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Despite the improving imaging techniques, it remains challenging to produce magnetic resonance (MR) imaging fingerprints depicting severity of acute ischemia. The aim of this study was to evaluate the potential of the overall high-field 1 H MR Spectroscopy (1 H-MRS) neurochemical profile as a metabolic signature for acute ischemia severity in rodent brains. We modeled global ischemia with one-stage 4-vessel-occlusion (4VO) in rats. Vascular structures were assessed immediately by magnetic resonance angiography. The neurochemical responses in the bilateral cortex were measured 1 h after stroke onset by 1 H-MRS. Then we used Partial-Least-Squares discriminant analysis on the overall neurochemical profiles to seek metabolic signatures for ischemic severity subgroups. This approach was further tested on neurochemical profiles of mouse striatum 1 h after permanent middle cerebral artery occlusion, where vascular blood flow was monitored by laser Doppler. Magnetic resonance angiography identified successful 4VO from controls and incomplete global ischemia (e.g., 3VO). 1 H-MR spectra of rat cortex after 4VO showed a specific metabolic pattern, distinct from that of respective controls and rats with 3VO. Partial-Least-Squares discriminant analysis on the overall neurochemical profiles revealed metabolic signatures of acute ischemia that may be extended to mice after permanent middle cerebral artery occlusion. Fingerprinting severity of acute ischemia using neurochemical information may improve MR diagnosis in stroke patients.

Assisted reproductive technology (ART) has been using increasingly over the years as infertility treatment globally among women of different ages since the first baby was born as a result of in vitro fertilization in the UK in 1978. Despite this diffusion, the success rate of assisted reproductive technology is relatively low. The main reasons are poor quality of embryos and eggs, age of the woman, small uterine cavity, immune system disorders and genetic factors such as chromosomal alterations. ART procedures are associated with risk for mothers and infants (e.g., miscarriage, premature delivery, low birth weight infants, and long-term disability among infants). Furthermore, since these treatments are highly expensive and time-consuming, their repetition is not affordable for most infertile couples. An adequate design of a decision support system and its capability to support ART outcome prediction can help infertile couples. In this work, we propose an approach to predict the outcome of ART procedures, based on the identification of the situation of the infertile couple (mainly in terms of physiological parameters), and to provide the doctor with a set of feedback aimed at supporting the doctor’s decision to start or continue ART process. A prototypical system is proposed to preliminary verify the feasibility and utility of the approach.

Sertraline, a selective serotonin reuptake inhibitor, is commonly prescribed for the treatment of moderate-to-severe depression. We report a case of a 36-year-old male taking sertraline for 7 weeks prior to developing a dry cough, pleuritic chest pain, hypoxia and diffuse ground-glass attenuation with mediastinal lymphadenopathy on imaging. No infectious aetiology was identified and multiple causes of pneumonitis excluded. Sertraline-induced interstitial lung disease was subsequently diagnosed. Sertraline was discontinued and treatment commenced with a weaning course of oral dexamethasone, leading to a rapid reduction in oxygen requirement and successful discharge. Given the increasing prevalence of selective serotonin reuptake inhibitor use, it is vital that medical professionals can recognize sertraline as a rare, albeit potentially life-threatening, cause of interstitial lung disease—allowing for the rapid diagnosis and appropriate management of this condition.

The correct allocation of human resources is of utmost importance for any kind of enterprise and organization. Many approaches have been defined so far to support team formation leveraging on different techniques, from knowledge engineering to operational research and computational intelligence. Unfortunately, these approaches are often specifically thought for large organizations owning the right set of technological assets and human resources able to manage and use these approaches. In this work, we propose an original approach to team formation, namely the KnowMIS-Team approach, specifically designed for knowledge-intensive small and medium enterprises. This is a lightweight hybrid approach that combines three different techniques: a knowledge-driven technique for finding the most competent team for a given project based on a lightweight semantic model of knowledge, skills and attitudes; a top-down, leader-selected approach wherein the competent members selected in the previous phase can propose their candidate teams; a bottom-up fuzzy consensus-based mechanism in which the employees of the organization can express their preferences on the candidate teams. A conceptual architecture of an intelligent system implementing the approach is also presented. The KnowMIS-Team approach is the overall result of many years of experience in team formation and management for a research center and embeds all the best practices therein adopted, and it has been experimented in the same center and in other university spin-offs for many years, contributing to the realization of successful projects.

