Procedia in vaccinology最新文献

{"title":"Alternative methods and strategies to reduce, refine, and replace animal use for veterinary vaccine post-licensing safety testing: state of the science and future directions","authors":"Jodie Kulpa-Eddy ,&nbsp;Geetha Srinivas ,&nbsp;Marlies Halder ,&nbsp;Karen Brown ,&nbsp;Hans Draayer ,&nbsp;Jeffrey Galvin ,&nbsp;Ivo Claassen ,&nbsp;Glen Gifford ,&nbsp;Ralph Woodland ,&nbsp;Vivian Doelling ,&nbsp;Brett Jones ,&nbsp;William S Stokes","doi":"10.1016/j.provac.2011.10.007","DOIUrl":"10.1016/j.provac.2011.10.007","url":null,"abstract":"<div><p>NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. Six topics were addressed in detail by speakers and workshop participants and are reported in a series of six reports. This workshop report, the last in the series, addresses methods and strategies for veterinary vaccine post-licensing safety testing that can reduce, refine, and replace animal use (the 3Rs). It also provides recommendations for priority research and other activities necessary to advance the development and/or implementation of 3Rs methods for veterinary vaccine post-licensing safety testing. Workshop participants gave priority for future efforts to vaccines that (1) use large numbers of animals per test, (2) produce large numbers of serials annually, (3) use additional animals for safety testing. They also prioritized poultry vaccines for which <em>in vivo</em> extraneous agent testing is still performed, adjuvanted vaccines that cause a site reaction, and vaccines that are well characterized. Vaccines identified as the highest priorities were those for avian diseases, rabies, <em>Clostridium spp</em>., and subunit protein and DNA vaccines, in addition to modified live viral products that do not contain excipients. Workshop participants recommended priority research, development, and validation activities to address critical knowledge and data gaps, including opportunities to apply new science and technology. Recommendations included further assessment of the need for a general safety test; expanded application of primary cell culture and polymerase chain reaction (PCR) techniques to replace <em>in vivo</em> chicken tests for extraneous agents; development of in-process safety testing to verify detoxification of selected vaccines; and further investigation of cell-based assays to measure residual toxicity. Implementation of the workshop recommendations is expected to advance alternative methods for veterinary vaccine post-licensing safety testing that will benefit animal welfare and reduce or replace animal use while ensuring continued protection of human and animal health.</p></div>","PeriodicalId":89221,"journal":{"name":"Procedia in vaccinology","volume":"5 ","pages":"Pages 106-119"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.provac.2011.10.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54989215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Animal Refinement and Reduction: Alternative Approaches for Potency Testing of Diphtheria and Tetanus Vaccines","authors":"Paul Stickings ,&nbsp;Peter Rigsby ,&nbsp;Laura Coombes ,&nbsp;Jason Hockley ,&nbsp;Rob Tierney ,&nbsp;Dorothea Sesardic","doi":"10.1016/j.provac.2011.10.020","DOIUrl":"10.1016/j.provac.2011.10.020","url":null,"abstract":"<div><p>Evaluation and quality control of diphtheria and tetanus vaccines have traditionally relied on the use of <em>in vivo</em> protection models involving challenge of laboratory animals with toxins. However, for routine lot release, validated serological assays are routinely being used that offer significant advantages in terms of reduction in animal numbers because responses to multiple vaccine components can be measured in a single group. Use of a serological assay also represents a refinement of procedures since the requirement for toxin challenge is removed. The National Institute for Biological Standards and Control (NIBSC, UK) contributed to international validation studies on the use of serology for diphtheria and tetanus potency testing, which led to revisions of the relevant European Pharmacopoeia method chapters. Here we describe the impact of routine use of a serological assay for testing diphtheria and tetanus components of a combined vaccine used for primary immunization of children as part of the UK immunization schedule. Opportunities for further reduction in animal numbers are also discussed.