabilitation referrals, and appointments scheduled and attended in post-ACS patients.

Thoracic endovascular aortic repair (TEVAR) results have been studied in short-term time frames. This study aimed to evaluate midterm and long-term outcomes of TEVAR, emphasizing postoperative aortic remodeling and need for reintervention.This is an institutional retrospective review of TEVAR for isolated descending thoracic aortic aneurysms. Data were collected from 2004 to 2018. Primary outcomes studied included aneurysm sac remodeling, freedom from reintervention, and all-cause mortality. Other outcomes studied include endoleak rates, neurologic complication rates, and any overall postoperative complication rates.During the study period, 219 patients underwent TEVAR for descending thoracic aortic aneurysms. The median effect of TEVAR on sac diameter was a 0.7-cm decrease in size (interquartile range, -1.4 to 0.0 cm). During the study period, 80% (n = 147) of patients experienced aneurysm sac regression or stability. Perioperative neurologic complications occurred in 16% (n = 34) of patients. Significant predictors of sac growth were endoleak (odds ratio [OR], 65; P .001), preoperative carotid-subclavian bypass (OR, 8; P = .003), and graft oversizing 20% (OR, 15; P = .046). Every 1-mm increase in aortic diameter at the proximal TEVAR landing zone led to an increased odds of endoleak (OR, 2; P = .049). Access complications (OR, 8) and subclavian artery coverage (OR, 6) significantly increased the odds of reintervention, whereas every percentage of graft oversizing protected against reintervention (OR, 0.005). Life-table analysis revealed an overall survival of 78% (71%-83%) at median follow-up. At 3 years, survival was 88% (80%-93%) for those with aneurysm sac stability or regression, whereas it was 70% (49%-84%) for those with aneurysm sac growth (P = .0402). Cox proportional hazards model showed that the only protective factor for mortality was percentage oversizing, with every 1% of oversizing having a hazard ratio (HR) of .001 (P = .032). This was counterbalanced by the fact that patients with graft oversizing30% had an increased odds of mortality with HR10 (P = .049). Other significant factors that increased the odds of mortality included endoleak (HR, 3.6; P = .033), diabetes (HR, 4.1; P = .048), age (every 1-year increase in age; HR, 1.2; P = .002), year of surgery (every year subsequent to 2004; HR, 1.3; P = .012), and peripheral artery disease (HR, 5.2; P = .041).The majority of patients (80%) experience sac stability or regression after TEVAR, which offers a clear survival advantage. Endoleaks are predictive of sac growth, conferring increased mortality. Rigorous surveillance is necessary to prevent future aortic events through reintervention.

Societal Impact Statement Plants and fungi have provided, or inspired, key pharmaceuticals for global health challenges, including cancer, heart disease, dementia, and malaria, and are valued as traditional medicines worldwide. Global demand for medicinal plants and fungi has threatened certain species, contributing to biodiversity loss and depletion of natural resources that are important for the health of humanity. We consider the evolving role of plants and fungi in global healthcare as new challenges to human health and to biodiversity arise. We present current and emerging scientific approaches, to uncover and preserve nature‐based health solutions for the future, through harmonization with biodiversity conservation strategies. Summary Non‐communicable diseases, including cardiovascular disease, cancer, and diabetes, are the main causes of deaths globally, and communicable diseases such as malaria and tuberculosis affect billions of people. Plants and fungi have provided key pharmaceuticals in our armory against these global health challenges, while in some regions of the world, they continue to have a central role in healthcare systems as traditional medicines. Consequently, global demand for plants and fungi in healthcare has threatened certain medicinal species, and is a driving factor in biodiversity loss. Yet the future of therapeutics from nature is evolving. Scientific advances are enabling the untapped potential of the world's plants and fungi to be explored for their medicinal value, and to reveal other roles they may have for improving health and well‐being; this demonstrates the value of natural capital as an incentive for biodiversity conservation. Emerging technologies also offer new hope for safeguarding essential medicines for the future, by revealing more sustainable solutions for sourcing key natural products. This review discusses recent developments and future approaches for the discovery of natural products as medicines, for health and well‐being, and strategies to harmonize the therapeutic use of biodiversity with its proactive conservation through nature‐based solutions.

Introdução: A par dos modelos nacionais e internacionais de intervenção na fase inicial das perturbações psicóticas, teve início, em 2010, um Programa de Intervenção Precoce em Psicose (PIPP) na instituição dos autores. Este proporciona um acompanhamento multidisciplinar intensivo, a doentes nos primeiros cinco anos de apresentação de sintomas psicóticos, visando otimizar a abordagem para que alcancem uma melhor recuperação e evolução. Foi objetivo do presente trabalho avaliar o impacto dessa intervenção especializada sobre a evolução dos doentes em fase inicial de uma perturbação psicótica. Metodologia: Foi efetuado um estudo retrospetivo de um conjunto de variáveis clínicas e sociais de uma amostra de doentes admitidos consecutivamente no PIPP, desde 2010, por um diagnóstico de psicose com menos de cinco anos de evolução, e acompanhados durante os cinco anos seguintes no programa. Comparativamente, analisámos o comportamento das mesmas variáveis numa amostra histórica de doentes com psicose inicial tratados de forma genérica (N-PIPP), previamente à criação do programa. A análise estatística fez-se com recurso ao programa informático SPSS 22. Resultados: Comparativamente ao grupo N-PIPP, os doentes do grupo PIPP apresentaram, ao fim de cinco anos, um risco significativamente menor de reinternamento (RR=0,33, p=0,043) e de abandono definitivo do tratamento (RR=0,21, p=0,011); e uma maior probabilidade de ocupação social ou profissional (RR= 1,83, p=0,048). Apresentaram também maior remissão sintomática apesar de não se ter apurado significância estatística nessa associação (RR= 1,33, p=0,184). Conclusões: O acompanhamento dos doentes em fase de psicose inicial num programa especializado tem um efeito favorável na sua evolução clínica e social.

