Laboratory Infection

实验室感染
  • 文章类型: Journal Article
    实验室获得性感染(LAI)和实验室环境中的意外病原体逃逸(APELS)是社区的主要关注点。建议在标准生物安全管理框架内采用基于风险的病原体研究管理方法,但由于风险承受能力和感知不一致等原因而具有挑战性。这里,我们使用公开的方法进行了范围审查,2000年至2021年间对LAIs和APELS实例的同行评审期刊和媒体报道。我们在94份报告中的309名个体中鉴定了51种病原体的LAI。8例死亡(占所有LAIs的2·6%)是由脑膜炎奈瑟菌感染引起的(n=3,37·5%),鼠疫耶尔森氏菌(n=2,25%),沙门氏菌血清型鼠伤寒(鼠伤寒沙门氏菌;n=1,12·5%),或埃博拉病毒(n=1,12·5%)或由于牛海绵状脑病(n=1,12·5%)。LAI前五名病原菌为鼠伤寒沙门氏菌(n=154,49·8%),肠炎沙门氏菌(n=21,6·8%),痘苗病毒(n=13,4·2%),布鲁氏菌属(n=12,3·9%),和布鲁氏菌(n=11,3·6%)。报告了16例APELS,包括炭疽杆菌,SARS-CoV,和脊髓灰质炎病毒(每个n=3,18·8%);布鲁氏菌和口蹄疫病毒(n=2,12·5%);和天花病毒,假伯克霍尔德菌,和流感病毒H5N1(n=1,6·3%)。通过根本原因分析和对此类事件的彻底调查,持续改进LAI和APELS管理对于防止未来发生至关重要。由于对公开信息的依赖,结果存在偏见,强调需要正式的全球LAI和APELS报告,以更好地了解这些事件的频率和情况。
    Laboratory-acquired infections (LAIs) and accidental pathogen escape from laboratory settings (APELS) are major concerns for the community. A risk-based approach for pathogen research management within a standard biosafety management framework is recommended but is challenging due to reasons such as inconsistency in risk tolerance and perception. Here, we performed a scoping review using publicly available, peer-reviewed journal and media reports of LAIs and instances of APELS between 2000 and 2021. We identified LAIs in 309 individuals in 94 reports for 51 pathogens. Eight fatalities (2·6% of all LAIs) were caused by infection with Neisseria meningitidis (n=3, 37·5%), Yersinia pestis (n=2, 25%), Salmonella enterica serotype Typhimurium (S Typhimurium; n=1, 12·5%), or Ebola virus (n=1, 12·5%) or were due to bovine spongiform encephalopathy (n=1, 12·5%). The top five LAI pathogens were S Typhimurium (n=154, 49·8%), Salmonella enteritidis (n=21, 6·8%), vaccinia virus (n=13, 4·2%), Brucella spp (n=12, 3·9%), and Brucella melitensis (n=11, 3·6%). 16 APELS were reported, including those for Bacillus anthracis, SARS-CoV, and poliovirus (n=3 each, 18·8%); Brucella spp and foot and mouth disease virus (n=2 each, 12·5%); and variola virus, Burkholderia pseudomallei, and influenza virus H5N1 (n=1 each, 6·3%). Continual improvement in LAI and APELS management via their root cause analysis and thorough investigation of such incidents is essential to prevent future occurrences. The results are biased due to the reliance on publicly available information, which emphasises the need for formalised global LAIs and APELS reporting to better understand the frequency of and circumstances surrounding these incidents.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    真菌生长的蚂蚁依赖于真菌互助者,后者可能成为真菌病原体的牺牲品。这种互助者是由这些蚂蚁在称为真菌花园的结构中培养的。蚂蚁表现出除草行为,通过物理去除受损的碎片来保持真菌花园的健康。然而,蚂蚁如何检测其真菌花园的疾病是未知的。这里,我们使用环境真菌群落基因测序应用科赫的假设逻辑,真菌分离,和实验室感染实验,以确定木霉属。可以充当先前未识别的Trachymyrmexseptentrionalis真菌花园的病原体。我们的环境数据表明,木霉是野生T.septentrionalis真菌花园中最丰富的非品种真菌。我们进一步确定,木霉属产生的代谢物诱导蚂蚁除草反应,反映了它们对活木霉属的反应。将蚂蚁行为实验与木霉属提取物中代谢产物的生物活性指导分级分离和统计优先级相结合,证明了T.septentrionalis蚂蚁对peptaibol的响应会产生杂草,已知由木霉属真菌产生的一类特定的次级代谢产物。使用纯化的peptaibol进行类似的测定,包括两个先前未描述的peptaibles三环蛋白VIII和IX,表明除草可能是由peptaibol作为一类而不是由单个peptaibol代谢物引起的。除了他们在实验室实验中的存在,我们在野生真菌花园中检测到peptaibol。我们将环境数据和实验室感染实验相结合,强烈支持peptaibol作为木霉发病机理的化学线索。