</p></div>","PeriodicalId":89221,"journal":{"name":"Procedia in vaccinology","volume":"5 ","pages":"Pages 200-212"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.provac.2011.10.020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54989735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approaches to reducing animal numbers in vaccine potency testing","authors":"Jodie Kulpa-Eddy ,&nbsp;Geetha Srinivas","doi":"10.1016/j.provac.2011.10.023","DOIUrl":"10.1016/j.provac.2011.10.023","url":null,"abstract":"<div><p>Vaccine potency testing is conducted to provide manufacturers and regulatory officials information regarding the potency of vaccine products prior to market release. Post-licensing potency test protocols are often described and incorporated into regulation or guidance documents. This provides manufacturers with a consistent and uniform framework to follow for market release. Some of these protocols are based on widely accepted international test methods; others have been in existence for decades and were based on the best scientific information available at that time. In an effort to ensure that vaccine testing conducted on live animals provides optimal animal welfare, alternative test methods incorporating reduction, replacement, and refinement techniques should be considered and used when appropriate. Russell and Burch, in <em>The Principles of Humane Experimental Technique</em>, define <em>reduction</em> as “reduction in the numbers of animals used to obtain information of a given amount and precision.” This paper will focus on three methods of reducing the number of animals used for potency testing. These reduction methods include (1) a change in experimental design, (2) a change based on statistical review, and (3) changes resulting from the harmonization of test requirements.</p></div>","PeriodicalId":89221,"journal":{"name":"Procedia in vaccinology","volume":"5 ","pages":"Pages 227-231"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.provac.2011.10.023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54989767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccine Safety: An examination of the value and necessity of Phase III trials","authors":"R.E. Spier","doi":"10.1016/j.provac.2011.07.001","DOIUrl":"10.1016/j.provac.2011.07.001","url":null,"abstract":"<div><p>Phase III trials of vaccines may be holding back the benefits of, and increasing the costs of vaccines, to an extent that is harmful to society. The safety of a vaccine is assessed, in the main, in Phases I and II trials. Were Phase III trials to be rendered unnecessary, it would be desirable to more extensively and stringently examine the performance of the vaccine in the field as part of a post licensure Phase IV exercise. The acceptance of such costs (risk of disbenefit * the magnitude of the disbenefit) is discussed in relation to costs that are commonly incurred while engaged in a modern 21st century life.</p></div>","PeriodicalId":89221,"journal":{"name":"Procedia in vaccinology","volume":"4 ","pages":"Pages 1-8"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.provac.2011.07.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54988989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Production and purification of recombinant fragment of pneumococcal surface protein A (PspA) in Escherichia coli","authors":"Giovana C. Barazzone ,&nbsp;Rimenys Carvalho Jr. ,&nbsp;Stefanie Kraschowetz ,&nbsp;Antonio L. Horta ,&nbsp;Cíntia R. Sargo ,&nbsp;Adilson J. Silva ,&nbsp;Teresa C. Zangirolami ,&nbsp;Cibelly Goulart ,&nbsp;Luciana C.C. Leite ,&nbsp;Martha M. Tanizaki ,&nbsp;Viviane M. Gonçalves ,&nbsp;Joaquin Cabrera-Crespo","doi":"10.1016/j.provac.2011.07.005","DOIUrl":"10.1016/j.provac.2011.07.005","url":null,"abstract":"<div><p>New conjugated vaccines against <em>Streptococcus pneumoniae</em> are being developed using pneumococcal surface proteins as carriers. The pneumococcal surface protein A (PspA) was selected as carrier because it is indispensable for virulence of <em>S. pneumoniae</em>. The PspA can be classified into 3 families according to the homology of protein sequences, within each family there is immunological cross-reactivity and PspA from family 1 or 2 are present in 99% of strains associated with pneumococcal invasive disease. Hence, the purpose of this work was to develop an industrial production and purification process of His-tagged recombinant fragment of PspA in <em>E. coli</em> BL21 (DE3), rfPspA245 from family 1. Fed-batch cultivations in 5-L bioreactors with defined medium were carried out using glycerol as carbon source. It was obtained circa 60<!--> <!