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Management of telaprevir-based triple therapy for hepatitis C virus recurrence post liver transplant

World journal of Hepatology 2015年第9期7卷 1287-1296页

作者： Kerstin Herzer Angela Papadopoulos-Khn Anne Achterfeld Ali Canbay Katja Piras-Straub Andreas Paul Andreas Walker jrg timm Guido Gerken Department of Gastroenterology and Hepatology University Hospital Essen Department of General-Visceral and Transplantation Surgery University Hospital Essen Institute for Virology Heinrich Heine University

AIM: To characterize management of telaprevir(TVR)-based triple therapy of hepatitis C virus(HCV) reinfection after liver transplantation(LT).METHODS: We retrospectively analyzed safety and efficacy of telaprevir- based triple therapy in a single center cohort of 19 patients with HCV genotype(GT) 1 recurrence after LT, with respect to factors possibly predicting sustained viral response(SVR) or non-SVR. All patients were treated with TVR, pegylated(PEG) and ribavirine(RBV) for 12 wk followed by a dual phase with PEG/RBV for 12 wk in 7 patients and for 36 wk in 5 patients. RESULTS: In total 11/19(58%) of patients achieved a sustained response. All(11/11) SVR patients showed a rapid viral response at treatment weeks 4 and 11/14 rapid virological response(RVR) patients achieved SVR. Notably, all(7/7) patients who completed 48 wk of therapy and 80%(4/5) patients who completed 24 wk of therapy achieved SVR24. Treatment failure was significantly(P > 0.049) more frequent in GT1 a infection(5/7) compared to GT1b(3/12) infection and was associated with emergence of resistance-associated mutations in the NS3 protease domain. Bilirubin level at baseline is also related to SVR(P > 0.030). None of the patients had to discontinue treatment due to side effects. CONCLUSION: RVR, GT and bilirubin are clearly related to achievement of SVR. Providing a thorough patient selection and monitoring, a full course of TVR-based triple therapy in LT patients is feasible and achieves high SVR rates.

关键词： Liver transplantation Telaprevir HepatitisC virus recurrence Predictors Hepatitis C virus therapy

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Sequence diversity of hepatitis C virus: Implications for immune control and therapy

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World journal of Gastroenterology 2007年第36期13卷 4807-4817页

作者： joerg timm Michael Roggendorf University of Essen Instituteof Virology Essen 45122 Germany

With approximately 3% of the world’s population (170 million people) infected with the hepatitis C virus (HCV), the WHO has declared HCV a global health problem. Upon acute infection about 50%-80% of subjects develop chronic hepatitis with viral persistence being at risk to develop liver cirrhosis and hepatocellular carcinoma. One characteristic of HCV is its enormous sequence diversity, which represents a significant hurdle to the development of both effective vaccines as well as to novel therapeutic interventions. Due to a polymerase that lacks a proofreading function HCV presents with a high rate of evolution, which enables rapid adaptation to a new environment including an activated immune system upon acute infection. Similarly, novel drugs designed to specifically inhibit viral proteins will face the potential problem of rapid selection of drug resistance mutations. This review focuses on the sequence diversity of HCV, the driving forces of evolution and the impact on immune control and treatment response. An important feature of any therapeutic or prophylactic intervention will be an efficient attack of a structurally or functionally important region in the viral protein. The understanding of the driving forces, but also the limits of viral evolution, will be fundamental for the design of novel therapies.

关键词： Hepatitis C Virus Evolution Escape Drug resistance Selection

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Generalized Baumslag-Solitar Graphs with Soluble Fundamental Groups

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Algebra Colloquium 2014年第1期21卷 53-58页

作者： Alberto L. Delgado Derek j.S. Robinson Mathew timm vDepartment of Mathematics illinois State University Normal IL 61790 USA Department of Mathematics University of Illinois at Urbana-Champaign Urbana IL 61801 USA Department of Mathematics Bradley University Peoria IL 61625 USA

It is shown that the generalized Baumslag-Solitar graphs which have soluble fundamental groups can be constructed from four simple types of graph by a process of decoration. The method of proof is elementary and emplo... 详细信息

关键词： generalized Baumslag-Solitar graph soluble fundamental group

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Numerical investigation of the dynamics of a rigidspherical particle in a vortical cross-slot flow atmoderate inertia

