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Recovery rates of combination antibiotic therapy using in vitro microdialysis simulating in vivo conditions

Journal of Pharmaceutical Analysis 2018年第6期8卷 407-412页

作者： Jayesh A.Dhanani Suzanne L.Parker Jeffrey Lipman Steven C.Wallis Jeremy Cohen john fraser Adrian Barnett Michelle Chew Jason A.Roberts Burns Trauma and Critical Care Research Centre The University of Queensland UQ Centre for Clinical Research Department of Intensive Care Medicine Royal Brisbane & Women's Hospital Faculty of Health Queensland University of Technology Critical Care Research Group The University of Queensland Institute of Health and Biomedical Innovation & School of Public Health and Social Work Queensland University of Technology Department of Anaesthesiology and Intensive Care and Department of Medical and Health Sciences Link?ping University School of Pharmacy The University of Queensland Department of Pharmacy Royal Brisbane & Women's Hospital

Microdialysis is a technique used to measure the unbound antibiotic concentration in the interstitial spaces, the target site of action. In vitro recovery studies are essential to calibrating the microdialysis system for in vivo studies. The effect of a combination of antibiotics on recovery into microdialysate requires investigation. In vitro microdialysis recovery studies were conducted on a combination of vancomycin and tobramycin, in a simulated in vivo model. Comparison was made between recoveries for three different concentrations and three different perfusate flow rates. The overall relative recovery for vancomycin was lower than that of tobramycin. For tobramycin, a concentration of 20μg/mL and flow rate of 1.0μL/min had the best recovery. A concentration of 5.0μg/mL and flow rate of 1.0μL/min yielded maximal recovery for vancomycin. Large molecular size and higher protein binding resulted in lower relative recoveries for vancomycin. Perfusate flow rates and drug concentrations affected the relative recovery when a combination of vancomycin and tobramycin was tested. Low perfusate flow rates were associated with higher recovery rates. For combination antibiotic measurement which includes agents that are highly protein bound, in vitro studies performed prior to in vivo studies may ensure the reliable measurement of unbound concentrations.

关键词： Microdialysis Combination antibiotic therapy Relative recovery rate Pharmacokinetics Anti-infectives Protein binding

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The effects of perfluorocarbon dosing strategy on cerebral blood flow when starting partial liquid ventilation: A randomized, controlled, experimental study

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Open Journal of Pediatrics 2012年第3期2卷 197-213页

作者： Mark W. Davies Kimble R. Dunster john F. fraser Paul B. Colditz Department of Paediatrics & Child Health The University of Queensland Brisbane Australia Grantley Stable Neonatal Unit Royal Brisbane and Women’s Hospital Brisbane Australia Medical Engineering Research Facility Queensland University of Technology Brisbane Australia Perinatal Research Centre The University of Queensland Royal Brisbane and Women’s Hospital Brisbane Australia

Introduction: Partial liquid ventilation may benefit the lung disease in preterm neonates but intratracheal instillation of perfluorocarbon increases cerebral blood flow and may cause brain injury. We aimed to determine if the effects of perfluorocarbon administration on cerebral blood flow vary by dose-volume, rate of administration, endotracheal tube portal of entry, or closely targeting PaCO2. Methods: Forty-two dosing events (in eleven rabbits) were randomised to different dosing strategies, including a sham (i.e., placebo/control) dose of air over 20 min, 20 mL/kg of perfluorocarbon slowly over 20 min, 10 mL/kg of perfluorocarbon slowly over 20 min, 10 mL/kg of perfluorocarbon moderately fast over 10 min, 10 mL/kg of perfluorocarbon rapidly over 5 min, 10 mL/kg of perfluorocarbon slowly over 20 min via the endotracheal tube tip lumen (as opposed to the proximal end of the tube used in all other groups), or 10 mL/kg of perfluorocarbon slowly over 20 min whilst targeting a PaCO2 of 45 - 50 mmHg. Blood gases, haemodynamics, cortical cerebral blood flow and carotid flow were recorded continuously for 30 minutes from the start of each dose. Results: Carotid flow increased with 20 mL/kg perfluorocarbon and cortical cerebral blood flow was significantly more variable. Carotid and cortical cerebral blood flow increased using 10 mL/kg or 20 mL/kg with no difference between the two dose-volumes. There was no difference in cerebral blood flow by rate of administration, but carotid blood flow was more variable during slow administration. There were no differences in the increase in cerebral blood flow by portal of entry. If PaCO2 was maintained between 45 - 50 mmHg there was no increase in cerebral blood flow and there was less variable carotid flow. Conclusions: Cerebral blood flow increases with perfluorocarbon dosing. This occurs regardless of the dose-volume of perfluorocarbon. These effects were mitigated by closely targeting PaCO2.

