Polypill in cardiovascular disease prevention: recent advances.

Triple therapy with lipid‑lowering, antihypertensive, and antiplatelet agents reduces the risk of recurrent cardiovascular fatal and nonfatal events, cardiovascular mortality, and total mortality in secondary prevention. In real life, however, effective implementation of these optimal treatments both in primary and secondary prevention is low, and thus their contribution to cardiovascular prevention is much lower than it could be, based on research data. One of the main barriers to the adequate implementation of these strategies is low adherence to the elevated number of pills, as adherence is adversely affected by the complexity of the prescribed treatment regimen, and can be considerably improved by treatment simplification. This review updates the findings provided by recent epidemiological and clinical studies favoring a polypill‑based approach to cardiovascular prevention. The increased prevalence of patients with multiple cardiovascular risk factors and comorbidities provides the rationale for a therapeutic strategy based on a combination of drugs against different risk factors in a single pill. Pharmacologic studies have demonstrated that different cardiovascular drugs can be combined in a single pill with no loss of their individual efficacy, and this favors adherence to and persistence of treatment, as well as multiple risk factor control. Recently, a randomized clinical trial SECURE (Secondary Prevention of Cardiovascular Disease in the Elderly) has shown a significant, 30% reduction in cardiovascular events, and a 33% reduction in cardiovascular death in patients after myocardial infarction treated with a polypill, as compared with usual care, thus supporting the polypill use as an integral part of any cardiovascular prevention strategy.S

A free mind cannot be digitally transferred

The digital transfer of the mind to a computer system (i.e., mind uploading) requires representing the mind as a finite sequence of bits (1s and 0s). The classic “stored-program computer” paradigm, in turn, implies the equivalence between program and data, so that the sequence of bits themselves can be interpreted as a program, which will be algorithmically executed in the receiving device. Now, according to a previous proof, on which this paper is based, a computational or algorithmic machine, however complex, cannot be free (in the sense of ‘self-determined’). Consequently, a finite sequence of bits cannot adequately represent a free mind and, therefore, a free mind cannot be digitally transferred, quod erat demonstrandum. The impossibility of making this transfer, as demonstrated here, should be a concern especially for those who wish to achieve it. Since we intend this to be a rigorous demonstration, we must give precise definitions and conditions of validity. The most important part of the paper is devoted to explaining the meaning and reasonableness of these definitions and conditions (for example that being truly free means being self-determined). Special attention is paid, also, to the philosophical implications of the demonstration. Finally, this thesis is distinguished from other closely related issues (such as other possible technological difficulties to “discretize” the mind; or, whether it is possible to transfer the mind from one material support to another one in a non-digital way).This research has received funding from the RESTART project “Continuous Reverse Engineering for Software Product Lines/Ingeniería Inversa Continua para Líneas de Productos de Software” (ref. RTI2018-099915-B-I00, Convocatoria Proyectos de I + D Retos Investigación del Programa Estatal de I + D + i Orientada a los Retos de la Sociedad 2018); MOMEBIA project “Monitorización del Mercado Eléctrico Basada en técnicas de Inteligencia Artificial" (ref. RTC2019-007501-7, Convocatoria de Proyectos de I + D + i «Retos-Colaboración» 2019—Ministerio de Ciencia e Innovación—Agencia Estatal de Investigación); it has also been supported by the Madrid Government (Comunidad de Madrid-Spain) under the Multiannual Agreement with UC3M in the line of Excellence of University Professors (EPUC3M17), and in the context of the V PRICIT (Regional Programme of Research and Technological Innovation)

Machine Ethics: Do Androids Dream of Being Good People?

