Transformations of Logic Programs on Infinite Lists

We consider an extension of logic programs, called \omega-programs, that can be used to define predicates over infinite lists. \omega-programs allow us to specify properties of the infinite behavior of reactive systems and, in general, properties of infinite sequences of events. The semantics of \omega-programs is an extension of the perfect model semantics. We present variants of the familiar unfold/fold rules which can be used for transforming \omega-programs. We show that these new rules are correct, that is, their application preserves the perfect model semantics. Then we outline a general methodology based on program transformation for verifying properties of \omega-programs. We demonstrate the power of our transformation-based verification methodology by proving some properties of Buechi automata and \omega-regular languages.Comment: 37 pages, including the appendix with proofs. This is an extended version of a paper published in Theory and Practice of Logic Programming, see belo

The central role of exploration in designing business concepts and strategy

Design thinking is described as a combination of thinking and acting that leads to new solution possibilities for design problems. Though traditionally linked to the design of objects and services, it can be applied to organizational processes as well. This paper examines design thinking in developing a new business, focusing on the business concept and strategy formation in the start-up phase of the company. How and what elements of design thinking are manifested in the process of designing a business concept and forming a strategy? What is the importance of these elements in this process? The results reveal the experimental and iterative nature of developing the business concept and strategy. In addition, these organizational processes were strongly influenced by the product offering, stakeholders, and environment that the company operated in. While the results highlighted the importance of emergence, they also illustrated a need for structure and planning, thus reminding of the need of balancing between the two. Overall, the results suggest that many of the fundamental elements of design thinking are found in the development process of a company.Peer reviewe

Framing activities and the co-evolvement of products and operations in new ventures

New ventures need to simultaneously develop both their first offering and the operations of the venture itself. This paper extends the notion of problem-solution co-evolvement from product design to venture design, presenting results from four new Finnish ventures in the midst of creating their first offering market-ready. Based on qualitative analysis of interviews of the entrepreneur teams of these ventures, it is suggested that differences in how the venture idea is initially approached translates into different types of co-evolvement between the offering and the operations of the new ventures. In two of the companies, the product frame had been collaboratively created and remained relatively stable. Development activities within product, business model and working practices did not require large changes in the other arenas. In contrast, the product frame was shifting in the two other ventures, and the co- evolvement of the product problem and solutions had major implications for the business model and operations, and vice versa. The entrepreneurs in these companies would have seemingly benefited from having more structured systematic micro-level working practices to balance the variance in the offering and operations. By conceptually linking venture formation to co-evolvement resulting from the initial frame of development efforts, the study serves to strengthen the link between product development and entrepreneurship research.Peer reviewe

Usefulness of regional right ventricular and right atrial strain for prediction of early and late right ventricular failure following a left ventricular assist device implant: A machine learning approach

Background: Identifying candidates for left ventricular assist device surgery at risk of right ventricular failure remains difficult. The aim was to identify the most accurate predictors of right ventricular failure among clinical, biological, and imaging markers, assessed by agreement of different supervised machine learning algorithms. Methods: Seventy-four patients, referred to HeartWare left ventricular assist device since 2010 in two Italian centers, were recruited. Biomarkers, right ventricular standard, and strain echocardiography, as well as cath-lab measures, were compared among patients who did not develop right ventricular failure (N = 56), those with acute–right ventricular failure (N = 8, 11%) or chronic–right ventricular failure (N = 10, 14%). Logistic regression, penalized logistic regression, linear support vector machines, and naïve Bayes algorithms with leave-one-out validation were used to evaluate the efficiency of any combination of three collected variables in an “all-subsets” approach. Results: Michigan risk score combined with central venous pressure assessed invasively and apical longitudinal systolic strain of the right ventricular–free wall were the most significant predictors of acute–right ventricular failure (maximum receiver operating characteristic–area under the curve = 0.95, 95% confidence interval = 0.91–1.00, by the naïve Bayes), while the right ventricular–free wall systolic strain of the middle segment, right atrial strain (QRS-synced), and tricuspid annular plane systolic excursion were the most significant predictors of Chronic-RVF (receiver operating characteristic–area under the curve = 0.97, 95% confidence interval = 0.91–1.00, according to naïve Bayes). Conclusion: Apical right ventricular strain as well as right atrial strain provides complementary information, both critical to predict acute–right ventricular failure and chronic–right ventricular failure, respectively

Thirty years of evidence on the efficacy of drug treatments for chronic heart failure with reduced ejection fraction: A network meta-analysis

Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor–neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction

Prototyping in practice – Paths and partners for testing novel industrial product and service ideas

Prototyping is a core activity in developing new products, processes, and organisations alike. This paper describes the prototyping activities of 31 engineering design professionals in a high-technology industrial company, examining the distribution of different types of activities across different phases of development based on thematic interviews. Examining 62 prototyping and testing pathways, we found that most prototyping paths started with the practitioners’ own activities, which was also more likely to lead to paths with more prototyping steps than if the first prototyping activity took place with a stakeholder. Overall, the paths were short, indicating a lack of iteration. Both internal and external stakeholders were involved in collaborative prototyping. This collaboration was enabled by personal and unit level relationships, and different stakeholders were involved in different phases of development. Taken together, our results suggest that practitioner attention in prototyping may focus on latter development phases and demonstrate less iteration than what literature might suggest, with opportunities for prototyping highly dependent on personal networks in the high-technology context in the absence of flexible prototyping budgets