Background Non-classical congenital adrenal hyperplasia (NC-CAH) is a chronic disease characterised by excessive androgen production that may negatively affect the quality of life (QoL) of affected patients. Pediatric Quality of Life Inventory 4.0 (PedsQL™) is a validated tool to assess health-related QoL (HRQoL). Methods A cross-sectional study including 19 patients with NC-CAH was carried out in the pediatric endocrinology department. NC-CAH patients who agreed to participate were included. Anthropometric data was collected. PedsQL™ was applied to the patients and their parents. Patients were divided into four groups according to age: 2-4, 5-7, 8-12, and 13-18 years old. The control group consisted of healthy individuals from the instrument's validation studies for the Portuguese population and the standard control population used in the PedsQL™ validation study. Results The only difference found concerns the parents' score results for children aged 8-12, which showed physical health and emotional dimension scores significantly higher (86.16±9.86 vs.68.90±23.02 p=0.004, 69.17±14.14 vs. 65.82±19.24 p=0.004), while psychosocial health's score and total scale score were significantly lower than the control group (59.99±9.90 vs. 69.34±14.07 p=0.047, 73.11±4.65 vs.78.86±16.61 p=0.017). Conclusion HRQoL scores are not negatively affected by NC-CAH in most group ages, with the exception of the parents' reports on HRQoL for children aged 8-12. Further studies with a greater number of patients are needed to determine the impact of this chronic disease on the HRQoL of children.

The Brazilian state of Amapa=-notable for having 70% of its area consisting of unexplored Amazonian forests-experienced a massive power blackout in November 2020. An internal short-circuit in a transformer led to an explosion followed by a fire at the Macapa substation. This event left about 90% of the Amapa's population without power for several days in the middle of the COVID-19 pandemic, disrupting the lives of hundreds of thousands of people and raising concerns from several electricity sector stakeholders. This paper discusses select lessons learned from the power blackout and presents future opportunities to improve power system reliability and resilience for the grids in Amapa, and other similar Brazilian states, with a special focus on the increasingly important role of of distributed energy resources and smart grid technologies.

This paper presents a methodology for battery energy storage systems (BESS) management considering the concept of transactive energy. Transactive energy is defined as the economic and control technique used for energy management that allows the dynamic balance of supply and demand across the electrical system. In a transactive energy market, the consumer can produce energy and inject it into the grid, becoming a prosumer. Also, it is possible to have the presence of private aggregators. Aggregators have large energy production capacity and can negotiate this energy with the grid. The system is composed by two private aggregators, the consumers, and the distribution system operator (DSO). The aggregators are assigned to supply a specific number of consumers defined in the contractual demand with the DSO, and the DSO is responsible for serving the rest of the system. Both aggregators and the DSO have distributed energy resources (DERs), such as energy storage and/or photovoltaic generation. A neural network based on group method of data handling (GMDH) is used for forecasting the grid demand, energy prices and solar generation for the day-ahead operation. The BESS reserve for the day-ahead is optimized based on prediction model. The methodology is validated in a 33-bus distribution network simulated on software OpenDSS. The curve profiles are taken from real data of the Canadian distribution system.

Recently in the power system, different scales of micro-grid can connect to the distribution system to support the distribution system operation. However, depending on the power purchase agreement terms determined by the distribution system operator for the microgrid investors, cost of energy could become elevated, making the inclusion of distributed energy resources less attractive to some other stakeholders in terms of cost. This study presents the analysis of microgrid operation for distribution system support considering different power purchase agreement terms. A two-level approach is proposed. In the first level, the optimal capacity of the MGs is determined. The second level includes the yearly cooperation of the distribution system operator and microgrids. The decision-making of the distribution system operator and microgrids under the management of a responsible aggregator and their consequences on the distribution system customer cost of energy is analyzed. Case studies are performed on a modified IEEE 33 -Bus System. Relevant results and suggestions are provided for an effective stakeholders' participation.

BackgroundObesity is a multifactorial disease, which is strongly associated to other metabolic disorders. Bariatric surgery is the most effective treatment of morbid obesity. The role of beta cell function in weight loss after bariatric surgery is uncertain.AimTo evaluate the association between beta cell function and percentage of total body weight loss (TBWL%) 1, 2, 3, and 4 years after bariatric surgery in patients with morbid obesity.MethodsRetrospective longitudinal study in patients with morbid obesity followed in our center between January 2010 and July 2018. Patients were excluded if they had diabetes at baseline or missing data on the needed parameters. We evaluated baseline Homeostatic Model Assessment of IR, Homeostatic Model Assessment of β-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index, and Matsuda and DeFronzo index, and TBWL% at years 1 to 4. Linear regression models were used to evaluate the association of indexes of insulin resistance with TBWL% (unadjusted and adjusted for age, sex, BMI, and type of surgery).ResultsThere were 1,561 patients included in this analysis. HOMA-beta was negatively associated with TBWL% at second, third, and fourth years post-surgery (β = −1.04 [−1.82 to −0.26], pConclusionβ-cell function at baseline seems to be associated to long-term weight loss, explicitly after the first year post bariatric surgery. This might be a helpful predictor of weight loss in clinical practice.

Background Given the challenges associated with timely delivery of monoclonal antibody (mAb) therapy to outpatients with coronavirus disease 2019 (COVID-19) who are most likely to benefit, it is critical to understand the effectiveness of such therapy outside the context of clinical trials. Methods This was a case–control study of 1257 adult outpatients with COVID-19, ≥65 years of age or with body mass index (BMI) ≥35, who were entered into a lottery for mAb therapy. Results Patients who were called to be offered mAb therapy had a statistically significant 44% reduction in the odds of hospitalization within 30 days of a positive severe acute respiratory syndrome coronavirus 2 test compared with those who were not called (odds ratio [OR], 0.56; 95% CI, 0.36–0.89; P=.01). Patients who actually received bamlanivimab had a statistically significant 68% reduction in the odds of hospitalization compared with those who did not receive bamlanivimab (OR, 0.32; 95% CI, 0.11–0.93; P=.04). Conclusions This study supports the effectiveness of bamlanivimab in reducing COVID-19-related hospitalizations in patients ≥65 or with BMI ≥35.