Is ethics a computable function? Can machines learn ethics like humans do? If teaching consists in no more than programming, training, indoctrinating¿ and if ethics is merely following a code of conduct, then yes, we can teach ethics to algorithmic machines. But if ethics is not merely about following a code of conduct or about imitating the behavior of others, then an approach based on computing outcomes, and on the reduction of ethics to the compilation and application of a set of rules, either a priori or learned, misses the point. Our intention is not to solve the technical problem of machine ethics, but to learn something about human ethics, and its rationality, by reflecting on the ethics that can and should be implemented in machines. Any machine ethics implementation will have to face a number of fundamental or conceptual problems, which in the end refer to philosophical questions, such as: what is a human being (or more generally, what is a worthy being); what is human intentional acting; and how are intentional actions and their consequences morally evaluated. We are convinced that a proper understanding of ethical issues in AI can teach us something valuable about ourselves, and what it means to lead a free and responsible ethical life, that is, being good people beyond merely "following a moral code". In the end we believe that rationality must be seen to involve more than just computing, and that value rationality is beyond numbers. Such an understanding is a required step to recovering a renewed rationality of ethics, one that is urgently needed in our highly technified society.This work has been supported by the Madrid Government (Comunidad de Madrid-Spain) under the terms of the Multi-Annual Agreement with UC3M in the line of Excellence of University Professors (EPUC3M17), and in the context of the V PRICIT (Regional Programme of Research and Technological Innovation). This research has received funding also from the RESTART project – “Continuous Reverse Engineering for Software Product Lines / Ingeniería Inversa Continua para Líneas de Productos de Software” (ref. RTI2018-099915-B-I00, Convocatoria Proyectos de I + D Retos Investigación del Programa Estatal de I + D + i Orientada a los Retos de la Sociedad 2018, grant agreement nº: 412122; and from the CritiRed project – “Elaboración de un modelo predictivo para el desarrollo del pensamiento crítico en el uso de las redes sociales”, Convocatoria Retos de Investigación del Ministerio de Ciencia, Innovación y Universidades (2019–2022), ref. RTI2018-095740-B-I00

Automatic classification of web images as UML static diagrams using machine learning techniques

Our purpose in this research is to develop a method to automatically and efficiently classify web images as Unified Modeling Language (UML) static diagrams, and to produce a computer tool that implements this function. The tool receives a bitmap file (in different formats) as an input and communicates whether the image corresponds to a diagram. For pragmatic reasons, we restricted ourselves to the simplest kinds of diagrams that are more useful for automated software reuse: computer-edited 2D representations of static diagrams. The tool does not require that the images are explicitly or implicitly tagged as UML diagrams. The tool extracts graphical characteristics from each image (such as grayscale histogram, color histogram and elementary geometric forms) and uses a combination of rules to classify it. The rules are obtained with machine learning techniques (rule induction) from a sample of 19,000 web images manually classified by experts. In this work, we do not consider the textual contents of the images. Our tool reaches nearly 95% of agreement with manually classified instances, improving the effectiveness of related research works. Moreover, using a training dataset 15 times bigger, the time required to process each image and extract its graphical features (0.680 s) is seven times lower.This research has received funding from the CRYSTAL project – Critical System Engineering Acceleration (European Union’s Seventh Framework Program, FP7/2007-2013, ARTEMIS Joint Undertaking grant agreement n° 332830); and from the AMASS project – Architecture-driven, Multi-concern and Seamless Assurance and Certification of Cyber-Physical Systems (H2020-ECSEL grant agreement nº 692474; Spain’s MINECO ref. PCIN-2015-262)

Application of machine learning techniques to the flexible assessment and improvement of requirements quality

