Magnetic tracking of gastrointestinal motility.

OBJECTIVE: Capsule-based methods for assessment of gastrointestinal (GI) motility have seen great improvements in recent decades. The most recent development is the electromagnetic Motilis 3D-Transit system (3D-Transit). The aim of this paper is to review and discuss the development and technical properties of magnetic tracking of GI motility. APPROACH: We performed a comprehensive literature review on magnetic tracking in GI research. MAIN RESULTS: The Motility Tracking System was the first capsule based magnetic system to be used in GI motility research. However, the potential of the system was hampered by its stationary and hospitalizing nature. This led to the development of the electromagnetic Motilis 3D-Transit system. The 3D-Transit system is a portable system that allows for assessment of both whole gut and regional transit times and contraction patterns in a fully ambulatory setting in the patients' home environment with only minor restrictions on movements. The spatiotemporal resolution of 3D-Transit allows assessment of segmental colonic transit times and permits an analysis of gastric and colonic movements with a degree of detail unrivalled by other ambulatory methods, such as the Wireless Motility Capsule. Recently, robust normative data on 3D-Transit have been published. SIGNIFICANCE: This review provides a current perspective on the use of capsule-based magnetic tracking systems in GI research and how they represent a potentially valuable clinical resource for GI physicians and in GI research

Tangled Nature: A model of emergent structure and temporal mode among co-evolving agents

Understanding systems level behaviour of many interacting agents is challenging in various ways, here we'll focus on the how the interaction between components can lead to hierarchical structures with different types of dynamics, or causations, at different levels. We use the Tangled Nature model to discuss the co-evolutionary aspects connecting the microscopic level of the individual to the macroscopic systems level. At the microscopic level the individual agent may undergo evolutionary changes due to mutations of strategies. The micro-dynamics always run at a constant rate. Nevertheless, the system's level dynamics exhibit a completely different type of intermittent abrupt dynamics where major upheavals keep throwing the system between meta-stable configurations. These dramatic transitions are described by a log-Poisson time statistics. The long time effect is a collectively adapted of the ecological network. We discuss the ecological and macroevolutionary consequences of the adaptive dynamics and briefly describe work using the Tangled Nature framework to analyse problems in economics, sociology, innovation and sustainabilityComment: Invited contribution to Focus on Complexity in European Journal of Physics. 25 page, 1 figur

Technology Cards : a design game for navigating in a future of digital technologies

Digitalisation has had a game-changing effect on society—but how will future changes unfold? In this paper, we introduce the Technology Cards—a novel dialogue-based design game that enables users to explore the impact of multiple technologies on their future business. We review 14 card-based design games that focus on emerging technologies or futures thinking and identify an unmet need for design games that will help business managers navigate in a digital future. We describe the iterative development of the Technology Cards, including their testing in 17 Tech Session workshops with 257 participants from 40 private and public sector organisations. The findings reveal that the Technology Cards are “instruments of inquiry” that aid users in a) framing current challenges, b) imagining how multiple technologies affect the future, c) identifying synergies between technologies, and d) facilitating constructive dialogue. We discuss the importance of involving non-technology-savvy stakeholders in envisioning digital futures and creating design tools to help stakeholders grasp the implications of technology. The paper contributes to practice through a detailed description of the design game development process and lessons learned in this process through its use in industrial practice, as well as agenda-setting impacts on the business strategies of the participating organisations. The paper contributes to research by demonstrating how a design game helps stakeholders anticipate the impacts of new technologies on the future of their business

Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury.

BACKGROUND: New evidence shows that high density lipoproteins (HDL) have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL) offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion injury (IRI). However, basic rHDL composition is limited to apolipoprotein AI (apoAI) and phospholipids; addition of bioactive compound may enhance its beneficial effects. OBJECTIVE: The aim of this study was to investigate the role of rHDL in post-ischemic model, and to analyze the potential impact of sphingosine-1-phosphate (S1P) in rHDL formulations. METHODS AND RESULTS: The impact of HDL on IRI was investigated using complementary in vivo, ex vivo and in vitro IRI models. Acute post-ischemic treatment with native HDL significantly reduced infarct size and cell death in the ex vivo, isolated heart (Langendorff) model and the in vivo model (-48%, p<0.01). Treatment with rHDL of basic formulation (apoAI + phospholipids) had a non-significant impact on cell death in vitro and on the infarct size ex vivo and in vivo. In contrast, rHDL containing S1P had a highly significant, protective influence ex vivo, and in vivo (-50%, p<0.01). This impact was comparable with the effects observed with native HDL. Pro-survival signaling proteins, Akt, STAT3 and ERK1/2 were similarly activated by HDL and rHDL containing S1P both in vitro (isolated cardiomyocytes) and in vivo. CONCLUSION: HDL afford protection against IRI in a clinically relevant model (post-ischemia). rHDL is significantly protective if supplemented with S1P. The protective impact of HDL appears to target directly the cardiomyocyte

Decreased PGC1-α levels and increased apoptotic protein signaling are associated with the maladaptive cardiac hypertrophy in hyperthyroidism