[EN] Pathophysiology at NOVA Medical School adopted the concept mapping methodology to promote the visual display of pathophysiological reasoning and learning, based on clinical vignettes. The objective of this project is to identify and label the linking words, in order to study their role in the structure and organization of the concept maps constructed by the students. We used an adopted classification of linking words, categorized in 5 groups: dynamic, static, illustrative, definition and clinical case information. At the end of the semester the concept maps related to the respiratory (mid-semester) and endocrine systems (end of semester) were analyzed and compared. We found linking words not included in any of the five categories, thus a group named “other” has been created. Statistically significant differences were found in dynamic and “other” categories (p=0,049 and p= 0,011, respectively; Wilcoxon signed-rank test). The dynamic words were the most commonly used, probably reflecting students’ need to better describe pathophysiological mechanisms, and the difference found was probably due an improvement in the learning process and concept maps building technic. It would be interesting next year to conduct a more detailed analysis, increasing the sample and ensuring a more robust dataset., Grateful thanks are due to the teaching staff of pathophysiology, tutors Manuel Almeida, Patrícia Santos, Diana Ferreira, Miguel Proença, Ana Rita Franco, Luísa Quaresma, Vasco Gaspar and António Mesquita, and the junior students Sofia Ribeiro, Pedro Vilão Silva, Joana Vigeant Gomes and Margarida Flores that acted as mentors during the tutorial sessions.

Superficial gastrointestinal (GI) neoplasms can be treated with endoscopic mucosal resection (EMR) and/or endoscopic submucosal dissection (ESD). These techniques are widely used in Eastern countries; however, its use in the West is limited. The aim of this study was to evaluate the current implementation of ESD in Western countries.Western endoscopists (A total of 58 endoscopists (21%) completed the survey. Thirty performed ESD in the esophagus (52%), 45 in the stomach (78%), 36 in the co-lorectum (62%), and 6 in the duodenum (10%). The median total number of lesions ever treated per endoscopist was 190, with a median number per endoscopist in 2016 of 41 (7 [IQR 1-21], 6 [IQR 4-16], and 28 [5-63] in the esophagus, in the stomach, and in the colon and rectum, respectively). En bloc resection rates were 97% in the esophagus, 95% in the stomach, and 84% in the colorectum. Complete resection (R0) was achieved in 88, 91, and 81%, respectively. Curative rates were 69, 70, and 67%, respectively. Major complications (perforation or delayed bleeding) occurred more often in colorectal ESD (12 vs. 6% in the esophagus and 7% in the stomach). In the upper GI tract, the majority of resected lesions were intramucosal adenocarcinoma (59% in the esophagus; 47% in the stomach), while in the colorectum the majority were adenomas (59%).ESD seems to be performed by a large number of centers and endoscopists. Our results suggest that ESD is being successfully implemented in Western countries, achieving a good rate of efficacy and safety according to European guidelines.As lesões superficiais gastrointestinais podem ser tratadas por musectomia (EMR) e/ou disseção endoscópica da submucosa (ESD). Estas técnicas são usadas frequentemente nos países asiáticos, mas a experiência é mais limitada nos países ocidentais. O objetivo deste estudo foi avaliar a implementação atual da ESD nos países ocidentais.Gastroenterologistas ocidentais (Um total de 58 gastroenterologistas (21%) completou o inquérito. Trinta realizaram ESD esofágica (52%); 45 gástrica (78%); 36 coloretal (62%); e 6 duodenal (10%). A mediana do número total de lesões ressecadas por endoscopista foi 190, sendo que, em 2016, a mediana de lesões tratadas por cada gastroenterologista foi 41 (7 [IQR 1–21] no esófago, 6 [IQR 4–16] no estómago e 28 [5–63] no côlon e reto). A taxa de ressecção em bloco foi de 97% nas lesões esofágicas; 95% nas lesões gástricas e 84% nas lesões coloretais, com uma proporção de casos RO de 88, 91 e 81%, respetivamente. A taxa de casos curados foi de 69, 70 e 67%, respetivamente. A taxa de complicações graves (perfuração e hemorragia tardia) foi maior na ESD coloretal (12% dos casos vs. 6% no esófago e 7% no estômago). A maioria das lesões esofagogástricas eram adenocarcinomas intramucosos (59% no esófago; 47% no estômago), enquanto as lesões coloretais eram maioritariamente adenomas (59%).Este estudo mostra uma disseminação da ESD na europa por um maior número de centros e gas-trenterologistas. Os nossos resultados sugerem uma utilização e eficácia global de acordo corn as recomendações europeias.

Nonalcoholic fatty liver disease is increasingly recognized as the hepatic counterpart of metabolic syndrome. It is hypothesized that structural and functional cardiac changes may be associated with this metabolic disease. We aimed to gather the existing information on the association of nonalcoholic fatty liver disease with cardiac alterations, and to evaluate a possible correlation between them. Systematic review of Medline searching results for original articles studying NAFLD and cardiac parameters until August 2018. A meta-analysis was conducted to each parameter of cardiac structure and function selected, using Review Manager 5.3 software. This study was conducted according to preferred reporting items for systematic reviews and meta-analysis (PRISMA). A total of 16 studies met the eligibility criteria and were included in the meta-analysis. There was a significant association between nonalcoholic fatty liver disease and (1) higher left ventricle mass and ratios between left ventricle mass and both height and body surface area; (2) higher LVEDD; (3) higher left atrium diameter and ratio between left atrial volume and body surface area; (4) higher posterior wall and septum thickness; (5) lower E/A wave ratio; (6) higher E/E’ ratio; (7) longer deceleration time and (8) longer relaxation time. NAFLD associates with adverse structural alterations and cardiac dysfunction. Our results highlight the importance of identifying NAFLD in patients with metabolic dysfunction as this may represent an additional contributor to cardiovascular risk.

