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| 1 | Portal vein thrombosis, mortality and hepatic decompensation in patients with cirrhosis: A meta-analysis显示文摘AIM: To determine the clinical impact of portal vein thrombosis in terms of both mortality and hepatic decompensations(variceal hemorrhage, ascites, portosystemic encephalopathy) in adult patients with cirrhosis.METHODS: We identified original articles reported through February 2015 in MEDLINE, Scopus, Science Citation Index, AMED, the Cochrane Library, and relevant examples available in the grey literature. Two independent reviewers screened all citations for inclusion criteria and extracted summary data. Random effects odds ratios were calculated to obtain aggregate estimates of effect size across included studies, with 95%CI.RESULTS: A total of 226 citations were identified and reviewed, and 3 studies with 2436 participants were included in the meta-analysis of summary effect. Patients with portal vein thrombosis had an increased risk of mortality(OR = 1.62, 95%CI: 1.11-2.36, P = 0.01). Portal vein thrombosis was associated with an increased risk of ascites(OR = 2.52, 95%CI: 1.63-3.89, P < 0.001). There was insufficient data available to determine the pooled effect on other markers of decompensation including gastroesophageal variceal bleeding or hepatic encephalopathy. CONCLUSION: Portal vein thrombosis appears to increase mortality and ascites, however, the relatively small number of included studies limits more generalizable conclusions. More trials with a direct comparison group are needed. | Jonathan G Stine Puja M Shah Scott L Cornella Sean R Rudnick Marwan S Ghabril George J Stukenborg Patrick G Northup | 2015 | World Journal of Hepatology2015,7,27: | 42 |
| 2 | Review of risk factors for human echinococcosis prevalence on the Qinghai-Tibet Plateau, China: a prospective for control options显示文摘Objective: Echinococcosis is a major parasitic zoonosis of public health importance in western China. In 2004, the Chinese Ministry of Health estimated that 380,000 people had the disease in the region. The Qinghai-Tibet Plateau is highly co-endemic with both alveolar echinococcosis (AE) and cystic echinococcosis (CE). In the past years, the Chinese government has been increasing the financial support to control the diseases in this region. Therefore, it is very important to identify the significant risk factors of the diseases by reviewing studies done in the region in the past decade to help policymakers design appropriate control strategies. Review: Selection criteria for which literature to review were firstly defined. Medline, CNKI (China National Knowledge Infrastructure), and Google Scholar were systematically searched for literature published between January 2000 and July 2011. Significant risk factors found by single factor and/or multiple factors analysis were listed, counted, and summarized. Literature was examined to check the comparability of the data;age and sex specific prevalence with same data structures were merged and used for further analysis. A variety of assumed social, economical, behavioral, and ecological risk factors were studied on the Plateau. Those most at risk were Tibetan herdsmen, the old and female in particular. By analyzing merged comparable data, it was found that females had a significant higher prevalence, and a positive linearity relationship existed between echinococcosis prevalence and increasing age. In terms of behavioral risk factors, playing with dogs was mostly correlated with CE and/or AE prevalence. In terms of hygiene, employing ground