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1基于SfM方法的高密度点云数据生成及精度分析显示文摘地形数据的质量(精度和分辨率)影响着地球科学的研究水平。Li DAR测量是目前获取高分辨率地形数据的有效技术方法之一,但是其高昂的测量成本和相对复杂的后期数据处理限制了Li DAR技术的大众化应用。近年来,一种被称为Sf M(Structure from Motion)的适合大众化使用的新的高精度3维地形数据获取技术开始引起人们的注意。这种新型数字摄影测量技术可以利用高效的图像特征匹配算法从多视角照片中提取重叠区域的3维地形数据。由于Sf M技术仅需要目标物体的照片,而且对相机拍摄位置、图像尺度及拍摄焦距没有要求,因此利用简单测量平台采集地面照片就可以获取高质量的3维地形数据。与Li DAR技术相比,大大降低了获取高精度数据的成本,使得高精度3维地形数据的使用大众化。文中介绍了Sf M技术的基本原理和流程,展示了Sf M技术获取高精度3维地形数据的简单而有效的特性,特别适合于植被稀少的区域。文中利用近千米高空拍摄的、具有约70%重叠度的一套随Li DAR飞行采集的数字航空照片生成具有真彩色的高密度Sf M点云数据,点密度高达25.5个/m2,可生成分辨率0.2m的DEM(数字高程模型)。对比相同区域的LiDAR点云数据,统计分析表明58.3%的Li DAR数据与Sf M数据的垂直偏差<0.1m,88.3%的Li DAR数据的垂直偏差<0.2m;而且发现不同地貌的Sf M数据精度存在差异,平缓地形的Sf M数据精度高于陡峭地形的Sf M数据精度。文中还介绍了以氦气球作为拍摄平台的Sf M测量系统,可以快捷地获取高精度的3D地形数据和正射影像,比目前常用的差分GPS测量具有更高的效率和数据精度。魏占玉 Arrowsmith Ramon 何宏林 高伟 2015地震地质2015,37,2:71
2InSAR技术在矿区沉降监测中的应用研究显示文摘介绍了应用InSAR技术监测矿区地表沉降以及地下开采活动的原理;利用重轨差分InSAR技术获得了峰峰矿区地表ENVISAT和JERS 1的雷达形变干涉相位图;分析了在矿区地表沉降过程中ENVISATC波段和JERS 1 L波段形变干涉相位图的相干特性、相位特性以及干涉测量技术在矿区地表沉降监测中应用的可行性和局限性。实验结果表明,利用C波段和L波段雷达数据可以实施对矿区地表沉降的监测,但是C波段雷达受到空间干涉基线的限制更加严格,如果要实现对矿区地表沉降的监测,需要充分利用每个卫星回访时期的雷达数据,建立长时序的星载雷达形变干涉相位图序列,才能较好地实现矿区地表沉降监测。刘广 郭华东 Ramon Hanssen Zbigniew Perski 李新武 岳焕印 范景辉 2008国土资源遥感2008,20,2:34
3Gene Targeting by Homology-Directed Repair in Rice Using a Geminivirus-Based CRISPR/Cas9 System显示文摘Mugui Wang Yuming Lu Jose Ramon Botella Yanfei Mao Kai Hua Jian-kang Zhu 2017Molecular Plant2017,10,7:34
4A Single Active Trehalose-6-P Synthase (TPS) and a Family of Putative Regulatory TPS-Like Proteins in Arabidopsis显示文摘更高的植物典型地不在大数量生产 trehalose,但是他们的染色体序列揭示通常认为的 trehalose 新陈代谢酶的大家庭。在植物生长和开发的一个重要规章的角色也为新陈代谢的中间的 trehalose-6-P (T6P ) 正在出现。这里,我们在场 Arabidopsis trehalose 新陈代谢上的更改和为进一步详细的分析的一个资源。另外,我们提供 Arabidopsis 靠着可能在活跃地种纸巾完成特定的规章的功能的催化地不活跃的象 TPS 一样蛋白质的一个家庭编码单个 trehalose-6-P synthase (TPS ) 的证据。Lies Vandesteene Matthew Ramon Katrien Le Roy Patrick Van Dijck Filip Rolland 2010Molecular Plant2010,3,2:22
5Perspectives on the Application of Genome-Editing Technologies in Crop Breeding显示文摘Most conventional and modern crop-improvement methods exploit natural or artificially induced genetic variations and require laborious characterization of the progenies of multiple generations derived from time-consuming genetic crosses.Genome-editing systems,in contrast,provide the means to rapidly modify genomes in a precise and predictable way,making it possible to introduce improvements directly into elite varieties.Here,we describe the range of applications available to agricultural researchers using existing genome-editing tools.In addition to providing examples of genome-editing applications in crop breeding,we discuss the technical and social challenges faced by breeders using genome-editing tools for crop improvement.Kai Hua Jinshan Zhang Jose Ramon Botella Changle Ma Fanjiang Kong Baohui Liu Jian-Kang Zhu 2019Molecular Plant2019,12,8:19