Thyroid hormones have a central role in cardiovascular homeostasis. In myocardium, these hormones stimulate both diastolic myocardial relaxation and systolic myocardial contraction, have a pro-angiogenic effect and an important role in extracellular matrix maintenance. Thyroid hormones modulate cardiac mitochondrial function. Dysfunction of thyroid axis impairs myocardial bioenergetic status. Both overt and subclinical hypothyroidism are associated with a higher incidence of coronary events and an increased risk of heart failure progression. Endothelial function is also impaired in hypothyroid state, with decreased nitric oxide-mediated vascular relaxation. In heart disease, particularly in ischemic heart disease, abnormalities in thyroid hormone levels are common and are an important factor to be considered. In fact, low thyroid hormone levels should be interpreted as a cardiovascular risk factor. Regarding ischemic heart disease, during the late post-myocardial infarction period, thyroid hormones modulate left ventricular structure, function and geometry. Dysfunction of thyroid axis might even be more prevalent in the referred condition since there is an upregulation of type 3 deiodinase in myocardium, producing a state of local cardiac hypothyroidism. In this focused review, we summarize the central pathophysiological and clinical links between altered thyroid function and ischemic heart disease. Finally, we highlight the potential benefits of thyroid hormone supplementation as a therapeutic target in ischemic heart disease.

The advertising–sales relationship remains paramount. This study—believed to be the largest that focuses on automotive sales and advertising—investigates ceilings and thresholds by optimizing budget allocations among media. The study considered 12 vehicle brands in South Africa, spanning 8 years of sales, reflecting sales and media expenditure. It also considers the effect of competitors9 advertising expenditure and familiarity on the ceilings and thresholds of each medium, as well as the decay rate of advertising goodwill. Findings suggest that the allocation of expenditure among media types is subject to threshold phenomena. The findings also establish the impact of clutter and familiarity on market share, advertising efficacy, and ceilings and thresholds. Results highlight the interaction between current market share and advertising efficacy.

A germplasm collection of sweet cherry cultivars has been studied for several years in order to know which of them are more suitable for the climatic conditions of the Region of Murcia. The collection comprises 77 cultivars coming from different origins such as France, Hungary, Italy, Spain, and the USA. In 2007, all of the cultivars were grafted on 'Mariana 2624' rootstock using 'Adara' as an interstock. Phenological dates, fruit quality traits, and productivity have been recorded since 2009 to determine which cultivars are better adapted to the semi-arid conditions present in southeastern Spain. After selecting the most adapted cultivars, verification of the genetic identity of the cultivars is advisable in order to select a group of cultivars which maximize genetic diversity and minimize conservation costs. Molecular techniques provide assistance when it comes to designating this representative selection. However, it is important to select a minimum set of markers which allow to establish a difference between cultivars and to reduce laboratory costs while increasing effectiveness. For this study, microsatellites (SSR) were selected as markers, considering that generated results could be compared between laboratories. In a first analysis, a set of 12 markers recommended by the European Cooperative Programme for Plant Genetics Resources (ECPGR) was used, but this group of markers was not valid to establish a distinction between all the cultivars. Thus, we included more markers to try to make a discrimination between all of the studied cultivars. Moreover, we include three linked markers with important quality traits that generated useful information for breeder's work.

Distribution systems are undergoing structural and topological changes, mainly due to the influence of the new distributed energy resources inserted along the feeders. In this context, the growth of the Smart Grids requires the evolution of the control and operation tools, since the decision-making should promote proactive actions. In this sense, the present paper proposes a method for subdividing the distribution system into grid functional blocks, associated to a method of forecasting of distributed electric quantities. The functional blocks allow the assets to be organized in a way to provide sufficient information to perform advanced analyzes of a geoelectric region. The proactive decisions, in the grid functional blocks, are taken from the very short term forecast of variables (voltage, current, active power and reactive power). These forecasts are based on an innovative method of selection of forecasting techniques, which takes into account the online and historical information for the performance ranking of forecasting techniques. The developed methodologies by authors provide greater flexibility for the Smart Grids regarding to the dynamic changes that occur in the distribution grids in the presence of distributed flexible resources, demand management, Volt-VAR Optimization, Conservation Voltage Reduction, protection, automatic reconfiguration, self-healing, storage and electric vehicles.

Meditation and positive psychology have been reported as promising approaches to deal with stress. This exploratory pilot study aims to evaluate the efficacy of meditation and positive psychology-based intervention on stress. Two experiments are reported, in the first one, 29 healthcare professionals were included (intervention = 14, control = 15), and the second one included 57 women managers (intervention = 27, control = 30). All participants were evaluated before and after eight weeks for levels of stress, anxiety, depression, and psychiatric symptoms. In Experiment 1, intervention group participants showed a reduction in stress levels and anxiety symptoms, and in Experiment 2, participants in the intervention group showed a decrease in stress, psychiatric symptoms, and sleep quality, when compared to the control group. A multi-component intervention based on positive psychology and meditation practices was effective at reducing stress as well as improving related stress parameters such as anxiety, psychiatric symptoms, and sleep quality.

Background. Thyroid hormones (TH) are crucial for cardiovascular homeostasis. Recent evidence suggests that acute cardiovascular conditions, particularly acute heart failure (AHF), significantly impair the thyroid axis. Our aim was to evaluate the association of thyroid function with cardiovascular parameters and short- and long-term clinical outcomes in AHF patients. Methods. We performed a single-centre retrospective cohort study including patients hospitalized for AHF between January 2012 and December 2017. We used linear, logistic, and Cox proportional hazard regression models to analyse the association of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) with inpatient cardiovascular parameters, in-hospital mortality, short-term adverse clinical outcomes, and long-term mortality. Two models were used: (1) unadjusted, and (2) adjusted for age and sex. Results. Of the 235 patients included, 59% were female, and the mean age was 77.5 (SD 10.4) years. In the adjusted model, diastolic blood pressure was positively associated with TSH [β = 2.68 (0.27 to 5.09); p = 0.030 ]; left ventricle ejection fraction (LVEF) was negatively associated with FT4 [β = -24.85 (-47.87 to -1.82); p = 0.035 ]; and a nonsignificant trend for a positive association was found between 30-day all-cause mortality and FT4 [OR = 3.40 (0.90 to 12.83); p = 0.071 ]. Among euthyroid participants, higher FT4 levels were significantly associated with a higher odds of 30-day all-cause death [OR = 4.40 (1.06 to 18.16); p = 0.041 ]. Neither TSH nor FT4 levels were relevant predictors of long-term mortality in the adjusted model. Conclusions. Thyroid function in AHF patients is associated with blood pressure and LVEF during hospitalization. FT4 might be useful as a biomarker of short-term adverse outcomes in these patients.