water as the drinking water source was significantly correlated with CE and AE prevalence. For definitive hosts, dog related factors were most frequently identified with prevalence of CE or/and AE;fox was a potential risk factor for AE prevalence only. Overgrazing and deforestation were significant for AE prevalence only. Conclusion: Tibetan herdsmen communities were at the highest risk of echinococcosis prevalence and should be the focus of echinococcosis control. Deworming both owned and stray dogs should be a major measure for controlling echinococcosis;treatment of wild definitive hosts should also be considered for AE endemic areas. Health education activities should be in concert with the local people's education backgrounds and languages in order to be able to improve behaviors. Further researches are needed to clarify the importance of wild hosts for AE/CE prevalence, the extent and range of the impacts of ecologic changes (overgrazing and deforestation) on the AE prevalence, and risk factors in Tibet. | Qian Wang Yan Huang Liang Huang Wenjie Yu Wei He Bo Zhong Wei Li Xiangman Zeng Dominique A Vuitton Patrick Giraudoux Philip S Craig Weiping Wu | 2014 | Infectious Diseases of Poverty2014,3,1: | 35 |
| 3 | Hepatocellular carcinoma surveillance:An evidence-based approach显示文摘Hepatocellular carcinoma(HCC) makes up 75%-85% of all primary liver cancers and is the fourth most common cause of cancer related death worldwide. Chronic liver disease is the most significant risk factor for HCC with 80%-90% of new cases occurring in the background of cirrhosis. Studies have shown that early diagnosis of HCC through surveillance programs improve prognosis and availability of curative therapies. All patients with cirrhosis and high-risk hepatitis B patients are at risk for HCC and should undergo surveillance. The recommended surveillance modality is abdominal ultrasound(US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with non-alcoholic fatty liver disease(NAFLD). With the current obesity epidemic and rise in the prevalence of NAFLD, abdominal computed tomography or magnetic resonance imaging may be indicated as the primary screening modality in these patients. The addition of alpha-fetoprotein to a surveillance regimen is thought to improve the sensitivity of HCC detection.Further investigation of serum biomarkers is needed. Semiannual screening is the suggested surveillance interval. Surveillance for HCC is underutilized and low adherence disproportionately affects certain demographics such as nonCaucasian race and low socioeconomic status. | Patrick S Harris Ross M Hansen Meagan E Gray Omar I Massoud Brendan M McGuire Mohamed G Shoreibah | 2019 | World Journal of Gastroenterology2019,25,13: | 31 |
| 4 | Impact of overgrazing on the transmission of Echinococcus multilocularis in Tibetan pastoral communities of Sichuan Province,China显示文摘背景过度放牧被假定增加是包虫 multilocularis 的中间的主人的小哺乳动物的人口密度,在 Qinghai 西藏高原的牙槽的包虫病的病原体。这研究测试了过度放牧可能支持的假设通过增加小哺乳动物的人口的包虫 multilocularis 传播,在擦伤惯例的西藏的牧剧 communities.Methods 的中间的主人,小哺乳动物索引和狗包虫 rnultilocularis 感染数据被收集分析在用的 nonpararnetric 测试和多重逐步的逻辑 regression.Results 过度放牧和包虫 rnultilocularis 传播之间的关系调查一公社的牧场存在,可得到的牧草为放牧是缺乏的。开(普通) 牧场被过度放牧并且与附近的 fenced 相比有小哺乳动物的更高的洞穴密度(私人) 牧场;由附近的 fenced 区域测量的开的牧场上的这个高过度放牧压力在开的牧场导致了小哺乳动物的更高的洞穴密度。在开的牧场的小哺乳动物的中部的洞穴密度独立地与附近犬的包虫 multilocularis 感染被联系(P=0.003, OR=1.048 ) 过度放牧的 .Conclusion 可以通过增加小哺乳动物的人口密度支持包虫 multilocularis 的传播。 | WANG Qian XIAO Yong-fu Dominique A Vuitton Peter M Schantz Francis Raoul Christine Budke Maiza Campos-Ponce Philip S Craig Patrick Giraudoux | 2007 | Chinese Medical Journal2007,,3: | 20 |