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Microsystems & Nanoengineering 2023年第4期9卷 181-195页

作者： Konstantinos Kechagidis Benjamin Owen Lionel Guillou Henry Tse Dino Di Carlo timm Krüger School of Engineering Institute for Multiscale ThermofluidsUniversity of EdinburghW Mains RdEdinburgh EH93JW ScotlandUK Cytovale Inc.Executive Park Blvd.San Fransisco CA 90095 CAUSA Department of Bioengineering University of CaliforniaWestwood PlazaLos Angeles 610101 CAUSA

The study of flow and particle dynamics in microfluidic cross-slot channels is of high relevance for lab-on-a-chipapplications. In this work, we investigate the dynamics of a rigid spherical particle in a cross-slot junction for a channelheight-to-width ratio of 0.6 and at a Reynolds number of 120 for which a steady vortex exists in the junction *** an in-house immersed-boundary-lattice-Boltzmann code, we analyse the effect of the entry position of theparticle in the junction and the particle size on the dynamics and trajectory shape of the particle. We find that thedynamics of the particle depend strongly on its lateral entry position in the junction and weakly on its vertical entryposition;particles that enter close to the centre show trajectory oscillations. Larger particles have longer residencetimes in the junction and tend to oscillate less due to their confinement. Our work contributes to the understanding ofparticle dynamics in intersecting flows and enables the design of optimised geometries for cytometry and particlemanipulation.

关键词： particle dynamics spherical

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Restoration of the joint geometry and outcome after stemless TESS shoulder arthroplasty

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World journal of Orthopedics 2017年第10期8卷 790-797页

作者： Lars V von Engelhardt Michael Manzke Andreas Breil-Wirth timm j Filler joerg jerosch Faculty of Health University of Witten/Herdecke Department of Orthopedics Trauma Surgery and Sports MedicineJohanna Etienne Hospital Department of Anatomy Heinrich-Heine University of Duesseldorf

AIM To evaluate the joint geometry and the clinical outcome of stemless, anatomical shoulder arthroplasty with the TESS *** Twenty-one shoulders with a mean follow-up 18 of months were included. On scaled digital radiographs the premorbid center of rotation(CoR) was assessed and compared to the CoR of the prosthesis by using the MediC AD~? software. Additionally, the pre-and post-operative geometry of the CoR was assessed in relation to the glenoid, the acromion as well as to the proximal humerus. Radiological changes, such as radiolucencies, were also assessed. Clinical outcome was assessed with the Constant and DASH score. RESULTS Both, the Constant and DASH scores improved signifi-cantly from 11% to 75% and from 70 to 30 points, P 0.05). The pre-and postoperative humeral offset, the lateral glenohumeral offset, the height of the CoR, the acromiohumeral distance as well as neckshaft angle showed no significant changes(P > 0.05). The mean deviation of the CoR of the prosthesis from the anatomic center was 1.0 ± 2.8 mm. Three cases showed a medial deviation of more than 3 mm. These deviations of 5.1, 5.7 and 7.6 mm and were caused by an inaccurate humeral neck cut. These 3 patients showed a relatively poor outcome *** TESS arthroplasty allows an anatomical joint reconstruction with a very good outcome. Outliers described in this study sensitize the surgeon for an accurate humeral neck cut.

关键词： Anatomical shoulder arthroplasty Stemless Omarthrosis Total shoulder replacement joint geometry

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Transcutaneous perianal sonography:A sensitive method for the detection of perianal inflammatory lesions in Crohn's disease

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World journal of Gastroenterology 2004年第19期10卷 2859-2863页

作者： jochen Wedemeyer timm Kirchhoff Gernot Sellge Oliver Bachmann joachim Lotz Michael Galanski Michael P.Manns Michael j.Gebel jrg S.Bleck Department of Gastroenterology Hepatology and EndocrinologyMedical School of HannoverCarl Neuberg Str.130623 HannoverGermany M.D. Department of Diagnostic Radiology Medical School of HannoverCarl Neuberg Str.130623 HannoverGermany Department of Gastroenterology Hepatology and EndocrinologyMedical School of HannoverCarl Neuberg Str.130623 HannoverGermany