Introduction: Endoscopic Submucosal Dissection (ESD)was introduced in the West later than in the East. Our aim was to assess how Western endoscopists performing ESD have been trained and how they value animal models for training. Material and methods: An online survey regarding training in ESD was sent to Western endoscopists who published articles on advanced resection techniques. Results: From 279 endoscopists, 58 (21%) completed the questionnaire, of which 50 confirmed performance of clinical ESD. Endoscopists had a median of 15 years of endoscopic experience (IQR 9.75–20.25) and all of them were performing conventional EMR, before starting ESD. Prior to clinical ESD, 74% (n = 37) underwent training with ex vivo models, 84% (n = 42) with live animal models and 92% (n = 46) with at least, one of the two models. After starting clinical ESD, as trainers, 52% (n = 26) were involved with ex vivo and 60% (n = 30) with live animal models. Personal usefulness of ex vivo and live animal models was rated with a median of 9 (IQR 8–10) and 10 (IQR 8–10), out of 10, respectively. Courses with ex vivo and live animal models were considered a prerequisite before clinical practice by 84% (n = 42) and 78% (n = 39), respectively. Conclusions: Western endoscopists have extensive endoscopic experience before starting ESD. The majority had pre-clinical training with ex vivo and live animal models and more than half are acting as trainers of other endoscopists with these models. Animal models are considered very useful and deemed a prerequisite before clinical practice by the majority of the endoscopists.

Marta Borges-Canha,1,2 João Sérgio Neves,1,2 Fernando Mendonça,1 Maria Manuel Silva,1 Cláudia Costa,3 Pedro M Cabral,4 Vanessa Guerreiro,1 Rita Lourenço,5 Patrícia Meira,5 Daniela Salazar,1 Maria João Ferreira,1 Jorge Pedro,1 Ana Rita Leite,2 Madalena von-Hafe,2 Catarina Vale,2 Sara Viana,1 Ana Sande,1 Sandra Belo,1 Eva Lau,1 Paula Freitas,1,6 Davide Carvalho1,6 1Serviço de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universitário de São João, Porto, Portugal; 2Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal; 3Serviço de Endocrinologia do Instituto Português de Oncologia do Porto, Porto, Portugal; 4Serviço de Patologia Clínica do Centro Hospitalar Universitário Cova da Beira, Covilhã, Portugal; 5Faculdade de Ciências da Nutrição e Alimentação da Universidade do Porto, Porto, Portugal; 6Investigação e Inovação Em Saúde (I3s), Faculdade de Medicina da Universidade do Porto, Porto, PortugalCorrespondence: Marta Borges-CanhaServiço de Endocrinologia, Diabetes e Metabolismo do Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, Porto, 4200-319, PortugalTel +351918935390Email marta.canha@gmail.comPurpose: We aimed to evaluate the association between vitamin D status and hepatic function parameters and scores: Fatty Liver Index (FLI, predictor of hepatic steatosis) and BARD (BMI, AST/ALT ratio and DM, predictor of hepatic fibrosis) in patients with morbid obesity.Patients and Methods: Cross-sectional study including patients with morbid obesity followed in our centre between January 2010 and July 2018. Patients with missing vitamin D levels or hepatic profile parameters were excluded. We divided the population according to two cut-offs of vitamin D levels (12ng/mL and 20ng/mL).Results: The included population (n=1124) had an average age of 43.3± 10.7 years and 84.3% were female. Seventy-point eight percent of the population had vitamin D levels lower than 20ng/mL and 34.8% lower than 12ng/dL. Patients with lower vitamin D levels (< 12ng/mL) had higher BMI, hip and waist circumferences and higher prevalence of hypertension. Higher FLI scores [OR= 0.77 (0.07), p< 0.01] and ALP levels [β= − 0.03 (− 0.06, − 0.01), p< 0.01] associated to lower vitamin D levels.Conclusion: Vitamin D deficiency is associated with a higher risk of hepatic steatosis in individuals with morbid obesity. Correction of vitamin D deficiency may have a beneficial role in the management of NAFLD in patients with morbid obesity.Keywords: vitamin D, fatty liver, NAFLD, obesity

The number of connections with distributed generation has been growing steadily in Brazil, however, there is still a problem associated with it, the intermittence. Although a consumer with photovoltaic solar system (PVSS) is able to generate energy even when the grid is unavailable, the load is still susceptible to power outages given the intermittence of the source, one possible solution for this is the use of energy storage elements to supply part of the load, or even all of it when needed. In this study is analyzed, under the economic viability point of view, the impact of using a Battery Energy Storage System (BESS) coupled with a PVSS to supply a residential consumer in the event of power outages.

The diversity of the energy matrix in the world is one of the challenges demanding fornew researches with alternative energy sources to bring exibility and sustainability in their use.According with this panorama, the generation of electric energy with solar photovoltaic systemsemerges as an important goal, and its technology is constantly advancing as an immediatesolution for this quest of diversity. This paper presents a predictive control for a solar trackingalgorithm to be used in single or double axis photovoltaic systems. The main characteristicand contribution of this algorithm represents a functional technological innovation because itdoes not use any sensors to determine the position of the Sun with respect to the panel. Suchalgorithm avoids unnecessary movements in cases of shadows on the panels caused by clouds,or some animal that could interfere on systems using the conventional sensors. The proposedsolar time algorithm was tested and compared with eld values, predicting the correct Sunposition with accuracy of less than 1o. The qualitative and quantitative results presented hereevidenced the real gain of the proposed algorithm-based system without any sensors to increasethe generation gain of photovoltaic power plants.

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Gout is a rare phenomenon in reproductive age women due to the uricosuric effects of estrogen. Furthermore, gout in pregnancy has been reported in only a scant number of case reports. We present the case of a 21-year-old gravida-4 para-3 female at four-weeks gestation presenting with acute polyarticular gout, complicated by Haemophilus influenzae sepsis and hyperemesis gravidarum. The gout flare was likely precipitated by primary H. influenzae bacteremia, which was successfully treated with intravenous antibiotics. The treatment of gout in pregnancy is challenging because of the limited number of guidelines. We demonstrate successful management of an acute gout flare in pregnancy with colchicine and steroid injection of the affected joint. Unfortunately, the patient suffered a miscarriage, but the link between gout flare and spontaneous abortion is tenuous.