Background Temporal artery biopsy (TAB) is considered the gold standard for diagnosing Giant Cell Arteritis (GCA). The aim of this study was to compare the functional utility of the 2016 revised ACR (rACR) criteria against the original ACR criteria with a view to avoiding TABs in select groups. We also aimed to investigate the temporal relationship of positive biopsies. Methods A retrospective study was conducted of patients undergoing TAB from August 2014 to August 2016, at a DGH. Data collected included patient demographics, history, biochemistry, time to TAB from commencement of steroids and histology. The ACR and the rACR scores and the relative TAB results were analysed using ROC to determine statistical measures of performance. Different score thresholds were applied to propose a clinical tool to be used as an adjunct in the management of suspected GCA. Results and Discussion Forty two TABs were performed during this period of which 10 were males and 32 females. ROC analysis showed significant relationships between both ACR and rACR to TAB result. The AUC for rACR was 0.880 (p Conclusion This study demonstrates the potential value of the rACR criteria and a simple clinical tool is proposed to stratify relevant patients with a view to avoiding unnecessary TAB. Prolonged wait between referral to TAB is also likely to reduce its validity.

Percutaneous endoscopic gastrostomy was first described in 1980 (Gauderer et al, 1980), superseding surgical gastrostomy as a means of providing long-term enteral nutrition. Despite the commonality of this procedure, its associated morbidity and mortality rates are significant, with directly attributable rates of 1:30 and 1:150 respectively. Poor patient selection and poor management are the principal factors contributing to adverse outcomes. The 2004 National Confidential Enquiry into Patient Outcome and Death recorded that 19% of percutaneous endoscopic gastrostomy procedures performed were ‘futile or not indicated at all’. This article provides a practical approach to avoiding and treating complications associated with percutaneous endoscopic gastrostomy feeding.

Real time adaptation of marketing strategies and actions in smart commerce environments, such as shops and malls, is an open challenge with a tremendous impact for the survival of traditional retailers. A main issue of traditional retailers, in comparison with e-commerce shops, is that they usually rely on analysis of point-of-sales data after purchase and/or focus groups and self-reports where customers are asked about what they like or want. This techniques, even if solid grounded to marketing and consumer research, do not allow analysis of data and decision making in real time, i.e., when consumers are inside a shop. In this paper we present our results on the definition and validation of a decision support system for real time decision making on discount and promotion actions. The system makes decision on the basis of recognition and assessment of situations of interest for the consumers, modelled with heuristics related to behavioural economics results. We validated our solution in a virtual shop simulated with V-REP, demonstrating its capabilities to adapt with regards to the changes in the environments, in terms of sensors, people, products, and different situations.

AIMS: In the adult heart, Notch signalling regulates the response to injury. Notch inhibition leads to increased cardiomyocyte apoptosis, and exacerbates the development of cardiac hypertrophy and fibrosis. The role of Notch in the mesenchymal stromal cell fraction, which contains cardiac fibroblasts and cardiac precursor cells, is, however, largely unknown. In the present study, we evaluate, therefore, whether forced activation of the Notch pathway in mesenchymal stromal cells regulates pathological cardiac remodelling. METHODS AND RESULTS: We generated transgenic mice overexpressing the Notch ligand Jagged1 on the surface of cardiomyocytes to activate Notch signalling in adjacent myocyte and non-myocyte cells. In neonatal transgenic mice, activated Notch sustained cardiac precursor and myocyte proliferation after birth, and led to increased numbers of cardiac myocytes in adult mice. In the adult heart under pressure overload, Notch inhibited the development of cardiomyocyte hypertrophy and transforming growth factor-β/connective tissue growth factor-mediated cardiac fibrosis. Most importantly, Notch activation in the stressed adult heart reduced the proliferation of myofibroblasts and stimulated the expansion of stem cell antigen-1-positive cells, and in particular of Nkx2.5-positive cardiac precursor cells. CONCLUSIONS: We conclude that Notch is pivotal in the healing process of the injured heart. Specifically, Notch regulates key cellular mechanisms in the mesenchymal stromal cell population, and thereby controls the balance between fibrotic and regenerative repair in the adult heart. Altogether, these findings indicate that Notch represents a unique therapeutic target for inducing regeneration in the adult heart via mobilization of cardiac precursor cells.

Temporal artery biopsy is the gold standard for Giant Cell Arteritis. However, timing of biopsy in crucial. Delay leads to false negative results.

