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Current Therapeutics in Primary Sclerosing Cholangitis

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1267-1281页

作者： Natassia Tan John Lubel William Kemp stuart Roberts Ammar Majeed Department of Gastroenterology and Hepatology Alfred HealthCentral Clinical SchoolMonash UniversityMelbourneAustralia

Primary sclerosing cholangitis(PSC)is an orphan,cholestatic liver disease that is characterized by inflammatory biliary strictures with variable progression to end-stage liver *** pathophysiology is poorly *** biliary inflammation is likely driven by immune dysregulation,gut dysbiosis,and environmental exposures resulting in gutliver crosstalk and bile acid metabolism *** is no proven medical therapy that alters disease progression in PSC,with the commonly prescribed ursodeoxycholic acid being shown to improve liver biochemistry at low-moderate doses(15–23 mg/kg/day)but not alter transplant-free survival or liver-related *** transplantation is the only option for patients who develop end-stage liver disease or refractory complications of *** and antifibrotic agents have not proven to be effective,but there is promise for manipulation of the gut microbiome with fecal microbiota transplantation and *** acid manipulation via alternate synthetic bile acids such as norursodeoxycholic acid,or interaction at a transcriptional level via nuclear receptor agonists and fibrates have shown potential in phase II trials in PSC with several leading to larger phase III *** view of the enhanced malignancy risk,statins,and aspirin show potential for reducing the risk of colorectal cancer and cholangiocarcinoma in PSC *** patients who develop clinically relevant strictures with cholestatic symptoms and worsening liver function,balloon dilatation is safer compared with biliary stent insertion with equivalent clinical efficacy.

关键词： Primary sclerosing cholangitis Bile acid Microbiome 24-Norursodeoxycholic acid Farnesoid X receptor agonists Liver transplant

Satellite remote sensing of grasslands:from observation to management

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Journal of Plant Ecology 2016年第6期9卷 649-671页

作者： Iftikhar Ali Fiona Cawkwell Edward Dwyer Brian Barrett stuart Green Department of Geography University College CorkCorkIreland Spatial Analysis Unit TeagascDublinIreland EurOcean-European Centre for Information on Marine Science and Technology LisbonPortugal School of Geographical and Earth Sciences University of GlasgowGlasgowUK

Aims Grasslands are the world’s most extensive terrestrial ecosystem,and are a major feed source for *** increasing demand for meat and other dairy products in a sustainable manner is a big *** a field scale,Global Positioning System and ground-based sensor technologies provide promising tools for grassland and herd management with high *** the growth in availability of spaceborne remote sensing data,it is therefore important to revisit the relevant methods and applications that can exploit this *** this article,we have reviewed the(i)current status of grassland monitoring/observation methods and applications based on satellite remote sensing data,(ii)the technological and methodological developments to retrieve different grassland biophysical parameters and management characteristics(***,grazing intensity)and(iii)identified the key remaining challenges and some new upcoming trends for future *** Findings The retrieval of grassland biophysical parameters have evolved in recent years from classical regression analysis to more complex,efficient and robust modeling approaches,driven by satellite data,and are likely to continue to be the most robust method for deriving grassland information,however these require more high quality calibration and validation *** found that the hypertemporal satellite data are widely used for time series generation,and particularly to overcome cloud contamination issues,but the current low spatial resolution of these instruments precludes their use for field-scale application in many *** trend may change with the current rise in launch of satellite constellations,such as RapidEye,Sentinel-2 and even the microsatellites such as those operated by Skybox *** imagery has not been widely used for grassland applications,and a better understanding of the backscatter behaviour from different phenological stages is needed for more reliable products i

关键词： remote sensing agricultural grassland grassland biomass pasture management grazing intensity

Pharmacologic rationale for treatments of peritoneal surface malignancy from colorectal cancer

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World Journal of Gastrointestinal Oncology 2010年第1期2卷 19-30页

作者： PaulH Sugarbaker Kurt Vander Speeten O Anthony stuart Washington Cancer Institute Washington Hospital Center Department of Surgical Oncology Ziekenhuis Oost-Limburg Schiepse Bos 6

The peritoneal surfaces of the abdomen and pelvis are important sites for the dissemination of gastrointestinal and gynecologic malignancy. Transcoelomic dissemination of cancer cells gives rise to carcinomatosis, which, without special treatment, is a fatal manifestation of these diseases. To treat peritoneal carcinomatosis, cytoreductive surgery removes gross disease plus perioperative intraperitoneal and perioperative intravenous chemotherapy eradicates microscopic residual disease and chemical compatibilities. Chemotherapy agents are administered either by the intraperitoneal or intravenous route, based on their pharmacologic properties. A peritoneal-plasma barrier, which retards the clearance of high molecular weight chemotherapy from the peritoneal cavity, results in a large exposure of small cancer nodules on abdominal and pelvic surfaces. Tissue penetration of the intraperitoneal chemotherapy is facilitated by moderate hyperthermia (41-42℃). Targeting of intravenous chemotherapy to the peritoneal surface is facilitated by the intraperitoneal heat. A constant dose of chemotherapy agent and volume of carrier solution, based on body surface area, allows prediction of systemic drug exposure and systemic toxicity. Timing of the hyperthermic chemotherapy as a scheduled part of the surgical procedure to uniformly expose all peritoneal surfaces is crucial to success.