关键词： Cerebral Blood Flow Fluorocarbons Infant Newborn Preterm Partial Liquid Ventilation

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美国玉米带的变迁

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世界农业 1987年第9期 14-17页

作者： john fraser Hart,郭谦美国明尼苏达大学地理系教授

新的科学技术已将玉米带的谷物—牲畜混合农业改造成为高度专业化的商品谷物农业。乡村景观亦随之改变,但家庭农场依然如故。农场规模增加了一倍,但仍反映了初期拓荒者向联邦政府购买土地的数量。不断增加的农业生产,需要国外市场;而全... 详细信息

新的科学技术已将玉米带的谷物—牲畜混合农业改造成为高度专业化的商品谷物农业。乡村景观亦随之改变,但家庭农场依然如故。农场规模增加了一倍,但仍反映了初期拓荒者向联邦政府购买土地的数量。不断增加的农业生产,需要国外市场;而全球性的经济萧条与美元坚挺使出口减少,价格跌到甚至低于生产成本,连第一流的经营者都产生了严重的问题。

关键词：农场主牲畜家畜家庭农场玉米带农场规模美利坚合众国北美洲美国

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Manipulation of photosensory and circadian signaling restricts phenotypic plasticity in response to changing environmental conditions in Arabidopsis

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Molecular Plant 2024年第9期17卷 1458-1471页

作者： Martin William Battle Scott fraser Ewing Cathryn Dickson Joseph Obaje Kristen N.Edgeworth Rebecca Bindbeutel Rea LAntoniou-Kourounioti Dmitri A.Nusinow Matthew Alan Jones Plant Science Group School of Molecular BiosciencesUniversity of GlasgowGlasgow G128QQUK Danforth Plant Science Center St.LouisMO 63132USA Department of Biological and Biomedical Sciences Washington University in St.LouisSt.LouisMO 63130USA Present address:School of Biological and Environmental Sciences Liverpool John Moores UniversityLiverpool L22QPUK

Plants exploit phenotypic plasticity to adapt their growth and development to prevailing environmental *** of light and temperature signals is aided by the circadian system,which provides a temporal *** plasticity provides a selective and competitive advantage in nature but is obstructive during large-scale,intensive agricultural practices since economically important traits(including vegetative growth and flowering time)can vary widely depending on local environmental *** prevents accurate prediction of harvesting times and produces a variable *** this study,we sought to restrict phenotypic plasticity and circadian regulation by manipulating signaling systems that govern plants'responses to environmental *** modeling of plant growth and develop-ment predicted reduced plant responses to changing environments when circadian and light signaling pathways were *** tested this prediction by utilizing a constitutively active allele of the plant photoreceptor phytochrome B,along with disruption of the circadian systemvia mutation of *** found that these manipulations produced plants that are less responsive to light and temper-ature cues and thus fail to anticipate *** engineered plants have uniform vegetative growth and flowering time,demonstrating how phenotypic plasticity can be limited while maintaining plant *** has significant implications for future agriculture in both open fields and controlled environments.

关键词： circadian developmental plasticity phenotypic plasticity external coincidence light temperature

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LOV to BLUF： Flavoprotein Contributions to the Optogenetic Toolkit

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Molecular Plant 2012年第3期5卷 533-544页

作者： john M. Christie Jayde Gawthorne Gillian Young Niall J. fraser^c and Andrew J. Roe Institute of Molecular Cell and Systems Biology College of Medical Veterinary and Life Sciences University of Glasgow UK Institute of Infection immunity and Inflammation College of Medical Veterinary and Life Sciences University of Glasgow UK Institute of Cardiovascular and Medical Sciences College of Medical Veterinary and Life Sciences University of Glasgow UK