6A detailed procedure for CRISPR/Cas9-mediated gene editing in Arabidopsis thaliana显示文摘The newly developed CRISPR(Clustered Regularly Interspaced Short Palindromic Repeats)/Cas(CRISPR-associated) system has emerged as an efficient tool for genome-editing, providing an alternative to classical mutagenesis and transgenic methods to study gene function and improve crop traits. CRISPR/Cas facilitates targeted gene editing through RNA-guided DNA cleavage followed by cellular DNA repair mechanisms that introduce sequence changes at the site of cleavage. Here we describe a detailed procedure for our previously developed and highly efficient CRISPR/Cas9 method that allows the generation of heritable-targeted gene mutations andcorrections in Arabidopsis. This protocol describes the strategies and steps for the selection of targets, design of single-guide RNA(sg RNA), vector construction and analysis of transgenic lines. We also offer a method to target two loci simultaneously using vectors containing two different sg RNAs. The principles described in this protocol can be applied to other plant species to generate stably inherited DNA modifications.Wenshan Liu Xiaohong Zhu Mingguang Lei Qingyou Xia Jose Ramon Botella Jian-Kang Zhu Yanfei Mao 2015Science Bulletin2015,60,15:18
7Gene editing in plants:progress and challenges显示文摘The clustered regularly interspaced short palindromic repeat(CRISPR)-associated protein 9(Cas9)genome editing system is a powerful tool for targeted gene modifications in a wide range of species,including plants.Over the last few years,this system has revolutionized the way scientists perform genetic studies and crop breeding,due to its simplicity,flexibility,consistency and high efficiency.Considerable progress has been made in optimizing CRISPR/Cas9 systems in plants,particularly for targeted gene mutagenesis.However,there are still a number of important challenges ahead,including methods for the efficient delivery of CRISPR and other editing tools to most plants,and more effective strategies for sequence knock-ins and replacements.We provide our viewpoint on the goals,potential concerns and future challenges for the development and application of plant genome editing tools.Yanfei Mao Jose Ramon Botella Yaoguang Liu Jian-Kang Zhu 2019National Science Review2019,6,3:17
8Epidermal growth factor receptor and K-Ras in non-small cell lung cancer-molecular pathways involved and targeted therapies显示文摘Lung cancer is currently the leading cause of cancer death in Western nations.Non-small cell lung cancer(NSCLC)represents 80%of all lung cancers,and adenocarcinoma is the predominant histological type.Despite the intensive research carried out on this field and therapeutic advances,the overall prognosis of these patients remains unsatisfactory,with a 5-year overall survival rate of less than 15%.Nowadays,pharmacogenetics and pharmacogenomics represent the key to successful treatment.Recent studies suggest the existence of two distinct molecular pathways in the carcinogenesis of lung adenocarcinoma:one associated with smoking and activation of the K-Ras oncogene and the other not associated with smoking and activation of the epidermal growth factor receptor(EGFR).The K-ras mutation is mainly responsible for primary resistance to new molecules which inhibit tyrosine kinase EGFR(erlotinib and gefitinib)and most of the EGFR mutations are responsible for increased tumor sensitivity to these drugs.This article aims to conduct a systematic review of the literature regarding the molecular pathways involving the EGFR,K-Ras and EGFR targeted therapies in NSCLC tumor behavior.Ramon Andrade de Mello Dania Sofia Marques Rui Medeiros António MF Araújo 2011World Journal of Clinical Oncology2011,2,11:16