In the western world, heart failure, which develops for instance secondary to myocardial infarction, is a major cause of death. Usually, the heart adapts to a primary insult through cardiomyocyte hypertrophy. The emerging concept, however, is that cardiac stem cells contribute to cardiomyocyte renewal in the myocardium. The rate of replacement is low in the normal heart, and is thought to be higher during the response to injury. In this context, the present work aims at generating a transgenic model of inducible cardiomyocyte death to evaluate the degree of cardiac stem cell mobilization during the adaptation of the heart to stress. Therefore, we produced transgenic mice with cardiac-specific overexpression of the human CD25 (hCD25) under control of the a-MHC promoter. This transmembrane protein is inactive in the mouse. However, LMB2, an immunotoxin derived from the Pseudomonas exotoxin directed against hCD25, can be administrated to specifically target hCD25-expressing cardiomyocytes and induce apoptosis. Cardiac-specific expression of hCD25 in transgenics was demonstrated by RT-PCR, Western blot analysis and immunohistochemistry. Administration of LMB2 to neonatal transgenic cardiomyocytes in culture resulted in significant cell death. Surviving cardiomyocytes showed abnormal, star-shaped morphology and disorganized sarcomeric structure. In vivo, administration of LMB2 to neonatal transgenics resulted in increased apoptosis after LMB2 injection and significant mortality. The number of dying mice increased proportionally to the dose of injected LMB2. Surviving transgenic mice sacrificed 3 days after LMB2 administration showed decreased cardiac weight, disorganized cardiac tissue and increased fibrosis. In adult transgenic mice, LMB2 treatment resulted in impaired cardiac function, as shown by echocardiography analysis, and animal death at doses of 300 ng/g and above. Post-mortem analysis revealed necrotic and fibrous cardiac tissues. This model is currently used to induce non-lethal apoptosis in adult animals in view to investigate cardiac precursor recruitment and potential regeneration in the damaged heart.

Open Innovation and Services Science are two distinct paradigms that share some principles 0. While some attempts to investigate open innovation according to a service science perspective exist, there is currently a gap with regards to the analysis of intermediaries of open innovation according to a service science perspective and even more regarding to recent trends about smart service system. This paper aims to fill this gap and, to this purpose, we present two interesting and original results. After an analysis of the key features of Open Innovation Intermediaries, we discuss a characterization of these intermediaries as service systems by mapping their features on the ten fundamental concepts of a service system. Next we propose a new model that goes in the direction of the convergence between service and cognitive system (smart service system) and aims at overcoming some traditional issues of the intermediaries. The new model foresees the distribution of Open Innovation Intermediaries features, enhanced with a set of cognitive assistants to the stakeholders within open innovation processes, and proposes the adoption of responsible innovation frameworks as a base to add right and responsibilities to cognitive assistants.

The Notch signaling pathway is a communication system between adjacent cells, mediated by transmembrane receptors (Notch1-4) and ligands (Jagged1 and 2, Delta-like1, 3, and 4). Notch is essential for the development and homeostasis of several self-renewing organ systems. Notch is also essential in the developing heart, and mutations in Notch genes cause cardiac malformations and congenital heart disease. Recently, using loss-of-function studies, we showed that the Notch1 receptor controlled the response to injury in the adult heart by limiting myocyte hypertrophy, enhancing myocyte survival, promoting precursor proliferation, controlling cardiogenic differentiation, and reducing interstitial fibrosis. In addition, our data suggested that upregulation of Jagged1 expression constituted a primary response in the stressed myocardium, suggesting that this ligand mediated Notch signaling in the postnatal heart. Therefore, to analyze the effects of a chronic Jagged1-induced Notch activation on the cardiac response to stress, we generated transgenic mice overexpressing Jagged1 in cardiomyocytes using the α-myosin heavy chain gene promoter (TGMHCJ1 mice). These mice expressed 100-500 fold Jagged1 mRNA relative to wild-type (WT) controls. The overexpression of Jagged1 on the surface of cardiomyocytes was confirmed by Western blotting and immunofluorescence staining. Consequently, the percentage of cardiac cells with an activated Notch pathway was higher in TGMHCJ1 mice than in WT animals. The expression of the Notch target genes Hes1 and Hey2 was also activated. Echocardiographic analysis under basal conditions revealed an enlargement of the right ventricle (RV) with a diminished left ventricle (LV) mass and chamber size in adults. TGMHCJ1 mice displayed increased juvenile mortality. The severity of the phenotype was dependent on the level of Jagged1 expression. Immunofluorescence analysis revealed myocyte hypertrophy and disarray in the RV of TGMHCJ1 mice whereas, myocytes in the LV were not affected. Moreover, when subjected to transaortic constriction (TAC), TGMHCJ1 mice demonstrated an impaired LV hypertrophic response to pressure overload and reduced cardiac fibrosis. These results indicate that chronic activation of Notch affects differently left and right ventricle integrity under physiological and pathological conditions.