Optogenetics is an emerging field that combines optical and genetic approaches to non-invasively interfere with cellular events with exquisite spatiotemporal control. Although it arose originally from neuroscience, optogenetics is widely applicable to the study of many different biological systems and the range of applications arising from this tech- nology continues to increase. Moreover, the repertoire of light-sensitive proteins used for devising new optogenetic tools is rapidly expanding. Light, Oxygen, or Voltage sensing （LOV） and Blue-Light-Utilizing flavin adenine dinucleotide （FAD）（BLUF） domains represent new contributors to the optogenetic toolkit. These small （100-140-amino acids） flavoprotein modules are derived from plant and bacterial photoreceptors that respond to UV-A/blue light. In recent years, considerable progress has been made in uncovering the photoactivation mechanisms of both LOV and BLUF domains. This knowledge has been applied in the design of synthetic photoswitches and fluorescent reporters with applications in cell biology and biotechnology. In this review, we summarize the photochemical properties of LOV and BLUF photosensors and highlight some of the recent advances in how these flavoproteins are being employed to artificially regulate and image a variety of biological processes.

关键词： Blue-Light.Utilizing FAD chromophore flavin fluorescence light, oxygen or voltage optogenetics photo- receptor protein engineering

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Climate change drives flooding risk increases in the Yellow River Basin

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Geography and Sustainability 2024年第2期5卷 193-199页

作者： Hengxing Lan Zheng Zhao Langping Li Junhua Li Bojie Fu Naiman Tian Ruixun Lai Sha Zhou Yanbo Zhu Fanyu Zhang Jianbing Peng john J.Clague State Key Laboratory of Resources and Environmental Information System Institute of Geographic Sciences and Natural Resources ResearchChinese Academy of SciencesBeijing 100101China School of Geological Engineering and Geomatics Chang’an UniversityXi’an 710064China University of Chinese Academy of Sciences Beijing 10049China Yellow River Institute of Hydraulic Research Yellow River Conservancy CommissionZhengzhou 450003China State Key Laboratory of Urban and Regional Ecology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China State Key Laboratory of Earth Surface Processes and Resources Ecology Beijing Normal UniversityBeijing 100875China Key Laboratory of Mechanics on Disaster and Environment in Western China The Ministry of Education of ChinaSchool of Civil Engineering and MechanicsLanzhou UniversityLanzhou 730000China Department of Earth Sciences Simon Fraser UniversityBurnabyCanada

The Yellow River Basin(YRB)has experienced severe floods and continuous riverbed elevation throughout *** climate change has been suggested to be driving a worldwide increase in flooding ***,owing to insufficient evidence,the quantitative correlation between flooding and climate change remains *** present a long time series of maximum flood discharge in the YRB dating back to 1843 compiled from historical documents and instrument *** in yearly maximum flood discharge show distinct periods:a dramatic decreasing period from 1843 to 1950,and an oscillating gentle decreasing from 1950 to 2021,with the latter period also showing increasing more extreme floods.A Mann-Kendall test analysis suggests that the latter period can be further split into two distinct sub-periods:an oscillating gentle decreasing period from 1950 to 2000,and a clear recent increasing period from 2000 to *** further predict that climate change will cause an ongoing remarkable increase in future flooding risk and an∼44.4 billion US dollars loss of floods in the YRB in 2100.

关键词： Flooding risk Risk management Climate change Flood discharge Extreme precipitation

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Early Weight Bearing Post Subchondral Microfracture Knee Arthroscopy: A Case Report

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Open Journal of Orthopedics 2022年第5期12卷 253-257页

作者： Katon Harwood Kelsey fraser john Spellman School of Osteopathic Medicine Campbell University Lillington NC USA Department of Orthopedic Surgery Carteret Health Care Morehead City NC USA

Traditionally physicians have advised patients to be non-weight bearing post arthroscopic knee microfracture surgery for at least 2 to 8 weeks. The microfracture procedure is a simple, low-risk method to induce self-cartilage regeneration to focal lesions. The procedure has shown that small fractures to the subchondral bone can recruit mesenchymal stem cells and growth factors to regenerate the fibrocartilage without compromising the subchondral plate. With the simplicity of this procedure and the positive effect it can have on patients, it is natural to want to push the bounds of rehabilitation to see what is necessary. The patient in this case report exhibits the potential for positive outcomes with early weight-bearing status in patients receiving microfractures via subchondral drilling. This positive outcome, along with others, should encourage clinicians to consider reestablishing evidence-guided rehabilitation post microfracture with new studies. Shortened rehabilitation time would decrease a barrier to surgery for many patients and would only enhance our treatment with this surgical modality.

