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Pharmacological pain management in chronic pancreatitis

World Journal of Gastroenterology 2013年第42期19卷 7292-7301页

作者： Sφren S Olesen Jacob Juel Carina Graversen Yuri Kolesnikov oliver HG wilder-smith Asbjφrn M Drewes MechSense Department of Gastroenterology and HepatologyAalborg University Hospital9000 AalborgDenmark Mech-Sense Department of RadiologyAalborg University Hospital9000 AalborgDenmark Department of Neurorehabilitation Engineering Bernstein Center for Computational NeuroscienceUniversity Medical Center G ttingenGeorg-August UniversityD-37077 GttingenGermany Pain Service Department of OncologyEast Tallinn Central Hospital19086 TallinnEstonia Pain and Nociception Neuroscience Research Group Department of AnaesthesiologyPain and Palliative CareRadboud University Nijmegen Medical Centre6525 NijmegenThe Netherlands Center for Sensory-Motor Interaction Department of Health Science and TechnologyAalborg University9000 AalborgDenmark

Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical *** studies of pancreatic nerves and experimental human pain research have provided evidence that pain processing is abnormal in these patients and in many cases resembles that seen in neuropathic and chronic pain *** important ultimate outcome of such aberrant pain processing is that once the disease has advanced and the pathophysiological processes are firmly established,the generation of pain can become self-perpetuating and independent of the initial peripheral nociceptive ***,the management of pain by traditional methods based on nociceptive deafferentation(e.g.,surgery and visceral nerve blockade)becomes difficult and often *** novel and improved understanding of pain aetiology requires a paradigm shift in pain management of chronic *** mechanism based pain treatments taking into account altered pain processing are likely to increasingly replace invasive therapies targeting the nociceptive source,which should be reserved for special and carefully selected *** this review,we offer an overview of the current available pharmacological options for pain management in chronic *** addition,future options for pain management are discussed with special emphasis on personalized pain medicine and multidisciplinarity.

关键词： Chronic pancreatitis Pain Treatment Pharmacology Analgesics Adjuvant analgesics

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Sensory testing of the human gastrointestinal tract

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World Journal of Gastroenterology 2009年第2期15卷 151-159页

作者： Christina Brock Lars Arendt-Nielsen oliver wilder-smith Asbjφrn Mohr Drewes Mech-Sense Department of Gastroenterology Aalborg Hospital DK-9000 Aalborg Denmark Center for Sensory-Motor Interactions Department of Health Science and Technology Aalborg University DK-9000 Aalborg Denmark Pain and Nociception Research Group Department of Anaesthesiology Radboud University Nijmegen Medical Centrethe Netherlands Mech-Sense Department of Gastro-enterology Aalborg Hospital DK-9000 Aalborg Denmark Author

The objective of this appraisal is to shed light on the various approaches to screen sensory information in the human gut. Understanding and characterization of sensory symptoms in gastrointestinal disorders is poor. Experimental methods allowing the investigator to control stimulus intensity and modality, as well as using validated methods for assessing sensory response have contributed to the understanding of pain mechanisms. Mechanical stimulation based on impedance planimetry allows direct recordings of luminal cross-sectional areas, and combined with ultrasound and magnetic resonance imaging, the contribution of different gut layers can be estimated. Electrical stimulation depolarizes free nerve endings non-selectively. Consequently, the stimulation paradigm （single, train, tetanic） influences the involved sensory nerves. Visual controlled electrical stimulation combines the probes with an endoscopic approach, which allows the investigator to inspect and obtain small biopsies from the stimulation site. Thermal stimulation （cold or warm） activates selectively mucosal receptors, and chemical substances such as acid and capsaicin （either alone or in combination） are used to evoke pain and sensitization. The possibility of multimodal （e.g. mechanical, electrical, thermal and chemical） stimulation in different gut segments has developed visceral pain research. The major advantage is involvement of distinctive receptors, various sensory nerves and different pain pathways mimicking clinical pain that favors investigation of central pain mechanisms involved in allodynia, hyperalgesia and referred pain. As impairment of descending control mechanisms partly underlies the pathogenesis in chronic pain, a cold pressor test that indirectly stimulates such control mechanisms can be added. Hence, the methods undoubtedly represent a major step forward in the future characterization and treatment of patients with various diseases of the gut, which provides knowledge to dinicians

关键词： Endoscopy Intestine Experimental Neurophysiology Pain

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Systematic mechanism-orientated approach to chronic pancreatitis pain

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World Journal of Gastroenterology 2015年第1期21卷 47-59页