Background: An association between hypothyroidism and the risk of Non-alcoholic Fatty Liver Disease (NAFLD) has been suggested. This association remains to be elucidated in patients with morbid obesity. Aim: To evaluate the association between thyroid function and parameters of liver function and hepatic scores in patients with morbid obesity. Methods: Patients with morbid obesity followed in our center between January 2010 and July 2018 were included. The ones without evaluation of liver and thyroid functions were excluded. Fatty Liver Index (FLI) and BARD scores were used as predictors of hepatic steatosis and fibrosis, respectively. Results: We observed a positive association between TSH and both BARD (OR 1.14; p = 0.035) and FLI (OR 1.19; p = 0.010) in the unadjusted analysis. We found a negative association between free triiodothyronine levels and BARD (OR 0.70; p

Renewable Energy Sources and Distributed Energy Resources are expected to transform the future of system planning and operation. Although, there is a widespread awareness that disruptive technologies will require innovative roles from distribution companies, there is a new set of rules and regulations that remain distant. This study presents an analysis of RES and DER impacts and the planning techniques in use to solve these problems. A Utility new business model reform is presented to allow the comprehension about the distribution role transformation. The Integrated Distribution Planning concept is demonstrated. The future of Utility Planning is idealized based in integration between technical and economical frameworks. The result is an Improved Integrated Distribution Planning method that targets the best Distribution Investment Roadmap and robust economic and financial analysis with the main indicators as EBITDA, Debt Capacity, CAPEX, Enterprise Value, etc. The conclusion is that with the integration presented is possible to reduce the concerns about increased retail electricity rates and cost-shifting to non prosumers, reduced utility shareholder profitability and earnings opportunities.

Electrical energy is a basic necessity for most activities in the daily life, especially for military operations. This dependency on energy is part of a national security context, especially for a military operation. Thus, the main objective of the paper is to provide a review of the energy storage and the new concepts in military facilities. Most of this energy is provided by long dated structures, both in the transmission and distribution aspect, and often not projected to a military conflict, especially in remote regions with difficult access. The electrical grid can be targeted both physically and by cyber-attacks, disrupting the energy supply to strategic regions. In response to this adversity, the military forces of several countries have been developing projects using microgrids. This new system has independent, controllable and unique energy generation, comprising renewable generation, electric vehicles, energy storage and control devices. To deploy renewable energy, it is necessary to first have an energy storage system that can support these sources. Thus, this paper proposes a review on the energy storage application in the military sector, and how this technological advance has impacted the military routine and operations, along with some real application and their economic and technical results.

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in Western countries and a common comorbidity with type 2 diabetes (T2D). It lacks effective pharmacotherapy. We aimed to summarize the evidence on the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on liver structure and function.Meta-analysis of randomized clinical trials in PubMed, Web of Science and ClinicalTrials.gov from their inception to April 2019. Trials evaluating liver function and/or structure and comparing SGLT2 inhibitors with placebo or other oral antidiabetic drugs in patients with T2D were included. Twenty studies (from 3033) were included. A total of 1950 patients with T2D, with or without NAFLD, were treated with SGLT2 inhibitors for at least 8 weeks, and 1900 patients were used as controls. Independent extraction was carried out by two observers. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis.SGLT2 inhibitors induced a significant decrease in serum alanine (-7.43U/L, [95%CI -12.14, -2.71], p0.01), in aspartate aminotransferases (-2.83U/L, [-4.71, -0.95], p0.01), as well as in gamma glutamyl transferase (-8.21U/L, [-9.52, -6.91], p0.01), and an increase in total plasma bilirubin (8.19% [0.79, 15.59], p0.01), comparing with placebo or other oral antidiabetic drugs. SGLT2 inhibitors treatment was associated with a decrease in liver steatosis (-3.39% [-6.01, -0.77], p0.0.1).Treatment with SGLT2 inhibitors improves liver structure and function in patients with T2D. This meta-analysis suggests that SGLT2 inhibitors are a promising pharmacological approach for treatment of NAFLD.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity, and the prevalence of both diseases is increasing notably. The lack of effective treatment options for NAFLD is leading to a great consideration towards the identification of new approaches. Aim: We aimed to evaluate the change one year after bariatric surgery of parameters of hepatic function and in the hepatic scores, Fatty Liver Index (FLI, predictor of hepatic steatosis), and BARD, BMI, AST/ALT ratio and DM, (predictor of hepatic fibrosis). Methods: Observational retrospective cohort study in morbidly obese patients that underwent bariatric surgery between January 2010 and July 2018. We excluded patients missing hepatic function parameters before or one year after the surgical procedure. We used two linear regression models: 1) unadjusted; 2) adjusted for surgery type (gastric sleeve, gastric band and gastric bypass), sex, age, body mass index, diabetes and dyslipidaemia. Results: The included population (n=1955) had an average age of 43.1±10 years and 85.8% were female. We observed a relevant decrease in transaminases (pre-operative AST and ALT, 24.8±12.4 and 29.5±19.5U/L, vs 22.4 ± 11.1 and 22.2±14.7 post-operatively, respectively, p Conclusion: Bariatric surgery is associated with a reduction of the hepatic enzymes and an improvement of FLI and BARD. Bariatric surgery may represent an effective therapeutic approach to NAFLD.