| 5 | Management of non-variceal upper gastrointestinal tract hemorrhage:Controversies and areas of uncertainty显示文摘Upper gastrointestinal tract hemorrhage(UGIH) remains a common presentation requiring urgent evaluation and treatment.Accurate assessment,appropriate intervention and apt clinical skills are needed for proper management from time of presentation to discharge.The advent of pharmacologic acid suppression,endoscopic hemostatic techniques,and recognition of Helicobacter pylori as an etiologic agent in peptic ulcer disease(PUD) has revolutionized the treatment of UGIH.Despite this,acute UGIH still carries considerable rates of morbidity and mortality.This review aims to discuss current areas of uncertainty and controversy in the management of UGIH.Neoadjuvant proton pump inhibitor(PPI) therapy has become standard empiric treatment for UGIH given that PUD is the leading cause of non-variceal UGIH,and PPIs are extremely effective at promoting ulcer healing.However,neoadjuvant PPI administration has not been shown to affect hard clinical outcomes such as rebleeding or mortality.The optimal timing of upper endoscopy in UGIH is often debated.Upon completion of volume resuscitation and hemodynamic stabilization,upper endoscopy should be performed within 24 h in all patients with evidence of UGIH for both diagnostic and therapeutic purposes.With rising healthcare cost paramount in today's medical landscape,the ability to appropriately triage UGIH patients is of increasing value.Upper endoscopy in conjunction with the clinical scenario allows for accurate decision making concerning early discharge home in low-risk lesions or admission for further monitoring and treatment in higher-risk lesions.Concomitant pharmacotherapy with non-steroidal anti-inflammatory drugs(NSAIDs) and antiplatelet agents,such as clopidogrel,has a major impact on the etiology,severity,and potential treatment of UGIH.Long-term PPI use in patients taking chronic NSAIDs or clopidogrel is discussed thoroughly in this review. | Eric P Trawick Patrick S Yachimski | 2012 | World Journal of Gastroenterology2012,18,11: | 19 |
| 6 | 四川西部石渠地区夏季藏狐巢穴选择的生境分析显示文摘通过对四川石渠地区夏季藏狐洞穴生境选择的研究 ,以水源距离、洞口朝向、坡向、坡度、坡位、植被类型及鼠兔和鼠类洞穴等 7项指标为变量 ,运用主成分分析和聚类分析相结合的方法对收集到的 5 4个藏狐洞穴样本进行了分析。主成分分析在 4个主成分下达到 85 %的显著性。在第一主成分中水源距离、坡度和坡位是重要的影响变量 ,在另外 3个主成分中鼠类洞穴数量以及植被类型两变量也非常重要。聚类分析显示 ,5 4个洞穴样本在 3个水平上聚成 5类。藏狐易于选择草甸地带 ,中缓坡和低坡位 ,坡向多为阳坡或半阳坡 ,水源距离小于5 0 0m的地方筑巢 ,其穴口朝向多位于 135°~ 36 0°之间。此外 ,鼠兔和鼠类洞穴在藏狐洞穴样方内的出现 ,但数量变异较大 ,揭示小型哺乳动物和藏狐之间可能存在着复杂的相互关系。通过对四川石渠地区夏季藏狐洞穴生境选择的研究 ,以水源距离、洞口朝向、坡向、坡度、坡位、植被类型及鼠兔和鼠类洞穴等 7项指标为变量 ,运用主成分分析和聚类分析相结合的方法对收集到的 5 4个藏狐洞穴样本进行了分析。主成分分析在 4个主成分下达到 85 %的显著性。在第一主成分中水源距离、坡度和坡位是重要的影响变量 ,在另外 3个主成分中鼠类洞穴数量以及植被类型两变量也非常重要。聚类分析显示 ,5 | 王正寰 王小明 吴巍 Patrick Giraudoux 邱加闽 高桥健一 Philip S Crai | 2003 | 兽类学报2003,23,1: | 10 |
| 7 | 包虫病手术患者1312例流行病学资料分析显示文摘目的了解青藏高原包虫病的分布特点。方法对1992-2006年的1312例包虫病手术患者的相关资料进行分析。结果囊型和泡型包虫病均有分布。患者主要集中于21~50岁,20岁以下的患者相对较少,以藏族为主。囊型包虫病分布于四川省甘孜州和阿坝州的17个县以及青海省果洛州的5个县,而泡型包虫病同时分布于其中的大部分地区。结论囊型和泡型包虫病同时流行于四川省的西北部和青海省的东南部。 | 仁真 李调英 廖万明 陈兴旺 赵晓东 肖宁 喻晓慧 张西春 Akira Ito 邱加闽 Patrick Giraudoux Philip S Craig | 2008 | 寄生虫病与感染性疾病2008,6,3: | 8 |