It is already common to compute quantitative metrics of requirements to assess their quality. However, the risk is to build assessment methods and tools that are both arbitrary and rigid in the parameterization and combination of metrics. Specifically, we show that a linear combination of metrics is insufficient to adequately compute a global measure of quality. In this work, we propose to develop a flexible method to assess and improve the quality of requirements that can be adapted to different contexts, projects, organizations, and quality standards, with a high degree of automation. The domain experts contribute with an initial set of requirements that they have classified according to their quality, and we extract their quality metrics. We then use machine learning techniques to emulate the implicit expert’s quality function. We provide also a procedure to suggest improvements in bad requirements. We compare the obtained rule-based classifiers with different machine learning algorithms, obtaining measurements of effectiveness around 85%. We show as well the appearance of the generated rules and how to interpret them. The method is tailorable to different contexts, different styles to write requirements, and different demands in quality. The whole process of inferring and applying the quality rules adapted to each organization is highly automatedThis research has received funding from the CRYSTAL project–Critical System Engineering Acceleration (European Union’s Seventh Framework Program FP7/2007-2013, ARTEMIS Joint Undertaking grant agreement no 332830); and from the AMASS project–Architecture-driven, Multi-concern and Seamless Assurance and Certification of Cyber-Physical Systems (H2020-ECSEL grant agreement no 692474; Spain’s MINECO ref. PCIN-2015-262)

El Poblament de petits mamífers "(Insectivora i Rodentia)" a Catalunya. Requeriments ambientals i distribució geogràfica

The present paper sets out to analyse the environmental requirements of the small mammals species (insectivores and rodents) of Catalonia and the consequences of these requirements on their distribution throughout the studied territory. Basing on the particular needs of the different species, it is possible to define the following groups: the first, of Mid-European requirements, includes Sorex coronatus, Marmots marmota and Arvicola terrestris, which live in the western Pyrenees; Microtus pyrenaicus, M. nivalis and M. arvalis, found throughout the Pyrenees; and Sorex minutus, S. araneus, Neomys fodiens, Clethrionomys glareolus and M. agrestis, uniformly distributed in the Pyrenees, part of the pre-Pyrenees and in the humid eastern area. Another group is made up of species with Mediterranean requirements: Erinaceus algirus, Neomys anomalus, Suncus etruscus, Crocidura russula, Mus spretus and Microtus duodecimcostatus. Of these, the last four can be considered indicators of strictly Mediterranean conditions. They live in the Mediterranean coastal band, the Central Depression and the western area. There is another group which does not have very strict general environmental requirements, although its presence may be due to particular specific conditions. It comprises: Erinaceus europaeus, Talpa europaea, Sciurus vulgaris, Eliomys quercinus, Glis glis, Apodemus sylvaticus and Arvicola sapidus. Finally, one finds those species whose distribution is determined by man's presence: Rattus rattus, R. norvegicus and Mus musculus. In general, small mammal distribution in Catalonia is related to the physiography, climatic conditions and the dominant type of vegetation

Parental and self-reported dietary and physical activity habits in pre-school children and their socio-economic determinants.

OBJECTIVE: To assess the agreement between self-reported and parent-reported dietary and physical activity habits in children; and to evaluate the socio-economic determinants of healthier habits (Mediterranean diet and physical activity) among children. DESIGN: Cross-sectional analysis of children recruited to a cluster-randomized controlled trial (Program SI!). Information about children's and parents' dietary and physical activity habits was obtained through validated questionnaires (Program SI! questionnaires, Kidmed, Krece Plus and Predimed scores). SETTING: Twenty-four schools in Madrid, Spain. SUBJECTS: Children (n 2062) aged 3-5 years and their parents (n 1949). RESULTS: There was positive agreement between parental- and self-reporting for three of the six children's habits examined. Parents' dietary and physical activity patterns were associated with those of their children. The main determinants of higher scores in children were higher parental age, the mother's scores, Spanish origin and higher awareness of human health (P<0·005). Children from parents with a low educational level had lower odds for scoring positively on items such as using olive oil (OR=0·23; 95 % CI 0·13, 0·41) and not skipping breakfast (OR=0·36; 95 % CI 0·23, 0·55), but higher odds for meeting the recommendations for consuming pulses (OR=1·71; 95 % CI 1·14, 2·55). Other habits being influenced by parental socio-economic status included the consumption of vegetables, fish, nuts, avoidance of fast food, and consumption of bakery products for breakfast. CONCLUSIONS: Children's habits may be influenced by their parents' health awareness and other socio-economic characteristics. These findings suggest that intervention strategies, even in very young children, should also target parents in order to achieve maximum success

Progression of Early Subclinical Atherosclerosis (PESA) Study: JACC Focus Seminar 7/8.