作者： Stefan AW Bouwense Marjan de Vries Luuk TW Schreuder Soren S Olesen Jens B Frokjær Asbjorn M Drewes Harry van Goor oliver HG wilder-smith Pain and Nociception Neuroscience Research Group Department of SurgeryRadboud University Medical Center6500HB GelderlandThe Netherlands Department of Gastroenterology and Hepatology and Clinical Medicine Aalborg University Hospital9100 AalborgDenmark Center for Sensory-Motor Interaction Department of Health Science and TechnologyAalborg University9100 AalborgDenmark Department of Anaesthesiology Pain and Palliative MedicineRadboud University Medical Center6500HB GelderlandThe Netherlands

Pain in chronic pancreatitis(CP) shows similarities with other visceral pain syndromes(i.e.,inflammatory bowel disease and esophagitis),which should thus be managed in a similar *** causes of CP pain include increased intrapancreatic pressure,pancreatic inflammation and pancreatic/extrapancreatic ***,CP pain continues to be a major clinical *** is recognized that ongoing pain may induce altered central pain processing,e.g.,central sensitization or pro-nociceptive pain *** this is present conventional pain treatment targeting the nociceptive focus,e.g.,opioid analgesia or surgical/endoscopic intervention,often fails even if technically *** central nervous system pain processing is altered,specific treatment targeting these changes should be instituted(e.g.,gabapentinoids,ketamine or tricyclic antidepressants).Suitable tools are now available to make altered central processing visible,including quantitative sensory testing,electroencephalograpy and(functional) magnetic resonance *** techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain *** present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms *** research should address the circumstances under which central nervous system pain processing changes in CP,and how this is influenced by ongoing nociceptive input and *** we hope to predict which patients are at risk for developing chronic pain or not responding to therapy,leading to improved treatment of chronic pain in CP and other visceral pain disorders.

关键词： Chronic pancreatitis Pain Pain treatment Central sensitization Quantitative sensory testing Electroencephalograpy Magnetic resonance imaging

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Early Warning Systems: Lost in Translation or Late by Definition? A FORIN Approach

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International Journal of Disaster Risk Science 2019年第3期10卷 317-331页

作者： Irasema Alcántara-Ayala Anthony oliver-smith Institute of Geography National Autonomous University of Mexico(UNAM)04510 Mexico CityMexico University of Florida GainesvilleFL 32611USA

Early warning systems(EWSs) are widely considered to be one of the most important mechanisms to prevent disasters around the globe. But as disasters continue to affect countries where EWSs have already been implemented, the striking disaster consequences have led us to reflect on the focus, architecture, and function of the warning systems. Since the 2004 Indian Ocean tsunami there has been a rapid rise in the promotion and use of EWSs to minimize disaster losses and damage. However,few researchers have addressed the question of their acceptability as an adaptive measure to the existing exposure conditions. EWSs are far more linked to emergency response and humanitarian crises and accepted technological interventions as solutions than they are to explicitly advance integrated analysis, disaster risk reduction, and policy making. A major flaw of EWSs is that the term‘‘early’’ has been essentially used in reference to the speed of hazard onset, founded on a physicalist perspective that has encouraged a considerable dependence on *** this article we address the need for a clear understanding of the root causes and risk drivers of disaster risk creation,as advanced in the FORIN(forensic investigation of disasters) approach, as a prerequisite for the development of more articulated EWSs that could contribute to disaster risk reduction through policy making and practice, based on integrated and transdisciplinary management, in the interest of sustainable development, and human welfare and well-being.

关键词： Disaster risk drivers Disaster root causes Early warning systems Forensic disaster investigations FORIN

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Abnormal endogenous pain modulation and somatic and visceral hypersensitivity in female patients with irritable bowel syndrome

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World Journal of Gastroenterology 2007年第27期13卷 3699-3704页

作者： Clive H wilder-smith Joan Robert-Yap Brain-Gut Research Group Gastroenterology Group Practice Berne Switzerland Supported by the Brain-Gut Research Group Berne Switzerland

AIM： To investigate the role of endogenous pain modulatory mechanisms in the central sensitization implicated by the visceral hypersensitivity demonstrated in patients with irritable bowel syndrome （IBS）. Dysfunction of modulatory mechanisms would be expected to also result in changes of somatic sensory function. METHODS： Endogenous pain modulatory mechanisms were assessed using heterotopic stimulation and somatic and visceral sensory testing in IBS. Pain intensities （visual analogue scale, VAS 0-100） during suprathreshold rectal distension with a barostat, cold pressor stimulation of the foot and during both stimuli simultaneously （heterotopic stimulation） were recorded in 40 female patients with IBS and 20 female healthy controls. RESULTS： Rectal hypersensitivity （defined by 95% Cl of controls） was seen in 21 （53%）, somatic hypersensitivity in 22 （55%） and both rectal and somatic hypersensitivity in 14 of these IBS patients. Heterotopic stimulation decreased rectal pain intensity by 6 （-11 to -1） in controls, but increased rectal pain by 2 （-3 to ＋6） in all IBS patients （P 〈 0.05） and by 8 （-2 to ＋19） in IBS patients with somatic and visceral hypersensitivity （P 〈 0.02）. CONCLUSION： A majority of IBS patients had abnormal endogenous pain modulation and somatic hypersensitivity as evidence of central sensitization.