    Fungus-growing ants depend on a fungal mutualist that can fall prey to fungal pathogens. This mutualist is cultivated by these ants in structures called fungus gardens. Ants exhibit weeding behaviors that keep their fungus gardens healthy by physically removing compromised pieces. However, how ants detect diseases of their fungus gardens is unknown. Here, we applied the logic of Koch\'s postulates using environmental fungal community gene sequencing, fungal isolation, and laboratory infection experiments to establish that Trichoderma spp. can act as previously unrecognized pathogens of Trachymyrmex septentrionalis fungus gardens. Our environmental data showed that Trichoderma are the most abundant noncultivar fungi in wild T. septentrionalis fungus gardens. We further determined that metabolites produced by Trichoderma induce an ant weeding response that mirrors their response to live Trichoderma. Combining ant behavioral experiments with bioactivity-guided fractionation and statistical prioritization of metabolites in Trichoderma extracts demonstrated that T. septentrionalis ants weed in response to peptaibols, a specific class of secondary metabolites known to be produced by Trichoderma fungi. Similar assays conducted using purified peptaibols, including the two previously undescribed peptaibols trichokindins VIII and IX, suggested that weeding is likely induced by peptaibols as a class rather than by a single peptaibol metabolite. In addition to their presence in laboratory experiments, we detected peptaibols in wild fungus gardens. Our combination of environmental data and laboratory infection experiments strongly support that peptaibols act as chemical cues of Trichoderma pathogenesis in T. septentrionalis fungus gardens.
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  • 文章类型: Journal Article
    Omicron及其亚谱系目前占主导地位,由于其高传播性和强大的免疫逃逸能力,在全球范围内引发了SARS-CoV-2的流行病学浪潮。疫苗是控制COVID-19负担的关键措施。自2022年3月以来,OmicronBA.2在上海引发了大规模疫情,导致超过60万例实验室确诊感染。上海市3岁及以上居民初次免疫疫苗覆盖率超过90%,COVID-19灭活疫苗主要交付。在疫苗覆盖率高的情况下,我们进行了一项队列研究,以评估疫苗在降低感染或非严重病例出现症状或疾病严重程度的概率方面的效果.共有48,243名符合条件的参与者被纳入本研究,其中大多数患有无症状感染(31.0%)和轻度至中度疾病(67.9%)。国内开发的COVID-19疫苗提供有限的保护,以防止无症状感染发展为轻度至中度疾病,并提供持久的保护,以防止非严重疾病发展为由OmicronBA.2引起的严重疾病。部分疫苗接种在任何情况下都不能提供有效的保护。与其他年龄组相比,80岁以上老年人的疫苗对疾病进展的影响水平相对较低。我们的研究结果为针对Omicron感染的疫苗性能提供了有力的证据,并可以提高疫苗的信心。
    Omicron and its sublineages are currently predominant and have triggered epidemiological waves of SARS-CoV-2 around the world due to their high transmissibility and strong immune escape ability. Vaccines are key measures to control the COVID-19 burden. Omicron BA.2 caused a large-scale outbreak in Shanghai since March 2022 and resulted in over 0.6 million laboratory-confirmed infections. The vaccine coverage of primary immunization among residents aged 3 years and older in Shanghai exceeded 90%, and inactivated COVID-19 vaccines were mainly delivered. In the context of high vaccine coverage, we conducted a cohort study to assess vaccine effects on reducing the probability of developing symptoms or severity of disease in infections or nonsevere cases. A total of 48,243 eligible participants were included in this study, the majority of whom had asymptomatic infections (31.0%) and mild-to-moderate illness (67.9%). Domestically developed COVID-19 vaccines provide limited protection to prevent asymptomatic infection from developing into mild-to-moderate illness and durable protection to prevent nonsevere illness from progressing to severe illness caused by Omicron BA.2. Partial vaccination fails to provide effective protection in any situation. The level of vaccine effects on disease progression in the elderly over 80 years old was relatively lower compared with other age groups. Our study results added robust evidence for the vaccine performance against Omicron infection and could improve vaccine confidence.