关键词： Intraperitoneal chemotherapy 5-fluorouracil Doxorubicin Mitomycin C Peritoneal-plasma barrier Appendiceal cancer Colorectal cancer Peritoneal mesothelioma Ovarian cancer

The Australian approach to geospatial capabilities;positioning,earth observation,infrastructure and analytics:issues,trends and perspectives

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Geo-Spatial Information Science 2017年第2期20卷 109-125页

作者： Peter Woodgate Isabel Coppa Suelynn Choy stuart Phinn Lesley Arnold Matt Duckham Australia and New Zealand Cooperative Research Centre for Spatial Information MelbourneAustralia School of Science RMIT UniversityMelbourneAustralia Remote Sensing Research Centre University of QueenslandBrisbaneAustralia Australia and New Zealand Cooperative Research Centre for Spatial Information PerthAustralia

This paper examines the current state of three of the key areas of geospatial science in Australia:positioning;earth observation(EO);and spatial *** paper discusses the limitations and challenges that will shape the development of these three areas of geospatial science over the next decade and then profiles what each may look like in about ***’s national positioning infrastructure plan is guiding the development of a nation-wide,sub decimeter,real-time,outdoor positioning capability based on multi-GNSS and in particular the emerging precise point positioning−real-time kinematic(PPP-RTK)*** positioning systems including the ground-based Locata system,location-based indoor systems,and beacons,among others are also *** importance of the underpinning role of a next generation dynamic datum is *** development of Australia’s first EO strategy is described along with the key national needs of the products of remote *** development of massive on-line multi-decadal geospatial imagery data stores and processing engines for co-registered stacks of continuous base-line satellite imagery are ***,perspectives on the evolution of a future spatial knowledge infrastructure(SKI)emerging from today’s traditional spatial data infrastructures(SDIs)are provided together with discussion of the growing importance of geospatial analytics for transforming whole supply chains.

关键词： Australia geospatial Information positioning earth observation remote sensing spatial knowledge infrastructure(SKI) trends enablers

Forewordto the Special Issue on Nanomanufacturing and Atomic& Close-to-Atomic Scale Manufacturing (ACSM)

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Nanomanufacturing and Metrology 2022年第3期5卷 189-190页

作者： Nan Yu stuart Reid Rebecca Cheung Vasileios Koutsos Institute for Materials and Processes The University of EdinburghEdinburgh EH89FBUK SUPA Department of Biomedical Engineering The University of StrathclydeGlasgow G11QEUK Institute for Integrated Micro and Nano Systems The University of EdinburghEdinburgh EH89FBUK

Nanomanufacturing(NM),developed over the past three decades,bridges nanosciencediscoveries tonanotechnology products by scaled-up,reliable,and cost-effective manufacturing materials,structures,devices,and systems at the nanoscale(1-100 nm).At this scale,physical and chemical properties of the materials and tools have been dominated by classical Newtonian mechanics,although quantum confinementeffects become *** of top-down and bottom-up approaches were developed,including nanomechanical machining,nanolithography,energy beam machining,deposition and etching,nanoprinting,nano assembly,nano replication,etc.[1].These techniques enabled a range of applications from medical imaging and renewable energy to sensor devices and quantum computing.

关键词： bridges printing machining

A global invasion by the thrip,Frankliniella occidentalis:Current virus vector status and its management

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Insect Science 2020年第4期27卷 626-645页

作者： Zhen He Jing-Fei Guo stuart RReitz Zhong-Ren Lei Sheng-Yong Wu State Key Laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijingChina School of Horticulture and Plant Protection Yangzhou UniversityYangzhouJiangsu ProvinceChina Malheur Experiment Station Oregon State UniversityOntarioORUSA

Western flower thrip,Frankliniella occidentalis(Pergande),is among the most economically important agricultural pests globally,attacking a wide range of vegetable and horticultural *** addition to causing extensive crop damage,the species is notorious for vectoring destructive plant viruses,mainly belonging to the genera Orthotospovirus,*** and *** infected by orthotospoviruses,thrips can remain virulent throughout their lifespan and continue transmitting viruses to host plants when and wherever they *** irruptive viral outbreaks in crops will permanently disrupt functional integrated pest management systems,and typically require a remedial treatment involving insecticides,contributing to further development of insecticide *** mitigate against this continuing cycle,the most effective management is early and comprehensive surveillance of the pest species and recognition of plant viruses in the *** review provides information on the pest status of ***,discusses the current global status of the viruses vectored by this thrip species,examines the mechanisms involved in transmitting virus-induced diseases by thrips,and reviews different management strategies,highlighting the potential management tactics developed for various cropping *** early surveillance and the utilization of potential methods for control of both F occidentalis and viruses are proposed.