关键词： Microfracture Patellofemoral Chondrosis Patellar Maltracking

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Distal small bowel motility and lipid absorption in patients following abdominal aortic aneurysm repair surgery

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World Journal of Gastroenterology 2006年第4期12卷 582-587页

作者： Robert J fraser Marc Ritz Addolorata C Di Matteo Rosalie Vozzo Monika Kwiatek Robert Foreman Brendan Stanley Jack Walsh Jim Burnett Paul Jury john Dent Department of Medicine University of AdelaideSouth Australia Department of Gastroenterology Royal Adelaide HospitalAdelaide South Australia Vascular Unit Royal Adelaide Hospital AdelaideSouth Australia Gastrointestinal Investigation Unit Repatriation General Hospital Daw Park South Australia Vascular Unit Repatriation General Hospital Daw Park SouthAustralia

AIM： To investigate distal small bowel motility and lipid absorption in patients following elective abdominal aortic aneurysm （AAA） repair surgery, METHODS： Nine patients （aged 35-78 years; body mass index （BMI） range： 23-36 kg/m2） post-surgery for AAA repair, and seven healthy control subjects （20-50 years; BMI range： 21-29 kg/m^2） were studied, Continuous distal small bowel manometry was performed for up to 72 h, during periods of fasting and enteral feeding （Nutrison）. Recordings were analyzed for the frequency, odgin, length of migration, and direction of small intestinal burst activity. Lipid absorption was assessed on the first day and the third day post surgery in a subset of patients using the ^13C-triolein-breath test, and compared with healthy controls. Subjects received a 20-min intraduodenal infusion of 50 mL liquid feed mixed with 200μL ^13C-triolein. End-expiratory breath samples were collected for 6 h and analyzed for ^13CO2 concentration. RESULTS： The frequency of burst activity in the proximal and distal small intestine was higher in patients than in healthy subjects, under both fasting and fed conditions （P〈 0.005）. In patients there was a higher proportion of abnormally propagated bursts （71% abnormal）, which began to normalize by d 3 （25% abnormal） *** absorption data was available for seven patients on d 1 and four patients on d 3 post surgery. In patients, absorption on d 1 post-surgery was half that of healthy control subjects （AUC ^13CO2 1323±244 vs 2646±365; P〈0.05, respectively）, and was reduced to the one-fitch that of healthy controls by d 3 （AUC ^13CO2 470±832 vs 2646±365; P〈 0.05, respectively）. CONCLUSION： Both proximal and distal small intestinal motor activity are transiently disrupted in critically ill patients immediately after major surgery, with abnormal motility patterns extending as far as the ileum. These motor disturbances may contribute to impaired absorption of enteral nutrition, especially when intralumi

关键词： Critical illness Small intestine Motility Lipid absorption

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Football injuries of the ankle: A review of injury mechanisms, diagnosis and management

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World Journal of Orthopedics 2016年第1期7卷 8-19页

作者： Raymond J Walls Keir A Ross Ethan J fraser Christopher W Hodgkins Niall A Smyth Christopher J Egan James Calder john G Kennedy Department of Foot and Ankle Surgery Hospital for Special Surgery New York University of Miami/Jackson Memorial Hospital Department of Trauma and Orthopaedic Surgery Chelsea and Westminster Hospital

Football is the most popular sport worldwide and is associated with a high injury rate, most of which are the result of trauma from player contact. Ankle injuries are among the most commonly diagnosed injuries in the game. The result is reduced physical activity and endurance levels, lost game time, and considerable medical cost. Sports medicine professionals must employ the correct diagnostic tools and effective treatments and rehabilitation protocols to minimize the impact of these injuries on the player. This review examines the diagnosis, treatment, and postoperative rehabilitation for common football injuries of the ankle based on the clinical evidence provided in the current literature.

关键词： Management Soccer Football Ankle Injury

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Importance of Quaternary research to society

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Episodes 2008年第2期31卷 203-206页

作者： john J. Clague Cenlre for Natural Hazard Research Simon Fraser University Burnaby BC Canada V5A 1S6

The Quaternary Period, although only an instant in the 4.5 billion year expanse of geologic time, is disproportionately important because it is the interval during which humans evolved and because it includes the present. Events of the Quaternary are preserved in sediments, ice sheets, and landforms with a greater degree of completeness and temporal resolution than those of any earlier period of comparable length. Studies of these historical and environmental archives continue to provide the essential context that allows scientists to evaluate what is happening with Earth＇s climate today and to clarify our vulnerability to hazardous natural processes, for example earthquakes, tsunami, volcanic eruptions, floods, and landslides.

关键词：地质学科学研究第四纪地质年代

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