关键词： Diffuse noxious inhibitory controls Endogenous pain modulation Hypersensitivity Irritable Bowel Syndrome Quantitative sensory testing Visceral pain Sensitization

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Chemistry-led investigations into the mode of action of NAMPT activators,resulting in the discovery of non-pyridyl class NAMPT activators

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Acta Pharmaceutica Sinica B 2023年第2期13卷 709-721页

作者： Siyuan Tang Miguel Garzon Sanz oliver smith Andreas Krämer Daniel Egbase Paul W.Caton Stefan Knapp Sam Butterworth Division of Pharmacy and Optometry School of Health SciencesManchester Academic Health Sciences CentreUniversity of ManchesterManchester M139PLUK Structural Genomics Consortium(SGC) 60438 Frankfurt Am MainGermany Buchmann Institute for Life Sciences(BMLS) 60438 Frankfurt Am MainGermany Institut für Pharmazeutische Chemie Goethe University60438 Frankfurt Am MainGermany Frankfurt Cancer Institute(FCI) 60596 Frankfurt Am MainGermany Department of Diabetes School of Cardiovascular and Metabolic Medicine&SciencesFaculty of Life Sciences&MedicineKing's College LondonLondon SE11ULUK

The cofactor nicotinamide adenine dinucleotide(NAD+)plays a key role in a wide range of physiological processes and maintaining or enhancing NAD+levels is an established approach to enhancing healthy ***,several classes of nicotinamide phosphoribosyl transferase(NAMPT)activators have been shown to increase NAD+levels in vitro and in vivo and to demonstrate beneficial effects in animal *** best validated of these compounds are structurally related to known urea-type NAMPT inhibitors,however the basis for the switch from inhibitory activity to activation is not well *** we report an evaluation of the structure activity relationships of NAMPT activators by designing,synthesising and testing compounds from other NAMPT ligand chemotypes and mimetics of putative phosphoribosylated adducts of known *** results of these studies led us to hypothesise that these activators act via a through-water interaction in the NAMPT active site,resulting in the design of the first known urea-class NAMPT activator that does not utilise a pyridine-like warhead,which shows similar or greater activity as a NAMPT activator in biochemical and cellular assays relative to known analogues.

关键词： Nicotinamide phosphoribosyl transferase activator Healthy aging Drug discovery Bioisosteres Medicinal chemistry

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Modelling the test, trace and quarantine strategy to control the COVID-19 epidemic in the state of São Paulo, Brazil

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Infectious Disease Modelling 2021年第1期6卷 46-55页

作者： Marcos Amaku Dimas Tadeu Covas Francisco Antonio Bezerra Coutinho Raymundo Soares Azevedo Neto Claudio Struchiner Annelies wilder-smith Eduardo Massad School of Medicine University of Sao Paulo and LIM01-HCFMUSPSao PauloBrazil Instituto Butantan Sao PauloBrazil School of Applied Mathematics Fundacao Getulio VargasRio de JaneiroBrazil School of Veterinary Medicine University of Sao PauloSao PauloBrazil Department Public Health and Clinical Heidelberg Institute of Global HealthUniversity of HeidelbergGermany Medicine Epidemiology and Global HealthUmeåUniversitySE-90185UmeåSweden Department of Disease Control London School of Hygiene and TropicalMedicineUK

Testing for detecting the infection by SARS-CoV-2 is the bridge between the lockdown and the opening of *** this paper we modelled and simulated a test-trace-andquarantine strategy to control the COVID-19 outbreak in the State of São Paulo,*** State of São Paulo failed to adopt an effective social distancing strategy,reaching at most 59%in late March and started to relax the measures in late June,dropping to 41%in 08 ***,São Paulo relies heavily on a massive testing strategy in the attempt to control the *** alternative strategies combined with economic evaluations were *** strategy included indiscriminately testing the entire population of the State,reaching more than 40 million people at a maximum cost of 2.25 billion USD,that would reduce the total number of cases by the end of 2020 by 90%.The second strategy investigated testing only symptomatic cases and their immediate contacts e this strategy reached a maximum cost of 150 million USD but also reduced the number of cases by 90%.The conclusion is that if the State of São Paulo had decided to adopt the simulated strategy on April the 1st,it would have been possible to reduce the total number of cases by 90%at a cost of 2.25 billion US dollars for the indiscriminate strategy but at a much smaller cost of 125 million US dollars for the selective testing of symptomatic cases and their contacts.