9Damage control orthopaedics: State of the art显示文摘Damage control orthopaedics(DCO) originally consisted of the provisional immobilisation of long bone-mainly femur-fractures in order to achieve the advantages of early treatment and to minimise the risk of complications, such as major pain, fat embolism, clotting, pathological inflammatory response, severe haemorrhage triggering the lethal triad, and the traumatic effects of major surgery on a patient who is already traumatised(the 'second hit' effect). In recent years, new locations have been added to the DCO concept, such as injuries to the pelvis, spine and upper limbs. Nonetheless, this concept has not yet been validated in well-designed prospective studies, and much controversy remains.Indeed, some researchers believe the indiscriminate application of DCO might be harmful and produce substantial and unnecessary expense. In this respect, too,normalised parameters associated with the acid-base system have been proposed,under a concept termed early appropriate care, in the view that this would enable patients to receive major surgical procedures in an approach offering the advantages of early total care together with the apparent safety of DCO. This paper discusses the diagnosis and treatment of severely traumatised patients managed in accordance with DCO and highlights the possible drawbacks of this treatment principle.Enrique Guerado Maria Luisa Bertrand Juan Ramon Cano Ana María Cerván Adolfo Galán 2019World Journal of Orthopedics2019,10,1:16
10Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets显示文摘Bin Gao Ramon Bataller 2011Gastroenterology2011,,5:13
11Increased postoperative complications after protective ileostomy closure delay: An institutional study显示文摘AIM: To study the morbidity and complications as-sociated to ileostomy reversal in colorectal surgery pa-tients, and if these are related to the time of closure. METHODS: A retrospective analysis of 93 patients, who had undergone elective ileostomy closure between 2009 and 2013 was performed. Demographic, clinical and surgical variables were reviewed for analysis. All complications were recorded, and classified according to the Clavien-Dindo Classification. Statistical univariate and multivariate analysis was performed, setting a P value of 0.05 for significance.RESULTS: The patients had a mean age of 60.3 years, 58% male. The main procedure for ileostomy cre-ation was rectal cancer(56%), and 37% had received preoperative chemo-radiotherapy. The average delay from creation to closure of the ileostomy was 10.3 mo. Postoperative complications occurred in 40% of the pa-tients, with 1% mortality. The most frequent were ileus(13%) and wound infection(13%). Pseudomembra-nous colitis appeared in 4%. Increased postoperative complications were associated with delay in ileostomyclosure(P = 0.041). Male patients had more complica-tions(P = 0.042), mainly wound infections(P = 