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  • 文章类型: Journal Article
    背景:这项研究比较了跨波的入院发生率风险,以及OmicronBA.4/BA.5波的死亡风险,到OmicronBA.1/BA.2和Delta波。
    方法:来自南非国家医院监测系统的数据,对SARS-CoV-2病例名单和电子疫苗数据系统进行了链接和分析。当该国每周发生30例/100,000人时,定义了波浪期。三角洲地区的住院病死率(CFR),采用插补后随机效应多变量Logistic回归模型比较了OmicronBA.1/BA.2和OmicronBA.4/BA.5波周期。
    结果:CFR为25.9%(N=37,538/144,778),三角洲地区的10.9%(N=6,123/56,384)和8.2%(N=1,212/14,879),OmicronBA.1/BA.2和OmicronBA.4/BA.5波分别。在调整了年龄之后,性别,种族,合并症,卫生部门和省,与OmicronBA.4/BA.5波相比,在OmicronBA.1/BA.2波(校正比值比[aOR]1.3;95%置信区间[CI]1.2~1.4)和Delta波(aOR3.0;95%CI2.8~3.2)中,患者的死亡风险较高.部分接种疫苗(aOR0.9,CI0.9-0.9),完全接种(aOR0.6,CI0.6-0.7)和加强(aOR0.4,CI0.4-0.5);和先前实验室确认的感染(aOR0.4,CI0.3-0.4)与死亡率风险降低相关。
    结论:总体而言,入院风险和住院死亡率,在南非的前三波浪潮中逐渐增加,在第四次O微米BA.1/BA.2波中下降,在第五次O微米BA.4/BA.5波中进一步下降。自然感染和疫苗接种者的死亡风险较低,随着疫苗剂量的增加,进一步下降。
    In this study, we compared admission incidence risk and the risk of mortality in the Omicron BA.4/BA.5 wave to previous waves.
    Data from South Africa\'s SARS-CoV-2 case linelist, national COVID-19 hospital surveillance system, and Electronic Vaccine Data System were linked and analyzed. Wave periods were defined when the country passed a weekly incidence of 30 cases/100 000 population. In-hospital case fatality ratios (CFRs) during the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves were compared using post-imputation random effect multivariable logistic regression models.
    The CFR was 25.9% (N = 37 538 of 144 778), 10.9% (N = 6123 of 56 384), and 8.2% (N = 1212 of 14 879) in the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves, respectively. After adjusting for age, sex, race, comorbidities, health sector, and province, compared with the Omicron BA.4/BA.5 wave, patients had higher risk of mortality in the Omicron BA.1/BA.2 wave (adjusted odds ratio [aOR], 1.3; 95% confidence interval [CI]: 1.2-1.4) and Delta wave (aOR, 3.0; 95% CI: 2.8-3.2). Being partially vaccinated (aOR, 0.9; 95% CI: .9-.9), fully vaccinated (aOR, 0.6; 95% CI: .6-.7), and boosted (aOR, 0.4; 95% CI: .4-.5) and having prior laboratory-confirmed infection (aOR, 0.4; 95% CI: .3-.4) were associated with reduced risks of mortality.
    Overall, admission incidence risk and in-hospital mortality, which had increased progressively in South Africa\'s first 3 waves, decreased in the fourth Omicron BA.1/BA.2 wave and declined even further in the fifth Omicron BA.4/BA.5 wave. Mortality risk was lower in those with natural infection and vaccination, declining further as the number of vaccine doses increased.
