United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU)

Background:There have been substantial improvements in the management of chronic pancreatitis, leading to the publication of several national guidelines during recent years. In collaboration with United European Gastroenterology, the working group on Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed these European guidelines using an evidence-based approach. Methods: Twelve multidisciplinary review groups performed systematic literature reviews to answer 101 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation system and the answers were assessed by the entire group in a Delphi process online. The review groups presented their recommendations during the 2015 annual meeting of United European Gastroenterology. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting (Test and Evaluation Directorate). After a final round of adjustments based on these comments, a draft version was sent out to external reviewers. Results: The 101 recommendations covered 12 topics related to the clinical management of chronic pancreatitis: aetiology (working party (WP)1), diagnosis of chronic pancreatitis with imaging (WP2 and WP3), diagnosis of pancreatic exocrine insufficiency (WP4), surgery in chronic pancreatitis (WP5), medical therapy (WP6), endoscopic therapy (WP7), treatment of pancreatic pseudocysts (WP8), pancreatic pain (WP9), nutrition and malnutrition (WP10), diabetes mellitus (WP11) and the natural course of the disease and quality of life (WP12). Using the Grading of Recommendations Assessment, Development and Evaluation system, 70 of the 101 (70%) recommendations were rated as strong' and plenary voting revealed strong agreement' for 99 (98%) recommendations. Conclusions:The 2016 HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

Immunosuppression and neurotoxicity: how IDO contributes to pathogenesis of SIV infection

In the thirty years since the discovery of human immunodeficiency virus (HIV) as the causative agent of acquired immune deficiency syndrome (AIDS), the world has witnessed one of the most triumphant advances in modern medicine: the transformation of HIV infection from being a death sentence to being a treatable, chronic condition with the advent of combination antiretroviral therapy (cART). However, as the HIV-infected population ages, the face of the epidemic continues to evolve. For example, HIV-infected individuals have an increased rate and earlier onset of a variety of medical complications, particularly in the central nervous system, compared to their peers. The neurological manifestations include neurocognitive impairments as well as neuropsychological disorders such as depression. Understanding the pathogenic mechanisms that persist with and without cART is a critical step towards improving the lives of the aging, HIV-infected population. The kynurenine pathway of tryptophan catabolism has both immunosuppressive and neurotoxic potential and is therefore uniquely positioned to affect a wide range of comorbidities in HIV/SIV infection. In this dissertation, we examined whether this pathway was elevated to pathogenic levels in the periphery and in the central nervous system of SIV-infected pigtailed macaques, utilizing gas chromatography mass spectrometry for the analysis of pathway metabolites and transcriptional assays for the analysis of pathway enzymes. We found evidence for toxic elevations in kynurenine pathway metabolites in all tissues examined and identified specific kynurenine metabolites in the plasma and CSF as predictive biomarkers of disease in the periphery and in the brain. We also tested the efficacy of two drug therapies, a four-drug combination antiretroviral therapy and the tetracycline derivative minocycline, on attenuation of kynurenine pathway activation in SIV-infected macaques. Results from these drug studies revealed that neither cART nor minocycline was able to normalize kynurenine pathway activation. This dissertation provides insights into several unanswered questions regarding the kynurenine pathway during HIV/SIV infection. Additionally, our findings of kynurenine pathway metabolites as predictive biomarkers of disease may translate into useful prognostic indicators in patients

Parallel visual search and rapid animal detection in natural scenes.