AIM:Pelvic magnetic resonance imaging(MRI)and endoanal ultrasound which are established imaging methods for perianal inflammatory lesions in patients with Crohn's disease require expensive specialized equipments and *** investigated the feasibility and sensitivity of transcutaneous perianal ultrasound(PAUS)using regular ultrasound probes in the imaging of perianal inflammatory *** sonographic findings were correlated to pelvic MR]-scans. METHODS:We performed PAUS in 25 patients with Crohn's disease and clinical signs of perianal inflammatory disease. Wibhin a median of 10 d(range 0-75)these patients underwent MRI of the *** convex and linear high resolution probes were used for *** sonographic findings were correlated to the MRI findings by blinded investigators. RESULTS:The sonographic investigations were well tolerated by all *** typically presented as hypoechoic ***-nine fistulae were detected in 22 *** were detected in 7 patients and presented as hypo-or anechoic ***-six of 29 fistulae and 6 of 7 abscesses could be confirmed by *** statistics showed an excellent agreement (kappa>0.83)between the two imaging methods. CONCLUSION:PAUS is a simple,painless,feasible,real- time method that can be performed without specific patient preparation which is comparable in its sensitivity to pelvic MRI in the detection of perianal fistulae and/or abscesses. PAUS can especially be recommended as a screening tool in acute perianal disorders such as perianal abscess and for follow-up studies of perianal inflammatory disease.

关键词： Anal Canal histology Anus Diseases Crohn Disease Humans Inflammation Ultrasonography, Doppler, Color

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Perioperative treatment options in resectable pancreatic cancer-how to improve long-term survival

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World journal of Gastrointestinal Oncology 2016年第3期8卷 248-257页

作者： Marianne Sinn Marcus Bahra timm Denecke Sue Travis Uwe Pelzer Hanno Riess Department of Medical Oncology and Haematology Charité-Universitatsmedizin Berlin Department of General Visceral and Transplantation SurgeryCharité-Universitatsmedizin Berlin Institute of Radiology Charité-Universitatsmedizin Berlin

Surgery remains the only chance of cure for pancreatic cancer, but only 15%-25% of patients present with resectable disease at the time of primary diagnosis. Important goals in clinical research must therefore be to allow early detection with suitable diagnostic procedures, to further broaden operation techniques and to determine the most effective perioperative treatment of either chemotherapy and/or radiation therapy. More extensive operations involving extended pancreatectomy, portal vein resection and pancreatic resection in resectable pancreatic cancer with limited liver metastasis, performed in specialized centers seem to be the surgical procedures with a possible impact on survival. After many years of stagnation in pharmacological clinical research on advanced pancreatic ductal adenocarcinomas(PDAC)- since the approval of gemcitabine in 1997- more effective cytotoxic substances(nab-paclitaxel) and combinations(FOLFIRINOX) are now available for perioperative treatment. Additionally, therapies with a broader mechanism of action are emerging(stroma depletion, immunotherapy, antiinflammation), raising hopes for more effective adjuvant and neoadjuvant treatment concepts, especially in the context of "borderline resectability". Only multidisciplinary approaches including radiology, surgery, medical and radiation oncology as the backbones of the treatment of potentially resectable PDAC may be able to further improve the rate of cure in the future.

关键词： Pancreatic cancer Perioperative treatment Perioperative radiology Chemotherapy

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Synchrotron microtomography reveals insights into the degradation kinetics of bio-degradable coronary magnesium scaffolds

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Bioactive Materials 2024年第2期32卷 1-11页

作者： Roman Menze Bernhard Hesse Maciej Kusmierczuk Duote Chen timm Weitkamp Stephanie Bettink Bruno Scheller MeKo Manufacturing e.K. Im Kirchenfelde 12-1431157SarstedtGermany Xploraytion GmbH Bismarckstr.10-1210625BerlinGermany Synchrotron SOLEIL L’Orme des MerisiersDépartementale 12891190Saint-AubinFrance InnoRa GmbH Robert-Koch-Platz 410115BerlinGermany Universität des Saarlandes Campus Homburg66421HomburgGermany

Bioresorbable magnesium scaffolds are a promising future treatment option for coronary artery stenosis,especially for young *** to the degradation of these scaffolds(<1 year),long-term device-related clinical events c... 详细信息