To evaluate the variation in parameters of hepatic function and in the scores Fatty Liver Index (FLI; predictor of hepatic steatosis) and BARD (BMI, AST/ALT ratio and DM, predictor of hepatic fibrosis), 1 year after bariatric surgery. This is a observational retrospective cohort study in patients with morbid obesity that underwent bariatric surgery in our centre. We used two linear regression models: (1) unadjusted and (2) adjusted for surgery type, sex, age, body mass index, diabetes, and dyslipidaemia. The included population (n = 1955) had an average age of 43.1 ± 10 years and 85.8% were female. Diabetes was present in 32.4% of the patients, 45.1% had dyslipidaemia, and 62.2% had hypertension. Twelve percent were submitted to gastric band, 29.6% to sleeve gastrectomy, and 58.4% to gastric bypass. We observed a relevant decrease in transaminases and gamma-glutamyltransferase, and an increase in alkaline phosphatase and total bilirubin. Both FLI and BARD markedly decrease 1 year after surgery (p

Background PCSK9 (Proprotein convertase subtilisin/kexin type 9) binds low‐density lipoprotein receptor, preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis. The PCSK9‐rs562556 variant has been reported as a gain‐of‐function mutation. The aim of this study was to determine whether the PCSK9–low‐density lipoprotein receptor–rs562556 axis is associated with carotid artery plaques between 2 visits separated by almost 20 years in a longitudinal population cohort. Methods and Results The STANISLAS (Suivi Temporaire Annuel Non‐Invasif de la Santé des Lorrains Assurés Sociaux) cohort is a longitudinal familial cohort from the Lorraine region of France. Participants attending 2 visits (visit 1 and visit 4) separated by 18.5 years (mean) were included (n=997). Carotid artery plaques were determined with standardized vascular echography. The mean age of the adult population at visit 1 was 42±5 years. At visit 4, 203 (20.4%) participants had arterial plaques. Participants who developed arterial plaques were older (42.7±5.4 versus 41.7±4.7 years), more often male (60% versus 49%), smokers (29% versus 18%), with diabetes mellitus (6% versus 3%), and higher cholesterol levels (low‐density lipoprotein cholesterol, 1.6±0.4 versus 1.5±0.3 g/L) (all P Conclusions Higher PCSK9 concentration was associated with the development of arterial plaques almost 20 years in advance in a healthy middle‐aged population. Mutations of the single‐nucleotide polymorphism rs562556 associated with both PCSK9 levels and arterial plaques reinforce the potential causality of our findings. PCSK9 inhibitors could be useful for primary cardiovascular prevention.

Endothelial dysfunction is one of the earliest indicators of cardiovascular (CV) dysfunction, and its evaluation would be of considerable importance to stratify CV risk of many diseases and to assess the efficacy of atheroprotective treatments. Flow-mediated dilation is the most widely used method to study endothelial function. However, it is operator-dependent and can be influenced by physiological variations. Circulating biomarkers are a promising alternative. Due to the complexity of endothelial function, many of the biomarkers studied do not provide consistent information about the endothelium when measured alone. New circulating markers are being explored and some of them are thought to be suitable for the clinical setting. In this review, we focus on novel biomarkers of endothelial dysfunction, particularly endothelial microparticles, endocan, and endoglin, and discuss whether they fulfill the criteria to be applied in clinical practice.

This work presents a new methodology for the classification and substitution of power transformers in substations. The paper proposes the use of the operational vulnerability indicator, which consists of two groups of criteria, technical condition and operational condition. This indicator allows identifying which power transformers from a set of substations have priority for substitution, considering technical-operational information available in the substations. The technical condition is composed by the parallelism index, reserve transformer availability, nominal power and transformation ratio. Through criteria such as the parallelism index developed for this work, it is possible to identify the percentage of the load that is assured by a transformer in parallel at the moment of a contingency. The operational condition representing the physical situation of the power transformer, typically found in the literature as health index. It assesses factors such as deterioration of the cellulose paper that makes up the insulation and oil, age of the equipment and loading factor, resulting in a life expectancy for the power transformer. The operational vulnerability indicator can be used as an important guide for the strategic planning of the resource application of electric power companies. The methodology is verified through a case study involving real data from 7 substations and 39 power transformers, belonging to a Brazilian electricity company. In the validation of the method, the effectiveness of the proposed method is compared with the ranking obtained through the traditional health index.

As there are different types of energy storage systems (ESS), it is important to have a tool that determines the best alternative to be installed in the distribution systems. This study presents a methodology for optimal determination of size, type and site of ESS in distribution systems with distributed generation (DG). The methodology uses a genetic algorithm and a power flow calculated by the Electric Power Research Institute software OPENDSS. For the optimal ESS charge and discharge management uses a non-linear optimisation model that has as objective an energy cost and loss reduction. In addition, the methodology makes an energy management of the system by limiting the reverse flow with a load shifting process and a cost penalty. Solar and wind power are considered as DG modelled in Homer. Then, a genetic algorithm is used to select the size, type and site of the ESS, considering different lifecycles and costs. This methodology is tested in the IEEE 123 nodes system simulated and adapted in the OPENDSS and the formulation is implemented in MATLAB via COM interface. Finally, results of the methodology are presented and discussed.

Background Clostridium difficile is the main cause of healthcare-associated diarrhoea. Its incidence, severity and relapse rates increased over the past two decades. Aim To study epidemiologic characteristics and treatment of Clostridium difficile infection (CDI) and compare with a previous cohort from the same hospital. Method Retrospective analysis of clinical records of CDI diagnosed from 2010 to 2015 and comparison with data from 2004 to 2009. Results 259 cases were diagnosed, compared to 83 in 2004–2009. There was no difference in mean annual incidence (8.66 versus 7.11 per 1000 patients; p = .116), but a dramatic increase was observed in 2009/2010 (peak incidence: 21.63 cases per 1000 admissions). Females were more affected (61.4% versus 69.9%; p = .177). Median age was 80 and 83 (p = .097). We observed an increase in median number of antibiotics previously used (2 versus 3; p = .147) and in community-associated CDI (6% versus 19.7%; p = .003). There was a continued increase in the use of carbapenems and quinolones until 2010 and a high percentage of refractory cases in 2010. Female gender (p = .043), long-term care facility (LTCF) residency (p = .022) and a higher number of previous antibiotics (median of 3; p = .025) were independent predictors for refractory and recurrent CDI. Conclusions CDI incidence achieved a peak in 2009/2010 coinciding with the introduction of alcohol-based hand products, increase in quinolone and carbapenem prescription and a possible outbreak of an epidemic strain. Female gender, LTCF residency and exposure to three or more antibiotics are risk factors for refractory and recurrent CDI. We emphasize the need to restrict use of large spectrum antibiotics.