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  • 文章类型: Journal Article
    豚鼠是用于研究斑点发烧立克次体病(SFR)的原始动物模型。由于豚鼠对SFR剂的传播的促进作用以及通过包括发烧在内的临床体征在人类中概括SFR的能力,该模型系统得以持续。萎靡不振,在某些情况下还有焦痂的发展。豚鼠是SFR的最小动物模型,可以在死前收集多个血液和皮肤样本进行纵向研究。该单元提供了建立所需的基本协议,保持,并利用豚鼠-蜱-立克次体模型监测斑点热组立克次体(SFGR)的感染过程和对感染的免疫反应,可以在生物安全水平2(BSL-2)和节肢动物遏制水平2(ACL-2);必须对BSL-3试剂进行适应。协议涵盖了蜱虫喂食和菌落发育的方法,蜱的实验室感染,立克次体蜱传播给豚鼠,并通过临床体征监测感染过程,立克次体的负担,和免疫反应。采用这些方法研究其他蜱传病原体应该是可行的。©2022作者WileyPeriodicalsLLC出版的当前协议。基本方案1:SFGR向豚鼠的滴答传递支持方案1:通过注射对蜱进行实验室感染替代方案1:对豚鼠进行针头接种SFGR基本方案2:监测豚鼠立克次体感染的过程:临床体征基本方案3:监测豚鼠立克次体感染的过程支持方案2:通过免疫流式细胞术对豚鼠的免疫反应方案4:通过免疫流式细胞术对豚鼠的免疫反应方案5:通过免疫免疫免疫免疫免疫免疫免疫免疫
    The guinea pig was the original animal model developed for investigating spotted fever rickettsiosis (SFR). This model system has persisted on account of the guinea pig\'s conduciveness to tick transmission of SFR agents and ability to recapitulate SFR in humans through clinical signs that include fever, unthriftiness, and in some cases the development of an eschar. The guinea pig is the smallest animal model for SFR that allows the collection of multiple blood and skin samples antemortem for longitudinal studies. This unit provides the basic protocols necessary to establish, maintain, and utilize a guinea pig-tick-Rickettsia model for monitoring the course of infection and immune response to an infection by spotted fever group Rickettsia (SFGR) that can be studied at biosafety level 2 (BSL-2) and arthropod containment level 2 (ACL-2); adaptations must be made for BSL-3 agents. The protocols cover methods for tick feeding and colony development, laboratory infection of ticks, tick transmission of Rickettsia to guinea pigs, and monitoring of the course of infection through clinical signs, rickettsial burden, and immune response. It should be feasible to adapt these methods to study other tick-borne pathogens. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Tick transmission of SFGR to guinea pigs Support Protocol 1: Laboratory infection of ticks by injection Alternate Protocol 1: Needle inoculation of SFGR to guinea pigs Basic Protocol 2: Monitoring the course of guinea pig rickettsial infection: clinical signs Basic Protocol 3: Monitoring the course of guinea pig rickettsial infection: collection of biological specimens Support Protocol 2: Guinea pig anesthesia Basic Protocol 4: Monitoring rickettsial burden in guinea pigs by multiplex qPCR Basic Protocol 5: Monitoring guinea pig immune response to infection: blood leukocytes by flow cytometry Basic Protocol 6: Monitoring immune response to guinea pig rickettsial infection: leukocyte infiltration of skin at the tick bite site by flow cytometry Basic Protocol 7: Monitoring the immune response to guinea pig rickettsial infection: antibody titer by ELISA Support Protocol 4: Coating ELISA Plates Alternate Protocol 2: Monitoring immune response to guinea pig rickettsial infection: antibody titer by immunofluorescence assay.