| 8 | Priorities for research and control of cestode zoonoses in Asia显示文摘Globally,cestode zoonoses cause serious public health problems,particularly in Asia.Among all neglected zoonotic diseases,cestode zoonoses account for over 75%of global disability adjusted life years(DALYs)lost.An international symposium on cestode zoonoses research and control was held in Shanghai,China between 28th and 30th October 2012 in order to establish joint efforts to study and research effective approaches to control these zoonoses.It brought together 96 scientists from the Asian region and beyond to exchange ideas,report on progress,make a gap analysis,and distill prioritizing settings with a focus on the Asian region.Key objectives of this international symposium were to agree on solutions to accelerate progress towards decreasing transmission,and human mortality and morbidity caused by the three major cestode zoonoses(cystic echinococcosis,alveolar echinococcosis,and cysticercosis);to critically assess the potential to control these diseases;to establish a research and validation agenda on existing and new approaches;and to report on novel tools for the study and control of cestode zoonoses. | Ning Xiao Jia-Wen Yao Wei Ding Patrick Giraudoux Philip S Craig Akira Ito | 2013 | Infectious Diseases of Poverty2013,2,1: | 6 |
| 9 | Screening and identification of mimotopes of the major shrimp allergen tropomyosin using one-bead-one- compound peptide libraries显示文摘one-bead-one-compound (OBOC ) 组合的肽图书馆是一个强大的工具识别 ligand 和受体相互作用。这里,我们使用了 OBOC 图书馆技术识别对主要贝壳变应原 tropomyosin 的免疫球蛋白 E (IgE ) epitopes 特定的 mimotopes。有 8-12 氨基酸残余的 OBOC 肽图书馆为 tropomyosin 的 IgE mimotopes 与贝壳过敏症从病人与浆液样品被屏蔽。25 mimotopes 从屏蔽被识别,他们到 tropomyosin 特定的 IgE 的有约束力的反应被肽 ELISA 证实。这些 mimotopes 能基于顺序相同被划分成七簇,并且由聚类的 mimotopes 的 EpiSearch 印射的 epitope 被执行描绘并且证实 mimotopes 的有效性。五从六预言的 epitopes 被发现与 tropomyosin 的以前识别的 epitopes 重叠。为了推进,证实 mimotopes 的模仿潜力, BALB/c 老鼠被使免疫, mimotopes 结合了到锁眼恋栈者 hemocyanin 和 assayed 让他们的能力导致 tropomyosin 特定的抗体。那收到的 mimotope 免疫被发现有 tropomyosin 特定的免疫球蛋白 G 的提高的水平的 BALB/c 老鼠,然而并非收到了无关的 mimotope 的老鼠。这研究用整个 sera 开创 OBOC 图书馆的成功的申请屏蔽并且识别多重虾变应原 mimotopes 并且验证他们在 vitro 使用的模仿潜力,在 vivo,并且在 silico 方法。 | Nicki YH Leung Christine YY Wai Marco HK Ho Ruiwu Liu Kit S Lam Jin Jun Wang Shang An Shu Ka Hou Chu Patrick SC Leung | 2017 | Cellular & Molecular Immunology2017,14,3: | 6 |
| 10 | Transjugular intrahepatic portosystemic stent shunt for medically refractory hepatic hydrothorax:A systematic review and cumulative meta-analysis显示文摘AIM:To assess the effectiveness of transjugular intrahepatic portosystemic stent shunt(TIPSS) in refractory hepatic hydrothorax(RHH) in a systematic review and cumulative meta-analysis.METHODS:A comprehensive literature search was conducted on MEDLINE,EMBASE,and Pub Med covering the period from January 1970 to August 2014.Two authors independently selected and abstracted data from eligible studies.Data were summarized using a random-effects model.Heterogeneity was assessed using the I2 test.RESULTS:Six studies involving a total of 198 patients were included in the analysis.The mean(SD) age of patients was 56(1.8) years.Most patients(56.9%) had Child-Turcott-Pugh class C disease.The mean duration of follow-up was 10 mo(range,5.7-16 mo).Response to TIPSS was complete in 55.8%(95%CI:44.7%-66.9%),partial in 17.6%(95%CI:10.9%-24.2%),and absent in 21.2%(95%CI:14.2%-28.3%).The mean change in hepatic venous pressure gradient post-TIPSS was 12.7 mm Hg.The incidence of TIPSS-related encephalopathy was 11.7%(95%CI:6.3%-17.2%),and the 45-d mortality was 17.7%(95%CI:11.34%-24.13%).CONCLUSION:TIPSS is associated with a clinically relevant response in RHH.TIPSS should be considered early in these patients,given its poor prognosis. | Ivo C Ditah Badr F Al Bawardy Behnam Saberi Chobufo Ditah Patrick S Kamath | 2015 | World Journal of Hepatology2015,7,13: | 5 |
| 11 | Acute-on chronic liver failure显示文摘 | Rajiv Jalan Pere Gines Jody C Olson Rajeshwar P Mookerjee Richard Moreau Guadalupe Garcia-Tsao Vicente Arroyo Patrick S Kamath | 2012 | Journal of Hepatology2012,,6: | 4 |