-->g/L of dry cell weight and 3.0<!--> <!-->g/L of rfPspA. Cells were disrupted with 96.7% of efficiency by high pressure continuous homogenizer. The clarification step was done by centrifugation. The results of chromatographic steps were analyzed by densitometry of SDS-PAGE protein bands. Using the chromatographic sequence anion exchange (Q-Sepharose) followed by metal affinity (IMAC-Sepharose), the rfPspA245 was obtained with 67% and 97% of purity respectively for each step and final recovery of 23%. In conclusion, the purification process was developed and rfPspA245 was obtained with high purity, but the recovery should still be improved.</p></div>","PeriodicalId":89221,"journal":{"name":"Procedia in vaccinology","volume":"4 ","pages":"Pages 27-35"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.provac.2011.07.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54989026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical evaluation of influenza vaccines based on replication-deficient poxvirus vector MVA","authors":"Guus F. Rimmelzwaan ,&nbsp;Joost H.C.M. Kreijtz ,&nbsp;Yasemin Suezer ,&nbsp;Astrid Schwantes ,&nbsp;Albert D.M.E. Osterhaus ,&nbsp;Gerd Sutter","doi":"10.1016/j.provac.2011.07.011","DOIUrl":"10.1016/j.provac.2011.07.011","url":null,"abstract":"<div><p>The zoonotic transmissions of highly pathogenic avian influenza viruses of the H5N1 subtype hat occur since 1997 have sparked the development of novel influenza vaccines. The advent of reverse genetics technology, cell culture production techniques and novel adjuvants has improved the vaccine strain preparation, the production process and the immunogenicity of the vaccines respectively and would accelerated the availability of pandemic influenza vaccines. However, there is still room for improvement and alternative vaccine preparations are explored such as recombinant antigens (e.g. baculovirus expression) and viral vectors. Modified Vaccinia virus Ankara (MVA), originally developed as a safe smallpox vaccine can be exploited as a viral vector. It has favourable properties, which makes it an attractive candidate as a pandemic influenza vaccine (for review see reference <span>[1]</span>). Recently we have evaluated a MVA-based vaccine for highly pathogenic influenza virus of the H5N1 subtype in mice and macaques. To this end, recombinant MVA was constructed expressing the gene encoding the hemagglutinin of H5N1 influenza virus A/Vietnam/1194/04 (clade 1) (MVA-HA-VN/04) and used to immunize C57BL/6 mice and cynomolgus macaques (macaca fascicularis). Two immunizations induced strong virus specific antibody responses in both species and protected the animals from the development of severe disease observed in control animals inoculated with empty MVA vector or PBS after challenge infection with the homologous or the antigenically distinct influenza virus A/Indonesia/5/05 (clade 2.1). In vaccinated animals virus replication in the respiratory tract was not detectable and the development of histopathological changes in the lungs was prevented. Furthermore, a MVA-based 2009 pandemic H1N1 vaccine protected against severe disease in a pH1N1 ferret model. The preclinical evaluation of MVA-based candidate vaccines indicated that they have potential as vaccines against highly pathogenic H5N1 and pH1N1 influenza viruses. The MVA-based vaccines proved to be immunogenic and induced broad-protective immune responses. MVA has favourable properties for the production, storage and use as a pandemic influenza vaccine and further clinical development seems warranted.</p></div>","PeriodicalId":89221,"journal":{"name":"Procedia in vaccinology","volume":"4 ","pages":"Pages 78-83"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.provac.2011.07.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54989067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perspective of using the recombinant DNA-technology to control the spread of the African swine fever","authors":"N.N. Vlasova,&nbsp;V.M. Balyshev,&nbsp;A.S. Kazakova","doi":"10.1016/j.provac.2011.07.013","DOIUrl":"10.1016/j.provac.2011.07.013","url":null,"abstract":"<div><p>The causative agent of ASF is a large deoxyvirus that has been assigned to <em>Asfarviridae</em> family. Previous studies have shown that ASFV p54 and p30 are essential viral proteins involved in the early steps of viral infection, whereas the adsorption of ASFV to susceptible cells is mediated by the structural virus protein p12, located within the outer envelope of the virion. It is believed that