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  • 文章类型: Journal Article
    对从事病原和传染病剂工作的微生物实验室人员的最重要要求之一是遵守预防措施和实施一套预防措施,统称为生物安全(生物安全)。在很大程度上,生物安全问题也与所有使用生物底物的临床实验室有关,其中含有血源性感染病原体的潜在威胁。2020年12月30日,俄罗斯联邦总统签署联邦法律第492号“关于俄罗斯联邦的生物安全”(第492号FZ),它规范了生物安全问题的基本法律规范和监管,以及一系列措施,以防止由于事故而导致感染传播的风险,生物恐怖主义行为和破坏活动.目前冠状病毒感染COVID-19的大流行表明,一方面,单一世界空间的流行病学脆弱性,另一方面,生物紧急情况对国际社会负面政治和经济进程的出现的决定性影响。在这方面,在保护人员和环境免受意外或无意感染传播的背景下,确保微生物实验室工作中的生物安全问题是相关的。在微生物实验室中使用致病性生物制剂经常与员工的事故风险和可能的实验室感染(实验室获得性感染)相关,如果不符合生物安全法规文件的要求,则会造成环境污染。根据第492-FZ条的要求,为了防止生物威胁,在处理任何受感染材料时,有必要建立一个监测微生物实验室生物风险的系统。
    One of the most important requirements for the personnel of microbiological laboratories working with pathogenic and infectious agents is the observance of precautionary measures and the implementation of a set of preventive measures, collectively interpreted as biological safety (biosafety). To a large extent, biosafety problems are also relevant for all clinical laboratories working with biosubstrates, with the potential threat of containing pathogens of bloodborne infections in them. On December 30, 2020, the President of the Russian Federation signed Federal Law № 492 «On the Biological Safety of the Russian Federation» (№ 492-FZ), which regulates the basic legal norms and regulation of biosafety issues, as well as a list of measures to prevent the risks of the spread of infections due to accidents, bioterrorist acts and sabotage. The current pandemic of the coronavirus infection COVID-19 has demonstrated, on the one hand, the epidemiological vulnerability of the single world space, and on the other hand, the decisive influence of biological emergencies on the emergence of negative political and economic processes in the world community. In this regard, the issues of ensuring biosafety in the work of microbiological laboratories in the context of protecting personnel and the environment from accidental or unintentional spread of infections are relevant. Working with pathogenic biological agents in microbiological laboratories is constantly associated with the risk of accidents and possible laboratory infection (laboratory-acquired infections) of employees, environmental pollution if the requirements of regulatory documents on biological safety are not met. In accordance with the requirements of № 492-FZ, in order to prevent biological threats, it is necessary to create a system for monitoring biological risks in microbiological laboratories when working with any infected material.
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  • 文章类型: Journal Article
    实验室获得的大肠杆菌O157:H7感染与包括溶血性尿毒症综合征在内的严重后遗症相关,发生在实验室工作的个体中,该个体在土壤-生物炭混合物中混合了耐萘啶酸(NalR)O157:H7突变菌株。该患者住院并接受甲硝唑和左氧氟沙星的静脉组合治疗。本研究调查了这种严重的实验室获得性感染的来源,并进一步检查了治疗期间使用的抗生素对志贺毒素表达和产生的影响。对从患者粪便中分离出的两个Stx2a和eae阳性O157:H7菌株的基因组以及两对wt菌株及其衍生的NalR突变体进行了测序。高分辨率SNP分型确定了菌株的个体遗传相关性,并明确确定了两个实验室衍生的NalR突变菌株为研究人员威胁生命的疾病的来源,而不是可以想象的摄入同时循环的无关的O157:H7分离株。进一步证实,在亚致死剂量下,抗生素增加了毒素的表达和产生。我们的结果支持在实验室中与临床菌株同时合并感染,是之前O157:H7爆发的病原体,此外,抗生素的使用可能会影响感染的结果。
    A laboratory-acquired E. coli O157:H7 infection with associated severe sequelae including hemolytic uremic syndrome occurred in an individual working in the laboratory with a mixture of nalidixic acid-resistant (NalR) O157:H7 mutant strains in a soil-biochar blend. The patient was hospitalized and treated with an intravenous combination of metronidazole and levofloxacin. The present study investigated the source of this severe laboratory acquired infection and further examined the influence of the antibiotics used during treatment on the expression and production of Shiga toxin. Genomes of two Stx2a-and eae-positive O157:H7 strains isolated from the patient\'s stool were sequenced along with two pairs of the wt strains and their derived NalR mutants used in the laboratory experiments. High-resolution SNP typing determined the strains\' individual genetic relatedness and unambiguously identified the two laboratory-derived NalR mutant strains as the source of the researcher\'s life-threatening disease, rather than a conceivable ingestion of unrelated O157:H7 isolates circulating at the same time. It was further confirmed that in sublethal doses, the antibiotics increased toxin expression and production. Our results support a simultaneous co-infection with clinical strains in the laboratory, which were the causative agents of previous O157:H7 outbreaks, and further that the administration of antibiotics may have impacted the outcome of the infection.