The place of vericiguat in the landscape of treatment for heart failure with reduced ejection fraction

The significant morbidity and mortality associated with heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF) justify the search for novel therapeutic agents. The nitric oxide (NO)–soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in the regulation of cardiovascular function. This pathway is disrupted in HF resulting in decreased protection against myocardial injury. The sGC activator cinaciguat increases cGMP levels by direct, NO-independent activation of sGC, and may be particularly effective in conditions of increased oxidative stress and endothelial dysfunction, and then reduced NO levels, but this comes at the expense of a greater risk of hypotension. Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, and then exert a more physiological action. The phase 3 VICTORIA trial found that vericiguat is safe and effective in patients with HFrEF and recent HF decompensation. Therefore, adding vericiguat may be considered in individual patients with HFrEF, particularly those at higher risk of HF hospitalization; the efficacy of the sacubitril/valsartan-vericiguat combination in HFrEF is currently unknown

The use of pulse-compression thermography for detecting defects in paintings

Interest in the conservation of paintings grows year by year. Their periodic inspection is essential for their conservation over the time. Thermographic non-destructive inspection is one technique useful for paintings, but it is essential to be able to detect buried defects while minimising the level of thermal stimulus. This paper describes a pulse-compression infrared thermography technique whereby defect detection is optimized while minimising the rise in temperature. To accomplish this task, LED lamps driven by a coded waveform based on a linear frequency modulated chirp signal have been used on paintings on both a wooden panel and a canvas layer. These specimens contained artificially fabricated defects. Although the physical condition of each painting was different, the experimental results show that the proposed signal processing procedure is able to detect defects using a low temperature contrast

How cardiologists can manage excess body weight and related cardiovascular risk. An expert opinion

Obesity is an important independent cardiovascular (CV) risk factor and a chronic inflammatory disease related to the development of insulin resistance, type 2 diabetes, dyslipidaemia, coronary artery disease, hypertension, heart failure, atrial fibrillation and obstructive sleep apnoea. Body Mass Index (BMI) values >27 kg/m2 are associated with an exponential increase in the risk for Major Adverse Cardiac Events (MACE). On the other hand, weight reduction can significantly reduce metabolic, CV and oncological risk. Orlistat, bupropion/naltrexone, liraglutide and semaglutide, combined with lifestyle changes, have proven to be effective in weight loss; the last two have been tested in randomized clinical trials (RCTs) with CV outcomes only in diabetic patients, and not in obese patients. To fill a fundamental gap of knowledge, the SELECT trial on patients with obesity and CV disease treated with semaglutide is ongoing, aiming at MACE as the primary endpoint. The battle against the social and clinical stigma towards obesity must be counteracted by promoting an awareness that elevates obesity to a complex chronic disease. Several actions should be implemented to improve the management of obesity, and cardiologists have a key role for achieving a global approach to patients with excess weight also through the correct implementation of available treatment strategies

Safety and efficacy of the partial adenosine A1 receptor agonist neladenoson bialanate in patients with chronic heart failure with reduced ejection fraction:a phase IIb, randomized, double-blind, placebo-controlled trial

Aims Neladenoson bialanate is a partial adenosine A1 receptor agonist with demonstrated beneficial effects on cardiac function in animal models. We aimed to assess the dose-response effect of neladenoson bialanate on cardiac structure and function, clinical outcome, and safety in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods and results PANTHEON was a dose-finding, phase IIb, randomized, double-blind, placebo-controlled trial conducted in 92 centres in 11 countries including 462 patients with chronic HFrEF, randomized to once daily oral dose of neladenoson bialanate (5, 10, 20, 30, and 40 mg) or placebo. The primary endpoints were change from baseline to 20 weeks in left ventricular ejection fraction (LVEF) (echocardiography) and in N-terminal pro-B-type natriuretic peptide (NT-proBNP). Mean age of the patients was 67 years, 17% were female, mean LVEF was 28%, mean NT-proBNP was 2085 ng/L. After 20 weeks of treatment, there was no dose-effect of neladenoson bialanate on changes in NT-proBNP or LVEF (primary endpoints). No effect of neladenoson bialanate was found on left ventricular volumes, high-sensitivity troponin T, or cardiovascular mortality, HF hospitalization, and urgent visits for HF (secondary endpoints). There was a dose-dependent increase in creatinine and cystatin C, and a dose-dependent decrease in estimated glomerular filtration rate and heart rate. Conclusions In patients with chronic HFrEF, treatment with neladenoson bialanate was not associated with dose-dependent favourable effects on cardiac structure and function, cardiac risk markers, or clinical outcome but was associated with a dose-dependent decrease in renal function. Clinical Trial Registration: identifier NCT02992288