Bioresorbable magnesium scaffolds are a promising future treatment option for coronary artery stenosis,especially for young *** to the degradation of these scaffolds(rging high resolution SR-μCT with deep learning(DL)supported data *** total,30 scaffolds,made of the rare earth alloy Resoloy^(®),with different strut designs were implanted into the coronary arteries of 10 domestic pigs for 28 days using drug-coated or uncoated angioplasty balloons for *** degradation morphology was analyzed using scanning electron microscopy,energy dispersive x-ray spectroscopy and SR-μ*** data from these methods were then related to data from angiography,optical coherence tomography and histology.A thinner strut size(95 vs.130μm)and the presence of paclitaxel indicated a slower degradation rate at 28 d in vivo,which positively influences the late lumen loss(0.5 and 0.6 mm vs.1.0 and 1.1 mm)and recoil values(0 and 1.7%vs.6.1 and 22%).

关键词： Resoloy Magnesium scaffold DCB Paclitaxel Degradation Inflammation Artificial intelligence

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High resolution scanning gate microscopy measurements on InAs/GaSb nanowire Esaki diode devices

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Nano Research 2014年第6期7卷 877-887页

作者： james L. Webb Olof Perssor Kimberly A. Dick Claes Thelander Rainer timm Anders Mikkelsen Division of Synchrotron Radiation Research Lund University Sweden Center forAnalysis and Synthesis Lund University Sweden Division of Solid State Physics Lund University Sweden

Gated transport measurements are the backbone of electrical characterization of nanoscale electronic devices. Scanning gate microscopy （SGM） is one such gating technique that adds crucial spatial information, accessing the localized properties of semiconductor devices. Nanowires represent a central device concept due to the potential to combine very different materials. However, SGM on semiconductor nanowires has been limited to a resolution in the 50-100 nm range. Here, we present a study by SGM of newly developed III-V semiconductor nanowire InAs/GaSb heterojunction Esaki tunnel diode devices under ultra-high vacuum. Sub-5 nm resolution is demonstrated at room temperature via use of quartz resonator atomic force microscopy sensors, with the capability to resolve InAs nanowire facets, the InAs/GaSb tunnel diode transition and nanoscale defects on the device. We demonstrate that such measurements can rapidly give important insight into the device properties via use of a simplified physical model, without the requirement for extensive calculation of the electrostatics of the system. Interestingly, by precise spatial correlation of the device electrical transport properties and surface structure we show the position and existence of a very abrupt （〈10 nm） electrical transition across the InAs/GaSb junction despite the change in material composition occurring only over 30-50 nm. The direct and simultaneous link between nanostructure composition and electrical properties helps set important limits for the precision in structural control needed to achieve desired device performance.

关键词： nanowire,scanning gate microscopy Esaki tunnel diode,InAs,GaSb,III-V,heterostructure

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Perceived damage and areas of needed research for wildlife pests of California agriculture

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Integrative Zoology 2014年第3期9卷 265-279页

作者： Roger A.BALDWIN Terrell P.SALMON Robert H.SCHMIDT Robert M.timm Statewide IPM Program University of California Cooperative ExtensionParlierCAUSA University of California Cooperative Extension San DiegoCAUSA Department of Environment and Society Utah State UniversityLoganUTUSA Hopland Research and Extension Center University of CaliformniaHoplandCAUSA

Many wildife species cause extensive damage to a variety of agricultural commodities in California,with es-timates of damage in the hundreds of millions *** the limited availability of resources to solve all human-wildlife conficts,we should focus management efforts on issues that provide the greatest benefit to ag-ricultural commodities in *** survey provides quantitative data on research needs to better guide future efforts in developing more effective,practical and appropriate methods for managing these *** found that ground squirels,pocket gophers,birds,wild pigs,coyotes and voles were the most common agricul-tural wildlife pest species in *** damage caused by these species could be quite high,but varied by agricultural *** most species,common forms of damage included loss of crop production and di-rect death of the plant,although livestock depredation was the greatest concern for *** methods used most frequently and those deemed most effective varied by pest species,although greater advancements in control methods were listed as a top research priority for all ***,the use of toxicants,biocon-trol and trapping were the most preferred methods for control,but this varied by *** general,integrated pest management practices were used to control wildlife pests,with a special preference for those approaches that were efficacious and quick and inexpensive to *** information and survey design should be useful in establishing research and management priorities for wildlife pest species in California and other similar re-gions.

关键词： agriculture California human-wildlife conflict integrated pest management survey

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