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  • 文章类型: Journal Article
    兰州一家生物制药厂的消毒工艺不足,中国,在2019年7月和8月期间,导致布鲁氏菌的雾化,随后通过风传播到附近的定居点和学术机构,导致>10000例人类布鲁氏菌病病例,截至2020年11月。泄漏,可能是传染病史上最大的实验室事故,强调布鲁氏菌的特殊特征,使病原体成为生物防御研究中的历史实体,也是实验室相关感染的主要原因。它进一步强调了对类似设施提高警惕和严格监管干预的必要性。
    An inadequacy in sanitizing processes in a biopharmaceutical plant in Lanzhou, China, during July and August 2019, led to the aerosolization of Brucella that was subsequently spread through wind to nearby settlements and academic institutes, resulting in >10 000 human brucellosis cases, as of November 2020. The leak, possibly the largest laboratory accident in the history of infectious diseases, underlines the particular characteristics of Brucella that have made the pathogen a historical entity in biodefense research and a major cause of laboratory-associated infections. It further underlines the need for enhanced vigilance and strict regulatory interventions in similar facilities.
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  • 文章类型: Journal Article
    发展中国家在实验室实施生物风险管理系统方面面临各种挑战。此外,教育环境被认为是有生物危害风险的工作场所。实验室设施中的每项活动都会带来许多潜在危害,可能会影响人类健康和环境,并可能导致实验室事故,包括实验室获得性感染(LAIs)。为了尽量减少这些事件的影响和发生,有必要评估涉及处理生物制剂的每项活动中生物风险管理系统的实施情况。这项研究是在印度尼西亚的一所高等教育机构中进行的,这里编码为Y大学。这是一个描述性的,半定量研究旨在通过分析每个实验室获得的成就来分析和评估实验室中使用的生物风险管理系统的实施情况。该研究使用了使用清单收集的主要数据,该清单参考了ISO35001:2019关于实验室生物风险管理的清单。清单由202个项目组成,构成七个主要要素。此外,还使用了从文献和文献综述获得的次要数据.结果显示,在11个实验室中,只有2个实验室满足了50%的要求,实验室A和B,实现良好的性能。关于标准的条款,差距分析确定了领导力,绩效评估,和支持作为成就最低的元素。因此,纠正措施应通过加强管理层的承诺和改进文件来制定,政策,教育和培训。
    Developing countries face various challenges in implementing bio-risk management systems in the laboratory. In addition, educational settings are considered as workplaces with biohazard risks. Every activity in a laboratory facility carries many potential hazards that can impact human health and the environment and may cause laboratory incidents, including Laboratory Acquired Infections (LAIs). In an effort to minimize the impact and occurrence of these incidents, it is necessary to evaluate the implementation of a bio-risk management system in every activity that involves handling biological agents. This study was conducted in an Indonesian higher-education institution, herein coded as University Y. This is a descriptive, semi-quantitative study aimed at analysing and evaluating the implementation of the bio-risk management systems used in laboratories by analysing the achievements obtained by each laboratory. The study used primary data that were collected using a checklist which referred to ISO 35001:2019 on Laboratory Bio-risk Management. The checklist consisted of 202 items forming seven main elements. In addition, secondary data obtained from literature and document review were also used. The results show that out of 11 laboratories examined, only 2 laboratories met 50% of the requirements, which were Laboratory A and B, achieving good performance. Regarding the clauses of standards, a gap analysis identified leadership, performance evaluation, and support as elements with the lowest achievement. Therefore, corrective action should be developed by enhancing the commitment from management as well as improving documentation, policy, education and training.
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