Atherosclerosis starts early in life and progresses silently for decades. Considering atherosclerosis as a "systemic disease" invites the use of noninvasive methodologies to detect disease in various regions before symptoms appear. The PESA-(Progression of Early Subclinical Atherosclerosis) CNIC-SANTANDER study is an ongoing prospective cohort study examining imaging, biological, and behavioral parameters associated with the presence and progression of early subclinical atherosclerosis. Between 2010 and 2014, PESA enrolled 4,184 asymptomatic middle-aged participants who undergo serial 3-yearly follow-up examinations including clinical interviews, lifestyle questionnaires, sampling, and noninvasive imaging assessment of multiterritorial subclinical atherosclerosis (carotids, iliofemorals, aorta, and coronaries). PESA tracks the trajectories of atherosclerosis and associated disorders from early stages to the transition to symptomatic phases. A joint venture between the CNIC and the Santander Bank, PESA is expected to run until at least 2029, and its significant contributions to date are presented in this review paper.The PESA study is funded by the CNIC and Santander Bank. The study has also received funding from the Carlos III Institute of Health (ISCIII, PI15/02019, PI17/00590, and PI20/00819) and the European Regional Development Fund. The CNIC is supported by the ISCIII, the MICIN, and the Pro CNIC Foundation. Dr Ibanez is the recipient of a European Research Council grant MATRIX (ERC-COG-2018-ID: 819775). Dr Andrés is supported by grant PID2019-108489RB-I00 from the Spanish Ministerio de Ciencia e Innovación (MICIN), with cofunding from the European Regional Development Fund/Fondo Europeo de Desarrollo Regional (ERDF/FEDER, “A way to build Europe”). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.S

The CNIC-Polypill reduces recurrent major cardiovascular events in real-life secondary prevention patients in Spain: The NEPTUNO study.

To evaluate the effectiveness of a cardiovascular polypill including aspirin, ramipril and atorvastatin (CNIC-Polypill), on the incidence of recurrent major cardiovascular events (MACE) and risk factor control in patients with established atherosclerotic cardiovascular disease (ASCVD) vs different pharmacological therapeutic strategies. Retrospective, observational study using data from electronic-health records. Patients were distributed into 4 different cohorts: CNIC-Polypill (case cohort) vs 3 control cohorts: same monocomponents taken separately (Monocomponents), equipotent drugs (Equipotent) and other drugs not included in the previous cohorts (Other therapies). Patients were followed for 2 years or until MACE or death. After propensity score matching, a total of 6456 patients (1614 patients per cohort) were analysed. After 2 years, the risk of recurrent MACE was lower in the CNIC-Polypill cohort compared to the control groups (22%; p = 0.017, 25%; p = 0.002, 27%; p = 0.001, higher in the Monocomponents, Equipotent and Other therapies cohorts, respectively). The incremental proportion of patients who achieved blood pressure (BP) and low-density lipoprotein cholesterol (LDLc) control from baseline was higher in the CNIC-Polypill cohort vs control cohorts (BP controlled patients: +12.5% vs + 6.3%; p < 0.05, +2.2%; p < 0.01, +2.4%; p < 0.01, LDLc controlled patients: +10.3% vs + 4.9%; p < 0.001, +5.7%; p < 0.001, +4.9%; p < 0.001, respectively). Medication persistence was higher in patients treated with the CNIC-Polypill (72.1% vs 62.2%, 60.0% and 54.2%, respectively; p < 0.001) at study end. In secondary prevention patients, compared with control groups, treatment with the CNIC-Polypill was associated with significant reductions in the accumulated incidence of recurrent MACE, improved BP and LDLc control rates, and increased medication persistence.FerrerS