0.007). Pseudomembranous colitis was also associated with the delay in ileostomy closure(P = 0.003). End-to-end in-testinal anastomosis without resection was significantly associated with postoperative ileus(P = 0.037). CONCLUSION: Although closure of a protective il-eostomy is a fairly common surgical procedure, it has a high rate of complications, and this must be taken into account when the indication is made. The delay in stoma closure can increase the rate of complications in general, and specifically wound infections and colitis.Ines Rubio-Perez Miguel Leon Daniel Pastor Joaquin Diaz Dominguez Ramon Cantero 2014World Journal of Gastrointestinal Surgery2014,6,9:11
12Hypoxia inducible factor-1αaccumulation in steatotic liver preservation:Role of nitric oxide显示文摘AIM:To examine the relevance of hypoxia inducible factor(HIF-1)and nitric oxide(NO)on the preservation of fatty liver against cold ischemia-reperfusion injury(IRI). METHODS:We used an isolated perfused rat liver model and we evaluated HIF-1αin steatotic and non-steatotic livers preserved for 24 h at 4℃in University of Wisconsin and IGL-1 solutions,and then subjected to 2 h of normothermic reperfusion.After normoxic reperfusion,liver enzymes,bile production,bromosulfophthalein clearance,as well as HIF-1αand NO[endothelial NO synthase(eNOS)activity and nitrites/nitrates]were also measured.Other factors associated with the higher susceptibility of steatotic livers to IRI,such as mitochondrial damage and vascular resistance were evaluated. RESULTS:A significant increase in HIF-1αwas found in steatotic and non-steatotic livers preserved in IGL-1 after cold storage.Livers preserved in IGL-1 showed a significant attenuation of liver injury and improvement in liver function parameters.These benefits were enhanced by the addition of trimetazidine(an antiischemic drug),which induces NO and eNOS activation, to IGL-1 solution.In normoxic reperfusion,the presence of NO favors HIF-1αaccumulation,promoting also the activation of other cytoprotective genes,such as hemeoxygenase-1. CONCLUSION:We found evidence for the role of the HIF-1α/NO system in fatty liver preservation,especially when IGL-1 solution is used.Mohamed Amine Zaouali Ismail Ben Mosbah Eleonora Boncompagni Hassen Ben Abdennebi Maria Teresa Mitjavila Ramon Bartrons Isabel Freitas Antoni Rimola Joan Roselló-Catafau 2010World Journal of Gastroenterology2010,16,28:11
13联合应用氯吡格雷和质子泵抑制剂对急性冠状动脉综合征患者经皮冠状动脉介入术后预后的影响显示文摘目的探讨联合应用氯吡格雷和质子泵抑制剂(PPI)对急性冠状动脉综合征(ACS)患者经皮冠状动脉介入(PCI)术后预后的影响。方法回顾性分析2003年至2014年来自10个国家(加拿大,巴西,德国,波兰,荷兰,西班牙,意大利,希腊,中国,日本)15个临床中心的ACS合并PCI术后18077例患者的临床资料。研究氯吡格雷、PPI与ACS患者PCI术后预后的关系。比较患者的基本临床特征、既往病史、生化指标、药物应用,以及终点事件的发生率情况。通过Cox回归模型进行分析及倾向性评分调整其他可能影响患者的预后因素包括人口学信息(年龄、性别)和临床指标,计算PPI这一干预因素的风险比并评价其是否能够明显影响患者的预后。结果基于国际多中心Blee MACs注册登记研究分析,排除关键数据缺失过多患者2676例。根据纳入与排除标准及倾向性评分调整整理后,再排除患者6461例,最终列队患者8940例。根据患者用药不同,将患者分为氯吡格雷+PPI组(4814例)和氯吡格雷组(4126例)。