| 12 | Chronic peripheral inflammation: a possible contributor to neurodegenerative diseases显示文摘The contribution of chronic peripheral inflammation to the pathogenesis of neurodegenerative diseases is an outstanding question. Sustained activation of the peripheral innate and adaptive immune systems occurs in the context of a broad array of disorders ranging from chronic infectious diseases to autoimmune and metabolic diseases. In addition, progressive systemic inflammation is increasingly recognized during aging. Peripheral immune cells could potentially modulate the cellular brain environment via the secretion of soluble molecules. There is an ongoing debate whether peripheral immune cells have the potential to migrate into the brain under certain permissive circumstances. In this perspective, we discuss the possible contribution of chronic peripheral inflammation to the pathogenesis of age-related neurodegenerative diseases with a focus on microglia, the resident immune cells of the brain parenchyma. | Patrick Süβ Addison J.Lana Johannes C.M.Schlachetzki | 2021 | Neural Regeneration Research2021,16,9: | 3 |
| 13 | Patterns of genomic and phenomic diversity in wine and table grapes显示文摘Grapes are one of the most economically and culturally important crops worldwide,and they have been bred for both winemaking and fresh consumption.Here we evaluate patterns of diversity across 33 phenotypes collected over a 17-year period from 580 table and wine grape accessions that belong to one of the world’s largest grape gene banks,the grape germplasm collection of the United States Department of Agriculture.We find that phenological events throughout the growing season are correlated,and quantify the marked difference in size between table and wine grapes.By pairing publicly available historical phenotype data with genome-wide polymorphism data,we identify large effect loci controlling traits that have been targeted during domestication and breeding,including hermaphroditism,lighter skin pigmentation and muscat aroma.Breeding for larger berries in table grapes was traditionally concentrated in geographic regions where Islam predominates and alcohol was prohibited,whereas wine grapes retained the ancestral smaller size that is more desirable for winemaking in predominantly Christian regions.We uncover a novel locus with a suggestive association with berry size that harbors a signature of positive selection for larger berries.Our results suggest that religious rules concerning alcohol consumption have had a marked impact on patterns of phenomic and genomic diversity in grapes. | ZoëMigicovsky Jason Sawler Kyle M Gardner Mallikarjuna K Aradhya Bernard H Prins Heidi R Schwaninger Carlos D Bustamante Edward S Buckler Gan-Yuan Zhong Patrick J Brown Sean Myles | 2017 | Horticulture Research2017,4,1: | 3 |
| 14 | 一种房颤风险评分系统的建立(Framingham心脏研究):基于社区的队列研究显示文摘背景房颤导致了发病率和病死率的显著上升。本研究旨在建立一种预测个体罹患房颤绝对风险的风险评分系统,并提供研究人员评价新危险因素的流程。方法作者评估了Framingham心脏研究中于1968年6月至1987年9月间进行了8044次检测的4764例参与者(55%为女性,年龄45~95岁)。此后,参与者被随访至房颤首发,随访期最长达10年。多变量Coxi回归确认出1(1年内罹患房颤的临床危险因素。次级分析纳入了常规超声心动图检测指标(5152例4参与者,7156次检测)对房颤风险进行再分层评估,并评价超声检测指标能否提高风险预测能力。结果4764例参与者中的457例4(10%)罹患房颤。年龄、性别、体重指数、收缩压、降压治疗、PR间期、有临床意义的心脏杂音及心力衰竭与房颤相关,并被纳入了风险评分模型(除体重指数P=0.08外,其余均为P〈0.05),模型的C统计量为0.78(95%CI0.76~0.80)。10年房颤风险随年龄变化:年龄〈65岁的人群中53例(1%)风险高于15%,而〉65岁的人群中为783例(27%)。为提高预测能力而纳入超声检测指标仅使模型C统计量略微增高,由0.78(95%C10.75~0.80)增至0.79(95%CI0.77~0.82:P=0.005)。超声心动图检测指标并不能改善风险再分层评估(P=0.18)。结论基于社区医疗中易得的临床因素建立的风险评分系统,有助于确认社区个体罹患房颤的风险,评估技术或标志物能否改善风险预测,以及针对高危个体采取预防措施。 | Renate B Schnabel Lisa M Sullivan Daniel Levy Michael J Pencina Joseph M Massaro Ralph B D'Agostino Sr Christopher Newton-Cheh Jennifer F Yamamoto Jared W Magnani Thomas M Tadros William B Kannel Thomas J Wang Patrick T Ellinor Philip A Wolf Ramachanclran S Vasan Emelia J Benjamin 黄刚(译) | 2009 | 世界临床医学2009,,9: | 2 |