Background: Obesity is a multifactorial disease that is strongly associated to other metabolic disorders, such as insulin resistance and type 2 diabetes. Bariatric surgery is nowadays considered the most effective treatment of morbid obesity. The role of insulin resistance (IR) in weight loss after bariatric surgery is highly unknown. Aim: To evaluate the association between Insulin Resistance (IR) and percentage of excess weight loss (EWL%) one, two, three and four years after bariatric surgery in patients with morbid obesity. Methods: Retrospective longitudinal study in patients with morbid obesity followed in our centre between January 2010 and July 2018 were included. Patients were excluded if they had diabetes. We evaluated baseline Homeostatic Model Assessment of IR (HOMA-IR), Homeostatic Model Assessment of β-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index (QUICKI) and Matsuda and DeFronzo index, and performed a linear regression concerning each year’s EWL%. Results: After applying the exclusion criteria, 1723 patients were included in this analysis. The logarithm of HOMA-beta was negatively associated with EWL% at second-, third- and fourth-years post-surgery (β=-1.04 [-1.82 to -0.26], p Conclusion: IR at baseline seems to be associated to long term weight loss, explicitly after the first year post bariatric surgery.

Introduction: Bariatric surgery (BS) is an effective therapeutic approach for obese patients. It is associated with important gastrointestinal anatomic changes, predisposing these subjects to altered nutrient absorption that impact phosphocalcium metabolism. This study aims to clarify the prevalence of secondary hyperparathyroidism (SHPT) and its predictors in patients submitted to BS. Methods: Retrospective unicentric study of 1431 obese patients who underwent metabolic surgery between January/2010 and June/2017 and who were followed for, at least, a year. In this group, 185 subjects were submitted to laparoscopic adjustable gastric banding (LAGB), 830 underwent Roux-en-Y gastric bypass (RYGB) and 416 sleeve gastrectomy (SG). Data comprising 4 years of follow-up were available for 333 patients. We compared the clinical and analytical characteristics of patients with and without secondary hyperparathyroidism (considering SHPT a PTH˃69pg/mL), taking also into account the type of surgery. A multiple logistic regression was performed to study the predictors of SHPT after BS. Results: The overall prevalence of SHPT before surgery was 24.9%, 11.2% one year after surgery and 21.3% four years after surgery. At 12 months after surgery, LAGB had the highest prevalence of patients with SHPT (19.4%, N=36), RYGB had 12.8% (N=274) and SG 5.3% (N=131). At 48 months after surgery, RYGB had the highest prevalence of SHPT (27.0%, N=222), LAGB had 13.2% (N=53) and SG 6.9% (N=58). Multi-variate logistic analysis showed that increased body mass index and age, decreased levels of vitamin D and RYGB were independent predictors of SHPT one year after surgery. The only independent predictor of SHPT four years after surgery was RYGB. Conclusion: The prevalence of SHPT is considerably higher before and four years after BS than 1 year after surgery. This fact raises some questions about the efficacy of the implemented follow-up plans of vitamin D supplementation on the long term, mainly among patients submitted to RYGB.

This paper presents a new methodology to define a priority scale for maintenance actions in substations, based on the development of a Composite Risk Index (CRI) associated with each device. Two auxiliary indices are built: Basic Condition (BC) and Operating Condition (OC), representing the physical and functional characteristics of the equipment that can compromise their performance and contribute to the occurrence of failures. Their evaluation is helped by a Technical Capacity Index (TCI), which evaluates how much the equipment has been affected by wear and tear, in the assessment of the Basic Condition, and the classification of the equipment defects by degrees of severity, in the assessment of the Operating Condition. Two cascading Fuzzy Inference Systems of the Mandani type are used, the first in defining the BC, and the second to obtain the equipment CRI denoting maintenance priority, which may then be used in planning maintenance actions. The methodology is verified through an SF6 circuit breaker CRI assessment, and its priority scale for maintenance planning. The method for evaluating the SF6 circuit breakers reliability is validated through a comparison with a statistical approach, using real data collected from equipment installed in Eletrobras Eletronorte Transmission System, in Rondonia, Amazon region of Brazil.

Background: Hypothyroidism and hyperthyroidism are associated with marked changes in cardiac structure and function. However, the association of thyroid function within the normal range with cardiac structure and function in the general population remains uncertain. Methods: Eight hundred thirty-five subjects aged ≥45 years from the EPIPorto cohort (evaluation between 2006 and 2008) were cross-sectionally analyzed. We excluded participants with TSH, free T4 (FT4), or free T3 (FT3) outside of the reference range or with self-reported cardiovascular or thyroid disease. Cardiac structure and function were evaluated by echocardiography. We used linear regression models unadjusted and adjusted for sex and age (model 1), and sex, age, BMI, diabetes, hypertension, and smoking (model 2). Nonlinear associations were assessed using restricted cubic splines. Results: The mean age was 61.5 years (SD 10.5); 61.1% of the patients were women. In the adjusted model 2, heart rate was positively associated with FT3; diastolic blood pressure was positively associated with TSH; LV end-diastolic and end-systolic volumes were inversely associated with TSH, and ejection fraction was nonlinearly associated with FT3, with higher ejection fractions near the limits of the reference range. Left ventricle (LV) posterior wall thickness was nonlinearly associated with FT4 in the adjusted model 1, with a greater thickness near the limits of the reference range. Regarding diastolic function, no significant associations were observed in adjusted models. Conclusions: Thyroid function within the reference range was associated with heart rate, blood pressure, cardiac structure, and function. Increasing thyroid function (lower TSH, higher FT4, or higher FT3) was associated with a higher heart rate, a lower diastolic blood pressure, and larger LV volumes. LV wall thickness and ejection fraction had a U-shaped association with thyroid hormones. This work was supported by the DOCnet project (NORTE-01-0145-FEDER-000003), supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and the NETDIAMOND project (POCI-01-0145-FEDER-016385), supported by European Structural and Investment Funds, Lisbon’s Regional Operational Program 2020, and national funds from the Portuguese Foundation for Science and Technology – both projects through the Cardiovascular Research Center (UnIC, FCT 51/94) – and by the Portuguese Foundation for Science and Technology (grant POCI/SAU-ESP/61492/2004) and the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862, ref. info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/DTP/04750/2013/PT).