Hyperthyroidism can lead to the activation of proteins which are associated with inflammation, apoptosis, hypertrophy, and heart failure. This study aimed to explore the inflammatory and apoptotic proteins involved in the hyperthyroidism-induced cardiac hypertrophy establishment. Male Wistar rats were divided into control and hyperthyroid (12 mg/L L-thyroxine, in drinking water for 28 days) groups. The expression of inflammatory and apoptotic signaling proteins was quantified in the left ventricle by Western blot. Hyperthyroidism was confirmed by evaluation of T3 and T4 levels, as well as cardiac hypertrophy development. There was no change in the expression of HSP70, HIF1-a, TNF-a, MyD88, p-NFjB, NFjB, p-p38, and p38. Reduced expression of p53 and PGC1-a was associated with increased TLR4 and decreased IL-10 expression. Decreased Bcl-2 expression and increased Bax/Bcl-2 ratio were also observed. The results suggest that reduced PGC1-a and IL-10, and elevated TLR4 proteins expression could be involved with the diminished mitochondrial biogenesis and anti-inflammatory response, as well as cell death signaling, in the establishment of hyperthyroidism-induced maladaptive cardiac hypertrophy

Team Reasoning and Collective Intentionality

Different versions of the idea that individualism about agency is the root of standard game theoretical puzzles have been defended by Regan 1980, Bacharach (Research in Economics 53: 117–147, 1999), Hurley (Behavioral and Brain Sciences 26: 264–265, 2003), Sugden (Philosophical Explorations 6(3):165–181, 2003), and Tuomela 2013, among others. While collectivistic game theorists like Michael Bacharach provide formal frameworks designed to avert some of the standard dilemmas, philosophers of collective action like Raimo Tuomela aim at substantive accounts of collective action that may explain how agents overcoming such social dilemmas would be motivated. This paper focuses on the conditions on collective action and intention that need to be fulfilled for Bacharach’s “team reasoning” to occur. Two influential approaches to collective action are related to the idea of team reasoning: Michael Bratman’s theory of shared intention and Raimo Tuomela’s theory of a we-mode of intending. I argue that neither captures the “agency transformation” that team reasoning requires. That might be an acceptable conclusion for Bratman but more problematic for Tuomela, who claims that Bacharach’s results support his theory. I sketch an alternative framework in which the perspectival element that is required for team reasoning - the ‘we-perspective’ - can be understood and functionally characterized in relation to the traditional distinction between mode and content of intentional states. I claim that the latter understanding of a collective perspective provides the right kind of philosophical background for team reasoning, and I discuss some implications in relation to Tuomela’s assumption that switching between individual and collective perspectives can be a matter of rational choice

Nordic Walking and chronic low back pain: design of a randomized clinical trial

BACKGROUND: Low Back Pain is a major public health problem all over the western world. Active approaches including exercise in the treatment of low back pain results in better outcomes for patients, but it is not known exactly which types of back exercises are most beneficial or whether general physical activity provide similar benefits. Nordic Walking is a popular and fast growing type of exercise in Northern Europe. Initial studies have demonstrated that persons performing Nordic Walking are able to exercise longer and harder compared to normal walking thereby increasing their cardiovascular metabolism. Until now no studies have been performed to investigate whether Nordic Walking has beneficial effects in relation to low back pain. The primary aim of this study is to investigate whether supervised Nordic Walking can reduce pain and improve function in a population of chronic low back pain patients when compared to unsupervised Nordic Walking and advice to stay active. In addition we investigate whether there is an increase in the cardiovascular metabolism in persons performing supervised Nordic Walking compared to persons who are advised to stay active. Finally, we investigate whether there is a difference in compliance between persons receiving supervised Nordic Walking and persons doing unsupervised Nordic Walking. METHODS: One hundred and fifty patients with low back pain for at least eight weeks and referred to a specialized secondary sector outpatient back pain clinic are included in the study. After completion of the standard back centre treatment patients are randomized into one of three groups: A) Nordic Walking twice a week for eight weeks under supervision of a specially trained instructor; B) Unsupervised Nordic Walking for eight weeks after one training session with an instructor; C) A one hour motivational talk including advice to stay active. Outcome measures are pain, function, overall health, cardiovascular ability and activity level. RESULTS: No results available at this point. DISCUSSION: This study will investigate the effect of Nordic Walking on pain and function in a population of people with chronic LBP. TRIAL REGISTRATION: registration # NCT0020982

Automated Non-Sterile Pharmacy Compounding: A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets.

Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination, and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from eight countries in Europe utilized a novel automated dosing approach inspired by 3D printing for the compounding of non-sterile propranolol hydrochloride tablets. CuraBlend <sup>®</sup> excipient base, a GMP-manufactured excipient base (pharma-ink) intended for automated compounding applications, was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in four different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from Phase 1 to Phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this automated and quality controlled compounding approach, extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies

Highly efficient separation of actinides from lanthanides by a phenanthroline-derived bis-triazine ligand

The synthesis, lanthanide complexation, and solvent ex- traction of actinide(III) and lanthanide(III) radiotracers from nitric acid solutions by a phenanthroline-derived quadridentate bis-triazine ligand are described. The ligand separates Am(III) and Cm(III) from the lanthanides with remarkably high efficiency, high selectivity, and fast extraction kinetics compared to its 2,2'-bipyridine counterpart. Structures of the 1:2 bis-complexes of the ligand with Eu(III) and Yb(III) were elucidated by X-ray crystallography and force field calculations, respec-tively. The Eu(III) bis-complex is the first 1:2 bis-complex of a quadridentate bis-triazine ligand to be characterized by crystallography. The faster rates of extraction were verified by kinetics measurements using the rotating membrane cell technique in several diluents. The improved kinetics of metal ion extraction are related to the higher surface activity of the ligand at the phase interface. The improvement in the ligand's properties on replacing the bipyridine unit with a phenanthroline unit far exceeds what was anticipated based on ligand design alone