Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airway. Current treatment options (long acting β-adrenoceptor agonists and glucocorticosteroids) are ...not optimal as they are only effective in certain patient groups and safety concerns exist regarding both compound classes. Therefore, novel bronchodilator and anti-inflammatory strategies are being pursued. Prostaglandin E2 (PGE2) is an arachidonic acid-derived eicosanoid produced by the lung which acts on four different G-protein coupled receptors (EP1-4) to cause an array of beneficial and deleterious effects. The aim of this study was to identify the EP receptor mediating the anti-inflammatory actions of PGE2 in the lung using a range of cell-based assays and in vivo models.
It was demonstrated in three distinct model systems (innate stimulus, lipopolysaccharide (LPS); allergic response, ovalbumin (OVA); inhaled pollutant, cigarette smoke) that mice missing functional EP4 (Ptger4(-/-)) receptors had higher levels of airway inflammation, suggesting that endogenous PGE2 was suppressing inflammation via EP4 receptor activation. Cell-based assay systems (murine and human monocytes/alveolar macrophages) demonstrated that PGE2 inhibited cytokine release from LPS-stimulated cells and that this was mimicked by an EP4 (but not EP1-3) receptor agonist and inhibited by an EP4 receptor antagonist. The anti-inflammatory effect occurred at the transcriptional level and was via the adenylyl cyclase/cAMP/ cAMP-dependent protein kinase (PKA) axis.
This study demonstrates that EP4 receptor activation is responsible for the anti-inflammatory activity of PGE2 in a range of disease relevant models and, as such, could represent a novel therapeutic target for chronic airway inflammatory conditions.
We present a novel and simple experimental method called physical human interactive guidance to study human-planned grasping. Instead of studying how the human uses his/her own biological hand or how ...a human teleoperates a robot hand in a grasping task, the method involves a human interacting physically with a robot arm and hand, carefully moving and guiding the robot into the grasping pose, while the robot's configuration is recorded. Analysis of the grasps from this simple method has produced two interesting results. First, the grasps produced by this method perform better than grasps generated through a state-of-the-art automated grasp planner. Second, this method when combined with a detailed statistical analysis using a variety of grasp measures (physics-based heuristics considered critical for a good grasp) offered insights into how the human grasping method is similar or different from automated grasping synthesis techniques. Specifically, data from the physical human interactive guidance method showed that the human-planned grasping method provides grasps that are similar to grasps from a state-of-the-art automated grasp planner, but differed in one key aspect. The robot wrists were aligned with the object's principal axes in the human-planned grasps (termed low skewness in this paper), while the automated grasps used arbitrary wrist orientation. Preliminary tests show that grasps with low skewness were significantly more robust than grasps with high skewness (77-93%). We conclude with a detailed discussion of how the physical human interactive guidance method relates to existing methods to extract the human principles for physical interaction.
Most research in psychiatry on extremism focuses on the question whether there is a connection between extremism and psychiatric diagnoses. In addition, practitioners are increasingly asked to take ...part in programs aimed at preventing and countering violent extremism by assessing risk for radicalization. However, an issue that remains largely unaddressed is that the rise of the far right in many countries during the last years poses a challenge for psychiatric services as working with right-wing patients can be a source of conflict for practitioners and patients alike. In this article, we assert that the narrow conceptual scope on psychological vulnerabilities and the practical focus on risk assessment contribute to processes of psychiatrization and limit the scope of research on right-wing extremism in psychiatry. By giving a brief overview of social research into right-wing extremism, the article argues that right wing beliefs should not be conceptualized as an expression of psychological vulnerabilities but rather as attempts to deal with conflict-laden social reality. Thus, a shift of perspective in psychiatric research on extremism is needed. On a conceptional level, the scope needs to be broadened to grasp the interplay of individual and social factors in radicalization with sufficient complexity. On a practical level, it is necessary to further investigate challenges for practitioners and institutions working with right-wing extremist patients.
Epigenome-modifying tools in asthma Brook, Peter O; Perry, Mark M; Adcock, Ian M ...
Epigenomics,
09/2015, Volume:
7, Issue:
6
Journal Article
Peer reviewed
Open access
Asthma is a chronic disease which causes recurrent breathlessness affecting 300 million people worldwide of whom 250,000 die annually. The epigenome is a set of heritable modifications and tags that ...affect the genome without changing the intrinsic DNA sequence. These marks include DNA methylation, modifications to histone proteins around which DNA is wrapped and expression of noncoding RNA. Alterations in all of these processes have been reported in patients with asthma. In some cases these differences are linked to disease severity and susceptibility and may account for the limited value of genetic studies in asthma. Animal models of asthma suggest that epigenetic modifications and processes are linked to asthma and may be tractable targets for therapeutic intervention.