氯吡格雷+PPI组患者女性、高血压病史、高脂血症病史、糖尿病史、外周血管疾病史、既往急性心肌梗死史、慢性肾功能不全病史、消化道溃疡病史、冠状动脉旁路移植术病史、既往出血病史、恶性肿瘤病史、不稳定型心绞痛、非sT段抬高型心肌梗死、心功能Killip分级≥2级、经皮腔内冠状动脉成形术、出院后血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂应用比例、年龄和入院时血肌酐水平明显高于氯吡格雷组[25.4%(1225/4814)比21.0%(865/4126)、59.9%(2882/4814)比49.2%(2032/4126)、48.3%(2327/4814)比42.7%(1762/4126)、26.4%(1272/4814)比22.1%(910/4126)、8.0%(386/4814)比5.6%(231/4126)、12.3%(593/4814)比10.6%(436/4126)、2.0%(98/4814)比0.7%(30/4126)、2.3%(112/4814)比1.0%(42/4126)、3.6%(172/4814)比2.2%(92/4126)、4.5%(219/4814)比3.0%(123/4126)、8.0%(387/4814)比4.7%(193/4126)、13.4%(644/4814)比9.1%(374/4126)、29.1%(1400/4814)比15.9%(656/4126)、14.5%(699/4814)比11.2%(462/4126)、56.0%(2697/4814)比55.7%(2300/4126)、75.5%(3633/4814)比68.6%(2829/4126)、(66±12)岁比(61±13)岁、(10±6)mg/L比(9±4)mg/L];且入院时血红蛋白水平和出院后β受体阻滞剂应用比例明显低于氯吡格雷组[(138±19)g/L比(141±16)g/L、80.6%(3880/4814)比83.1%(3428/4126)],差异均有统计学意义(均P〈0.05)。调整前,氯吡格雷+PPI组主要终点事件(全因死亡/再发心肌梗死/出血)发生率明显高于氯吡格雷组,差异有统计学意义(风险比为1.331,95%置信区间为1.161-1.524)。调整后,氯吡格雷+PPI组主要终点事件(全因死亡/再发心肌梗死/出血)发生率与氯吡格雷组比较,差异无统计学意义(风险比为1.036,95%置信区间为0.903-1.189)。结论ACS患者PCI术后联合应用PPI与氯吡格雷是合理的,尤其在胃肠道出血高危患者中。严研 王晓 范婧尧 聂绍平 Sergio Raposeiras-Roubin Emad Abu-Assi Jose Paulo Simao Henriques Fabrizio D'Ascenzo Jorge Saucedo Jose Ramon Gonzalez-Juanatey Stephen B. Wilton Wouter J. Kikkert Ivan Nunez-Gil Albert Ariza-Sole Dimitrios Alexopoulos Christoph Liebetrau Testuma Kawaji Claudio Moretti Zenon Huczek Toshiharu Fujii Luis Claudio Correia Masa-aki Kawashiri Sasko Kedev 2017中国医药2017,12,2:10
14Primary liver cancer: Worldwide incidence and trends显示文摘F.Xavier Bosch Josepa Ribes Mireia Díaz Ramon Cléries 2004Gastroenterology2004,,5:10
15相同基因型而不同表现型的PRKAG2基因突变一家系报道显示文摘目的 位于7号染色体上的腺苷一磷酸激活的蛋白激酶γ^2调节亚单位基因(PRKAG2基因)调节代谢通路。报道一个具有PRKAG2基因突变而临床表现型不同的家系。方法 使用DNA直接测序法,对一个具有多种形式心律失常的患者家系(13例患者)进行PRKAG2外显子及外显子和内含子拼接部位序列筛查寻找基因突变。结果 心电图显示患者家系存在窦性心动过缓、短PR间期、完全性右束支传导阻滞、房室传导阻滞和房性心动过速。其中3例患者在年轻时发生猝死,没有1例有预激综合征(预激)表现,只有1例有心肌肥厚。DNA测序结果显示,该家系所有患者皆有一个PRKAG2错义突变(R302Q)。这个基因突变以前曾描述并与预激和左室肥厚有关。结论 PRKAG2基因突变不仅导致预激而且与多种临床表现型有关。完全性右束支传导阻滞、窦性心动过缓、短PR间期应该高度怀疑有PRKAG2基因突变的可能。洪葵 Antonio Oliva 程晓曙 Pedro Brugada Joseph Brugada Eduardo-back Sternick Ramon Brugada 2007中华心血管病杂志2007,35,6:9
16Predicting scenic beauty of forest stands in Catalonia (North-east Spain)显示文摘森林看台,相片和虚拟现实图象的 90 幅图象的相对偏爱被因特网调查为在看台水平估计美景偏爱开发一个量的模型。从 259 个法官的一个总数的问询表获得的相对优先级价值为对用回归方法被分析明智的比较。二个模型基于看台的二个不同的组被开发。两个模型显示一个森林的优先级承受增加与一在灌木丛和树的数字的 augment,并且另外与树的吝啬的直径。在另一方面,优先级与松和小树的大数字是低的。相片代表的看台比虚拟现实图象代表的那些收到更好的优先级价值。当法官(性,国家或职业) 的背景作为另外的预言者被包括进模型时,没有重要改进被完成。Elena Blasco Jose Ramon Gonzalez-Olabarria Pedro Rodriguez-Veiga Timo Pukkala Osmo Kolehmainen Marc Palahi 2009Journal of Forestry Research2009,20,1:9
17急性冠状动脉综合征患者经皮冠状动脉介入术后出血情况分析显示文摘目的分析急性冠状动脉综合征(ACS)经皮冠状动脉介入(PCI)术后出血情况。方法回顾性分析2003年1月至2014年12月来自11个国家16个临床中心的18077例行PCI的ACS患者的临床资料。根据是否出现出血事件,将患者分为出血组(558例)和非出血组(17519例),比较2组患者的基本临床特征、手术情况及生化指标。分析ACS患者PCI术后出血相关情况。结果马其顿中心数据因关键变量缺失过多而被排除患者2676例,故最终纳入10个国家15个中心15401例ACS患者。排除缺失数据,本研究共有12910例患者收集到出血部位的数据,409例患者存在出血事件。胃肠道是最常见出血部位,占48.7%(199/409),颅内出血占7.6%(31/409)。Logistic逐步回归方法多因素分析显示,既往出血病史、高血压病史是术后1年内消化道出血的危险因素。排除马其顿中心数据(2676例)与Cox回归模型和倾向性评分调整再排除5972例,剩余9429例作分层分析。根据是否联用质子泵抑制剂(PPI),将出院应用氯吡格雷生存患者8942例分为氯吡格雷联合应用PPI组(4814例)和氯吡格雷未联合应用PPI组(4126例);将出院应用替格瑞洛生存患者489例分为替格瑞洛联合应用PPI组(351例)和替格瑞洛未联合应用PPI组(138例)。Kaplan-Meier法分析显示氯吡格雷联合应用PPI组1年出血事件发生率明显高于氯吡格雷未联合应用PPI组,差异有统计学意义(P=0.004);替格瑞洛联合应用PPI组1年出血事件发生率与替格瑞洛未联合应用PPI组比较,差异无统计学意义(P=0.573)。结论ACS患者PCI术后最常见的出血部位为消化道,PPI与替格瑞洛联合应用在胃肠道出血风险较高患者中适用。严研 王晓 范婧尧 聂绍平 宋现涛 Sergio Raposeiras-Roubin Emad Abu-Assi Jose Paulo Simao Henriques Fabrizio D'Ascenzo Jorge Saucedo Jose Ramon Gonza1ez-Juanatey Stephen B. Wilton Ivan Nufiez-Gil Albert Ariza-Sole Dimitrios Alexopoulos Christoph Liebetrau Testuma Kawaji Zenon Huczek Toshiharu Fujii Luis Claudio Correia Masa-aki Kawashiri Sasko Kedev 2017中国医药2017,12,6:8