关键词： global distribution integrated pest management invasion thrips viruses transmission

Electrophysiological assessment of primary cortical neurons genetically engineered using iron oxide nanoparticles

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Nano Research 2017年第8期10卷 2881-2890页

作者： Michael G. Evans Arwa Al-Shakli stuart I. Jenkins Divya M. Chari School of Life Sciences Keele University Keele Staffordshire ST5 5BG UK Institute for Science and Technology in Medicine Keele University Keele Staffordshire ST5 5BG UK

The development of safe technologies to genetically modify neurons is of great interest in regenerative neurology, for both translational and basic science applications. Such approaches have conventionally been heavily reliant on viral transduction methods, which have safety and production limitations. Magnetofection （magnet-assisted gene transfer using iron oxide nanoparticles as vectors） has emerged as a highly promising non-viral alternative for safe and reproducible genetic modification of neurons. Despite the high potential of this technology, there is an important gap in our knowledge of the safety of this approach, namely, whether it alters neuronal function in adverse ways, such as by altering neuronal excitability and signaling. We have investigated the effects of magnetofection in primary cortical neurons by examining neuronal excitability using the whole cell patch clamp technique. We found no evidence that magnetofection alters the voltage-dependent sodium and potassium ionic currents that underpin excitability. Our study provides important new data supporting magnetofection as a safe technology for bioengineering of neuronal cell populations.

关键词： transfection magnetic nanoparticle green fluorescent protein (GFP) whole-cell patch clamp fluorescence microscopy

On the Mechanism of the Seasonal Variability of SST in the Tropical Indian Ocean

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Advances in Atmospheric Sciences 2005年第3期22卷 451-462页

作者：胡瑞金刘秦玉孟祥凤 J.stuart GODFREY Physical Oceanography Laboratory and Ocean-Atmosphere Interaction and Climate LaboratoryOcean University of China Qingdao 266003 Physical Oceanography Laboratory and Ocean-Atmosphere Interaction and Climate LaboratoryOcean University of China Qingdao 266003 CSIRO Division of Marine Research GPO Box 1538HobartTasmaniaAustralia

A general form of an equation that 'explicitly' diagnoses SST change is derived. All other equations in wide use are its special case. Combining with the data from an ocean general circulation model (MOM2) with an integration of 10 years (1987-1996), the relative importances of various processes that determine seasonal variations of SST in the tropical Indian Ocean are compared mainly for January, April, July and October. The main results are as follows. (1) The net surface heat flux is the most important factor affecting SST over the Arabian Sea, the Bay of Bengal and the region south of the equator in January; in April, its influence covers almost the whole region studied; whereas in July and October, this term shows significance only in the regions south of 10°S and north of the equator, respectively. (2) The horizontal advection dominates in the East African-Arabian coast and the region around the equator in January and July; in October, the region is located south of 10°S. (3) The entrainment is significant only in a narrow band centered on 10°S in April and the coastal region around the Arabian Sea and the equator in July. (4) As for SST, it decreases in January and July but increases in April and October in the Arabian Sea and the Bay of Bengal, showing a (asymmetrical) semiannual variability; by contrast, the SST in the region south of the equator has an annual variability, decreasing in April and July and increasing in October and January.

关键词： new equation SST seasonal variation mechanism tropical Indian Ocean

Macrophage polarization in response to wear particles in vitro

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Cellular & Molecular Immunology 2013年第6期10卷 471-482页

作者： Joseph K Antonios Zhenyu Yao Chenguang Li Allison J Rao stuart B Goodman Orthopaedic Research Laboratories Department of Orthopaedic Surgery Stanford University School of Medicine Stanford CA USA

Total joint replacement is a highly successful surgical procedure for treatment of patients with disabling arthritis and joint dysfunction. However, over time, with high levels of activity and usage of the joint, implant wear particles are generated from the articulating surfaces. These wear particles can lead to activation of an inflammatory reaction, and subsequent bone resorption around the implant （periprosthetic osteolysis）. Cells of the monocyte/macrophage lineage orchestrate this chronic inflammatory response, which is dominated by a pro-inflammatory （M 1） macrophage phenotype rather than an anti-inflammatory pro-tissue healing （M2） macrophage phenotype. While it has been shown that interleukin-4 （IL-4） selectively polarizes macrophages towards an M2 anti-inflammatory phenotype which promotes bone healing, rather than inflammation, little is known about the time course in which this occurs or conditions in which repolarization through I L-4 is most effective. The goal of this work was to study the time course of murine macrophage polarization and cytokine release in response to challenge with combinations of polymethyl methacrylate （PMMA） particles, lipopolysaccharide （LPS） and IL-4 in vitro. Treatment of particle-challenged monocyte/macrophages with IL-4 led to an initial suppression of pro-inflammatory cytokines and inducible nitric oxide synthase （iNOS） production and subsequent polarization into an M2 anti-inflammatory phenotype. This result was optimized when IL-4 was delivered before PMMA particle challenge, to an M 1 phenotype rather than to uncommitted （MO） macrophages. The effects of this polarization were sustained over a 5-day time course. Polarization of M1 macrophages into an M2 phenotype may be a strategy to mitigate wear particle associated periprosthetic osteolysis.

关键词： IL-4 macrophage polarization osteolysis PMMA particles total joint replacement