International audienceHuman observers are capable of detecting animals within novel natural scenes with remarkable speed and accuracy. Recent studies found human response times to be as fast as 120 ms in a dual-presentation (2-AFC) setup (H. Kirchner & S. J. Thorpe, 2005). In most previous experiments, pairs of randomly chosen images were presented, frequently from very different contexts (e.g., a zebra in Africa vs. the New York Skyline). Here, we tested the effect of background size and contiguity on human performance by using a new, contiguous background image set. Individual images contained a single animal surrounded by a large, animal-free image area. The image could be positioned and cropped in such a manner that the animal could occur in one of eight evenly spaced positions on an imaginary circle (radius 10-deg visual angle). In the first (8-Choice) experiment, all eight positions were used, whereas in the second (2-Choice) and third (2-Image) experiments, the animals were only presented on the two positions to the left and right of the screen center. In the third experiment, additional rectangular frames were used to mimic the conditions of earlier studies. Average latencies on successful trials differed only slightly between conditions, indicating that the number of possible animal locations within the display does not affect decision latency. Detailed analysis of saccade targets revealed a preference toward both the head and the center of gravity of the target animal, affecting hit ratio, latency, and the number of saccades required to reach the target. These results illustrate that rapid animal detection operates scene-wide and is fast and efficient even when the animals are embedded in their natural backgrounds

Towards the tree automata workbench marbles

Abstract: The conceptual ideas that are intended to become the basis for the tree automata workbench MARBLES 1 are sketched. The goal is to design and implement an extensible system that facilitates experiments with virtually any kind of algorithm on tree automata. Moreover, the system will be released with a library and an application programmer’s interface to make it accessible to anyone who wants to apply tree automata algorithms in research and development

A Novel Analytical Approach to Assessing Sorption of Trace Organic Compounds into Micro- and Nanoplastic Particles

Assessing the sorption of trace organic compounds (TOrCs) into micro- and nanoplastic particles has traditionally been performed using an aqueous phase analysis or solvent extractions from the particle. Using thermal extraction/desorption–gas chromatography/mass spectrometry (TD-Pyr-GC/MS) offers a possibility to analyze the TOrCs directly from the particle without a long sample preparation. In this study, a combination of two analytical methods is demonstrated. First, the aqueous phase is quantified for TOrC concentrations using Gerstel Twister® and TD-GC/MS. Subsequently, the TOrCs on the particles are analyzed. Different polymer types and sizes (polymethyl methacrylate (PMMA), 48 µm; polyethylene (PE), 48 µm; polystyrene (PS), 41 µm; and PS, 78 nm) were analyzed for three selected TOrCs (phenanthrene, triclosan, and α-cypermethrin). The results revealed that, over a period of 48 h, the highest and fastest sorption occurred for PS 78 nm particles. This was confirmed with a theoretical calculation of the particle surface area. It was also shown for the first time that direct quantification of TOrCs from PS 78 nm nanoparticles is possible. Furthermore, in a mixed solute solution, the three selected TOrCs were sorbed onto the particles simultaneously

Organic Contaminants and Interactions with Micro- and Nano-Plastics in the Aqueous Environment: Review of Analytical Methods

Micro- and nanoplastic particles are increasingly seen not only as contaminants themselves, but also as potential vectors for trace organic chemicals (TOrCs) that might sorb onto these particles. An analysis of the sorbed TOrCs can either be performed directly from the particle or TOrCs can be extracted from the particle with a solvent. Another possibility is to analyze the remaining concentration in the aqueous phase by a differential approach. In this review, the focus is on analytical methods that are suitable for identifying and quantifying sorbed TOrCs on micro- and nano-plastics. Specific gas chromatography (GC), liquid chromatography (LC) and ultraviolet-visible spectroscopy (UV-VIS) methods are considered. The respective advantages of each method are explained in detail. In addition, influencing factors for sorption in the first place are being discussed including particle size and shape (especially micro and nanoparticles) and the type of polymer, as well as methods for determining sorption kinetics. Since the particles are not present in the environment in a virgin state, the influence of aging on sorption is also considered