the lack of efficient ASFV vaccines might be due to unique molecular and biological properties of ASFV proteins responsible for virus–cell interactions: p30, p54 and p12. In this report, we describe the effect of <em>in vitro</em> blockage of ASF virus–cell interactions mediated by p54, p30 and p12. Computer analysis of p54 gene sequences of different ASFV field strains form GenBank was performed. According to this analysis ASFV viruses were distributed in several groups matching their serotype classification developed at our institute earlier. Immunization of rabbits with recombinant p54, p12 or p30 proteins induced antibodies which inhibited virus attachment or internalization. The serum of rabbits immunized with p54 of Magadi strain prevented virus attachment of Magadi group viruses only. In contrast, the serum from rabbits immunized with p30 (Magadi strain) rendered an <em>in vitro</em> inhibition of different ASFV groups replication.</p></div>","PeriodicalId":89221,"journal":{"name":"Procedia in vaccinology","volume":"4 ","pages":"Pages 92-99"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.provac.2011.07.013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54989091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of Currently Approved Serological Methods with a Focus On Diphtheria and Tetanus Toxoid Potency Testing","authors":"James E. Keller","doi":"10.1016/j.provac.2011.10.019","DOIUrl":"10.1016/j.provac.2011.10.019","url":null,"abstract":"<div><p>Vaccines are biological products made from living organisms. The natural complexity of biological molecules along with the inherent uncertainties of product manufacturing introduces the likelihood that random alterations can impact the quality of the vaccine each time it is made. The factors that can affect the final product are often unknown. Testing for potency of vaccine bulk or product dispensed into final containers was designed with the hope of ensuring that a vaccine is effective when used during its approved dating period and that its protective activity was not inadvertently altered during any phase of production. Ideally, potency testing measures a biological or biochemical property of the vaccine that is related to its ability to elicit protective immunity in the target population and provide some assurance that consistent clinical benefit is derived from each lot of product. Potency methods vary depending on the nature and composition of the vaccine. <em>In vivo</em> potency testing might entail immunizing groups of laboratory animals and then challenging them directly to measure survival, or involve serological potency assays in which sera from immunized laboratory animals are tested for the ability to neutralize pathogens or toxins. In the U.S., diphtheria toxoid and tetanus toxoid potency tests have customarily involved a serological method. This approach uses fewer animals than would have been required using a direct challenge method, while providing satisfactory evidence that each toxoid lot could induce protective immunity. This paper will discuss the details of the original U.S. test method for diphtheria and tetanus toxoid potency and present issues that must be considered when developing and validating non-animal-based approaches to refine or replace these tests.</p></div>","PeriodicalId":89221,"journal":{"name":"Procedia in vaccinology","volume":"5 ","pages":"Pages 192-199"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.provac.2011.10.019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54989716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Humane endpoints in vaccine potency testing","authors":"Coenraad F.M. Hendriksen","doi":"10.1016/j.provac.2011.10.022","DOIUrl":"10.1016/j.provac.2011.10.022","url":null,"abstract":"<div><p>Vaccine potency and safety testing is characterized by extensive use of laboratory animals and a relatively high percentage of test methods that involve severe pain and distress. This is particularly true for tests that are based on infection or challenge with a virulent microorganism. Traditionally, vaccine potency tests on inactivated vaccines require a vaccination–challenge procedure using severe clinical signs or even lethality as endpoints. For several of these vaccines, 3R methods have been developed that include a nonclinical endpoint, ultimately resulting in reduction of animal numbers and a significant decrease in severity level. An example is the use of serology in potency testing of tetanus and diphtheria toxoid vaccines. For some