The Oxford Handbook of Pain Management is an essential resource for all clinicians involved in the management of pain. It brings together the information necessary to provide a truly biopsychosocial ...approach to the care of patients in pain, and helps the practitioner define the most appropriate therapy for individual conditions.
Abstract Systems engineering's evolutionary trajectory has been far from linear, and its future direction is uncertain. We present an assessment and vision of how SE might evolve to enduringly be ...impactful and relevant, despite growing complexity and radical technological change. We discuss how SE started out focused on achieving technical objectives, then drifted towards a more process and methodology focus, and is now responding to calls to return to its roots under the banner of “attaining elegant solutions to complex problems.” We discuss how SE has always been a transdiscipline, although it was not always so recognized, and how SE is now increasingly recognizing and valuing its transdisciplinary nature. We present our view that the future of SE as an impactful and relevant engineering discipline lies in the strengthening of its transdisciplinarity and an increased focus on attaining elegant solutions to complex problems. We present a framework for understanding the nature of SE and the way in which it evolves in terms of its principles, methods and purposes. We show that SE is informed by, and informs many disciplines and social institutions in a dynamic ecology of discovery, achievement and vision. Lastly, we discuss the value of this framework, and show how it can serve as a basis for developing a common understanding of the value and potential of SE, and support institutions such as INCOSE as they engage in the wider social agenda of building a better and more sustainable world.
ABSTRACT The future value of systems engineering may well be measured by its contribution to INCOSE's vision of “a better world through a systems approach.” To stay relevant, systems engineering must ...expand its scope beyond the technical realm by addressing today's most pressing and complex problems, which span technical, social, and ecological domains. This paper builds on our previous work on the evolving architecture of the systems engineering discipline, detailing how it can maintain its value by effectively engaging in eco‐socio‐technical challenges. We propose collaborative strategies with other disciplines to enhance and broaden its foundational base, which will be crucial for realizing its potential as a transdisciplinary field in an increasingly complex world.
ABSTRACT Systems engineering has numerous guiding propositions scattered across various publications and classified under different schema, leading to confusion and inconsistency. This paper presents ...a framework for understanding the origin and evolution of any guiding proposition and developing such a guiding proposition into a principle to meet the challenges of Industry 4.0 and Society 5.0. We argue that following this process will enhance the elegance and transdisciplinary value of systems engineering principles and aid in solving complex problems.
ABSTRACT In an increasingly complex landscape of advanced technologies, the question of how systems engineering can retain its relevance is more pertinent than ever. Originating with a pragmatic ...focus on achieving technical objectives, systems engineering has shifted towards process and methodology. We argue, however, that it's time for this discipline to return to its roots and embrace its nature as a transdiscipline. Transdisciplinarity is not just a characteristic of systems engineering; it's necessary for devising elegant solutions to today's complex challenges. In this article, we present a comprehensive framework around the nature of systems engineering, detailing its principles, methods, and purposes. This framework demonstrates how systems engineering is linked to numerous disciplines and social institutions, showcasing its multifaceted impact. By understanding and using this framework as a lens on the discipline, we can foster a common recognition of systems engineering's value, ensuring its continued significance in a rapidly evolving world.
As the Story Goes Brook, Peter
Scenario (Cork),
07/2018, Volume:
XII, Issue:
2
Journal Article
Peer reviewed
Open access
In the rubric Texts around Theatre (TaT) we present various perspectives on theatre – historical and contemporary, intercultural and culture-specific, unexpectedly weird, unusually suspenseful, ...disturbedly gripping, fascinatingly enigmatic etc. Through the following story renowned theatre director Peter Brook reminds us that what happens on the theatre stage has to be of interest to everyone in the audience, and he leaves us with the question: How can this be achieved? God, seeing how desperately bored everyone was on the seventh day of creation, racked his overstretched imagination to find something more to add to the completeness he had just conceived. Suddenly his inspiration burst even beyond his own limitless bounds and he saw a further aspect of reality: its possibility to imitate itself. So he invented theatre. He called his angels together and announced this in the following terms, which are still contained in an ancient Sanskrit document. “The theatre will be the field in which people can learn to understand the sacred mysteries of the universe. And at the same time,” he added with deceptive casualness, “it will be a comfort to the drunkard and to the lonely.”The angels were very excited and could hardly wait for there to be ...
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