A Frequentist analysis of three right-handed neutrinos with GAMBIT

The extension of the Standard Model by right-handed neutrinos can not only explain the active neutrino masses via the seesaw mechanism, it is also able solve a number of long standing problems in cosmology. Especially, masses below the TeV scale are of particular interest as they can lead to a plethora of signatures in experimental searches. We present the first full frequentist analysis of the extension of the Standard Model by three right-handed neutrinos, with masses between 60 MeV and 500 GeV, using the Global and Modular BSM (beyond the Standard Model) Inference Tool GAMBIT. Our analysis is based on the Casas-Ibarra parametrisation and includes a large range of experimental constraints: active neutrino mixing, indirect constraints from, e.g., electroweak precision observables and lepton universality, and numerous direct searches for right-handed neutrinos. To study their overall effect, we derive combined profile likelihood results for the phenomenologically most relevant parameter projections. Furthermore, we discuss the role of (marginally) statistically preferred regions in the parameter space. Finally, we explore the flavour mixing pattern of the three right-handed neutrinos for different values of the lightest neutrino mass. Our results comprise the most comprehensive assessment of the model with three right-handed neutrinos model below the TeV scale so far, and provide a robust ground for exploring the impact of future constraints or detections.The extension of the Standard Model by right-handed neutrinos can not only explain the active neutrino masses via the seesaw mechanism, it is also able solve a number of long standing problems in cosmology. Especially, masses below the TeV scale are of particular interest as they can lead to a plethora of signatures in experimental searches. We present the first full frequentist analysis of the extension of the Standard Model by three right-handed neutrinos, with masses between 60 MeV and 500 GeV, using the Global and Modular BSM (beyond the Standard Model) Inference Tool GAMBIT. Our analysis is based on the Casas-Ibarra parametrisation and includes a large range of experimental constraints: active neutrino mixing, indirect constraints from, e.g., electroweak precision observables and lepton universality, and numerous direct searches for right-handed neutrinos. To study their overall effect, we derive combined profile likelihood results for the phenomenologically most relevant parameter projections. Furthermore, we discuss the role of (marginally) statistically preferred regions in the parameter space. Finally, we explore the flavour mixing pattern of the three right-handed neutrinos for different values of the lightest neutrino mass. Our results comprise the most comprehensive assessment of the model with three right-handed neutrinos model below the TeV scale so far, and provide a robust ground for exploring the impact of future constraints or detections

Oxycodone:a review of its use in the management of pain

Background: Oxycodone is a strong opioid that acts at mu- and kappa-opioid receptors. It has pharmacological actions similar to strong opioids, but with a specific pharmacologic profile and greater analgesic potency to morphine. The efficacy of oxycodone in managing neuropathic and somatic pain, both of malignant and nonmalignant origin, has been established in a wide range of settings. Scope: This review aims to provide a comprehensive evaluation of oxycodone and its role within clinical settings in order to provide an evidence-based perspective on its use in the clinic. Literature searches using Medline, EMBASE and Cochrane Databases were used to compile data for review. The review provides information on the pharmacokinetics and pharmacodynamics of oxycodone and also profiles established clinical data in neuropathic and somatic pain as well as emerging data to support the use of oxycodone in visceral pain, which may be due to its interaction with kappa-opioid receptors. Oxycodone is available in a range of formulations for oral, intraspinal and parenteral administration. Findings: The prolonged-release form of oxycodone offers a fast onset of analgesia, controlling pain for 12 hours and providing clinically meaningful relief of moderate to severe pain and improving quality of life across a broad spectrum of pain types. Conclusions: Oxycodone provides significant pain relief. It has relevant points of difference from other opioids and as such may be a suitable alternative to morphine

Differences between opioids: pharmacological, experimental, clinical and economical perspectives

Clinical studies comparing the response and side effects of various opioids have not been able to show robust differences between drugs. Hence, recommendations of the regulatory authorities have been driven by costs with a general tendency in many countries to restrict physician's use of opioids to morphine. Although this approach is recognized as cost-effective in most cases there is solid evidence that, on an individual patient basis, opioids are not all equal. Therefore it is important to have an armamentarium of strong analgesics in clinical practice to ensure a personalized approach in patients who do not respond to standard treatment. In this review we highlight differences between opioids in human studies from a pharmacological, experimental, clinical and health economics point of view. We provide evidence that individuals respond differently to opioids, and that general differences between classes of opioids exist. We recommend that this recognition is used to individualize treatment in difficult cases allowing physicians to have a wide range of treatment options. In the end this will reduce pain and side effects, leading to improved quality of life for the patient and reduce the exploding pain related costs