18Gastroenteropancreatic neuroendocrine tumours显示文摘Irvin M Modlin Kjell Oberg Daniel C Chung Robert T Jensen Wouter W de Herder Rajesh V Thakker Martyn Caplin Gianfranco Delle Fave Greg A Kaltsas Eric P Krenning Steven F Moss Ola Nilsson Guido Rindi Ramon Salazar Philippe Ruszniewski Anders Sundin 2008Lancet Oncology2008,,1:8
19Role of Arabidopsis UV RESISTANCE LOCUS 8 in Plant Growth Reduction under Osmotic Stress and Low Levels of UV-B显示文摘在热点环境,植物暴露于压力的不同类型,例如触发普通 morphogenic 的 UV-B,而且 droughtstress 的过量适应反应导致植物生长的一般减小。这里,我们 reportthat Arabidopsis thaliana 紫外抵抗地点 8 (UVR8 ) 基因, UV-B morphogenic 反应的一个已知的管理者,能补充 Saccharomyces cerevisiae osmo 敏感的异种和它的表示在 Arabidopsis 植物在渗透或咸的应力以后被导致。在 UV-B 的底层下面,植物 overexpressing UVR8 与减少的根开发被相形见绌并且与控制植物相比积累更多的 flavonoids。生长 defectsare 主要由于细胞扩大的抑制。UVR8 overexpression 在 UV-B 的底层下面在植物触发的生长抑制被导致甘露糖醇的渗透的应力加重,但是它不是由离子的应力的 significantlyaffected。相反, uvr8-6 异种植物不在标准条件下面不同于野类型的植物,但是他们显示出一个增加的射击生长 underhigh 盐压力。我们的数据建议 flavonoid 并且可能的调停 UVR8 的累积在植物生长素 homeostasisare 改变观察生长显型的内在的机制并且 UVR8 可能为 integratingplant 生长和压力 signals.Key 词有一个重要角色:Rossella Fasano Nathalie Gonzalez Alessandra Tosco Fabrizio Dal Piaz Teresa Docimo Ramon Serrano Stefania Grillo Antonella Leone Dirk Inze 2014Molecular Plant2014,7,5:7
20New prospects in the diagnosis and treatment of immune-mediated inner ear disease显示文摘Autoimmune inner ear disease(AIED) represents a very fertile research field and the advancements in the understanding of this disease have a direct application not only in patients affected with this condition but also in other inner ear disorders that share the same injury mechanism, damage to the inner ear hair cells. AIED also presents many challenges that have still to be overcome. Firstly, access to the inner ear is limited, as many interventions such as biopsies can result in great irreversible damage. Secondly, there are no completely specific markers for AIED. Lack of a definitive diagnosis can result in the treatment of patients not affected with the disease and, therefore, no response. Finally, some patients become refractory to glucocorticoids and new therapies are needed. This review offers an overview of the animal models that have contributed to the understanding of AIED pathophysiology, the value of currently available diagnostic tests, and therapeutic options, with a special focus on new therapies for non responders or patients refractory to glucocorticoids. Among these new options for therapy, biological agents have been tested recently, whereas gene and stem celltherapy may have a role in the future. The intratympanic route of administration avoids the systemic side effects associated with currently used drugs, and may become a more frequent approach in the future.David R Lobo Jose Ramon García-Berrocal Rafael Ramírez-Camacho 2014World Journal of Methodology2014,4,2:7
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