| 15 | Galectin-3 Mediates Aldosterone-Induced Vascular Fibrosis显示文摘 | Laurent Calvier Maria Miana Pascal Reboul Victoria Cachofeiro Ernesto Martinez-Martinez Rudolf A. de Boer Fran?oise Poirier Patrick Lacolley Faiez Zannad Patrick Rossignol Natalia López-Andrés | 2013 | Arteriosclerosis, Thrombosis, and Vascular Biology2013,,1: | 2 |
| 16 | Outcomes after arthroscopic repair of rotator cuff tears in the setting of mild to moderate glenohumeral osteoarthritis显示文摘BACKGROUND Rotator cuff pathology is a very common source of shoulder pain.Similarly,osteoarthritis of the glenohumeral joint can cause shoulder pain and produce similar symptoms.Surgical management can be indicated for both pathologies,however,outcomes data is limited when examining rotator cuff repair(RCR) in the setting of glenohumeral arthritis(GHOA).Thus,this study sought to determine outcomes for patients who undergo RCR in the setting of GHOA.AIM To evaluate if a relationship exists between outcomes of RCR in the setting of GHOA.METHODS This was a retrospective analysis of patients who underwent arthroscopic rotator cuff repair with concurrent glenohumeral osteoarthritis between 2010-2017.Patients were stratified based on rotator cuff tear size and glenohumeral osteoarthritis severity.Cohorts were paired 1:1 with patients without glenohumeral osteoarthritis.Patients included had a minimum two year follow-up.Rate of conversion to total shoulder arthroplasty,complication rates following initial surgery,and patient-reported outcome measures were collected.RESULTS A total of 142 patients were included.The number of patients that required total shoulder arthroplasty within two years after index surgery was low.2/71(2.8%) patients with GHOA,and 1/71(1.4%) without GHOA.Following rotator cuff repair,both groups showed favorable patientreported outcomes.CONCLUSION Patients with glenohumeral osteoarthritis who underwent arthroscopic rotator cuff repair showed comparable outcomes to patients without glenohumeral osteoarthritis. | Ian S Hong Allison J Rao Tyler L CarlLee Joshua D Meade Daniel J Hurwit Gregory Scarola David P Trofa Shadley C Schiffern Nady Hamid Patrick M Connor James E Fleischli Bryan Michael Saltzman | 2022 | World Journal of Orthopedics2022,13,7: | 2 |
| 17 | Urban Modification of Thunderstorms: An Observational Storm Climatology and Model Case Study for the Indianapolis Urban Region*显示文摘 | Niyogi Dev Pyle Patrick Lei Ming Arya S Pal Kishtawal Chandra M Shepherd Marshall Chen Fei Wolfe Brian | 2011 | Journal of Applied Meteorology and Climatology2011,,5: | 2 |
| 18 | Crude Protein Content Determination of Potatoes by NIRS Technology显示文摘 | Ainara López Silvia Arazuri Carmen Jarén Jesús Mangado Pedro Arnal José Ignacio Ruiz de Galarreta Patrick Riga Raquel López | 2013 | Procedia Technology2013,,: | 2 |
| 19 | Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis显示文摘 | Pere Ginès Juan Uriz Blas Calahorra Guadalupe Garcia–Tsao Patrick S. Kamath Luis Ruiz Del Arbol Ramón Planas Jaime Bosch Vicente Arroyo Juan Rodés | 2002 | Gastroenterology2002,,6: | 2 |
| 20 | Contrasted effect of biochar and earthworms on rice growth and resource allocation in different soils显示文摘 | Diana Noguera Marco Rondón Kam-Rigne Laossi Valerio Hoyos Patrick Lavelle Maria Helena Cruz de Carvalho Sébastien Barot | 2010 | Soil Biology and Biochemistry2010,,7: | 2 |