potency tests, however, replacement of the challenge procedure is not (yet) possible, and the implementation of humane endpoints might be an approach to limit the level and duration of pain and distress. The application of these endpoints is now allowed in most pharmacopoeias. Establishing humane endpoints in vaccine potency testing requires the identification of parameters that are predictive of death, or severe clinical signs, in the animal during the observation period. As a case study, we present the results of work we performed on the identification of humane endpoints in whole cell pertussis (wP) vaccine potency testing (the mouse protection test or the Kendrick test). In this potency test, mice are challenged by intracerebral route 14 days after immunization with a lethal dose of virulent <em>B. pertussis</em> microorganisms. Animals are observed for 14 days, and the number of mice per dose group surviving this period is used for probit analysis and estimation of potency. We have studied two types of humane endpoints: clinical signs and pathophysiological parameters (body weight and body temperature). Clinical signs in a wP potency test range from piloerection, hunched back posture, apathy, and convulsions to moribund condition. Also body temperature drops, and animals lose up to 50% of their body weight post-challenge. Parameters were “validated” for relevance (prediction of death within the observation period) and reliability. Recommendations are given for implementation of humane endpoints in vaccine potency testing, also taking into account potential obstacles.</p></div>","PeriodicalId":89221,"journal":{"name":"Procedia in vaccinology","volume":"5 ","pages":"Pages 221-226"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.provac.2011.10.022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54989759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Target alternative vaccine safety testing strategies for pertussis toxin","authors":"Juan L Arciniega ,&nbsp;Laura Corvette ,&nbsp;Henry Hsu ,&nbsp;Freyja Lynn ,&nbsp;Theresa Romani ,&nbsp;Roland Dobbelaer","doi":"10.1016/j.provac.2011.10.026","DOIUrl":"10.1016/j.provac.2011.10.026","url":null,"abstract":"<div><p>All acellular pertussis (aP) vaccines in use contain chemically inactivated pertussis toxin (PT). The finding that mice, naturally resistant to the effects of histamine, become sensitive upon injection of minute amounts of PT, led to the development of the test for residual PT known as the histamine sensitization assay (HSA). The HSA used by U.S.-licensed manufacturers is a limit test that shows that the residual bioactivity of PT in a single human dose of vaccine is below a threshold. Limit tests do not allow quantitative measurement. When the method is newly established at the point of use, three or more dilutions of pure PT are used to verify that mice injected with the vaccine came from a shipment that have sensitivity consistent with historical values. Sensitizability is expressed as an HSD₅₀ (the dose that sensitizes 50% of a group of mice). However, once linearity of the dose response has been demonstrated, the assay may be simplified so as to include in each test only a single control group injected with PT. This assay simplification constitutes an example of the so-called “consistency approach.” A Japanese variant of the HSA uses a drop in body temperature as a nonlethal alternative index of PT-mediated sensitization and can provide a quantitative estimate of the residual PT activity of a vaccine. However, the advantage of a quantitative method is not obvious, because the amount of PT that is unsafe for humans is unknown. In addition, although the use of a nonlethal endpoint constitutes an important refinement, the need for a reference group in the test to obtain a quantitative estimate increases the number of animals required, relative to the number used in a simplified limit test. Moreover, the nonlethal endpoint might be adapted to the limit test format, and important steps have been taken in this regard. Finally, one option under early evaluation is the possibility of using the results from two <em>in vitro</em> assays, an enzymatic activity assay and a binding assay, to replace the HSA.</p></div>","PeriodicalId":89221,"journal":{"name":"Procedia in vaccinology","volume":"5 ","pages":"Pages 248-260"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.provac.2011.10.026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54989795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}