关键词： COVID-19 SARS-CoV-2 Testing Cost-analysis Modelling

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Estimating the size of Aedes aegypti populations from dengue incidence data: Implications for the risk of yellow fever outbreaks

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Infectious Disease Modelling 2017年第4期2卷 441-454页

作者： Eduardo Massad Marcos Amaku Francisco Antonio Bezerra Coutinho Claudio JoséStruchiner Luis Fernandez Lopez Annelies wilder-smith Marcelo Nascimento Burattini School of Medicine University of Sao PauloBrazil London School of Hygiene and Tropical Medicine UK College of Life and Natural Sciences The University of DerbyUK Programme of Scientific Computation Fundação Oswaldo CruzRio de JaneiroBrazil Li Ka Shing Knowledge Institute St Michael's HospitalTorontoCanada Institute of Public Health University of HeidelbergGermany Department Public Health and Clinical Medicine Epidemiology and Global HealthUmeåUniversitySE-90185 UmeåSweden Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore Hospital São Paulo Escola Paulista de MedicinaUniversidade Federal de São PauloSão PauloSPBrazil

In this paper we present a model to estimate the density of aedes mosquitoes in a community affected by *** method consists in fitting a continuous function to the incidence of dengue infections,from which the density of infected mosquitoes is derived *** derivations allow the calculation of the latent and susceptible mosquitoes'densities,the sum of the three equals the total mosquitoes'*** method is illustrated with the case of the risk of urban yellow fever resurgence in dengue infested areas but the same procedures apply for other aedes-transmitted infections like Zika and chikungunya viruses.

关键词： Aedes aegypti Mosquitoes'densities Dengue Zika virus Yellow fever

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E-technology social support programs for autistic children: Can they work?

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World Journal of Psychiatry 2021年第12期11卷 1239-1246页

作者： Natalie G Wall oliver smith Linda E Campbell Carmel Loughland Mark Wallis Frans Henskens Ulrich Schall Centre for Brain and Mental Health Research The University of NewcastleCallaghan 2308NSWAustralia The Brain and Mental Health Research Program Hunter Medical Research InstituteNew Lambton Heights 2305NSWAustralia School of Psychology The University of NewcastleCallaghan 2308NSWAustralia

Autism is a neurodevelopmental condition with associated difficulties that present differently across *** such difficulty is recognizing basic and complex facial *** has previously found that there are many evidence-based support programs available for building non-verbal communication *** programs are frequently administered with a therapist or in a group setting,making them inflexible in *** hosted on e-technology are becoming increasingly popular,with many parents supportive of ***(apps)that are hosted on technology such as iPads or mobile phones allow users to engage in building skills in real-time social settings and own what they are *** technologies are frequently used by autistic children,with apps typically focusing on identifying facial *** at this current time,there are mixed reviews of how to design such programs and what their theoretical backing is,with many studies using a mix of observation and psychological assessments as outcome ***-tracking and electroencephalography are established methodologies that measure neural processing and gaze behaviors while viewing *** better support the field moving forward,objective measures such as these are a way to measure outcomes of apps that are designed for helping children on the spectrum build skills in understanding facial expressions.

关键词： Autism Facial expression recognition Technology Eye-tracking Electroen-cephalography

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Energy shift： decline of easy oil and restructuring of eo-politics

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Frontiers in Energy 2016年第3期10卷 260-267页

作者： oliver R. INDERWILDI David A. KING smith School of Enterprise and the Environment University of OxfordOxford OX1 3QY United Kingdom

This paper critically assesses the geopolitical and geo-economic impact of novel fuel resources on both resource exporters and importers. Presently, very strong political and economic forces drive the utilisation of domestic, unconventional oil and gas recovery in the West as these enhance energy security and ease balance of payment issues. The additional capacity generated by this trend has, supported by other effects such as Saudi Arabia＇s decision to maintain current production, triggered a significant reduction ofoil prices. Consequently, it is now oil exporters that struggle with the balance of payment issues and often these countries base their fiscal budget completely on fossil fuel revenues. In fact, these unconventional resources help turn the tide while oil exporters are now politically significantly weakened due to the increased energy sufficiency of the West. The catch is that the extraction of unconventional types ofoil has many environmental implications. So, internalising the environ- mental externalities have to be considered. This paper, therefore, assesses, next to geopolitics and geo-economics, the environmental implications of this trend.

关键词： energy security climatic change geo-economics geopolitics unconventional resources macroeconomics

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